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Pseudomonas aeruginosa: Infections, Animal Modeling, and Therapeutics

Stephen J. Wood, Timothy M. Kuzel, Sasha H. Shafikhani

Cells · 2023 · Review · CC BY

doi:10.3390/cells12010199

Abstract

Pseudomonas aeruginosa is an important Gram-negative opportunistic pathogen which causes many severe acute and chronic infections with high morbidity, and mortality rates as high as 40%. What makes P. aeruginosa a particularly challenging pathogen is its high intrinsic and acquired resistance to many of the available antibiotics. In this review, we review the important acute and chronic infections caused by this pathogen. We next discuss various animal models which have been developed to evaluate P. aeruginosa pathogenesis and assess therapeutics against this pathogen. Next, we review current treatments (antibiotics and vaccines) and provide an overview of their efficacies and their limitations. Finally, we highlight exciting literature on novel antibiotic-free strategies to control P. aeruginosa infections.

Full text

From PubMed Central, U.S. National Library of Medicine, as current on Oct 20, 2026. Paragraph numbers are ours, so an answer can point at one.

1. Introduction

Charles-Emmanuel Sédillot, a French military physician, was the first to reference an infection involving Pseudomonas aeruginosa in 1850. Sédillot described how surgical dressings of patients both in the field and hospital beds often became colored with a blue-green substance having a grape-like sweet odor, which we now know as the diagnostic hallmarks of P. aeruginosa infections, due to pyocyanin and 2-aminoacetophenone productions, respectively. Thirty years later in 1882, a French pharmacist by the name of Carle Gessard reported the successful isolation of P. aeruginosa which he initially termed Bacillis pyocyaneus, in a publication entitled “On the blue and green coloration of bandages”. It is not surprising that the site of the infection these authors described were wound dressings of surgical incisions given that wounds are preferred niches for P. aeruginosa infection. After many taxonomic revisions over the past 100 years, at present, the Pseudomonas aeruginosa species is identified on the basis of 16S rRNA and genomic sequence comparisons, analysis of the cellular fatty acids, virulence factors, and differentiating physiological and biochemical tests.

P. aeruginosa is a rod-shaped Gram-negative bacterium of the class γ-proteobacteria and family Pseudomonadaceae. It is a facultative aerobe that prefers to use oxygen as the final electron acceptor during aerobic respiration, although it is also capable of anaerobic respiration using other alternative electron acceptors such as nitrate. P. aeruginosa can also catabolize a wide-range of organic molecules for nutrients, making it one of the most biochemically versatile and ubiquitous bacterium found in many environments such as soil, water, vegetation, and even human skin and oral mucosa. The ability P. aeruginosa to thrive in diverse environments increases P. aeruginosa reservoirs and the possibility for exposure, leading to higher incidence of infections. P. aeruginosa has been isolated from locations such as hot tubs, humidifiers, and soil. While in hospitals, P. aeruginosa has been isolated from respirators, physical therapy pools, sinks, and mops. Patients infected with P. aeruginosa can also act as sources for new infections in hospitals. These large reservoirs in both community and hospital settings allow for significant rates of infections. Because of its metabolic versatility and an arsenal of virulence factors it possesses, P. aeruginosa is responsible for many serious and life-threatening acute and chronic infections, particularly in the setting of immunocompromised hosts with mortality rates reaching as high as 40%.

P. aeruginosa is a killer of immunocompromised patients, a leading cause of bacteremia and sepsis in neutropenic cancer patients undergoing chemotherapy, and the number one cause of hospital-acquired pneumonia and respiratory failure. P. aeruginosa infections are also common in diabetic ulcers, burn wounds, corneal ulcers, and surgical wounds. Chronic infection by P. aeruginosa is a characteristic of individuals afflicted with cystic fibrosis (CF) and accounts for the pulmonary failure that leads to death in these individuals. Life-threatening infections with P. aeruginosa are also becoming increasingly frequent in patients with AIDS. Exacerbating the challenge with P. aeruginosa infections is this organism’s high intrinsic and acquired resistance to many current antibiotics. Because of this challenge and the severity of infections caused by P. aeruginosa, it has been placed amongst the priority pathogens, known as the ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species), for which new antimicrobial development is urgently needed according to the World Health Organization (WHO) and the Center for Disease Control (CDC). In this review, we review the important acute and chronic infections caused by this pathogen. We provide an overview of current antibiotic treatments and their failure due to development of antibiotic resistance in P. aeruginosa. Finally, we discuss various animal models, developed to assess P. aeruginosa acute and chronic infections, and highlight exciting literature on the development of novel antibiotic-free strategies to combat P. aeruginosa infections.

2. Pseudomonas aeruginosa Infections

In this section, we discuss the various acute and chronic infections that are caused by P. aeruginosa (summarized in Table 1).

2.1. Pseudomonas aeruginosa Acute Infections

P. aeruginosa can cause serious acute infections including, respiratory tract infections, hospital acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), keratitis and corneal ulcers in contact lens wearing individuals, urinary tract infection (UTI), blood stream infections (BSIs), osteomyelitis, and endocarditis. Between 1997–2008, P. aeruginosa was reported to be responsible for 21.8% of the hospital acquired pneumonia (HAP) or the ventilator associated pneumonia (VAP), second only to Staphylococcus aureus which accounted for 28%. A more recent report in 2016 also attributed similar HAP and VAP infection rates to P. aeruginosa. In a meta-analysis of 11 studies of VAP cases after post-cardiac surgery, P. aeruginosa was the causative agent in 23.2%, followed by S. aureus (20.2%). A prospective study of adult patients with nosocomial pneumonia involving 75 hospitals in 11 countries between 2008–2009, found P. aeruginosa to be the leading cause of HAP (15.6%) and the second-leading cause of VAP (25.9%) behind only Acinetobacter spp. (35.6%). In a meta-analysis of 50 studies in China between 2010 to 2014, P. aeruginosa was responsible for 19.4% (95% confidence interval (CI) 17.6–21.2%) of all isolates in VAP and 17.8% (95% CI 14.6–21.6%) in HAP. P. aeruginosa infections in VAP and HAP can be deadly with mortality rates ranging between 13% to nearly 50%. In one retrospective study involving 110 patients with P. aeruginosa VAP from 2008 to 2013 in Intensive Care Unit (ICU) in Italy, the mortality rate was reported to be 44.5%, the highest amongst all other pathogens. The higher mortality rates have been associated with the extent of antibiotic resistance of infecting P. aeruginosa strains (such as multidrug resistance (MDR) clinical isolates) or specific virulence factors such as the type 3 secretion system (T3SS) in the clinical isolates. Other co-morbidities, such as obesity, diabetes, and age have also been independently associated with higher mortality rates in VAP and HAP caused by P. aeruginosa.

P. aeruginosa is also a leading cause of keratitis and corneal ulcers. In a meta-analysis report, covering publications in PubMed and Google Scholars (until 2016), the prevalence of P. aeruginosa in bacterial keratitis was shown to range from 6.8 to 55%. In a multicenter retrospective study in Queensland, Australia between 2005–2015, involving 2176 patients with positive culture, P. aeruginosa was found to be the most prevalent Gram-negative pathogen, accounting for 17.7% of all infections. In another multicenter study in Tehran, Iran, involving 6282 corneal scrapings from keratitis patients tested for infection, 2479 (39.5%) were culture positive and P. aeruginosa was found to be the most common cause of infection in patients with keratitis, although the Gram-positive Streptococcus pneumonia was the most prevalent isolated bacterium in keratitis patients older than 50 years. In another study for the assessment of risk factors and the severity of disease in infection keratitis involving 231 patients, contact lens wear (53; 22%), ocular surface disease (45; 18%), ocular trauma (41; 16%), and prior ocular surgery (28; 11%) were found to be the major risk factors for infectious keratitis. They also found P. aeruginosa to be the most prevalent cause of infectious keratitis and its presence was associated with significantly more severe keratitis. P. aeruginosa keratitis has also been associated with worse outcomes and significant morbidity (i.e., worse initial visual acuity and size and extent of stromal involvement) in non-contact lens wearers in the elderly.

P. aeruginosa is also the third most common cause of urinary tract infections (UTIs), accounting for 7–15% reported infections. In a study involving UTI in children, P. aeruginosa infection was associated with significant UTI recurrence, more resistance to antibiotic therapy, and longer hospitalization. P. aeruginosa is a serious pathogen in the complicated UTIs, particularly in people with catheters, leading to life-threatening pyelonephritis. Catheter-associated UTIs (CAUTI) account for nearly a million additional extra hospital days per year in the USA.

Bloodstream infections (BSIs) are amongst the most serious infections, with mortality rates ranging from 18% to 61%. Not surprisingly, P. aeruginosa is also a major cause of BSIs. Results from a 13-year (2002–2015) prospective cohort study at Duke University Medical Center indicated significant increased mortality rate associated with BSI caused by P. aeruginosa as compared to other bacterial pathogens, including Staphylococcus aureus. In the same study, the unadjusted time-to-mortality among patients with P. aeruginosa blood infection was also found to be significantly shorter than the patients with S. aureus bloodstream infection. The long-term sequalae of BSIs include very serious and life-threatening complications, such as elevated risks for venous thromboembolism and myocardial infarction and stroke, and neurocognitive disorders. The SENTRY Antimicrobial Surveillance Program recently released a 20-year investigative report on the microbiology of blood stream infections from more than 264,901 BSI isolates collected from >200 medical centers in 45 nations between 1997 and 2016. P. aeruginosa was found to be the 4th leading cause of BSIs behind S. aureus, E. coli, and K. pneumoniae, accounting for 5.3% of all infections. Importantly, P. aeruginosa strains had the second highest incidence of MDR rates (26.3%). Collectively, these data highlight the deleterious impact of P. aeruginosa acute infections on public health, as has also been acknowledged by the World Health Organization (WHO) and The Center for Diseases Control (CDC).

2.2. Pseudomonas aeruginosa Chronic Infections

Perhaps the most notable chronic infection caused by P. aeruginosa is the lungs of individuals with Cystic Fibrosis (CF) genetic disorder. P. aeruginosa is the leading cause of mortality and a major contributor to loss of lung function in people with cystic fibrosis (CF). The pathology associated with P. aeruginosa chronic infection in CF lung is in part due to collateral damage caused by infiltrating leukocytes as they unsuccessfully attempt to clear P. aeruginosa infection from the lungs of these individuals. Colonization with P. aeruginosa occurs early in the life of CF patients, either through community or hospital exposure, and remains chronic throughout their lifespan.

Wounds are also highly vulnerable to P. aeruginosa infections. P. aeruginosa is the most abundant and frequently reported Gram-negative pathogenic bacterium in all chronic wounds—(wounds that do not heal within 3 months)—including diabetic foot ulcers, venous leg ulcers, and pressure ulcers. Moreover, presence of P. aeruginosa in these wounds correlates with poor prognosis for healing. P. aeruginosa-infected wounds have been reported to be significantly larger than wounds containing other bacteria—including Staphylococcus aureus, which is the most abundant Gram-positive bacterial pathogen reported in these wounds—suggesting that P. aeruginosa infection may be more detrimental to the process of tissue repair and wound healing than other pathogens. Corroborating these reports, P. aeruginosa has been demonstrated to prevent wound healing and exacerbate tissue damage in cell culture-based in vitro and in various in vivo animal wound infection models. In fact, a number of in vitro and in vivo studies indicate that wound is a preferred niche for P. aeruginosa.

2.3. P. aeruginosa Infections in Immunocompromised Patients

P. aeruginosa is one of the most commonly isolated Gram-negative bacterial pathogens responsible for severe infections in immunocompromised patients, such as HIV/AIDS patients, neutropenic cancer patients undergoing chemotherapy, or immunosuppressed hematopoietic stem cell transplantation (HSCT) patients. P. aeruginosa has been reported to be the causative pathogen in 8 to 25% of community acquired pneumonia, sepsis, and UTIs in HIV patients. The incidence of P. aeruginosa related-bacteremia was reported to be 10 times greater in patients infected with HIV, due to their immunocompromised condition.

Similarly, P. aeruginosa causes a variety of important infections (e.g., pneumonia, blood stream infections, UTI, and wound) with high morbidity and mortality rates in patients suffering from drug-induced neutropenia (reduced neutrophil count), drug-induced qualitative neutropenia (defects in neutrophil function), or drug-induced immunosuppressed patients. P. aeruginosa infections are reported to be more common in neutropenic patients with malignancy, particularly those with leukemias. Over 21% of bacteremia in patients with acute leukemia were reported to be due to P. aeruginosa infection. P. aeruginosa was also the most common cause of pneumonia in patients with solid tumors.

Solid organ transplant (SOT) recipients are another immunocompromised group that is highly vulnerable to P. aeruginosa infections (particularly UTI, pneumonia, and bacteremia) following transplant. The primary reason for the vulnerability of this group to infection is the use of potent immunosuppressive drugs to prevent transplant rejection. The morbidity rates associated with BSIs in SOT recipients have been reported to range from 4.8–11% in kidney, 8–24% in heart, 8–25.7% in lung, 61–69% in intestinal, and 10–34% in liver transplant recipients, respectively. Moreover, because prophylactic antibiotics are routinely administered in this group, the infecting pathogens tend to be highly resistant to antibiotics. A recent prospective study assessed the burden and timeline of infectious diseases in the first year after solid organ transplantation among SOT recipients. Out of 2761 SOT recipients, 1520 patients (55%) suffered 3520 episodes of infections, of which, bacterial infections accounted for 63%. P. aeruginosa was responsible for 9% of all infections and 23% of P. aeruginosa clinical isolates were MDR. In another study involving 191 episodes of BSI in SOT recipients, P. aeruginosa accounted for 5.2% of BSIs. Mortality rates amongst SOT recipients infected with P. aeruginosa was shown to be between 33–40%, highlighting the significance of P. aeruginosa infection in this cohort of patients.

Another immunocompromised patient group that is highly susceptible to P. aeruginosa infection are the burn patients. Hyperinflammatory cytokine response and hypo innate and adaptive immunity are the hallmark of immunosuppression following major burn traumas in human. P. aeruginosa has been reported as the most frequently recovered infectious pathogen in burn units and the clinical isolates display high resistance to antibiotics. In a recent large study involving 17119 patients at a burn ward in China between 2006 and 2019, S. aureus and P. aeruginosa were the predominant clinical pathogens responsible for bacterial infections in these patients. It is worth noting that while the rates of S. aureus infections appeared to remain stable during this study (17.06% in 2006 to 18.54% in 2019); the rates of P. aeruginosa infections rose from 10.59% in 2006 to 17.68% in 2019, suggesting an upward trajectory in P. aeruginosa infections among burn patients at least in this burn unit. In another retrospective study assessing bacteria from wounds, catheters, blood, feces, urine and sputum of 10,276 hospitalized patients in burn wards between 2007 and 2014 in China; 3005 pathogenic strains were isolated and identified. While S. aureus was the predominant strain in the beginning, its annual detection rates declined significantly over these years. In contrast, the annual detection rates of P. aeruginosa increased significantly during this period. Alarmingly, the detection rate increases in P. aeruginosa were associated with increased incidence of MDR bacteria in the culture, prompting the authors to caution against the use of ciprofloxacin, ceftazidime and cefoperazone/sulbactam to counter the related increase in resistance levels in P. aeruginosa. In another study involving 184 positive cultures from burn patients in burn unit in Iran, 205 different bacterial strains were isolated and identified, of which P. aeruginosa was the most prevalent, accounting for 57% of all clinical isolates; followed by Acinetobacter (17%), E. coli (12%), S. aureus (8%) and other organisms (6%). Importantly, over 90% of P. aeruginosa isolates displayed resistance to gentamicin, ceftizoxime, carbenicillin, cephalothin and ceftazidime. P. aeruginosa has also been the primary infective agent reported in other studies involving burn patients.

Another group of immunocompromised patients who are highly vulnerable to P. aeruginosa infection, are the individuals suffering from primary immunodeficiency disorders (PIDDs). PIDDs is a group of 300 diseases caused by rare genetic disorders, such as Caspase Eight Deficiency State (CEDS), Autoimmune Lymphoproliferative Syndrome (ALPS), Chronic Granulomatous Disease (CGD), etc.. P. aeruginosa has been reported to cause serious blood infections with high mortality rates in these individuals.

3. P. aeruginosa Infection Animal Models

In this section, we review the animal models which have been developed to study various infections caused by P. aeruginosa and assess the effectiveness of conventional and emerging therapies against this pathogen (summarized in Table 1).

3.1. Acute and Chronic Pneumonia Infection Models

Animal models have been extremely useful in advancing our understanding of P. aeruginosa pathogenesis and for the development and the therapeutic assessment of new antibiotics or novel biologicals to control this pathogen. Although most studies involving P. aeruginosa infections rely on mouse or rat models due to the cost and availability of reagents, larger animal modeling is also performed usually to fulfill the requirement by organizations—such as Food and Drug Administration (FDA)—to evaluate the efficacy and the safety profiles of new investigative biologics in two animal models that approximate human responses with respect to the condition under investigation. As was discussed above, P. aeruginosa is an important bacterial pathogen in acute and chronic pneumonia, including the ventilated-associated pneumonia (VAP) and hospital acquired pneumonia (HAP). The first animal model of chronic pulmonary infection was a rat model in which P. aeruginosa infection was initiated by intratracheal inoculation of P. aeruginosa bacteria enmeshed in agar beads. In this chronic model of infection, P. aeruginosa was detected during the 35 days of observation. Importantly, infected lungs in these rats exhibited lesions resembling those seen in lung tissues of humans with acute or chronic P. aeruginosa pneumonia, including the presence of goblet-cell hyperplasia, focal areas of necrosis, and acute and chronic inflammatory infiltrate. Since then, various similar animal models (in mouse, rat, rabbit, porcine, dog, cat, etc.) of P. aeruginosa infections for acute and chronic pneumonia (including VAP and HAP) have also been described, albeit with modifications in the P. aeruginosa strain, initial inoculum levels, and in the rout of P. aeruginosa delivery into animal.

3.2. Urinary Tract and Kidney Infection Models

P. aeruginosa also causes urinary tract and kidney infections as discussed above. The initial animal models to assess UTI caused by P. aeruginosa involved intravenous injection of P. aeruginosa into mice. In these systemic infection models, large doses (close to lethal doses) of P. aeruginosa—were needed to establish infection in the urinary tract and kidney. However, the high rate of mortality, due to systemic infection, made these murine models impractical. To overcome this difficulty, artificial manipulations, (e.g., administration of bromoethylamine hydrobromide or ferric sorbitol citrate), were used to make kidneys in animals more susceptible to P. aeruginosa colonization and growth. However, these artificial means made the interpretation of the data unreliable. These limitations then led to the development of methods (e.g., surgical implantation of glass beads laden with P. aeruginosa, or transvesical ureteral catheterization) to directly deliver P. aeruginosa into the rat kidney in order to cause infection in this organ. At present, urinary tract and kidney infection models frequently instill bacteria into the bladder using a catheter, based on the UTI protocol that was developed for Uropathogenic Escherichia coli (UPEC) by Hung et al..

3.3. Blood Stream and Systemic Infection Models

Different approaches have been used to cause blood and systemic infection in animals with P. aeruginosa. For example, intravenous (i.v.), intraperitoneal (i.p.), or tail vein injections have been used as technical means to cause systemic infection with P. aeruginosa. P. aeruginosa has also been delivered retro-orbitally to cause systemic infection and sepsis. P. aeruginosa systemic infection has been shown to increase pro-inflammatory cytokines both in the blood and tissues, leading to other morbidities such as septic arthritis and gallbladder damage.

3.4. Keratitis and Corneal Ulcers Infection Models

As this was discussed above, keratitis and corneal ulcer infections are relatively rare but they are very serious medical conditions requiring urgent medical care because of the possibility that they can lead to vision loss in the affected eye(s). In the murine models for corneal ulcer, 2–3 parallel scratches (~1 mm) are usually made by sterile 25-gauge needle on the cornea of anesthetized animal prior to bacterial inoculation. Animal models have been informative in showing the potency of antimicrobial activities in human tear; in establishing the crucial roles for IL-16 pro-inflammatory cytokine and cathelicidin antimicrobial peptide in corneal defenses against P. aeruginosa; and in demonstrating the therapeutic potential of the broad host range bacteriophage KPP12 in P. aeruginosa clearance and corneal healing.

3.5. Endocarditis Infection Models

Animal models of S. aureus infective endocarditis (IE), are commonly used to investigate the underlying pathogenesis, disease progression, potential diagnostic approaches, and therapeutic treatment for endocarditis caused by P. aeruginosa; Rabbits. These models are based on surgical valve trauma followed by intravenous injection of bacteria within 10–24 h following the surgical valve trauma. In a rabbit model of endocarditis, with sterile right ventricular cardiac vegetations, Archer et al. demonstrated 78% mortality within 3 weeks, following P. aeruginosa infection. In a follow-up study, the same group demonstrated that 14-day treatment with high dose gentamycin (7.5 mg/kg) and carbenicillin (400 mg/kg) was significantly more effective than either therapy alone, resulting in 64% sterilization of cardiac vegetations in this rabbit model of P. aeruginosa endocarditis. In a rat model of P. aeruginosa endocarditis, Oechslin et al. demonstrated that a combination of systemic vancomycin and phage therapy was highly effective against P. aeruginosa endocarditis.

3.6. Wound and Surgical Site Infection Models

Skin is a formidable barrier against invading pathogens, including P. aeruginosa. As an opportunistic pathogen, P. aeruginosa cannot colonize or cause infection in the skin of normal animal unless this barrier is breached by injury. Therefore, animal wound and surgical site models of infections for P. aeruginosa (and other pathogens) usually involve full or partial thickness excisional wounding, or addition of bacteria directly to implants or stents before or after their insertion into animals. In the settings of injury, P. aeruginosa can efficiently colonize and cause infection. In a recent study, P. aeruginosa was shown to thrive in wound environment, (in a mouse model of wound infection), by dampening the host innate immune responses in wound tissue via inhibition of the NLRC4 inflammasome mediated by its most conserved virulence factor, ExoT.

Chronic wounds are particularly vulnerable to P. aeruginosa infection. In a recent study involving db/db type 2 diabetic mouse, it was shown that impairment in the formyl peptide chemokine receptors (FPR) in diabetic neutrophils results in a delay in neutrophil response, rendering diabetic wounds vulnerable to colonization and infection by P. aeruginosa. Macrophage response has also been shown to be delayed in db/db diabetic wounds, due to dysregulation in IL-10 expression and signaling, further dampening innate immune responses and diabetic wound’s ability to prevent P. aeruginosa infection. In other studies, P. aeruginosa has been demonstrated to several other virulence factors (e.g., biofilm, type 3 secretion system (T3SS), pyocyanin, extracellular proteases, and Exotoxin A) to prevent wound healing and exacerbate tissue damage. In a burn wound model of infection, P. aeruginosa infection was shown to lead to bacteremia in a manner that was dependent on superoxide response regulator (soxR) expression and function in P. aeruginosa. In another report, quorum sensing (QS) was shown to be involved in biofilm maturation and P. aeruginosa colonization and pathogenesis a pressure ulcer infection model in rat.

3.7. Immunocompromised Infection Models

As was discussed above, immunocompromised people are highly vulnerable to infection with P. aeruginosa. Not surprisingly, animal models have been developed to assess the impact of P. aeruginosa infection in immunocompromised hosts. For example, Takase et al. demonstrated that P. aeruginosa infection in the calf muscle of immunocompromised mice, (generated by cyclophosphamide), caused high mortality in these mice, in a manner that was mediated by pyoverdine and pyochelin siderophore production in P. aeruginosa. In another study, P. aeruginosa was shown to induce death within 46 to 59 h in a leukopenic immunosuppressed mouse model. Similarly, Mahmoud et al. demonstrated that wounds in the neutropenic immunocompromised C57BL/6 mice are vulnerable to P. aeruginosa enhanced infection. In another study, P. aeruginosa infection was proved to be highly lethal in an immunosuppressed guinea pig model of pneumonia.

3.8. Cystic Fibrosis Infection Animal Models

Cystic Fibrosis (CF) is a genetic disorder caused by null mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes for the chloride channel. Not surprisingly, different transgenic animal species, (i.e., mice, rats, rabbits, ferrets, pigs, and sheep), harboring similar mutations in the CFTR gene have been constructed to model various CF pathologies. In one report, endobronchial infection with a mucoid P. aeruginosa strain was shown to elicit production of TNF-α, MIP-2, and KC/N51 inflammatory cytokines in bronchoalveolar lavage fluid and cause 80% mortality in CF mice (harboring the S489X mutation of the CFTR gene), thus phenocopying some of the CF hallmark pathologies observed in human. Corroborating these studies, van Heeckeren et. al., demonstrated that infection with P. aeruginosa resulted in significantly higher mortality rates, weight loss, higher lung pathology scores, and higher inflammatory mediator and neutrophil levels in the lungs of CF mice as compared to wildtype littermates. However, murine models do not completely develop human CF disease severity in the pancreas, lung, intestine, liver, and other organs, thus necessitating the need for the development of larger animal models for CF, such as newborn pigs and ferrets. For example, CF pigs were demonstrated to develop airway inflammation, mucus accumulation, and impaired bacterial clearance. CF pig lungs contained multiple bacterial species, suggesting impaired immune defenses against bacteria.

4. Current Treatments for P. aeruginosa Infections

Here, we provide an overview of conventional antibiotic treatments for P. aeruginosa infections. Full description on these therapies can be found in the guidelines from the Infectious Diseases Society of America (IDSA). Regardless of the antibiotic agent(s) administered, patients infected with P. aeruginosa should be closely monitored as P. aeruginosa can rapidly acquire additional resistance mechanisms while exposed to antibiotic therapy as discussed in Section 4 below and discussed previously. A summary of the antibiotic treatments, their limitations, and the mechanisms of resistance to these antibiotics can be found in Table 2.

4.1. β-Lactam Antibiotics (Alone and Combination Therapies)

β-lactam antibiotics generally are bactericidal antibiotics that destroy bacterial pathogens by disrupting their peptidoglycan cell wall via covalent binding to essential penicillin-binding proteins (PBPs) in bacteria. Non-carbapenem β-lactam antibiotics (e.g., ceftazidime, cefepime, piperacillin-tazobactam, aztreonam, etc.) are the preferred first line of therapy where P. aeruginosa clinical isolate tests susceptible to these antibiotics. The rational for their use is their clinical effectiveness using empiric regimes with fixed doses, their high potency and efficacy against a wide therapeutic range, and the low cytotoxicity and side-effects associated with their use. Ceftazidime may be considered a preferred first-line β-lactam therapy because its use has been associated with the lowest risk of resistance while on therapy. Carbapenems are a class broad spectrum β-lactam antibiotics broad spectrum of activity that are recommended to treat infections caused by bacteria, including P. aeruginosa, resistant to traditional β-lactams or fluoroquinolones (discussed below).

Cefiderocol is a novel injectable cephalosporin which was approved by FDA in 2019 for the treatment of complicated UTIs. It is also a preferred option for the treatment of uncomplicated and difficult-to-treat (DTR) cystitis caused by P. aeruginosa infection. Cefiderocol has been shown to be more potent than both ceftazidime-avibactam and meropenem against all resistance phenotypes of Pseudomonas aeruginosa because of its unique siderophore-like property (which enhances its entry into the bacterial periplasmic space) and because of its high stability to a variety of β-lactamases, including AmpC and extended-spectrum β-lactamases (ESBLs).

More novel β-lactam combination antibiotic regiments (e.g., ceftazidime/avibactam, ceftolozane/tazobactam, imipenem/cilastatin/relebactam, etc.) are also used but only as alternative options for MDR or extensively-drug resistant (XDR) P. aeruginosa strains. By definition, the MDR strains display acquired resistance to at least one agent in three antimicrobial categories, whereas the XDR strains show susceptibility to antibiotics in 2 or fewer categories and display resistance to at least one agent in the rest of available antibiotic categories. Ceftazidime, (a third-generation broad-spectrum cephalosporin antibiotic) is also used in combination with avibactam (a synthetic non–β-lactam, β-lactamase inhibitor which inactivates β-lactamase targets via covalent acylation), and has shown to be highly effective against MDR and XDR P. aeruginosa strains (>90% effectiveness). However, P. aeruginosa strains resistant to ceftazidime/avibactam have been reported and are on the rise, adding to the challenges associated with P. aeruginosa therapeutics. Ceftolozane, (a semi-synthetic broad-spectrum fifth-generation cephalosporin β-Lactam antibiotic), in combination with tazobactam, (an irreversible β-lactamase inhibitor), has been shown to be effective against most MDR and XDR resistant P. aeruginosa strains. Not surprisingly, resistance to this combination therapy in P. aeruginosa has also been reported. Combination therapy, imipenem (a β-lactam antibiotic belonging to the carbapenem subgroup), cilastatin (an inhibitor of imipenem-degrading human renal dehydropeptidase and bacterial metallo-β−lactamase), and relebactam (an inhibitor of β-lactamases); has been recently approved in the USA and Europe, and shown to be highly effective for the treatment of complicated urinary tract infections including pyelonephritis, complicated intra-abdominal infections, and hospital-acquired bacterial pneumonia caused by MDR and XDR Gram-negative bacterial pathogens including P. aeruginosa. Antibiotic resistance in P. aeruginosa will be discussed in the next section.

4.2. Fluoroquinolones

Fluoroquinolones (e.g., ciprofloxacin and levofloxacin) are broad-spectrum antibiotics that destroy bacteria by inhibiting DNA gyrase and topoisomerase IV (essential enzymes for DNA synthesis in bacteria). Fluoroquinolones are also recommended for the first line of treatment in acute otitis externa or skin and soft tissue infections and complicated UTI caused by P. aeruginosa strains that are found to be susceptible to these agents. Limitations with the use of fluoroquinolones include rapid development of resistance in bacteria and the sensitivity of fluoroquinolones to acidic conditions, which adversely affect their cell uptake, although recently developed novel fluoroquinolones (i.e., delafloxacin) show improved cellular uptake and maintain their antibacterial activities in acidic conditions.

4.3. Eravacycline (Tetracyclin)

Generally, tetracycline antibiotics are not very effective against P. aeruginosa infections and may even enhance its virulence by stimulating its T3SS virulence function. However, eravacycline (a novel fully synthetic fluorocycline) is different in that it exhibits potent activity against a broad spectrum of clinically relevant Gram-positive and Gram-negative aerobic and anaerobic bacteria, including P. aeruginosa, and has been recently approved in several countries for the treatment of complicated intra-abdominal infections in adult patients. It owes its potency to 2 modifications in the tetracyclic D ring at position C7 (fluorine atom addition) and C9 (pyrrolidinoacetamo group addition), which allow it to be effective even in pathogens that express tetracycline-specific efflux and ribosomal protection mechanisms in clinical isolates. Like all tetracyclines, it exerts its antimicrobial activities by inhibiting protein synthesis machinery in bacteria through its interaction with the 30S (and to a lesser extent 50S) ribosomal subunits.

4.4. Aminoglycosides

Aminoglycosides (e.g., gentamycin, amikacin, tobramycin) are broad-spectrum bactericidal antibiotics that destroy bacterial pathogens by targeting the 30S subunit of bacterial ribosomes, thus inhibiting protein synthesis. They are also routinely prescribed against P. aeruginosa infections. A meta-analysis of publications until 2018 found that a single intravenous dose of aminoglycosides was highly effective (94.5 ± 4.3%) for uncomplicated cystitis with the recurrence-free and cure rate of >73%, with minimal toxicity. In a large phase III clinical trial, plazomicin (a next-generation semisynthetic aminoglycoside) was shown to be noninferior to meropenem in the treatment of complicated urinary tract infections, even against Gram-negative pathogens, (including P. aeruginosa) with aminoglycoside-modifying enzymes that impart resistance to most aminoglycosides. Other reports have confirmed the effectiveness of plazomicin against hard-to-treat resistant Gram-negative pathogens. In another randomized trial involving seven U.S. centers for the treatment of cystic fibrosis, the short-term aerosol administration of a high dose of tobramycin in patients with clinically stable cystic fibrosis was shown to significantly increase lung function (as assessed by forced expiratory volume, forced vital capacity, and forced expiratory flow at the midportion of the vital capacity), and decrease the density of P. aeruginosa in sputum by a factor of 100, without any ototoxicity nor nephrotoxicity. Although, nebulized amikacin/fosfomycin was shown to be ineffective in improving clinical outcomes in pneumonia in 3 clinical trials, despite reducing bacterial burden in these patient cohorts.

4.5. Polymyxins (Colistin, Polymyxin B)

Therapeutic use of polymyxins as one of the last lines of therapy against MDR/XDR P. aeruginosa infections have skyrocketed during the past decade. Polymyxins kill Gram-negative bacterial pathogens by disrupting their membrane via targeting the Lipid A moiety of the lipopolysaccharide (LPS) in the outer membrane of these bacteria. Therapeutic use of polymyxins has been associated with relatively higher toxicity side-effects, (e.g., nephrotoxicity and neurotoxicity), as compared to other antimicrobials, thus dosing and the treatment protocol should be carefully designed to reduce these side-effects. IDSA recommends polymyxin B (over colistin) in combination with the β-lactam and β-lactamase inhibitor for the treatment of non-urinary tract infections, if no aminoglycoside is effective against P. aeruginosa isolate in vitro. The rational for this recommendation is that polymyxin B is not administered as a prodrug and therefore can achieve more reliable plasma concentrations than colistin which is administered as a prodrug and it converts to its active form in the urinary tract. For precisely the same reason, colistin (not polymyxin B) monotherapy has been recommended as an alternate consideration for treating urinary tract infections caused by MDR/XDR P. aeruginosa, although IDSA also warns that clinicians should remain cognizant of the associated risk of nephrotoxicity in these patients.

5. Antibiotic Resistance in P. aeruginosa

The rate of antimicrobial resistance among P. aeruginosa clinical isolates has climbed sharply over the past 5 decades worldwide. P. aeruginosa clinical isolates frequently exhibit resistance to various classes of antibiotics including β-lactams, aminoglycosides, fluoroquinolones, and even polymyxins with strains isolated from the Intensive Care Units (ICUs) demonstrating the highest incidence of resistance to these antibiotics. A retrospective 10-year study reported a 10% increase in antibiotic resistance rates in P. aeruginosa clinical isolates in ICU within a decade. Another study investigated the profile of antimicrobial resistance of Gram-negative bacteria in blood cultures in a university-affiliated hospital in China and found resistance rate to carbapenem among blood culture isolates of P. aeruginosa to increase significantly from 2004–2011. Of note, between 2000–2010, consumption of antibiotics (particularly carbapenems) increased by nearly 35% in China, thus establishing a direct correlation between antibiotic use and the emergence of antibiotic resistance in P. aeruginosa clinical isolates. Additionally, the incidence and the rate of infections with the multidrug resistant (MDR) P. aeruginosa strains—(resistant to at least one antibiotic in 3 or more antibiotic classes)—have been steadily rising over the past 20 years, as a direct consequence of increased antibiotic consumption. A meta-analysis report assessing the clinical and economic impacts of hospital-acquired resistance and MDR P. aeruginosa infections between the years 2000 to 2013, indicated a greater than 2-fold increased risk of mortality in patients infected with MDR P. aeruginosa strains and a 24% increased risk of mortality in patients infected with resistant P. aeruginosa strains as compared to patients infected with antibiotic susceptible P. aeruginosa strains. Not surprisingly, the same study found longer hospital stay and increased cost associated with resistant and MDR P. aeruginosa infections as compared to susceptible P. aeruginosa and control patients. Corroborating these data, an international multicenter retrospective study in 2015 reported significant increased association between mortality in nosocomial pneumonia and MDR P. aeruginosa infections.

Another frightening concern is the emergence of extensively drug resistant (XDR) P. aeruginosa infections among HAIs. XDR P. aeruginosa strains are defined as the strains that remain susceptible to only one or two classes of anti-Pseudomonas drugs and show resistance to at least 1 antibiotic in the other antibiotic groups. A retrospective study of a cohort of adult, hospitalized patients with P. aeruginosa in Thailand reported that 22% of P. aeruginosa infections were due to XDR strains, resulting in significantly higher mortality. Another prospective study involving 1915 ICU patients between 2014–2015 in India reported 47.7% of P. aeruginosa infections to be due to MDR and XDR P. aeruginosa strains. Recently, a nosocomial outbreak of P. aeruginosa infection with XDR strains was reported among ICU patients subjected to aromatherapy in Austria, which was successfully addressed through the implementation of restriction of oil sharing among patients. A systemic review and meta-analysis of 54 articles between 2000 and 2016 reported prior use of antibiotics and prior hospital or ICU stay as the most significant risk factors for nosocomial infections with MDR and XDR P. aeruginosa strains.

The emergence of multi-drug resistant P. aeruginosa poses even more serious threat in immunocompromised patients and complicates treatment options for these patients. A retrospective study involving 7386 clinical specimens collected from HIV patients, reported increasing antibiotic resistance rates to aztreonam, cefepime, levofloxacin, meropenem, piperacillin, piperacillin-tazobactam, ticarcillin, and tobramycin in P. aeruginosa clinical isolates in this patient cohort. Similar to HIV patients, in a 10-year study involving 149 solid organ transplant recipients, 43% of P. aeruginosa clinical isolates from transplant recipients were reported to be MDR.

6. The Mechanisms of Antibiotic Resistance

The mechanisms of antibiotic resistance in P. aeruginosa have been reviewed extensively elsewhere. In brief, resistance to antibiotics in P. aeruginosa is multifactorial involving various intrinsic (inherent) and extrinsic (acquired) mechanisms. The intrinsic mechanisms of antibiotic resistance in P. aeruginosa include: (i) expression of porin molecules (e.g., OprF) that are considerably more restrictive to antibiotics entry into P. aeruginosa as compared to other Gram-negative bacteria such as E. coli; (ii) reduction in the expression of outer-membrane porins, which further renders bacterial cell wall less permeable to antibiotics; (iii) expression of various efflux pumps (e.g., MexAB-OprM, MexCD-OprJ, MexEF-OprN, and MexXY-OprM), which impart resistance to β-lactams, fluoroquinolones, and aminoglycosides by pumping out these antibiotics thus reducing their effective concentrations in P. aeruginosa cytosol; (iv) biofilm production which imparts resistance to antibiotics through various mechanisms—(discussed in)—including (a) biofilm-specific protection against oxidative stress induced by bactericidal antibiotics, (b) biofilm-specific expression of efflux pumps; (c) the protection provided by matrix polysaccharides through chemical interactions between the chemical functional groups in biofilm and antibiotics, thus limiting their accessibility to biofilm bacteria, and (d) the reduced metabolic state of biofilm bacteria; (v) emergence of persister and antibiotic tolerant phenotypes—(due to metabolic slowdown, oxygen limitations, and stress conditions)—that substantially increases resistance to antibiotics in otherwise sensitive bacteria, particularly in chronic infections; (vi) mutations and polymorphism in the gene targets of antibiotics which reduce drug/target interactions, such as, quinolone resistance due to mutation in DNA Gyrase gene.

The extrinsic mechanisms of antibiotic resistance include acquisition of resistance genes through horizontal gene transfer (HGT) mechanisms, such as transformation, transduction, conjugation, transposons, outer membrane vesicles (OMVs), and insertion elements). These resistance genes can inactivate antibiotics by hydrolysis, such as metallo or extended spectrum β-lactamases; or by changing antibiotics through structural modifications, such as aminoglycoside modifying enzymes (e.g., acetyltransferases, nucleotidyltransferase, and phosphotransferases).

7. Emerging Therapies to Combat P. aeruginosa Infections

As discussed above, antibiotics are routinely prescribed for the treatment of P. aeruginosa infections. While antibiotics have saved numerous lives over the past 9 decades, their use is not without its problems. First, the widespread use of antibiotics has led to an explosion of antibiotic resistance. Second, currently, there is no antibiotic in the market that is effective against all bacterial pathogens, therefore, choosing the right antibiotic for prophylaxis use is crucial. The choice of prophylaxis antibiotic is empirical in that it is based on the most probable cause of infection. Prophylaxis antibiotics could fail if the patient encounters a different pathogen or a pathogen that is resistant to the administered antibiotic. Third, antibiotics have many undesirable and dangerous side-effects; including nephrotoxicity, ototoxicity, hepatotoxicity, acute renal failure, and dysbiosis in the gut microbiota which itself has been associated with obesity, diabetes, and immunological and neurological diseases such as Parkinson disease. Forth, prophylactic antibiotic use is associated with increased risk of infection with Clostridium difficile which is one of the deadliest causes of nosocomial infections, costing approximately $1.5 billion annually in USA alone. Fifth, antibiotic use has been shown to interfere with healing processes at surgical sites. In this section, we discuss the antibiotic-free strategies that are gaining tractions in dealing with P. aeruginosa infections and possible limitations associated with them (summarized in Table 3).

7.1. Immune System-Based Approaches against P. aeruginosa Infections

Innate immune system possesses powerful cellular, (e.g., neutrophils and macrophages), and humoral (e.g., antimicrobial peptides and complement), components that destroy pathogens via many mechanisms; such as phagocytosis, bursts of reactive oxygen and nitrogen species (ROS and RNS), antimicrobial peptides (AMPs) and complement-mediated direct microbial killing via membrane attack complex (MAC), and indirect microbial killing through opsonization and phagocytosis, and neutrophil extracellular trap (NET). Below, we discuss the two main immune system-based approaches to control infection.

7.1.1. Antimicrobial Peptides (AMPs)-Based Approaches against Bacterial Infections

AMPs are natural peptide-based antibiotics which are expressed by almost all life forms, including humans. Generally, AMPs destroy pathogens by attacking and permeabilizing their membranes but there are some AMPs that kill their targets via different mechanisms such as modulation of membrane fluidity, and inhibition of intracellular pathways such as DNA replication and protein synthesis. AMPs have been studied as promising new therapies to combat infections and some of them are even in clinical trials. In one cell-culture based study, LL-37 (also known as cathelicidin) or cecropin(1–7)-melittin A(2–9) amide (CAMA) AMPs were shown to reduce the minimum biofilm eradication concentrations (MBEC) against biofilm P. aeruginosa by 8-fold. In another in vitro study, immobilized Melimine and Mel4 chimeric cationic AMPs were shown to reduce biofilm P. aeruginosa viability by 82% and 63%, respectively, highlighting their therapeutic potential against device associated P. aeruginosa infections, such as catheter-associated pneumonia. In a rat model of systemic infection with P. aeruginosa, the AMPs (Magainin II and Cecropin A) exerted strong antimicrobial activity and achieved a significant reduction in bacterial levels, plasma endotoxin, and TNF-α concentrations when compared with control and rifampicin-treated groups. Rifampicin and Magainin II or Cecropin A combined therapies showed synergistic effect in reducing infection and mortality rates when compared with singly treated and control groups. In another set of in vitro and in vivo lung infections, peptide ZY4 (a cathelicidin mimetic) was shown to be highly effective against standard and clinical MDR P. aeruginosa and Acinetobacter baumannii, strains in a mouse septicemia infection model. Importantly, ZY4 showed low propensity to induce resistance, eradicated biofilm bacteria, (even killing persister bacteria), and decreased susceptibility to lung infection by P. aeruginosa and suppressed dissemination of P. aeruginosa and A. baumannii to other organs in mice. However, notable limitations have also hampered AMPs’ therapeutic use (including AMPs’ inherent cellular and tissue toxicities, potential limitations with their spectrum of activities against pathogens, and emergence of resistance to AMPs.

7.1.2. Immunomodulator-Based Approaches against P. aeruginosa Infections

In this approach, immunomodulators—primarily proinflammatory cytokines, such as CCL3, or bacterial products, such as N-Formylmethionine-leucyl-phenylalanine (fMLF)—are used to mobilize and activate innate immune responses at the possible site(s) of infection. Immunomodulator-based approaches to control infection theoretically have many advantageous over antibiotics, although they could also be used in combination with antibiotics to further enhance their effectiveness. First, it is highly unlikely for a pathogen to develop resistance to all antimicrobial weapons that our immune system has at its disposal, including phagocytosis, bursts of reactive oxygen species (ROS), hypochlorous acid (HOCl), neutrophil and macrophage extracellular traps and antimicrobial peptides as discussed above. Second, immunomodulator-based therapies would not be empirically based because, once mobilized to the site of infection, immune system could in theory be effective against majority of infections regardless of their origin (bacterial, fungal, or viral). Third, many pathogens, (including P. aeruginosa), possess stealth mechanisms that allow them to establish infection even in immunocompetent healthy individuals by dampening host’s immune responses. Immunomodulators could potentially overcome at least some of these stealth strategies and fortify tissue’s defenses against invading pathogens by mobilizing immune responses to the site of these stealth pathogens. Forth, immunomodulators likely have fewer undesirable side-effects and may be safer than antibiotics. For example, it is unlikely that topical application of immunomodulators would result in development of bacterial resistance, gut dysbiosis, or organ damage (all side-effects associated with the use antibiotics as discussed above).

In a wound model of infection in diabetic mice, Roy et al. demonstrated that one-time topical treatment with low level CCL3 reduced P. aeruginosa infection by >99% by enhancing the neutrophil response in diabetic wounds. Importantly, CCL3 treatment did not lead to persistent non-resolving inflammation in diabetic wounds, which is the hallmark of diabetic foot ulcers. Rather, inflammation subsided over time and CCL3-treated diabetic wounds healed substantially better even in the presence of P. aeruginosa infection, which has been shown to exacerbate healing and contribute to heightened inflammatory environment in diabetic wounds as they age and become chronic. In another wound infection model in immunocompetent C57BL/6 mice, Mahmud et al. recently demonstrated that one-time topical applications of CCL3, fMLF, or LPS immunomodulators were as effective, (if not more), as prophylactic tobramycin, in reducing P. aeruginosa infection (by nearly 90%) in wound. Interestingly, these immunomodulators did not adversely impact healing processes. Rather, they even modestly stimulated wound healing in this immunocompetent animal even in the absence of infection. In another study involving periprosthetic implant joint infection with Staphylococcus aureus, Hamilton et al. demonstrated treatment with fMLP significantly reduced S. aureus infection levels by >90%. In addition, fMLF therapy reduced infection-induced peri-implant periosteal reaction, focal cortical loss, and areas of inflammatory infiltrate in mice distal femora. Importantly, fMLP treatment reduced pain behavior and increased weight-bearing at the implant leg in infected mice. These reports highlight the therapeutic potential of immunomodulators in reducing infections and potentially as stimulants in wound healing even in uninfected animals. The possible drawback against this approach is their possible ineffectiveness in severely immunocompromised patients who may lack the ability to mount effective immune responses to immunomodulators.

7.2. Phage-Based Therapeutics against P. aeruginosa Infections

Lytic bacteriophages (also known as phages) are viruses that selectively target and kill bacteria by lysis. Phage effective killing of P. aeruginosa was first reported in 1957 by Kellenberger et al.. Since then, various animal models and clinical studies have demonstrated the effectiveness of phages as alternative or adjunctive therapies with antibiotics to treat P. aeruginosa infections particularly when infections with MDR or XDR P. aeruginosa strains are suspected. In a mouse burn wound model of fatal infection with P. aeruginosa, McVay et al. demonstrated that phage cocktail consisting of three different P. aeruginosa phages was effective in increasing survival rates by 87%, (when administered via intraperitoneal (i.p.) route), as compared to only 6% in the sham control group. In a CF zebra fish model, phage therapy was shown to substantially lower bacterial burden, reduce proinflammatory response, and significantly decrease lethality, caused by P. aeruginosa infection. In a case report involving a patient with a pan drug-resistant P. aeruginosa spinal abscess, local and intravenous injections of a purified personalized phage cocktail adjunct therapy with antibiotics was able to heal this patient, despite the strain’s resistance to all antibiotics including ceftazidime/avibactam, ceftolozane/tazobactam, and colistin. In another case report involving prosthetic vascular graft P. aeruginosa infection, single application of phage OMKO1 and ceftazidime was sufficient to resolve infection with no signs of recurrence. Despite these successful cases, clinical trials of phage therapies show low to moderate efficacy with large variations in infection clearance between subjects within the studies. In addition, phage therapies also have their own set of limitations, including development of resistance to phages in bacteria, the requirement for high dose of viral particles, and the potential serious but not life-threatening side-effects.

7.3. Therapeutics Targeting P. aeruginosa Virulence Factors

P. aeruginosa pathogenesis is due to an arsenal of cell-associated and secreted virulence factors. Therefore, disarming P. aeruginosa by reducing its virulence in vivo is a logical and promising therapeutic strategy that is gaining momentum. For example, the T3SS virulence structure is an essential virulence structure for T3SS-expressing P. aeruginosa strains during infection and without it, this organism is rendered avirulent and cannot cause disease. In a recent study, INP0341, a T3SS inhibitor, was shown to attenuate corneal infection by P. aeruginosa in an experimental model of murine keratitis. In another study, monoclonal antibodies against T3SS structural component PcrV provided strong prophylactic protection in several murine infection models and a post-infection therapeutic model. Quorum sensing (QS) is another major virulence mechanism that regulates the expression of many virulence factors and biofilm in P. aeruginosa. In one study, sitagliptin (a QS inhibitor) was shown to inhibit pyocyanin, hemolysin, protease, and elastase in addition to blocking swimming, swarming and twitching motilities, and biofilm formation in P. aeruginosa. In another recent report, the FDA-approved drug allopurinol showed anti-QS activity against P. aeruginosa and reduced the infiltration of P. aeruginosa and leucocytes and diminished the congestion in the liver and kidney tissues of infected mice. Other QS inhibitors have also shown effectiveness in the treatment of drug resistant P. aeruginosa. In another report, inhibition of Pseudomonas aeruginosa secreted virulence factors reduced lung inflammation in CF mice. Other virulence factors (e.g., pyoverdine, AlgR, CdpR, RpoN, CysB, and AnvM) have also been investigated as potential drug targets to inhibit P. aeruginosa virulence during infection.

7.4. Vaccine Development against P. aeruginosa

With the rapid rise in the MDR and XDR P. aeruginosa clinical strains, it is absolutely vital to develop effective vaccines against P. aeruginosa. To date, there have also been several vaccine candidates developed against P. aeruginosa membrane and LPS O antigens, outer-membrane porin proteins, the T3SS structural components (PcrV) and secreted effector peptides (ExoU), and combinations of these factors. One study assessed the effectiveness of oral and intraperitoneal (i.p.) vaccinations with attenuated Salmonella enterica serovar Typhimurium SL3261 expressing P. aeruginosa serogroup O11 O antigen against P. aeruginosa infection in an acute fatal pneumonia model in BALB/c mice. They reported that while both modes of immunization elicited O11-specific serum immunoglobulin G (IgG) antibodies, IgA was observed only after oral immunization. They further showed that oral vaccination significantly increased survival in an acute fatal P. aeruginosa pneumonia model. In another study, a multivalent live-attenuated mucosal vaccination (combining up to 4 attenuated strains having different LPS serogroups) elicited opsonophagocytic antibodies, which were directed not only to the LPS O antigens but also to the LPS core and surface proteins, correlated with protective immunity to P. aeruginosa lung infections. In another study, vaccination with Pseudomonas aeruginosa outer membrane vesicles (PA_OMVs), formulated with aluminum phosphate adjuvant, was shown to reduce bacterial colonization, cytokine secretion and tissue damage in the lung tissue, thus protecting mice from lethal challenge of P. aeruginosa.

As for vaccine candidates against the T3SS, active and passive immunization with the PcrV antigen was shown to protect mice against P. aeruginosa-induced lung inflammation and injury and ensured the survival of challenged mice. Interestingly, antibodies to PcrV also inhibited the translocation of type III toxins, thus reducing P. aeruginosa pathogenesis. In a follow up study, intramuscular injection of PcrVNH (a chimeric derivative of PcrV which contains the N-terminal domain (Met1-Lys127) and H12 domain (Leu251-Ile294) of PcrV)—elicited a multifactorial immune response and conferred broad protection in an acute P. aeruginosa pneumonia model and was equally effective to full-length PcrV. Moreover, passive immunization with anti-PcrVNH antibodies also showed significant protection, at least based on inhibition of the T3SS and mediation of opsonophagocytic killing activities. An important limitation with T3SS-directed vaccines is the emergence of PA7-like clade of P. aeruginosa strains which lack T3SS.

Vaccine candidates against recombinant outer membranes OprF–OprI conjugates have been shown to be well-tolerated in healthy volunteers patients following mucosal administration; or in patients with severe burns following intramuscular injection. These vaccines have also been shown to elicit specific serum IgG and s-IgA antibodies in these patients, respectively. Supporting these findings, in a clinical trial study involving 48 volunteers in six vaccination groups with either a systemic, a nasal, or four newly constructed oral live vaccines based on attenuated live Salmonella, expressing P. aeruginosa OprF-OprI recombinant as antigen, it was reported that while systemic and mucosal vaccines induced a comparable rise of serum antibody titers, a significant rise of IgA and IgG antibodies in the lower airways was only noted after nasal and oral vaccinations. Disappointingly, in a randomized placebo-controlled phase II study in ventilated ICU patients, OprF–OprI vaccination (via intramuscular injection) produced a significant immunogenic effect (increases specific IgG), but it did not reduce infection rates. Despite these considerable efforts, no vaccine has yet been found to be clinically efficacious against this pathogen. The main obstacles to achieve this goal include poor immunogenicity of the protective epitopes, a large variant subtype antigens, leading to high degree of serologic variability, a large genome facilitating adaptation to new environments, phenotypic plasticity between acute and chronic infection, and variations in animal responses to P. aeruginosa that make determination of the optimal vaccine formulations difficult from such studies.

7.5.1. Silver

Silver has been recognized for its antimicrobial properties for centuries and because it is considerably less toxic to human cells than pathogens, it has been used in a variety of applications to prevent infection. Silver has a broad spectrum of antibacterial, antifungal and antiviral properties. Many mechanisms have been postulated to underlie silver antimicrobial action, including cell wall and cytoplasmic membrane disruption, inhibition of protein synthesis machinery by denaturation of ribosomes, interference with ATP production and chemiosmosis, production of ROS, and interference with DNA replication machinery (reviewed in). Silver has been shown to be very effective against both planktonic and biofilm P. aeruginosa, although higher silver concentrations are needed for it to be effective against biofilm P. aeruginosa. In a murine model of wound infection, silver nanoparticles (AgNPs) were shown to reduce P. aeruginosa infection by nearly 5 log-orders as compared to control wounds on day 4 post-infection and stimulate complete wound closure by day 12, although AgNPs in combination with tetracycline was more effective. In another study, silver nanocomposite was used to deliver two pharmaceutical compounds (alginate lyase and ceftazidime) to degrade the alginate and eradicate biofilm P. aeruginosa from the lungs. Silver nanocomposites displayed a high dispersity, good biocompatibility, and high ceftazidime-loading capacity, and a low pH-dependent drug release and degradation profiles. Importantly, they were highly effective in eradicating P. aeruginosa from the mouse lungs and decreasing the lung injuries. In another wound infection studies in diabetic mice, combination of AgNPs—immobilized on chitin-nanofiber sheet (CNFS)—and weakly acidic hypochlorous acid (HClO) was shown to significantly reduce P. aeruginosa infection burden and stimulate healing in an otherwise impaired healing animal model. Because of its potent antimicrobial property, silver is routinely used as an adjunct in wound dressings. However, because it can also be toxic to keratinocytes, it also has the potential to impair healing. The application of silver as an adjunct therapy on medical devices may not be suitable. In a large randomized clinical trial involving 1309 hospitalized patients, coating urinary catheter with silver was not only ineffective in reducing the incidence of bacteriuria, it actually increased infection rates in male patients, particularly with S. aureus.

7.5.2. Honey

Honey has long been known for its antimicrobial and healing properties, dating back to ancient times, well before we gained the knowledge that microorganisms could cause infection and disease. Honey exhibits a broad-spectrum of antibacterial activity against both Gram-positive bacteria and Gram-negative bacteria. The antibacterial activity of honey has been attributed to several factors, including its high viscosity, its simple and complex sugar contents, its mild acidic nature, its hydrogen peroxide content, and its high levels of phenolic compounds with antimicrobial properties. Lu et al. recently demonstrated that honey, at substantially lower concentrations compared to those found in honey-based wound dressings, inhibited P. aeruginosa biofilm formation and significantly reduced established biofilms. In another recent investigation, Bouzo et al. demonstrated that no single component of honey can account for its total antimicrobial action against P. aeruginosa. They further showed that honey affects the expression of many genes, particularly the genes involved in the electron transport chain maintenance, causing proton leakage across membranes, and inducing membrane depolarization and permeabilization in P. aeruginosa. A randomized clinical trial (105 patients) to compare a medical grade antibacterial honey (Medihoney™) with conventional treatments in wound care, reported clinical benefits from using honey in wound care with 23% fewer episodes of infection.

7.5.3. Hyperbaric Oxygen Therapy (HBOT)

HBOT is used as an adjunctive therapy in the management of infections such as diabetic foot, osteomyelitis, gas gangrene, necrotizing fasciitis, and fungal infections. The underlying mechanisms of HBOT’s bactericidal functions involve activation of innate immune system (via restoration of neutrophils’ bactericidal functions under hypoxic environment or diabetic condition), and enhancement of ROS production in targeted bacteria. In another study to evaluate the therapeutic potential of HBOT as an adjuvant to tobramycin treatment, HBOT was able to significantly enhance the effect of tobramycin against aggregates of all the P. aeruginosa isolates from CF patients in vitro. The effect was attributed to increased O2 levels. In experimental subcutaneous and pulmonary rat infection models, oxygen therapy was shown to significantly reduce P. aeruginosa titers in the blood and bronchial aspirates, and protected animals against infection-induced mortality and morbidity as compared to control group. In combination with amikacin antibiotic, these effects were even more impressive, highlighting HBOT’s potential as an adjunctive therapy. Although the impact of HOBT on P. aeruginosa infection has not been directly examined, two systemic reviews of reports on randomized controlled trials comparing the effects of therapeutic regimens which include HBOT with those that exclude HBOT (with or without sham therapy)—have found HBOT to be beneficial for the treatment of necrotizing infections and to improve wound healing in diabetic ulcers and ischemic leg ulcers.

7.5.4. Negative Pressure Wound Therapy (NPWT)

NPWT has been shown to reduce surgical site infections (SSIs) by reducing fluid accumulation within the avascular dead space in a closed wound. NPWT was shown to reduce infection and decrease mortality in a murine model of burn wound sepsis with P. aeruginosa. In a rabbit wound model of infection, NPWT was shown to be significantly more effective than the control treatment (a sterile gauze dressing) in reducing the expression of virulence factors and P. aeruginosa bacteria counts. In another report, NPWT was shown to reduce the mobility of P. aeruginosa and enhance wound healing in a rabbit ear biofilm infection. NPWT was also shown to inhibit the invasion and proliferation of P. aeruginosa in burn-wounded tissue and decrease mortality in a murine model of burn-wound sepsis.

8. Concluding Remarks

Pseudomonas aeruginosa is a serious pathogen that can cause deadly acute and chronic infections particularly in immunocompromised hosts and CF patients. What makes this pathogen so successful in colonizing diverse environments within its host are its large genome, which gives this pathogen the metabolic flexibility to quickly adapt to changes within its environment; and its large arsenal of cell-associated and secreted virulence factors, which protect this pathogen from recognition and attack by host’s immune responses. What is alarming about P. aeruginosa is its high intrinsic and acquired resistance to many available antibiotics which further highlights the need and the impetus for the development of novel strategies to deal with this organisms.

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    Wood S.J., Goldufsky J.W., Dorafshar A.H., Shafikhani S.H. Pseudomonas aeruginosa Cytotoxins: Mechanisms of Cytotoxicity and Impact on Inflammatory Responses. Cells. 2023.

    Not in our library10.3390/cells12010195

  26. 26.
    Clinical utilization of genomics data produced by the international Pseudomonas aeruginosa consortium · 2015
    No notice
  27. 27.

    Gellatly S.L., Hancock R.E. Pseudomonas aeruginosa: New insights into pathogenesis and host defenses. Pathog. Dis. 2013;67:159-173.

    Not in our library10.1111/2049-632x.12033

  28. 28.

    Yoon S.S., Hennigan R.F., Hilliard G.M., Ochsner U.A., Parvatiyar K., Kamani M.C., Allen H.L., DeKievit T.R., Gardner P.R., Schwab U., et al. Pseudomonas aeruginosa anaerobic respiration in biofilms: Relationships to cystic fibrosis pathogenesis. Dev. Cell. 2002;3:593-603.

    Not in our library10.1016/s1534-5807(02)00295-2

  29. 29.

    Foght J.M., Westlake D.W., Johnson W.M., Ridgway H.F. Environmental gasoline-utilizing isolates and clinical isolates of Pseudomonas aeruginosa are taxonomically indistinguishable by chemotaxonomic and molecular techniques. Microbiology. 1996;142:2333-2340.

    Not in our library10.1099/00221287-142-9-2333

  30. 30.

    Morrison A.J., Wenzel R.P. Epidemiology of infections due to Pseudomonas aeruginosa. Rev. Infect. Dis. 1984;6((Suppl. 3)):S627-S642.

    Not in our library10.1093/clinids/6.supplement_3.s627

  31. 31.

    Cogen A.L., Nizet V., Gallo R.L. Skin microbiota: A source of disease or defence? Br. J. Dermatol. 2008;158:442-455.

    Not in our library10.1111/j.1365-2133.2008.08437.x

  32. 32.

    Harris A.A., Goodman L., Levin S. Community-acquired Pseudomonas aeruginosa pneumonia associated with the use of a home humidifier. West. J. Med. 1984;141:521-523.

    Not in our library

  33. 33.

    Pollack M., Mandell G.L., Dolin R., Bennett J.E. Pseudomonas aeruginosa. Principles and Practices of Infectious Diseases. 1995;1820-2003.

    Not in our library

  34. 34.

    Chitkara Y.K., Feierabend T.C. Endogenous and exogenous infection with Pseudomonas aeruginosa in a burns unit. Int. Surg. 1981;66:237-240.

    Not in our library

  35. 35.

    Phillips L.G., Heggers J.P., Robson M.C., Boertman J.A., Meltzer T., Smith D.J. The effect of endogenous skin bacteria on burn wound infection. Ann. Plast. Surg. 1989;23:35-38.

    Not in our library10.1097/00000637-198907000-00007

  36. 36.

    Koch C. Early infection and progression of cystic fibrosis lung disease. Pediatr. Pulmonol. 2002;34:232-236.

    Not in our library10.1002/ppul.10135

  37. 37.

    Engel J.N., Hauser A., Rello J. Molecular pathogenesis of acute Pseudomonas aeruginosa infections. Severe Infections Caused by Pseudomonas aeruginosa. 2003;201-230.

    Not in our library

  38. 38.

    Harbarth S., Ferriere K., Hugonnet S., Ricou B., Suter P., Pittet D. Epidemiology and prognostic determinants of bloodstream infections in surgical intensive care. Arch. Surg. 2002;137:1353-1359.

    Not in our library10.1001/archsurg.137.12.1353

  39. 39.

    Osmon S., Ward S., Fraser V.J., Kollef M.H. Hospital mortality for patients with bacteremia due to Staphylococcus aureus or Pseudomonas aeruginosa. Chest. 2004;125:607-616.

    Not in our library10.1378/chest.125.2.607

  40. 40.

    Parkins M.D., Somayaji R., Waters V.J. Epidemiology, biology, and impact of clonal Pseudomonas aeruginosa infections in cystic fibrosis. Clin. Microbiol. Rev. 2018;31:e00019-18.

    Not in our library10.1128/cmr.00019-18

  41. 41.

    Matos E.C.O.d., Andriolo R.B., Rodrigues Y.C., Lima P.D.L.d., Carneiro I.C.d.R.S., Lima K.V.B. Mortality in patients with multidrug-resistant Pseudomonas aeruginosa infections: A meta-analysis. Rev. Soc. Bras. Med. Trop. 2018;51:415-420.

    Not in our library10.1590/0037-8682-0506-2017

  42. 42.

    Shepp D.H., Tan I., Ramundo M.B., Kaplan M.H. Serious Pseudomonas aeruginosa infection in AIDS. J. Acq. Immun. Defic. Synd. 1994;7:823-831.

    Not in our library

  43. 43.

    Kielhofner M., Atmar R.L., Hamill R.J., Musher D.M. Life-threatening Pseudomonas aeruginosa infections in patients with human immunodeficiency virus infection. Clin. Infect. Dis. 1992;14:403-411.

    Not in our library10.1093/clinids/14.2.403

  44. 44.

    Pang Z., Raudonis R., Glick B.R., Lin T.-J., Cheng Z. Antibiotic resistance in Pseudomonas aeruginosa: Mechanisms and alternative therapeutic strategies. Biotechnol. Adv. 2019;37:177-192.

    Not in our library10.1016/j.biotechadv.2018.11.013

  45. 45.

    Antibiotic Resistance Threats in the United States. 2019.

    Not in our library

  46. 46.

    Shrivastava S.R., Shrivastava P.S., Ramasamy J. World health organization releases global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics. J. Med. Soc. 2018;32:76.

    Not in our library10.4103/jms.jms_25_17

  47. 47.

    Rice L.B. Federal Funding for the Study of Antimicrobial Resistance in Nosocomial Pathogens: No ESKAPE. 2008;Volume 197:1079-1081.

    Not in our library10.1086/533452

  48. 48.

    Neuhauser M.M., Weinstein R.A., Rydman R., Danziger L.H., Karam G., Quinn J.P. Antibiotic resistance among gram-negative bacilli in US intensive care units: Implications for fluoroquinolone use. JAMA. 2003;289:885-888.

    Not in our library10.1001/jama.289.7.885

  49. 49.

    Kollef M.H., Shorr A., Tabak Y.P., Gupta V., Liu L.Z., Johannes R. Epidemiology and outcomes of health-care–associated pneumonia: Results from a large US database of culture-positive pneumonia. Chest J. 2005;128:3854-3862.

    Not in our library10.1378/chest.128.6.3854

  50. 50.

    Sadikot R.T., Blackwell T.S., Christman J.W., Prince A.S. Pathogen-host interactions in Pseudomonas aeruginosa pneumonia. Am. J. Respir. Crit. Care Med. 2005;171:1209-1223.

    Not in our library10.1164/rccm.200408-1044so

  51. 51.

    Rello J., Mariscal D., March F., Jubert P., Sanchez F., Valles J., Coll P. Recurrent Pseudomonas aeruginosa pneumonia in ventilated patients: Relapse or reinfection? Am. J. Respir. Crit. Care Med. 1998;157:912-916.

    Not in our library10.1164/ajrccm.157.3.9703014

  52. 52.

    Stapleton F., Dart J., Seal D., Matheson M. Epidemiology of Pseudomonas aeruginosa keratitis in contact lens wearers. Epidemiol. Infect. 1995;114:395-402.

    Not in our library10.1017/s0950268800052109

  53. 53.

    Burns R.P. Pseudomonas aeruginosa keratitis: Mixed infections of the eye. Am. J. Ophthalmol. 1969;67:257-262.

    Not in our library10.1016/0002-9394(69)93156-0

  54. 54.
    The Microbiology of Bloodstream Infection: 20-Year Trends from the SENTRY Antimicrobial Surveillance Program · 2019
    No notice
  55. 55.

    Montero M.M., López Montesinos I., Knobel H., Molas E., Sorlí L., Siverio-Parés A., Prim N., Segura C., Duran-Jordà X., Grau S. Risk factors for mortality among patients with Pseudomonas aeruginosa bloodstream infections: What is the influence of XDR phenotype on outcomes? J. Clin. Med. 2020;9:514.

    Not in our library10.3390/jcm9020514

  56. 56.

    Fabre V., Amoah J., Cosgrove S.E., Tamma P.D. Antibiotic therapy for Pseudomonas aeruginosa bloodstream infections: How long is long enough? Clin. Infect. Dis. 2019;69:2011-2014.

    Not in our library10.1093/cid/ciz223

  57. 57.

    Norden C.W., Shinners E. Ciprofloxacin as therapy for experimental osteomyelitis caused by Pseudomonas aeruginosa. J. Infect. Dis. 1985;151:291-294.

    Not in our library10.1093/infdis/151.2.291

  58. 58.

    Carek P.J., Dickerson L.M., Sack J.L. Diagnosis and management of osteomyelitis. Am. Fam. Physician. 2001;63:2413-2420.

    Not in our library

  59. 59.

    Reyes M.P., Lerner A.M. Current problems in the treatment of infective endocarditis due to Pseudomonas aeruginosa. Rev. Infect. Dis. 1983;5:314-321.

    Not in our library10.1093/clinids/5.2.314

  60. 60.

    Lin T.-I., Huang Y.-F., Liu P.-Y., Chou C.-A., Chen Y.-S., Chen Y.-Y., Hsieh K.-S., Chen Y.-S. Pseudomonas aeruginosa infective endocarditis in patients who do not use intravenous drugs: Analysis of risk factors and treatment outcomes. J. Microbiol. Immunol. Infect. 2016;49:516-522.

    Not in our library10.1016/j.jmii.2014.08.019

  61. 61.

    Jones R.N. Microbial etiologies of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia. Clin. Infect. Dis. 2010;51:S81-S87.

    Not in our library10.1086/653053

  62. 62.

    Herkel T., Uvizl R., Doubravska L., Adamus M., Gabrhelik T., Htoutou Sedlakova M., Kolar M., Hanulik V., Pudova V., Langova K. Epidemiology of hospital-acquired pneumonia: Results of a Central European multicenter, prospective, observational study compared with data from the European region. Biomed. Pap. 2016;160:448-455.

    Not in our library10.5507/bp.2016.014

  63. 63.

    He S., Chen B., Li W., Yan J., Chen L., Wang X., Xiao Y. Ventilator-associated pneumonia after cardiac surgery: A meta-analysis and systematic review. J. Thorac. Cardiovasc. Surg. 2014;148:3148-3155.e5.

    Not in our library10.1016/j.jtcvs.2014.07.107

  64. 64.

    Chung D.R., Song J.-H., Kim S.H., Thamlikitkul V., Huang S.-G., Wang H., So T.M.-k., Yasin R.M., Hsueh P.-R., Carlos C.C. High prevalence of multidrug-resistant nonfermenters in hospital-acquired pneumonia in Asia. Am. J. Respir. Crit. Care Med. 2011;184:1409-1417.

    Not in our library10.1164/rccm.201102-0349oc

  65. 65.
    Prevalence of Pseudomonas aeruginosa and antimicrobial-resistant Pseudomonas aeruginosa in patients with pneumonia in mainland China: a systematic review and meta-analysis · 2016
    Not checked
  66. 66.

    Tumbarello M., De Pascale G., Trecarichi E.M., Spanu T., Antonicelli F., Maviglia R., Pennisi M.A., Bello G., Antonelli M. Clinical outcomes of Pseudomonas aeruginosa pneumonia in intensive care unit patients. Intensive Care Med. 2013;39:682-692.

    Not in our library10.1007/s00134-013-2828-9

  67. 67.

    Duszynska W., Idziak M., Smardz K., Burkot A., Grotowska M., Rojek S. Frequency, Etiology, Mortality, Cost, and Prevention of Respiratory Tract Infections—Prospective, One Center Study. J. Clin. Med. 2022;11:3764.

    Not in our library10.3390/jcm11133764

  68. 68.

    Hauser A.R., Cobb E., Bodi M., Mariscal D., Valles J., Engel J.N., Rello J. Type III protein secretion is associated with poor clinical outcomes in patients with ventilator-associated pneumonia caused by Pseudomonas aeruginosa. Crit. Care Med. 2002;30:521-528.

    Not in our library10.1097/00003246-200203000-00005

  69. 69.

    Ramírez-Estrada S., Borgatta B., Rello J. Pseudomonas aeruginosa ventilator-associated pneumonia management. Infect. Drug Resist. 2016;9:7.

    Not in our library10.2147/idr.s50669

  70. 70.

    Karaiskos I., Giamarellou H. Multidrug-resistant and extensively drug-resistant Gram-negative pathogens: Current and emerging therapeutic approaches. Expert Opin. Pharmacother. 2014;15:1351-1370.

    Not in our library10.1517/14656566.2014.914172

  71. 71.

    McEachern R., Campbell G.D. Hospital-acquired pneumonia: Epidemiology, etiology, and treatment. Infect. Dis. Clin. N. Am. 1998;12:761-779.

    Not in our library10.1016/s0891-5520(05)70209-9

  72. 72.
    Bacterial profile of ocular infections: a systematic review · 2017
    No notice
  73. 73.

    Green M., Carnt N., Apel A., Stapleton F. Queensland microbial keratitis database: 2005–2015. Br. J. Ophthalmol. 2019;103:1481-1486.

    Not in our library10.1136/bjophthalmol-2018-312881

  74. 74.

    Soleimani M., Tabatabaei S.A., Masoumi A., Mirshahi R., Ghahvechian H., Tayebi F., Momenaei B., Mahdizad Z., Mohammadi S.S. Infectious keratitis: Trends in microbiological and antibiotic sensitivity patterns. Eye. 2021;35:3110-3115.

    Not in our library10.1038/s41433-020-01378-w

  75. 75.

    Green M., Apel A., Stapleton F. Risk factors and causative organisms in microbial keratitis. Cornea. 2008;27:22-27.

    Not in our library10.1097/ico.0b013e318156caf2

  76. 76.

    Enzor R., Bowers E.M., Perzia B., Perera C., Palazzolo L., Mammen A., Dhaliwal D.K., Kowalski R.P., Jhanji V. Comparison of Clinical Features and Treatment Outcomes of Pseudomonas aeruginosa Keratitis in Contact Lens and Non–Contact Lens Wearers. Am. J. Ophthalmol. 2021;227:1-11.

    Not in our library10.1016/j.ajo.2021.02.024

  77. 77.

    Shirley R., Moore J. Pseudomonas aeruginosa urinary-tract infection. N. Engl. J. Med. 1965;273:283.

    Not in our library

  78. 78.

    Bitsori M., Maraki S., Koukouraki S., Galanakis E. Pseudomonas aeruginosa urinary tract infection in children: Risk factors and outcomes. J. Urol. 2012;187:260-264.

    Not in our library10.1016/j.juro.2011.09.035

  79. 79.

    Newman J.W., Floyd R.V., Fothergill J.L. The contribution of Pseudomonas aeruginosa virulence factors and host factors in the establishment of urinary tract infections. FEMS Microbiol. Lett. 2017;364.

    Not in our library10.1093/femsle/fnx124

  80. 80.

    Warren J.W. Catheter-associated urinary tract infections. Int. J. Antimicrob. Agents. 2001;17:299-303.

    Not in our library10.1016/s0924-8579(00)00359-9

  81. 81.

    Vidal F., Mensa J., Almela M., Martinez J., Marco F., Casals C., Gatell J., Soriano E., Jimenez de Anta M. Epidemiology and Outcome of Pseudomonas aeruginosa Bacteremia, With Special Emphasis on the Influence of Antibiotic Treatment. Arch. Intern. Med. 1996;156:2121-2126.

    Not in our library10.1001/archinte.1996.00440170139015

  82. 82.

    Nielsen S.L., Lassen A.T., Gradel K.O., Jensen T.G., Kolmos H.J., Hallas J., Pedersen C. Bacteremia is associated with excess long-term mortality: A 12-year population-based cohort study. J. Infect. 2015;70:111-126.

    Not in our library10.1016/j.jinf.2014.08.012

  83. 83.

    Thaden J.T., Park L.P., Maskarinec S.A., Ruffin F., Fowler V.G., Van Duin D. Results from a 13-year prospective cohort study show increased mortality associated with bloodstream infections caused by Pseudomonas aeruginosa compared to other bacteria. Antimicrob. Agents Chemother. 2017;61:e02671-16.

    Not in our library10.1128/aac.02671-16

  84. 84.
    Venous thromboembolism after community-acquired bacteraemia: a 20-year danish cohort study. · 2014
    Not checked
  85. 85.

    Dalager-Pedersen M., Søgaard M., Schønheyder H.C., Nielsen H., Thomsen R.W. Risk for myocardial infarction and stroke after community-acquired bacteremia: A 20-year population-based cohort study. Circulation. 2014;129:1387-1396.

    Not in our library10.1161/circulationaha.113.006699

  86. 86.

    Tal S., Guller V., Levi S., Bardenstein R., Berger D., Gurevich I., Gurevich A. Profile and prognosis of febrile elderly patients with bacteremic urinary tract infection. J. Infect. 2005;50:296-305.

    Not in our library10.1016/j.jinf.2004.04.004

  87. 87.

    Bright H.R., Babata K., Allred E.N., Erdei C., Kuban K.C., Joseph R.M., O’Shea T.M., Leviton A., Dammann O., Ware J. Neurocognitive outcomes at 10 years of age in extremely preterm newborns with late-onset bacteremia. J. Pediatr. 2017;187:43-49.e41.

    Not in our library10.1016/j.jpeds.2017.04.045

  88. 88.
    Pseudomonas aeruginosa Diversification during Infection Development in Cystic Fibrosis Lungs—A Review · 2014
    No notice
  89. 89.
    Pseudomonas aeruginosa Evolutionary Adaptation and Diversification in Cystic Fibrosis Chronic Lung Infections · 2016
    No notice
  90. 90.

    Mayer-Hamblett N., Kloster M., Rosenfeld M., Gibson R.L., Retsch-Bogart G.Z., Emerson J., Thompson V., Ramsey B.W. Impact of sustained eradication of new Pseudomonas aeruginosa infection on long-term outcomes in cystic fibrosis. Clin. Infect. Dis. 2015;61:707-715.

    Not in our library10.1093/cid/civ377

  91. 91.

    Li Z., Kosorok M.R., Farrell P.M., Laxova A., West S.E., Green C.G., Collins J., Rock M.J., Splaingard M.L. Longitudinal development of mucoid Pseudomonas aeruginosa infection and lung disease progression in children with cystic fibrosis. JAMA. 2005;293:581-588.

    Not in our library10.1001/jama.293.5.581

  92. 92.

    Malik A., Mohammad Z., Ahmad J. The diabetic foot infections: Biofilms and antimicrobial resistance. Diabetes Metab. Syndr. 2013;7:101-107.

    Not in our library10.1016/j.dsx.2013.02.006

  93. 93.

    Ramakant P., Verma A.K., Misra R., Prasad K.N., Chand G., Mishra A., Agarwal G., Agarwal A., Mishra S.K. Changing microbiological profile of pathogenic bacteria in diabetic foot infections: Time for a rethink on which empirical therapy to choose? Diabetologia. 2011;54:58-64.

    Not in our library10.1007/s00125-010-1893-7

  94. 94.

    Ge Y., MacDonald D., Hait H., Lipsky B., Zasloff M., Holroyd K. Microbiological profile of infected diabetic foot ulcers. Diabet. Med. 2002;19:1032-1034.

    Not in our library10.1046/j.1464-5491.2002.00696_1.x

  95. 95.

    James G.A., Swogger E., Wolcott R., Pulcini E., Secor P., Sestrich J., Costerton J.W., Stewart P.S. Biofilms in chronic wounds. Wound Repair Regen. 2008;16:37-44.

    Not in our library10.1111/j.1524-475x.2007.00321.x

  96. 96.
    Survey of bacterial diversity in chronic wounds using Pyrosequencing, DGGE, and full ribosome shotgun sequencing · 2008
    No notice
  97. 97.

    Shankar E.M., Mohan V., Premalatha G., Srinivasan R.S., Usha A.R. Bacterial etiology of diabetic foot infections in South India. Eur. J. Intern. Med. 2005;16:567-570.

    Not in our library10.1016/j.ejim.2005.06.016

  98. 98.

    Redel H., Gao Z., Li H., Alekseyenko A.V., Zhou Y., Perez-Perez G.I., Weinstock G., Sodergren E., Blaser M.J. Quantitation and composition of cutaneous microbiota in diabetic and nondiabetic men. J. Infect. Dis. 2013;207:1105-1114.

    Not in our library10.1093/infdis/jit005

  99. 99.

    Goldufsky J., Wood S., Hajihossainlou B., Rehman T., Majdobeh O., Kaufman H.L., Ruby C.E., Shafikhani S.H. Pseudomonas aeruginosa exotoxin T induces potent cytotoxicity against a variety of murine and human cancer cell lines. J. Med. Microbiol. 2015;64:164-173.

    Not in our library10.1099/jmm.0.000003

  100. 100.

    Bjarnsholt T., Kirketerp-Moller K., Jensen P.O., Madsen K.G., Phipps R., Krogfelt K., Hoiby N., Givskov M. Why chronic wounds will not heal: A novel hypothesis. Wound Repair Regen. 2008;16:2-10.

    Not in our library10.1111/j.1524-475x.2007.00283.x

  101. 101.

    Oyibo S.O., Jude E.B., Tarawneh I., Nguyen H.C., Armstrong D.G., Harkless L.B., Boulton A.J. The effects of ulcer size and site, patient’s age, sex and type and duration of diabetes on the outcome of diabetic foot ulcers. Diabet. Med. 2001;18:133-138.

    Not in our library10.1046/j.1464-5491.2001.00422.x

  102. 102.

    Mendes J.J., Leandro C.I., Bonaparte D.P., Pinto A.L. A rat model of diabetic wound infection for the evaluation of topical antimicrobial therapies. Comp. Med. 2012;62:37-48.

    Not in our library

  103. 103.

    Zhao G., Hochwalt P.C., Usui M.L., Underwood R.A., Singh P.K., James G.A., Stewart P.S., Fleckman P., Olerud J.E. Delayed wound healing in diabetic (db/db) mice with Pseudomonas aeruginosa biofilm challenge: A model for the study of chronic wounds. Wound Repair Regen. 2010;18:467-477.

    Not in our library10.1111/j.1524-475x.2010.00608.x

  104. 104.

    Zhao G., Usui M.L., Underwood R.A., Singh P.K., James G.A., Stewart P.S., Fleckman P., Olerud J.E. Time course study of delayed wound healing in a biofilm-challenged diabetic mouse model. Wound Repair Regen. 2012;20:342-352.

    Not in our library10.1111/j.1524-475x.2012.00793.x

  105. 105.

    Geiser T., Kazmierczak B., Garrity-Ryan L., Matthay M., Engel J. Pseudomonas aeruginosa ExoT inhibits in vitro lung epithelial wound repair. Cell Microbiol. 2001;3:223-236.

    Not in our library10.1046/j.1462-5822.2001.00107.x

  106. 106.

    Garrity-Ryan L., Shafikhani S., Balachandran P., Nguyen L., Oza J., Jakobsen T., Sargent J., Fang X., Cordwell S., Matthay M.A., et al. The ADP ribosyltransferase domain of Pseudomonas aeruginosa ExoT contributes to its biological activities. Infect. Immun. 2004;72:546-558.

    Not in our library10.1128/iai.72.1.546-558.2004

  107. 107.

    Mathews W.C., Caperna J., Toerner J.G., Barber R.E., Morgenstern H. Neutropenia is a risk factor for gram-negative bacillus bacteremia in human immunodeficiency virus-infected patients: Results of a nested case-control study. Am. J. Epidemiol. 1998;148:1175-1183.

    Not in our library10.1093/oxfordjournals.aje.a009606

  108. 108.

    Markou P., Apidianakis Y. Pathogenesis of intestinal Pseudomonas aeruginosa infection in patients with cancer. Front. Cell. Infect. Microbiol. 2014;3:115.

    Not in our library10.3389/fcimb.2013.00115

  109. 109.

    Afessa B., Green B. Bacterial pneumonia in hospitalized patients with HIV infection: The Pulmonary Complications, ICU Support, and Prognostic Factors of Hospitalized Patients with HIV (PIP) Study. Chest. 2000;117:1017-1022.

    Not in our library10.1378/chest.117.4.1017

  110. 110.

    Manfredi R., Nanetti A., Ferri M., Chiodo F. Pseudomonas spp. complications in patients with HIV disease: An eight-year clinical and microbiological survey. Eur. J. Epidemiol. 2000;16:111-118.

    Not in our library10.1023/a:1007626410724

  111. 111.

    Meynard J.L., Barbut F., Guiguet M., Batisse D., Lalande V., Lesage D., Guiard-Schmid J.B., Petit J.C., Frottier J., Meyohas M.C. Pseudomonas aeruginosa infection in human immunodeficiency virus infected patients. J. Infect. 1999;38:176-181.

    Not in our library10.1016/s0163-4453(99)90247-5

  112. 112.

    Zylberberg H., Vargaftig J., Barbieux C., Pertuiset N., Rothschild C., Viard J.P. Prolonged efficiency of secondary prophylaxis with colistin aerosols for respiratory infection due to Pseudomonas aeruginosa in patients infected with human immunodeficiency virus. Clin. Infect. Dis. 1996;23:641-643.

    Not in our library10.1093/clinids/23.3.641

  113. 113.

    Santin Cerezales M., Aranda Sanchez M., Podzamczer Palter D., Maiques Llacer J.M., Rufi Rigau G., Gudiol Munte F. The spectrum of bronchopulmonary infection caused by Pseudomonas aeruginosa in patients infected with the human immunodeficiency virus. Rev. Clin. Esp. 1996;196:692-697.

    Not in our library

  114. 114.

    Ali N.J., Kessel D., Miller R.F. Bronchopulmonary infection with Pseudomonas aeruginosa in patients infected with human immunodeficiency virus. Genitourin. Med. 1995;71:73-77.

    Not in our library10.1136/sti.71.2.73

  115. 115.

    Nesher L., Rolston K.V. The current spectrum of infection in cancer patients with chemotherapy related neutropenia. Infection. 2014;42:5-13.

    Not in our library10.1007/s15010-013-0525-9

  116. 116.

    Allen S., Brennan-Benson P., Nelson M., Asboe D., Bower M., Azadian B., Gazzard B., Stebbing J. Pneumonia due to antibiotic resistant Streptococcus pneumoniae and Pseudomonas aeruginosa in the HAART era. Postgrad. Med. J. 2003;79:691-694.

    Not in our library

  117. 117.

    Shenoy M.K., Iwai S., Lin D.L., Worodria W., Ayakaka I., Byanyima P., Kaswabuli S., Fong S., Stone S., Chang E. Immune response and mortality risk relate to distinct lung microbiomes in patients with HIV and pneumonia. Am. J. Respir. Crit. Care Med. 2017;195:104-114.

    Not in our library10.1164/rccm.201603-0523oc

  118. 118.

    Cribbs S.K., Park Y., Guidot D.M., Martin G.S., Brown L.A., Lennox J., Jones D.P. Metabolomics of bronchoalveolar lavage differentiate healthy HIV-1-infected subjects from controls. AIDS Res. Hum. Retrovir. 2014;30:579-585.

    Not in our library10.1089/aid.2013.0198

  119. 119.

    Wisplinghoff H., Bischoff T., Tallent S.M., Seifert H., Wenzel R.P., Edmond M.B. Nosocomial bloodstream infections in US hospitals: Analysis of 24,179 cases from a prospective nationwide surveillance study. Clin. Infect. Dis. 2004;39:309-317.

    Not in our library10.1086/421946

  120. 120.

    Paprocka P., Durnaś B., Mańkowska A., Król G., Wollny T., Bucki R. Pseudomonas aeruginosa infections in cancer patients. Pathogens. 2022;11:679.

    Not in our library10.3390/pathogens11060679

  121. 121.

    Vidal F., Mensa J., Martinez J.A., Almela M., Marco F., Gatell J.M., Richart C., Soriano E., Jimenez de Anta M.T. Pseudomonas aeruginosa bacteremia in patients infected with human immunodeficiency virus type 1. Eur. J. Clin. Microbiol. Infect. Dis. 1999;18:473-477.

    Not in our library10.1007/s100960050326

  122. 122.

    Crawford J., Dale D.C., Lyman G.H. Chemotherapy-induced neutropenia. Cancer. 2004;100:228-237.

    Not in our library10.1002/cncr.11882

  123. 123.

    Chrischilles E.A., Link B.K., Scott S.D., Delgado D.J., Fridman M. Factors associated with early termination of CHOP therapy and the impact on survival among patients with chemosensitive intermediate-grade non-Hodgkin’s lymphoma. Cancer Control. 2003;10:396-403.

    Not in our library10.1177/107327480301000507

  124. 124.

    Gudiol C., Royo-Cebrecos C., Laporte J., Ardanuy C., Garcia-Vidal C., Antonio M., Arnan M., Carratala J. Clinical features, aetiology and outcome of bacteraemic pneumonia in neutropenic cancer patients. Respirology. 2016;21:1411-1418.

    Not in our library10.1111/resp.12848

  125. 125.

    Marin M., Gudiol C., Ardanuy C., Garcia-Vidal C., Calvo M., Arnan M., Carratalà J. Bloodstream infections in neutropenic patients with cancer: Differences between patients with haematological malignancies and solid tumours. J. Infect. 2014;69:417-423.

    Not in our library10.1016/j.jinf.2014.05.018

  126. 126.

    Chatzinikolaou I., Abi-Said D., Bodey G.P., Rolston K.V., Tarrand J.J., Samonis G. Recent experience with Pseudomonas aeruginosa bacteremia in patients with cancer: Retrospective analysis of 245 episodes. Arch. Intern. Med. 2000;160:501-509.

    Not in our library10.1001/archinte.160.4.501

  127. 127.

    Funada H., Matsuda T. Changes in the incidence and etiological patterns of bacteremia associated with acute leukemia over a 25-year period. Intern. Med. 1998;37:1014-1018.

    Not in our library10.2169/internalmedicine.37.1014

  128. 128.

    Yuan X., Liu T., Wu D., Wan Q. Epidemiology, susceptibility, and risk factors for acquisition of MDR/XDR Gram-negative bacteria among kidney transplant recipients with urinary tract infections. Infect. Drug Resist. 2018;11:707.

    Not in our library10.2147/idr.s163979

  129. 129.

    Kritikos A., Manuel O. Bloodstream infections after solid-organ transplantation. Virulence. 2016;7:329-340.

    Not in our library10.1080/21505594.2016.1139279

  130. 130.

    Wan Q., Ming Y., Ma Y. A clinical analysis of 96 patients with bloodstream infections after solid organ transplantation. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2012;37:509-512.

    Not in our library10.3969/j.issn.1672-7347.2012.05.015

  131. 131.

    Fishman J.A. Infection in solid-organ transplant recipients. N. Engl. J. Med. 2007;357:2601-2614.

    Not in our library10.1056/nejmra064928

  132. 132.

    Moreno A., Cervera C., Gavalda J., Rovira M., De La Cámara R., Jarque I., Montejo M., De La Torre-Cisneros J., Miguel Cisneros J., Fortún J. Bloodstream infections among transplant recipients: Results of a Nationwide Surveillance in Spain 1. Am. J. Transplant. 2007;7:2579-2586.

    Not in our library10.1111/j.1600-6143.2007.01964.x

  133. 133.

    McClean K., Kneteman N., Taylor G. Comparative risk of bloodstream infection in organ transplant recipients. Infect. Control. Hosp. Epidemiol. 1994;15:582-584.

    Not in our library10.2307/30147434

  134. 134.

    Lee S.O., Kang S.H., Abdel-Massih R.C., Brown R.A., Razonable R.R. Spectrum of early-onset and late-onset bacteremias after liver transplantation: Implications for management. Liver Transplant. 2011;17:733-741.

    Not in our library10.1002/lt.22296

  135. 135.

    Palmer S.M., Alexander B.D., Sanders L.L., Edwards L.J., Reller L.B., Davis R.D., Tapson V.F. Significance of blood stream infection after lung transplantation: Analysis in 176 consecutive patients1. Transplantation. 2000;69:2360-2366.

    Not in our library10.1097/00007890-200006150-00025

  136. 136.

    Van Delden C., Stampf S., Hirsch H.H., Manuel O., Meylan P., Cusini A., Hirzel C., Khanna N., Weisser M., Garzoni C. Burden and timeline of infectious diseases in the first year after solid organ transplantation in the Swiss Transplant Cohort Study. Clin. Infect. Dis. 2020;71:e159-e169.

    Not in our library10.1093/cid/ciz1113

  137. 137.

    Ye Q., Zhao J., Wan Q., Qiao B., Zhou J. Frequency and clinical outcomes of ESKAPE bacteremia in solid organ transplantation and the risk factors for mortality. Transpl. Infect. Dis. 2014;16:767-774.

    Not in our library10.1111/tid.12278

  138. 138.

    Duke J.M., Bauer J., Fear M.W., Rea S., Wood F.M., Boyd J. Burn injury, gender and cancer risk: Population-based cohort study using data from Scotland and Western Australia. BMJ Open. 2014;4:e003845.

    Not in our library10.1136/bmjopen-2013-003845

  139. 139.

    Fear V.S., Boyd J.H., Rea S., Wood F.M., Duke J.M., Fear M.W. Burn injury leads to increased long-term susceptibility to respiratory infection in both mouse models and population studies. PLoS ONE. 2017;12:e0169302.

    Not in our library10.1371/journal.pone.0169302

  140. 140.

    Miller S.E., Miller C.L., Trunkey D.D. The immune consequences of trauma. Surg. Clin. N. Am. 1982;62:167-181.

    Not in our library10.1016/s0039-6109(16)42643-5

  141. 141.

    Chen H., Yang L., Cheng L., Hu X.-H., Shen Y.-M. Distribution and drug resistance of pathogens in burn patients in China from 2006 to 2019. World J. Clin. Cases. 2021;9:2228.

    Not in our library10.12998/wjcc.v9.i10.2228

  142. 142.

    Dou Y., Huan J., Guo F., Zhou Z., Shi Y. Pseudomonas aeruginosa prevalence, antibiotic resistance and antimicrobial use in Chinese burn wards from 2007 to 2014. J. Int. Med. Res. 2017;45:1124-1137.

    Not in our library10.1177/0300060517703573

  143. 143.

    Estahbanati H.K., Kashani P.P., Ghanaatpisheh F. Frequency of Pseudomonas aeruginosa serotypes in burn wound infections and their resistance to antibiotics. Burns. 2002;28:340-348.

    Not in our library10.1016/s0305-4179(02)00024-4

  144. 144.

    Panghal M., Singh K., Kadyan S., Chaudary U., Yadav J. The analysis of distribution of multidrug resistant Pseudomonas and Bacillus species from burn patients and burn ward environment. Burns. 2015;41:812-819.

    Not in our library10.1016/j.burns.2014.10.014

  145. 145.

    Lari A.R., Alaghehbandan R. Nosocomial infections in an Iranian burn care center. Burns. 2000;26:737-740.

    Not in our library10.1016/s0305-4179(00)00048-6

  146. 146.

    Song W., Lee K.M., Kang H.J., Shin D.H., Kim D.K. Microbiologic aspects of predominant bacteria isolated from the burn patients in Korea. Burns. 2001;27:136-139.

    Not in our library10.1016/s0305-4179(00)00086-3

  147. 147.

    Sheridan R.L. Sepsis in pediatric burn patients. Pediatr. Crit. Care Med. 2005;6:S112-S119.

    Not in our library10.1097/01.pcc.0000161577.27849.be

  148. 148.

    Redmond M.T., Scherzer R., Prince B.T. Novel Genetic Discoveries in Primary Immunodeficiency Disorders. Clin. Rev. Allergy Immunol. 2022;63:55-74.

    Not in our library10.1007/s12016-021-08881-2

  149. 149.

    Stergiopoulou T., Walsh T.J., Seghaye M.-C., Netea M.G., Casanova J.-L., Moutschen M., Picard C. Deficiency of interleukin-1 receptor-associated kinase 4 presenting as fatal Pseudomonas aeruginosa bacteremia in two siblings. Pediatr. Infect. Dis. J. 2015;34:299-300.

    Not in our library10.1097/inf.0000000000000550

  150. 150.
    EXOME SEQUENCING REVEALS PRIMARY IMMUNODEFICIENCIES IN CHILDREN WITH COMMUNITY-ACQUIRED PSEUDOMONAS AERUGINOSA SEPSIS · 2016
    Not checked
  151. 151.

    Picard C., Von Bernuth H., Ghandil P., Chrabieh M., Levy O., Arkwright P.D., McDonald D., Geha R.S., Takada H., Krause J.C. Clinical features and outcome of patients with IRAK-4 and MyD88 deficiency. Medicine. 2010;89:403.

    Not in our library10.1097/md.0b013e3181fd8ec3

  152. 152.

    Flinn A., McDermott M., Butler K.M. A child with septic shock and purpura. JAMA Pediatr. 2016;170:391-392.

    Not in our library10.1001/jamapediatrics.2015.2466

  153. 153.

    Al-Herz W., Bousfiha A., Casanova J.-L., Chatila T., Conley M.E., Cunningham-Rundles C., Etzioni A., Franco J.L., Gaspar H.B., Holland S.M. Primary immunodeficiency diseases: An update on the classification from the international union of immunological societies expert committee for primary immunodeficiency. Front. Immunol. 2011;2:54.

    Not in our library10.3389/fimmu.2011.00054

  154. 154.

    Prasad C.B. A review on drug testing in animals. Transl. Biomed. 2016;7:1-4.

    Not in our library10.21767/2172-0479.100099

  155. 155.

    Cash H.A., Woods D.E., McCullough B., Johanson W.G., Bass J.A. A rat model of chronic respiratory infection with Pseudomonas aeruginosa. Am. Rev. Resp. Dis. 1979;119:453-459.

    Not in our library10.1164/arrd.1979.119.3.453

  156. 156.

    Van Heeckeren A.M., Schluchter M. Murine models of chronic Pseudomonas aeruginosa lung infection. Lab. Anim. 2002;36:291-312.

    Not in our library10.1258/002367702320162405

  157. 157.

    Comolli J.C., Hauser A.R., Waite L., Whitchurch C.B., Mattick J.S., Engel J.N. Pseudomonas aeruginosa gene products PilT and PilU are required for cytotoxicity in vitro and virulence in a mouse model of acute pneumonia. Infect. Immun. 1999;67:3625-3630.

    Not in our library10.1128/iai.67.7.3625-3630.1999

  158. 158.

    Gras E., Vu T., Vu Vi Tran G., Quynh Nhu Nguyen T., Schneider-Smith E., Povoa N., Povoa H., Delaye T., Valour F., An Diep B. 2202. Validation of a Rabbit Model of Pseudomonas aeruginosa Acute Pneumonia. Open Forum Infect. Dis. 2019;6:S750-S751.

    Not in our library10.1093/ofid/ofz360.1882

  159. 159.

    Nguyen N.T., Gras E., Tran N.D., Nguyen N.N., Lam H.T., Weiss W.J., Doan T.N., Diep B.A. Pseudomonas aeruginosa ventilator-associated pneumonia rabbit model for preclinical drug development. Antimicrob. Agents Chemother. 2021;65:e02724-02720.

    Not in our library10.1128/aac.02724-20

  160. 160.

    Li Bassi G., Rigol M., Marti J.-D., Saucedo L., Ranzani O.T., Roca I., Cabanas M., Muñoz L., Giunta V., Luque N. A novel porcine model of ventilator-associated pneumonia caused by oropharyngeal challenge with Pseudomonas aeruginosa. Anesthesiology. 2014;120:1205-1215.

    Not in our library10.1097/aln.0000000000000222

  161. 161.

    Dear J.D. Bacterial pneumonia in dogs and cats: An update. Vet. Clin. Small Anim. Pract. 2020;50:447-465.

    Not in our library10.1016/j.cvsm.2019.10.007

  162. 162.

    Gorrill R. The Fate of Pseudontonas aeruginosa, Proteus mirabilis and Escherichia coli in the Mouse Kidney. J. Pathol. Bacteriol. 1965;89:81-88.

    Not in our library10.1002/path.1700890110

  163. 163.

    Gorrill R. Bacterial localisation in the kidney with particular reference to Pseudomonas pyocyanea. J. Pathol. Bacteriol. 1952;64:857-864.

    Not in our library10.1002/path.1700640417

  164. 164.

    Montgomerie J., Guze L. The renal response to infection. Kidney. 1976;2:1079-1112.

    Not in our library

  165. 165.

    Comber K. Pathogenesis of an experimental pyelonephritis model in the mouse and its use in the evaluation of antibiotics. Laboratory Aspects of Infections. 1976;311-316.

    Not in our library

  166. 166.

    Nishi T., Tsuchiya K. Experimental urinary tract infection with Pseudomonas aeruginosa in mice. Infect. Immun. 1978;22:508-515.

    Not in our library10.1128/iai.22.2.508-515.1978

  167. 167.

    Rocha H., De Almeida S.S. Experimental pyelonephritis in rats with a glass bead in the bladder. J. Pathol. Bacteriol. 1965;90:668-672.

    Not in our library10.1002/path.1700900240

  168. 168.

    Rocha H., Guze L.B., Freedman L.R., Beeson P.B. Experimental pyelonephritis: III. The influence of localized injury in different parts of the kidney on susceptibility to bacillary infection. Yale J. Biol. Med. 1958;30:341.

    Not in our library

  169. 169.

    Niijima T., Hinman F. Effect of prior bacterial immunization on the pathogenesis of retrograde pyelonephritis. J. Urol. 1966;95:476-484.

    Not in our library10.1016/s0022-5347(17)63481-5

  170. 170.

    Hung C.-S., Dodson K.W., Hultgren S.J. A murine model of urinary tract infection. Nat. Protoc. 2009;4:1230-1243.

    Not in our library10.1038/nprot.2009.116

  171. 171.

    Penaranda C., Chumbler N.M., Hung D.T. Dual transcriptional analysis reveals adaptation of host and pathogen to intracellular survival of Pseudomonas aeruginosa associated with urinary tract infection. PLoS Pathog. 2021;17:e1009534.

    Not in our library10.1371/journal.ppat.1009534

  172. 172.

    Jin T., Mohammad M., Hu Z., Fei Y., Moore E.R., Pullerits R., Ali A. A novel mouse model for septic arthritis induced by Pseudomonas aeruginosa. Sci. Rep. 2019;9:16868.

    Not in our library10.1038/s41598-019-53434-5

  173. 173.

    Hamilton J.R., Overall J., Glasgow L.A. Synergistic effect on mortality in mice with murine cytomegalovirus and Pseudomonas aeruginosa, Staphylococcus aureus, or Candida albicans infections. Infect. Immun. 1976;14:982-989.

    Not in our library10.1128/iai.14.4.982-989.1976

  174. 174.

    Xu L., Wang F., Shen Y., Hou H., Liu W., Liu C., Jian C., Wang Y., Sun M., Sun Z. Pseudomonas aeruginosa inhibits the growth of pathogenic fungi: In vitro and in vivo studies. Exp. Ther. Med. 2014;7:1516-1520.

    Not in our library10.3892/etm.2014.1631

  175. 175.

    Chahin A., Opal S.M., Zorzopulos J., Jobes D.V., Migdady Y., Yamamoto M., Parejo N., Palardy J.E., Horn D.L. The novel immunotherapeutic oligodeoxynucleotide IMT504 protects neutropenic animals from fatal Pseudomonas aeruginosa bacteremia and sepsis. Antimicrob. Agents Chemother. 2015;59:1225-1229.

    Not in our library10.1128/aac.03923-14

  176. 176.

    Bachta K.E., Allen J.P., Cheung B.H., Chiu C.-H., Hauser A.R. Systemic infection facilitates transmission of Pseudomonas aeruginosa in mice. Nat. Commun. 2020;11:543.

    Not in our library10.1038/s41467-020-14363-4

  177. 177.

    Sutterwala F.S., Mijares L.A., Li L., Ogura Y., Kazmierczak B.I., Flavell R.A. Immune recognition of Pseudomonas aeruginosa mediated by the IPAF/NLRC4 inflammasome. J. Exp. Med. 2007;204:3235-3245.

    Not in our library10.1084/jem.20071239

  178. 178.

    Kwong M.S., Evans D.J., Ni M., Cowell B.A., Fleiszig S.M. Human tear fluid protects against Pseudomonas aeruginosa keratitis in a murine experimental model. Infect. Immun. 2007;75:2325-2332.

    Not in our library10.1128/iai.01404-06

  179. 179.

    Huang L.C., Reins R.Y., Gallo R.L., McDermott A.M. Cathelicidin-deficient (Cnlp-/-) mice show increased susceptibility to Pseudomonas aeruginosa keratitis. Investig. Ophthalmol. Vis. Sci. 2007;48:4498-4508.

    Not in our library10.1167/iovs.07-0274

  180. 180.

    Cole N., Bao S., Stapleton F., Thakur A., Husband A.J., Beagley K.W., Willcox M.D. Pseudomonas aeruginosa keratitis in IL-6-deficient mice. Int. Arch. Allergy Immunol. 2003;130:165-172.

    Not in our library10.1159/000069006

  181. 181.
    Pseudomonas aeruginosa keratitis in mice: effects of topical bacteriophage KPP12 administration. · 2012
    Not checked
  182. 182.

    Ring J., Hoerr V., Tuchscherr L., Kuhlmann M.T., Löffler B., Faber C. MRI visualization of Staphyloccocus aureus-induced infective endocarditis in mice. PLoS ONE. 2014;9:e107179.

    Not in our library10.1371/journal.pone.0107179

  183. 183.

    Entenza J., Vouillamoz J., Glauser M., Moreillon P. Levofloxacin versus ciprofloxacin, flucloxacillin, or vancomycin for treatment of experimental endocarditis due to methicillin-susceptible or-resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 1997;41:1662-1667.

    Not in our library10.1128/aac.41.8.1662

  184. 184.

    Oechslin F., Piccardi P., Mancini S., Gabard J., Moreillon P., Entenza J.M., Resch G., Que Y.-A. Synergistic interaction between phage therapy and antibiotics clears Pseudomonas aeruginosa infection in endocarditis and reduces virulence. J. Infect. Dis. 2017;215:703-712.

    Not in our library10.1093/infdis/jiw632

  185. 185.

    Archer G., Fekety F.R. Experimental endocarditis due to Pseudomonas aeruginosa. I. Description of a model. J. Infect. Dis. 1976;134:1-7.

    Not in our library10.1093/infdis/134.1.1

  186. 186.

    Archer G., Fekety F.R. Experimental endocarditis due to Pseudomonas aeruginosa. II. Therapy with carbenicillin and gentamicin. J. Infect. Dis. 1977;136:327-335.

    Not in our library10.1093/infdis/136.3.327

  187. 187.

    Coates M., Blanchard S., MacLeod A.S. Innate antimicrobial immunity in the skin: A protective barrier against bacteria, viruses, and fungi. PLoS Pathog. 2018;14:e1007353.

    Not in our library10.1371/journal.ppat.1007353

  188. 188.

    Mahmud F., Roy R., Mohamed M.F., Aboonabi A., Moric M., Ghoreishi K., Bayat M., Kuzel T.M., Reiser J., Shafikhani S.H. Therapeutic evaluation of immunomodulators in reducing surgical wound infection. FASEB J. 2022;36:e22090.

    Not in our library10.1096/fj.202101019r

  189. 189.

    Hamilton J.L., Mohamed M.F., Witt B.R., Wimmer M.A., Shafikhani S.H. Therapeutic assessment of N-formyl-methionyl-leucyl-phenylalanine (fMLP) in reducing periprosthetic joint infection. Eur. Cells Mater. 2021;41:122-138.

    Not in our library10.22203/ecm.v042a09

  190. 190.

    Kroin J.S., Buvanendran A., Li J., Moric M., Im H.-J., Tuman K.J., Shafikhani S.H. Short-term glycemic control is effective in reducing surgical site infection in diabetic rats. Anesth. Analg. 2015;120:1289-1296.

    Not in our library10.1213/ane.0000000000000650

  191. 191.

    Kroin J.S., Li J., Goldufsky J.W., Gupta K.H., Moghtaderi M., Buvanendran A., Shafikhani S.H. Perioperative high inspired oxygen fraction therapy reduces surgical site infection with Pseudomonas aeruginosa in rats. J. Med. Microbiol. 2016;65:738-744.

    Not in our library10.1099/jmm.0.000295

  192. 192.

    Kroin J.S., Li J., Shafikhani S., Gupta K.H., Moric M., Buvanendran A. Local vancomycin effectively reduces surgical site infection at implant site in rodents. Reg. Anesth. Pain Med. 2018;43:795-804.

    Not in our library10.1097/aap.0000000000000820

  193. 193.

    Shandley S., Matthews K.P., Cox J., Romano D., Abplanalp A., Kalns J. Hyperbaric oxygen therapy in a mouse model of implant-associated osteomyelitis. J. Orthop. Res. 2012;30:203-208.

    Not in our library10.1002/jor.21522

  194. 194.

    Cirioni O., Ghiselli R., Silvestri C., Minardi D., Gabrielli E., Orlando F., Rimini M., Brescini L., Muzzonigro G., Guerrieri M. Effect of the combination of clarithromycin and amikacin on Pseudomonas aeruginosa biofilm in an animal model of ureteral stent infection. J. Antimicrob. Chemother. 2011;66:1318-1323.

    Not in our library10.1093/jac/dkr107

  195. 195.

    Rahim M.I., Szafrański S.P., Ingendoh-Tsakmakidis A., Stiesch M., Mueller P.P. Evidence for inoculum size and gas interfaces as critical factors in bacterial biofilm formation on magnesium implants in an animal model. Colloids Surf. B Biointerfaces. 2020;186:110684.

    Not in our library10.1016/j.colsurfb.2019.110684

  196. 196.

    Tosh P.K., Disbot M., Duffy J.M., Boom M.L., Heseltine G., Srinivasan A., Gould C.V., Berrios-Torres S.I. Outbreak of Pseudomonas aeruginosa surgical site infections after arthroscopic procedures: Texas, 2009. Infect. Control Hosp. Epidemiol. 2011;32:1179-1186.

    Not in our library10.1086/662712

  197. 197.

    Kirketerp-Moller K., Jensen P.O., Fazli M., Madsen K.G., Pedersen J., Moser C., Tolker-Nielsen T., Hoiby N., Givskov M., Bjarnsholt T. Distribution, organization, and ecology of bacteria in chronic wounds. J. Clin. Microbiol. 2008;46:2717-2722.

    Not in our library10.1128/jcm.00501-08

  198. 198.

    Serra R., Grande R., Butrico L., Rossi A., Settimio U.F., Caroleo B., Amato B., Gallelli L., de Franciscis S. Chronic wound infections: The role of Pseudomonas aeruginosa and Staphylococcus aureus. Expert Rev. Anti. Infect Ther. 2015;13:605-613.

    Not in our library10.1586/14787210.2015.1023291

  199. 199.
    Pro-Inflammatory Chemokine CCL2 (MCP-1) Promotes Healing in Diabetic Wounds by Restoring the Macrophage Response · 2014
    No notice
  200. 200.

    Roy R., Zayas J., Mohamed M.F., Aboonabi A., Delgado K., Wallace J., Bayat M., Kuzel T.M., Reiser J., Shafikhani S.H. IL-10 Dysregulation Underlies Chemokine Insufficiency, Delayed Macrophage Response, and Impaired Healing in Diabetic Wounds. J. Investig. Dermatol. 2022;142:692-704.e41.

    Not in our library10.1016/j.jid.2021.08.428

  201. 201.

    Muller M., Li Z., Maitz P.K. Pseudomonas pyocyanin inhibits wound repair by inducing premature cellular senescence: Role for p38 mitogen-activated protein kinase. Burns. 2009;35:500-508.

    Not in our library10.1016/j.burns.2008.11.010

  202. 202.

    Heggers J.P., Haydon S., Ko F., Hayward P.G., Carp S., Robson M.C. Pseudomonas aeruginosa Exotoxin A: Its Role in Retardation of Wound Healing The 1992 Lindberg Award. J. Burn Care Rehabil. 1992;13:512-518.

    Not in our library10.1097/00004630-199209000-00003

  203. 203.

    Ha U., Jin S. Expression of the soxR gene of Pseudomonas aeruginosa is inducible during infection of burn wounds in mice and is required to cause efficient bacteremia. Infect. Immun. 1999;67:5324-5331.

    Not in our library10.1128/iai.67.10.5324-5331.1999

  204. 204.

    Nakagami G., Morohoshi T., Ikeda T., Ohta Y., Sagara H., Huang L., Nagase T., Sugama J., Sanada H. Contribution of quorum sensing to the virulence of Pseudomonas aeruginosa in pressure ulcer infection in rats. Wound Repair Regen. 2011;19:214-222.

    Not in our library10.1111/j.1524-475x.2010.00653.x

  205. 205.

    Takase H., Nitanai H., Hoshino K., Otani T. Impact of siderophore production on Pseudomonas aeruginosa infections in immunosuppressed mice. Infect. Immun. 2000;68:1834-1839.

    Not in our library10.1128/iai.68.4.1834-1839.2000

  206. 206.

    Cryz S.J., Fürer E., Germanier R. Simple model for the study of Pseudomonas aeruginosa infections in leukopenic mice. Infect. Immun. 1983;39:1067-1071.

    Not in our library10.1128/iai.39.3.1067-1071.1983

  207. 207.

    Pennington J.E., Ehrie M.G. Pathogenesis of Pseudomonas aeruginosa pneumonia during immunosuppression. J. Infect. Dis. 1978;137:764-774.

    Not in our library10.1093/infdis/137.6.764

  208. 208.

    Rommens J.M., Iannuzzi M.C., Kerem B.-S., Drumm M.L., Melmer G., Dean M., Rozmahel R., Cole J.L., Kennedy D., Hidaka N. Identification of the cystic fibrosis gene: Chromosome walking and jumping. Science. 1989;245:1059-1065.

    Not in our library10.1126/science.2772657

  209. 209.

    Riordan J.R., Rommens J.M., Kerem B.-S., Alon N., Rozmahel R., Grzelczak Z., Zielenski J., Lok S., Plavsic N., Chou J.-L. Identification of the cystic fibrosis gene: Cloning and characterization of complementary DNA. Science. 1989;245:1066-1073.

    Not in our library10.1126/science.2475911

  210. 210.

    Welsh M.J., Smith A.E. Molecular mechanisms of CFTR chloride channel dysfunction in cystic fibrosis. Cell. 1993;73:1251-1254.

    Not in our library10.1016/0092-8674(93)90353-r

  211. 211.

    Gawenis L.R., Hodges C.A., McHugh D.R., Valerio D.M., Miron A., Cotton C.U., Liu J., Walker N.M., Strubberg A.M., Gillen A.E. A BAC transgene expressing human CFTR under control of its regulatory elements rescues Cftr knockout mice. Sci. Rep. 2019;9:11828.

    Not in our library10.1038/s41598-019-48105-4

  212. 212.

    Wilke M., Buijs-Offerman R.M., Aarbiou J., Colledge W.H., Sheppard D.N., Touqui L., Bot A., Jorna H., De Jonge H.R., Scholte B.J. Mouse models of cystic fibrosis: Phenotypic analysis and research applications. J. Cyst. Fibros. 2011;10:S152-S171.

    Not in our library10.1016/s1569-1993(11)60020-9

  213. 213.

    Dreano E., Bacchetta M., Simonin J., Galmiche L., Usal C., Slimani L., Sadoine J., Tesson L., Anegon I., Concordet J.P. Characterization of two rat models of cystic fibrosis—KO and F508del CFTR—Generated by Crispr-Cas9. Anim. Model. Exp. Med. 2019;2:297-311.

    Not in our library10.1002/ame2.12091

  214. 214.

    Sun X., Yan Z., Yi Y., Li Z., Lei D., Rogers C.S., Chen J., Zhang Y., Welsh M.J., Leno G.H. Adeno-associated virus–targeted disruption of the CFTR gene in cloned ferrets. J. Clin. Investig. 2008;118:1578-1583.

    Not in our library10.1172/jci34599

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    Xu J., Rajagopolan C., Hou X., Chen E., Boucher R.C., Sun F. Rabbit models for cystic fibrosis. Pediatr. Pulmonol. 2016;51:158-159.

    Not in our library

  216. 216.

    Fan Z., Perisse I.V., Cotton C.U., Regouski M., Meng Q., Domb C., Van Wettere A.J., Wang Z., Harris A., White K.L. A sheep model of cystic fibrosis generated by CRISPR/Cas9 disruption of the CFTR gene. JCI Insight. 2018;3:e123529.

    Not in our library10.1172/jci.insight.123529

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    Heeckeren A.v., Walenga R., Konstan M.W., Bonfield T., Davis P.B., Ferkol T. Excessive inflammatory response of cystic fibrosis mice to bronchopulmonary infection with Pseudomonas aeruginosa. J. Clin. Investig. 1997;100:2810-2815.

    Not in our library10.1172/jci119828

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    Van Heeckeren A.M., Schluchter M.D., Xue W., Davis P.B. Response to acute lung infection with mucoid Pseudomonas aeruginosa in cystic fibrosis mice. Am. J. Respir. Crit. Care Med. 2006;173:288-296.

    Not in our library10.1164/rccm.200506-917oc

  219. 219.

    Elferink R.O., Beuers U. Are pigs more human than mice? J. Hepatol. 2009;50:838-841.

    Not in our library10.1016/j.jhep.2008.12.014

  220. 220.
    Neutrophil-mediated phagocytic host defense defect in myeloid Cftr-inactivated mice. · 2014
    Not checked
  221. 221.

    Rogan M.P., Reznikov L.R., Pezzulo A.A., Gansemer N.D., Samuel M., Prather R.S., Zabner J., Fredericks D.C., McCray P.B., Welsh M.J. Pigs and humans with cystic fibrosis have reduced insulin-like growth factor 1 (IGF1) levels at birth. Proc. Natl. Acad. Sci. USA. 2010;107:20571-20575.

    Not in our library10.1073/pnas.1015281107

  222. 222.

    Stoltz D.A., Meyerholz D.K., Pezzulo A.A., Ramachandran S., Rogan M.P., Davis G.J., Hanfland R.A., Wohlford-Lenane C., Dohrn C.L., Bartlett J.A. Cystic fibrosis pigs develop lung disease and exhibit defective bacterial eradication at birth. Sci. Transl. Med. 2010;2:29ra31.

    Not in our library10.1126/scitranslmed.3000928

  223. 223.

    Tamma P., Aitken S., Bonomo R. IDSA Guidance on the Treatment of Antimicrobial-Resistant Gram-Negative Infections: Version 2.0. 2022.

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  224. 224.

    Tamma P., Aitken S., Bonomo R., Mathers A., van Duin D., Clancy C. IDSA Guidance on the Treatment of Antimicrobial-Resistant Gram-Negative Infections: Version 1.0. 2022.

    Not in our library10.1093/cid/ciad428

  225. 225.

    Bush K., Bradford P.A. β-Lactams and β-lactamase inhibitors: An overview. Cold Spring Harb. Perspect. Med. 2016;6:a025247.

    Not in our library10.1101/cshperspect.a025247

  226. 226.

    Pandey N., Cascella M. Beta lactam antibiotics. StatPearls [Internet]. 2022.

    Not in our library

  227. 227.

    KONG K.F., Schneper L., Mathee K. Beta-lactam antibiotics: From antibiosis to resistance and bacteriology. Acta Pathol. Microbiol. Immunol. Scand. 2010;118:1-36.

    Not in our library10.1111/j.1600-0463.2009.02563.x

  228. 228.

    Carmeli Y., Troillet N., Eliopoulos G.M., Samore M.H. Emergence of antibiotic-resistant Pseudomonas aeruginosa: Comparison of risks associated with different antipseudomonal agents. Antimicrob. Agents Chemother. 1999;43:1379-1382.

    Not in our library10.1128/aac.43.6.1379

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    Papp-Wallace K.M., Endimiani A., Taracila M.A., Bonomo R.A. Carbapenems: Past, present, and future. Antimicrob. Agents Chemother. 2011;55:4943-4960.

    Not in our library10.1128/aac.00296-11

  230. 230.

    FDA Approves New Antibacterial Drug to Treat Complicated Urinary Tract Infections as Part of Ongoing Efforts to Address Antimicrobial Resistance. 2019.

    Not in our library

  231. 231.

    Dobias J., Dénervaud-Tendon V., Poirel L., Nordmann P. Activity of the novel siderophore cephalosporin cefiderocol against multidrug-resistant Gram-negative pathogens. Eur. J. Clin. Microbiol. Infect. Dis. 2017;36:2319-2327.

    Not in our library10.1007/s10096-017-3063-z

  232. 232.

    Taheri Y., Joković N., Vitorović J., Grundmann O., Maroyi A., Calina D. The burden of the serious and difficult-to-treat infections and a new antibiotic available: Cefiderocol. Front. Pharmacol. 2021;11:578823.

    Not in our library10.3389/fphar.2020.578823

  233. 233.
    Siderophore Cephalosporin Cefiderocol Utilizes Ferric Iron Transporter Systems for Antibacterial Activity against Pseudomonas aeruginosa · 2016
    No notice
  234. 234.

    Ito A., Nishikawa T., Ota M., Ito-Horiyama T., Ishibashi N., Sato T., Tsuji M., Yamano Y. Stability and low induction propensity of cefiderocol against chromosomal AmpC β-lactamases of Pseudomonas aeruginosa and Enterobacter cloacae. J. Antimicrob. Chemother. 2018;73:3049-3052.

    Not in our library10.1093/jac/dky317

  235. 235.

    Zhanel G.G., Golden A.R., Zelenitsky S., Wiebe K., Lawrence C.K., Adam H.J., Idowu T., Domalaon R., Schweizer F., Zhanel M.A. Cefiderocol: A siderophore cephalosporin with activity against carbapenem-resistant and multidrug-resistant gram-negative bacilli. Drugs. 2019;79:271-289.

    Not in our library10.1007/s40265-019-1055-2

  236. 236.

    Horcajada J.P., Montero M., Oliver A., Sorlí L., Luque S., Gómez-Zorrilla S., Benito N., Grau S. Epidemiology and treatment of multidrug-resistant and extensively drug-resistant Pseudomonas aeruginosa infections. Clin. Microbiol. Rev. 2019;32:e00031-19.

    Not in our library10.1128/cmr.00031-19

  237. 237.

    Saderi H., Owlia P. Detection of multidrug resistant (MDR) and extremely drug resistant (XDR) P. aeruginosa isolated from patients in Tehran, Iran. Iran. J. Pathol. 2015;10:265.

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  238. 238.

    Rains C.P., Bryson H.M., Peters D.H. Ceftazidime. Drugs. 1995;49:577-617.

    Not in our library10.2165/00003495-199549040-00008

  239. 239.

    Ehmann D.E., Jahić H., Ross P.L., Gu R.-F., Hu J., Kern G., Walkup G.K., Fisher S.L. Avibactam is a covalent, reversible, non–β-lactam β-lactamase inhibitor. Proc. Natl. Acad. Sci. USA. 2012;109:11663-11668.

    Not in our library10.1073/pnas.1205073109

  240. 240.

    Zalas-Więcek P., Prażyńska M., Pojnar Ł., Pałka A., Żabicka D., Orczykowska-Kotyna M., Polak A., Możejko-Pastewka B., Głowacka E.A., Pieniążek I. Ceftazidime/Avibactam and Other Commonly Used Antibiotics Activity Against Enterobacterales and Pseudomonas aeruginosa Isolated in Poland in 2015–2019. Infect. Drug Resist. 2022;15:1289.

    Not in our library10.2147/idr.s344165

  241. 241.

    Daikos G.L., da Cunha C.A., Rossolini G.M., Stone G.G., Baillon-Plot N., Tawadrous M., Irani P. Review of ceftazidime-avibactam for the treatment of infections caused by Pseudomonas aeruginosa. Antibiotics. 2021;10:1126.

    Not in our library10.3390/antibiotics10091126

  242. 242.

    Sanz-García F., Hernando-Amado S., Martínez J.L. Mutation-driven evolution of Pseudomonas aeruginosa in the presence of either ceftazidime or ceftazidime-avibactam. Antimicrob. Agents Chemother. 2018;62:e01379-18.

    Not in our library10.1128/aac.01379-18

  243. 243.

    Winkler M.L., Papp-Wallace K.M., Hujer A.M., Domitrovic T.N., Hujer K.M., Hurless K.N., Tuohy M., Hall G., Bonomo R.A. Unexpected challenges in treating multidrug-resistant Gram-negative bacteria: Resistance to ceftazidime-avibactam in archived isolates of Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 2015;59:1020-1029.

    Not in our library10.1128/aac.04238-14

  244. 244.

    Hughes D.L. Patent review of manufacturing routes to fifth-generation cephalosporin drugs. Part 1, Ceftolozane. Org. Process Res. Dev. 2017;21:430-443.

    Not in our library10.1021/acs.oprd.7b00033

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    Barnes M.D., Taracila M.A., Rutter J.D., Bethel C.R., Galdadas I., Hujer A.M., Caselli E., Prati F., Dekker J.P., Papp-Wallace K.M. Deciphering the evolution of cephalosporin resistance to ceftolozane-tazobactam in Pseudomonas aeruginosa. mBio. 2018;9:e02085-18.

    Not in our library10.1128/mbio.02085-18

  246. 246.

    Wi Y.M., Greenwood-Quaintance K.E., Schuetz A.N., Ko K.S., Peck K.R., Song J.-H., Patel R. Activity of ceftolozane-tazobactam against carbapenem-resistant, non-carbapenemase-producing Pseudomonas aeruginosa and associated resistance mechanisms. Antimicrob. Agents Chemother. 2018;62:e01970-17.

    Not in our library10.1128/aac.01970-17

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    Haidar G., Philips N.J., Shields R.K., Snyder D., Cheng S., Potoski B.A., Hao B., Press E.G., Cooper V.S., Clancy C.J. Ceftolozane-tazobactam for the treatment of multidrug-resistant Pseudomonas aeruginosa infections: Clinical effectiveness and evolution of resistance. Clin. Infect. Dis. 2017;65:110-120.

    Not in our library10.1093/cid/cix182

  248. 248.

    Skoglund E., Abodakpi H., Diaz L., Rios R., Tran T.T., Arias C.A., Tam V.H. Ceftolozane/tazobactam resistance in Pseudomonas aeruginosa. Int. J. Antimicrob. Agents. 2017;50:S39.

    Not in our library

  249. 249.

    Hellinger W.C., Brewer N.S. Imipenem. Mayo Clin. Proc. 1991;66:1074-1081.

    Not in our library10.1016/s0025-6196(12)61732-7

  250. 250.

    Balfour J.A., Bryson H.M., Brogden R.N. Imipenem/cilastatin. Drugs. 1996;51:99-136.

    Not in our library10.2165/00003495-199651010-00008

  251. 251.

    Keynan S., Hooper N.M., Felici A., Amicosante G., Turner A.J. The renal membrane dipeptidase (dehydropeptidase I) inhibitor, cilastatin, inhibits the bacterial metallo-beta-lactamase enzyme CphA. Antimicrob. Agents Chemother. 1995;39:1629-1631.

    Not in our library10.1128/aac.39.7.1629

  252. 252.

    Campanella T.A., Gallagher J.C. A clinical review and critical evaluation of Imipenem-Relebactam: Evidence to date. Infect. Drug Resist. 2020;13:4297.

    Not in our library10.2147/idr.s224228

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    Lucasti C., Vasile L., Sandesc D., Venskutonis D., McLeroth P., Lala M., Rizk M.L., Brown M.L., Losada M.C., Pedley A. Phase 2, dose-ranging study of relebactam with imipenem-cilastatin in subjects with complicated intra-abdominal infection. Antimicrob. Agents Chemother. 2016;60:6234-6243.

    Not in our library10.1128/aac.00633-16

  254. 254.

    Motsch J., Murta de Oliveira C., Stus V., Köksal I., Lyulko O., Boucher H.W., Kaye K.S., File T.M., Brown M.L., Khan I. RESTORE-IMI 1: A multicenter, randomized, double-blind trial comparing efficacy and safety of imipenem/relebactam vs colistin plus imipenem in patients with imipenem-nonsusceptible bacterial infections. Clin. Infect. Dis. 2020;70:1799-1808.

    Not in our library10.1093/cid/ciz530

  255. 255.

    Heo Y.-A. Imipenem/cilastatin/relebactam: A review in Gram-negative bacterial infections. Drugs. 2021;81:377-388.

    Not in our library10.1007/s40265-021-01471-8

  256. 256.

    Bhatt S., Chatterjee S. Fluoroquinolone antibiotics: Occurrence, mode of action, resistance, environmental detection, and remediation–A comprehensive review. Environ. Pollut. 2022;315:120440.

    Not in our library10.1016/j.envpol.2022.120440

  257. 257.

    McKeage K. Finafloxacin: First global approval. Drugs. 2015;75:687-693.

    Not in our library10.1007/s40265-015-0384-z

  258. 258.

    Wagenlehner F., Nowicki M., Bentley C., Lückermann M., Wohlert S., Fischer C., Vente A., Naber K., Dalhoff A. Explorative randomized phase II clinical study of the efficacy and safety of finafloxacin versus ciprofloxacin for treatment of complicated urinary tract infections. Antimicrob. Agents Chemother. 2018;62:e02317-17.

    Not in our library10.1128/aac.02317-17

  259. 259.

    Kanj S.S., Sexton D.J. Pseudomonas aeruginosa Skin and Soft Tissue Infections. 2020.

    Not in our library

  260. 260.

    Ocheretyaner E.R., Park T.E. Delafloxacin: A novel fluoroquinolone with activity against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. Expert Rev. Anti-Infect. Ther. 2018;16:523-530.

    Not in our library10.1080/14787210.2018.1489721

  261. 261.

    Hooper D.C., Jacoby G.A. Mechanisms of drug resistance: Quinolone resistance. Ann. N. Y. Acad. Sci. 2015;1354:12-31.

    Not in our library10.1111/nyas.12830

  262. 262.

    Emrich N.-C., Heisig A., Stubbings W., Labischinski H., Heisig P. Antibacterial activity of finafloxacin under different pH conditions against isogenic strains of Escherichia coli expressing combinations of defined mechanisms of fluoroquinolone resistance. J. Antimicrob. Chemother. 2010;65:2530-2533.

    Not in our library10.1093/jac/dkq375

  263. 263.

    Lungu I.-A., Moldovan O.-L., Biriș V., Rusu A. Fluoroquinolones Hybrid Molecules as Promising Antibacterial Agents in the Fight against Antibacterial Resistance. Pharmaceutics. 2022;14:1749.

    Not in our library10.3390/pharmaceutics14081749

  264. 264.
    Responses of Pseudomonas aeruginosa to antimicrobials · 2014
    No notice
  265. 265.

    Lee Y.R., Burton C.E. Eravacycline, a newly approved fluorocycline. Eur. J. Clin. Microbiol. Infect. Dis. 2019;38:1787-1794.

    Not in our library10.1007/s10096-019-03590-3

  266. 266.

    Scott L.J. Eravacycline: A review in complicated intra-abdominal infections. Drugs. 2019;79:315-324.

    Not in our library10.1007/s40265-019-01067-3

  267. 267.

    Wang H., Nguyen N., Cruz C. Eravacycline for the treatment of complicated intra-abdominal infections. Adv. Dig. Med. 2021;8:203-210.

    Not in our library10.1002/aid2.13216

  268. 268.

    Zhanel G.G., Cheung D., Adam H., Zelenitsky S., Golden A., Schweizer F., Gorityala B., Lagacé-Wiens P.R., Walkty A., Gin A.S. Review of eravacycline, a novel fluorocycline antibacterial agent. Drugs. 2016;76:567-588.

    Not in our library10.1007/s40265-016-0545-8

  269. 269.

    Sutcliffe J., O’brien W., Fyfe C., Grossman T. Antibacterial activity of eravacycline (TP-434), a novel fluorocycline, against hospital and community pathogens. Antimicrob. Agents Chemother. 2013;57:5548-5558.

    Not in our library10.1128/aac.01288-13

  270. 270.

    Block M., Blanchard D.L. Aminoglycosides. StatPearls [Internet]. 2022.

    Not in our library

  271. 271.

    Goodlet K.J., Benhalima F.Z., Nailor M.D. A systematic review of single-dose aminoglycoside therapy for urinary tract infection: Is it time to resurrect an old strategy? Antimicrob. Agents Chemother. 2019;63:e02165-18.

    Not in our library10.1128/aac.02165-18

  272. 272.

    Cloutier D.J., Komirenko A.S., Cebrik D.S. Plazomicin versus meropenem for complicated urinary tract infection and acute pyelonephritis: Diagnosis-specific results from the Phase 3 EPIC study. Open Forum Infect. Dis. 2017;4:S532.

    Not in our library10.1093/ofid/ofx163.1385

  273. 273.

    Eljaaly K., Alharbi A., Alshehri S., Ortwine J.K., Pogue J.M. Plazomicin: A novel aminoglycoside for the treatment of resistant Gram-negative bacterial infections. Drugs. 2019;79:243-269.

    Not in our library10.1007/s40265-019-1054-3

  274. 274.

    Ramsey B.W., Dorkin H.L., Eisenberg J.D., Gibson R.L., Harwood I.R., Kravitz R.M., Schidlow D.V., Wilmott R.W., Astley S.J., McBurnie M.A. Efficacy of aerosolized tobramycin in patients with cystic fibrosis. N. Engl. J. Med. 1993;328:1740-1746.

    Not in our library10.1056/nejm199306173282403

  275. 275.

    Niederman M.S., Alder J., Bassetti M., Boateng F., Cao B., Corkery K., Dhand R., Kaye K.S., Lawatscheck R., McLeroth P. Inhaled amikacin adjunctive to intravenous standard-of-care antibiotics in mechanically ventilated patients with Gram-negative pneumonia (INHALE): A double-blind, randomised, placebo-controlled, phase 3, superiority trial. Lancet Infect. Dis. 2020;20:330-340.

    Not in our library10.1016/s1473-3099(19)30574-2

  276. 276.

    Rattanaumpawan P., Lorsutthitham J., Ungprasert P., Angkasekwinai N., Thamlikitkul V. Randomized controlled trial of nebulized colistimethate sodium as adjunctive therapy of ventilator-associated pneumonia caused by Gram-negative bacteria. J. Antimicrob. Chemother. 2010;65:2645-2649.

    Not in our library10.1093/jac/dkq360

  277. 277.

    Kollef M.H., Ricard J.-D., Roux D., Francois B., Ischaki E., Rozgonyi Z., Boulain T., Ivanyi Z., János G., Garot D. A randomized trial of the amikacin fosfomycin inhalation system for the adjunctive therapy of Gram-negative ventilator-associated pneumonia: IASIS Trial. Chest. 2017;151:1239-1246.

    Not in our library10.1016/j.chest.2016.11.026

  278. 278.

    Zavascki A.P., Goldani L.Z., Li J., Nation R.L. Polymyxin B for the treatment of multidrug-resistant pathogens: A critical review. J. Antimicrob. Chemother. 2007;60:1206-1215.

    Not in our library10.1093/jac/dkm357

  279. 279.

    Sorlí L., Luque S., Li J., Campillo N., Danés M., Montero M., Segura C., Grau S., Horcajada J.P. Colistin for the treatment of urinary tract infections caused by extremely drug-resistant Pseudomonas aeruginosa: Dose is critical. J. Infect. 2019;79:253-261.

    Not in our library10.1016/j.jinf.2019.06.011

  280. 280.
    Polymyxins and Bacterial Membranes: A Review of Antibacterial Activity and Mechanisms of Resistance · 2020
    No notice
  281. 281.

    Justo J.A., Bosso J.A. Adverse reactions associated with systemic polymyxin therapy. Pharmacotherapy. 2015;35:28-33.

    Not in our library10.1002/phar.1493

  282. 282.
    Toxicity of polymyxins: a systematic review of the evidence from old and recent studies · 2006
    No notice
  283. 283.

    Nation R.L., Rigatto M.H.P., Falci D.R., Zavascki A.P. Polymyxin acute kidney injury: Dosing and other strategies to reduce toxicity. Antibiotics. 2019;8:24.

    Not in our library10.3390/antibiotics8010024

  284. 284.

    Nation R.L., Velkov T., Li J. Colistin and polymyxin B: Peas in a pod, or chalk and cheese? Clin. Infect. Dis. 2014;59:88-94.

    Not in our library10.1093/cid/ciu213

  285. 285.

    Lynch III J.P., Zhanel G.G., Clark N.M., Ramírez-Estrada S., Borgatta B., Rello J., Kollef M., Chastre J., Fagon J., Tumbarello M. Emergence of Antimicrobial Resistance among Pseudomonas aeruginosa: Implications for Therapy. Semin. Respir. Crit. Care Med. 2017;38:326-345.

    Not in our library10.1055/s-0037-1602583

  286. 286.

    Potron A., Poirel L., Nordmann P. Emerging broad-spectrum resistance in Pseudomonas aeruginosa and Acinetobacter baumannii: Mechanisms and epidemiology. Int. J. Antimicrob. Agents. 2015;45:568-585.

    Not in our library10.1016/j.ijantimicag.2015.03.001

  287. 287.

    McCarthy K. Pseudomonas aeruginosa: Evolution of antimicrobial resistance and implications for therapy. Semin. Respir. Crit. Care Med. 2015;36:44-55.

    Not in our library10.1055/s-0034-1396907

  288. 288.

    Oliver A., Mulet X., López-Causapé C., Juan C. The increasing threat of Pseudomonas aeruginosa high-risk clones. Drug Resist. Updates. 2015;21:41-59.

    Not in our library10.1016/j.drup.2015.08.002

  289. 289.

    Lister P.D., Wolter D.J., Hanson N.D. Antibacterial-resistant Pseudomonas aeruginosa: Clinical impact and complex regulation of chromosomally encoded resistance mechanisms. Clin. Microbiol. Rev. 2009;22:582-610.

    Not in our library10.1128/cmr.00040-09

  290. 290.

    Pachori P., Gothalwal R., Gandhi P. Emergence of antibiotic resistance Pseudomonas aeruginosa in intensive care unit; a critical review. Genes Dis. 2019;6:109-119.

    Not in our library10.1016/j.gendis.2019.04.001

  291. 291.

    Abd El-Baky R.M., Masoud S.M., Mohamed D.S., Waly N.G., Shafik E.A., Mohareb D.A., Elkady A., Elbadr M.M., Hetta H.F. Prevalence and some possible mechanisms of colistin resistance among multidrug-resistant and extensively drug-resistant Pseudomonas aeruginosa. Infect. Drug Resist. 2020;13:323.

    Not in our library10.2147/idr.s238811

  292. 292.

    Obritsch M.D., Fish D.N., MacLaren R., Jung R. National surveillance of antimicrobial resistance in Pseudomonas aeruginosa isolates obtained from intensive care unit patients from 1993 to 2002. Antimicrob. Agents Chemother. 2004;48:4606-4610.

    Not in our library10.1128/aac.48.12.4606-4610.2004

  293. 293.

    Zhang X., Gu B., Mei Y., Wen Y., Xia W. Increasing resistance rate to carbapenem among blood culture isolates of Klebsiella pneumoniae, Acinetobacterbaumannii and Pseudomonas aeruginosa in a university-affiliated hospital in China, 2004–2011. J. Antibiot. 2015;68:115.

    Not in our library10.1038/ja.2014.119

  294. 294.

    Van Boeckel T.P., Gandra S., Ashok A., Caudron Q., Grenfell B.T., Levin S.A., Laxminarayan R. Global antibiotic consumption 2000 to 2010: An analysis of national pharmaceutical sales data. Lancet Infect. Dis. 2014;14:742-750.

    Not in our library10.1016/s1473-3099(14)70780-7

  295. 295.

    Carmeli Y., Armstrong J., Laud P.J., Newell P., Stone G., Wardman A., Gasink L.B. Ceftazidime-avibactam or best available therapy in patients with ceftazidime-resistant Enterobacteriaceae and Pseudomonas aeruginosa complicated urinary tract infections or complicated intra-abdominal infections (REPRISE): A randomised, pathogen-directed, phase 3 study. Lancet Infect. Dis. 2016;16:661-673.

    Not in our library10.1016/s1473-3099(16)30004-4

  296. 296.

    Karlowsky J.A., Jones M.E., Thornsberry C., Evangelista A.T., Yee Y.C., Sahm D.F. Stable antimicrobial susceptibility rates for clinical isolates of Pseudomonas aeruginosa from the 2001–2003 tracking resistance in the United States today surveillance studies. Clin. Infect. Dis. 2005;40((Suppl. 2)):S89-S98.

    Not in our library10.1086/426188

  297. 297.
    Clinical and economic consequences of hospital-acquired resistant and multidrug-resistant Pseudomonas aeruginosa infections: a systematic review and meta-analysis · 2014
    No notice
  298. 298.

    Degli Atti M.C., Bernaschi P., Carletti M., Luzzi I., García-Fernández A., Bertaina A., Sisto A., Locatelli F., Raponi M. An outbreak of extremely drug-resistant Pseudomonas aeruginosa in a tertiary care pediatric hospital in Italy. BMC Infect. Dis. 2014;14:494.

    Not in our library10.1186/1471-2334-14-494

  299. 299.
    An international multicenter retrospective study of Pseudomonas aeruginosa nosocomial pneumonia: impact of multidrug resistance · 2015
    No notice
  300. 300.

    Falagas M.E., Karageorgopoulos D.E. Pandrug resistance (PDR), extensive drug resistance (XDR), and multidrug resistance (MDR) among Gram-negative bacilli: Need for international harmonization in terminology. Clin. Infect. Dis. 2008;46:1121-1122.

    Not in our library10.1086/528867

  301. 301.

    Falagas M.E., Bliziotis I.A. Pandrug-resistant Gram-negative bacteria: The dawn of the post-antibiotic era? Int. J. Antimicrob. Agents. 2007;29:630-636.

    Not in our library10.1016/j.ijantimicag.2006.12.012

  302. 302.

    Palavutitotai N., Jitmuang A., Tongsai S., Kiratisin P., Angkasekwinai N. Epidemiology and risk factors of extensively drug-resistant Pseudomonas aeruginosa infections. PLoS ONE. 2018;13:e0193431.

    Not in our library10.1371/journal.pone.0193431

  303. 303.
    Prevalence of multidrug-resistant, extensively drug-resistant, and pandrug-resistant Pseudomonas aeruginosa from a tertiary level Intensive Care Unit · 2016
    Not checked
  304. 304.

    Mayr A., Hinterberger G., Lorenz I.H., Kreidl P., Mutschlechner W., Lass-Flörl C. Nosocomial outbreak of extensively drug-resistant Pseudomonas aeruginosa associated with aromatherapy. Am. J. Infect. Control. 2017;45:453-455.

    Not in our library10.1016/j.ajic.2016.11.002

  305. 305.
    Risk factors for hospitalized patients with resistant or multidrug-resistant Pseudomonas aeruginosa infections: a systematic review and meta-analysis · 2018
    No notice
  306. 306.

    Obritsch M.D., Fish D.N., MacLaren R., Jung R. Nosocomial infections due to multidrug-resistant Pseudomonas aeruginosa: Epidemiology and treatment options. Pharmacotherapy. 2005;25:1353-1364.

    Not in our library10.1592/phco.2005.25.10.1353

  307. 307.

    Hauser A.R., Sriram P. Severe Pseudomonas aeruginosa infections. Tackling the conundrum of drug resistance. Postgrad Med. 2005;117:41-48.

    Not in our library10.3810/pgm.2005.01.1571

  308. 308.

    Swathirajan C.R., Rameshkumar M.R., Solomon S.S., Vignesh R., Balakrishnan P. Changing drug resistance profile in Pseudomonas aeruginosa infection among HIV patients from 2010–2017—A retrospective study. J. Glob. Antimicrob. Resist. 2018;16:274-277.

    Not in our library10.1016/j.jgar.2018.10.019

  309. 309.

    Johnson L.E., D’Agata E.M., Paterson D.L., Clarke L., Qureshi Z.A., Potoski B.A., Peleg A.Y. Pseudomonas aeruginosa bacteremia over a 10-year period: Multidrug resistance and outcomes in transplant recipients. Transpl. Infect. Dis. 2009;11:227-234.

    Not in our library10.1111/j.1399-3062.2009.00380.x

  310. 310.

    Chatterjee M., Anju C., Biswas L., Kumar V.A., Mohan C.G., Biswas R. Antibiotic resistance in Pseudomonas aeruginosa and alternative therapeutic options. Int. J. Med. Microbiol. 2016;306:48-58.

    Not in our library10.1016/j.ijmm.2015.11.004

  311. 311.

    Hancock R.E., Speert D.P. Antibiotic resistance in Pseudomonas aeruginosa: Mechanisms and impact on treatment. Drug Resist. Updates. 2000;3:247-255.

    Not in our library10.1054/drup.2000.0152

  312. 312.

    Subedi D., Vijay A.K., Willcox M. Overview of mechanisms of antibiotic resistance in Pseudomonas aeruginosa: An ocular perspective. Clin. Exp. Optom. 2017;101:162-171.

    Not in our library10.1111/cxo.12621

  313. 313.

    Livermore D.M. Multiple mechanisms of antimicrobial resistance in Pseudomonas aeruginosa: Our worst nightmare? Clin. Infect. Dis. 2002;34:634-640.

    Not in our library10.1086/338782

  314. 314.

    Hancock R.E., Brinkman F.S. Function of Pseudomonas porins in uptake and efflux. Annu. Rev. Microbiol. 2002;56:17-38.

    Not in our library10.1146/annurev.micro.56.012302.160310

  315. 315.

    Bellido F., Martin N.L., Siehnel R.J., Hancock R. Reevaluation, using intact cells, of the exclusion limit and role of porin OprF in Pseudomonas aeruginosa outer membrane permeability. J. Bacteriol. 1992;174:5196-5203.

    Not in our library10.1128/jb.174.16.5196-5203.1992

  316. 316.

    Ochs M.M., McCusker M.P., Bains M., Hancock R.E. Negative regulation of the Pseudomonas aeruginosa outer membrane porin OprD selective for imipenem and basic amino acids. Antimicrob. Agents Chemother. 1999;43:1085-1090.

    Not in our library10.1128/aac.43.5.1085

  317. 317.

    Chuanchuen R., Beinlich K., Hoang T.T., Becher A., Karkhoff-Schweizer R.R., Schweizer H.P. Cross-Resistance between Triclosan and Antibiotics in Pseudomonas aeruginosa Is Mediated by Multidrug Efflux Pumps: Exposure of a Susceptible Mutant Strain to Triclosan Selects nfxB Mutants Overexpressing MexCD-OprJ. Antimicrob. Agents Chemother. 2001;45:428-432.

    Not in our library10.1128/aac.45.2.428-432.2001

  318. 318.

    Llanes C., Hocquet D., Vogne C., Benali-Baitich D., Neuwirth C., Plésiat P. Clinical strains of Pseudomonas aeruginosa overproducing MexAB-OprM and MexXY efflux pumps simultaneously. Antimicrob. Agents Chemother. 2004;48:1797-1802.

    Not in our library10.1128/aac.48.5.1797-1802.2004

  319. 319.

    Okamoto K., Gotoh N., Nishino T. Extrusion of penem antibiotics by multicomponent efflux systems MexAB-OprM, MexCD-OprJ, and MexXY-OprM of Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 2002;46:2696-2699.

    Not in our library10.1128/aac.46.8.2696-2699.2002

  320. 320.
    Antibiotics versus biofilm: an emerging battleground in microbial communities · 2019
    No notice
  321. 321.

    Stewart P.S., Costerton J.W. Antibiotic resistance of bacteria in biofilms. Lancet. 2001;358:135-138.

    Not in our library10.1016/s0140-6736(01)05321-1

  322. 322.

    Taylor P.K., Yeung A.T., Hancock R.E. Antibiotic resistance in Pseudomonas aeruginosa biofilms: Towards the development of novel anti-biofilm therapies. J. Biotechnol. 2014;191:121-130.

    Not in our library10.1016/j.jbiotec.2014.09.003

  323. 323.
    Mechanisms of Antimicrobial Resistance in ESKAPE Pathogens · 2016
    No notice
  324. 324.

    Hall C.W., Mah T.-F. Molecular mechanisms of biofilm-based antibiotic resistance and tolerance in pathogenic bacteria. FEMS Microbiol. Rev. 2017;41:276-301.

    Not in our library10.1093/femsre/fux010

  325. 325.

    Rossi E., La Rosa R., Bartell J.A., Marvig R.L., Haagensen J.A., Sommer L.M., Molin S., Johansen H.K. Pseudomonas aeruginosa adaptation and evolution in patients with cystic fibrosis. Nat. Rev. Microbiol. 2021;19:331-342.

    Not in our library10.1038/s41579-020-00477-5

  326. 326.

    Fauvart M., De Groote V.N., Michiels J. Role of persister cells in chronic infections: Clinical relevance and perspectives on anti-persister therapies. J. Med. Microbiol. 2011;60:699-709.

    Not in our library10.1099/jmm.0.030932-0

  327. 327.

    Borriello G., Werner E., Roe F., Kim A.M., Ehrlich G.D., Stewart P.S. Oxygen limitation contributes to antibiotic tolerance of Pseudomonas aeruginosa in biofilms. Antimicrob. Agents Chemother. 2004;48:2659-2664.

    Not in our library10.1128/aac.48.7.2659-2664.2004

  328. 328.

    Stewart P.S., Franklin M.J., Williamson K.S., Folsom J.P., Boegli L., James G.A. Contribution of stress responses to antibiotic tolerance in Pseudomonas aeruginosa biofilms. Antimicrob. Agents Chemother. 2015;59:3838-3847.

    Not in our library10.1128/aac.00433-15

  329. 329.
    The role of metabolism in bacterial persistence · 2014
    No notice
  330. 330.

    Yoshida H., Nakamura M., Bogaki M., Nakamura S. Proportion of DNA gyrase mutants among quinolone-resistant strains of Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 1990;34:1273-1275.

    Not in our library10.1128/aac.34.6.1273

  331. 331.

    Srinivas N., Jetter P., Ueberbacher B.J., Werneburg M., Zerbe K., Steinmann J., Van der Meijden B., Bernardini F., Lederer A., Dias R.L. Peptidomimetic antibiotics target outer-membrane biogenesis in Pseudomonas aeruginosa. Science. 2010;327:1010-1013.

    Not in our library10.1126/science.1182749

  332. 332.

    Jeukens J., Boyle B., Kukavica-Ibrulj I., Ouellet M.M., Aaron S.D., Charette S.J., Fothergill J.L., Tucker N.P., Winstanley C., Levesque R.C. Comparative genomics of isolates of a Pseudomonas aeruginosa epidemic strain associated with chronic lung infections of cystic fibrosis patients. PLoS ONE. 2014;9:e87611.

    Not in our library10.1371/journal.pone.0087611

  333. 333.

    Freschi L., Vincent A.T., Jeukens J., Emond-Rheault J.-G., Kukavica-Ibrulj I., Dupont M.-J., Charette S.J., Boyle B., Levesque R.C. The Pseudomonas aeruginosa pan-genome provides new insights on its population structure, horizontal gene transfer, and pathogenicity. Genome Biol. Evol. 2019;11:109-120.

    Not in our library10.1093/gbe/evy259

  334. 334.

    Uddin M.J., Dawan J., Jeon G., Yu T., He X., Ahn J. The role of bacterial membrane vesicles in the dissemination of antibiotic resistance and as promising carriers for therapeutic agent delivery. Microorganisms. 2020;8:670.

    Not in our library10.3390/microorganisms8050670

  335. 335.

    Poole K. Aminoglycoside resistance in Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 2005;49:479-487.

    Not in our library10.1128/aac.49.2.479-487.2005

  336. 336.
    Intestinal microbiome is related to lifetime antibiotic use in Finnish pre-school children · 2016
    No notice
  337. 337.
    The effects of antibiotics on the microbiome throughout development and alternative approaches for therapeutic modulation · 2016
    No notice
  338. 338.

    Kinch M.S., Patridge E., Plummer M., Hoyer D. An analysis of FDA-approved drugs for infectious disease: Antibacterial agents. Drug Discov. Today. 2014;19:1283-1287.

    Not in our library10.1016/j.drudis.2014.07.005

  339. 339.

    Davies J. Inactivation of antibiotics and the dissemination of resistance genes. Science. 1994;264:375-382.

    Not in our library10.1126/science.8153624

  340. 340.

    Ban K.A., Minei J.P., Laronga C., Harbrecht B.G., Jensen E.H., Fry D.E., Itani K.M., Dellinger E.P., Ko C.Y., Duane T.M. American College of Surgeons and Surgical Infection Society: Surgical site infection guidelines, 2016 update. J. Am. Coll. Surg. 2017;224:59-74.

    Not in our library10.1016/j.jamcollsurg.2016.10.029

  341. 341.

    Saunders K.T., Slaughter G.T., Mercer L., Gerkin R. Antibiotic Prophylaxis in Surgical Sterilization: Following the Recommendations [29g]. Obstet. Gynecol. 2018;131:82S-83S.

    Not in our library10.1097/01.aog.0000533379.96988.6a

  342. 342.

    Hughes W.T., Armstrong D., Bodey G.P., Bow E.J., Brown A.E., Calandra T., Feld R., Pizzo P.A., Rolston K.V., Shenep J.L., et al. 2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin. Infect. Dis. 2002;34:730-751.

    Not in our library10.1086/339215

  343. 343.

    Grill M.F., Maganti R.K. Neurotoxic effects associated with antibiotic use: Management considerations. Br. J. Clin. Pharmacol. 2011;72:381-393.

    Not in our library10.1111/j.1365-2125.2011.03991.x

  344. 344.

    Singh R., Sripada L., Singh R. Side effects of antibiotics during bacterial infection: Mitochondria, the main target in host cell. Mitochondrion. 2014;16:50-54.

    Not in our library10.1016/j.mito.2013.10.005

  345. 345.

    James A., Larson T. Acute renal failure after high-dose antibiotic bone cement: Case report and review of the literature. Ren. Fail. 2015;37:1061-1066.

    Not in our library10.3109/0886022x.2015.1052949

  346. 346.

    Balch A., Wendelboe A.M., Vesely S.K., Bratzler D.W. Antibiotic prophylaxis for surgical site infections as a risk factor for infection with Clostridium difficile. PLoS ONE. 2017;12:e0179117.

    Not in our library10.1371/journal.pone.0179117

  347. 347.

    Poeran J., Mazumdar M., Rasul R., Meyer J., Sacks H.S., Koll B.S., Wallach F.R., Moskowitz A., Gelijns A.C. Antibiotic prophylaxis and risk of Clostridium difficile infection after coronary artery bypass graft surgery. J. Thorac. Cardiovasc. Surg. 2016;151:589-597.e2.

    Not in our library10.1016/j.jtcvs.2015.09.090

  348. 348.

    Leffler D.A., Lamont J.T. Clostridium difficile infection. N. Engl. J. Med. 2015;372:1539-1548.

    Not in our library10.1056/nejmra1403772

  349. 349.

    Zimlichman E., Henderson D., Tamir O., Franz C., Song P., Yamin C.K., Keohane C., Denham C.R., Bates D.W. Health care–associated infections: A meta-analysis of costs and financial impact on the US health care system. JAMA Intern. Med. 2013;173:2039-2046.

    Not in our library10.1001/jamainternmed.2013.9763

  350. 350.

    McHugh S., Collins C., Corrigan M., Hill A., Humphreys H. The role of topical antibiotics used as prophylaxis in surgical site infection prevention. J. Antimicrob. Chemother. 2011;66:693-701.

    Not in our library10.1093/jac/dkr009

  351. 351.

    Akira S., Uematsu S., Takeuchi O. Pathogen recognition and innate immunity. Cell. 2006;124:783-801.

    Not in our library10.1016/j.cell.2006.02.015

  352. 352.

    Quintin J., Cheng S.-C., van der Meer J.W., Netea M.G. Innate immune memory: Towards a better understanding of host defense mechanisms. Curr. Opin. Immunol. 2014;29:1-7.

    Not in our library10.1016/j.coi.2014.02.006

  353. 353.

    Sotolongo J., Ruiz J., Fukata M. The role of innate immunity in the host defense against intestinal bacterial pathogens. Curr. Infect. Dis. Rep. 2012;14:15-23.

    Not in our library10.1007/s11908-011-0234-4

  354. 354.

    Dovi J.V., Szpaderska A.M., DiPietro L.A. Neutrophil function in the healing wound: Adding insult to injury? Thromb Haemost. 2004;92:275-280.

    Not in our library10.1160/th03-11-0720

  355. 355.

    Brinkmann V., Reichard U., Goosmann C., Fauler B., Uhlemann Y., Weiss D.S., Weinrauch Y., Zychlinsky A. Neutrophil extracellular traps kill bacteria. Science. 2004;303:1532-1535.

    Not in our library10.1126/science.1092385

  356. 356.

    Lei J., Sun L., Huang S., Zhu C., Li P., He J., Mackey V., Coy D.H., He Q. The antimicrobial peptides and their potential clinical applications. Am. J. Transl. Res. 2019;11:3919.

    Not in our library

  357. 357.

    Brogden K.A. Antimicrobial peptides: Pore formers or metabolic inhibitors in bacteria? Nat. Rev. Microbiol. 2005;3:238-250.

    Not in our library10.1038/nrmicro1098

  358. 358.

    Da Silva J., Leal E.C., Carvalho E. Bioactive Antimicrobial Peptides as Therapeutic Agents for Infected Diabetic Foot Ulcers. Biomolecules. 2021;11:1894.

    Not in our library10.3390/biom11121894

  359. 359.
    Development and Challenges of Antimicrobial Peptides for Therapeutic Applications · 2020
    No notice
  360. 360.

    Dosler S., Karaaslan E. Inhibition and destruction of Pseudomonas aeruginosa biofilms by antibiotics and antimicrobial peptides. Peptides. 2014;62:32-37.

    Not in our library10.1016/j.peptides.2014.09.021

  361. 361.
    Mechanism of Action of Surface Immobilized Antimicrobial Peptides Against Pseudomonas aeruginosa · 2020
    Not checked
  362. 362.

    Cirioni O., Silvestri C., Ghiselli R., Orlando F., Riva A., Mocchegiani F., Chiodi L., Castelletti S., Gabrielli E., Saba V. Protective effects of the combination of α-helical antimicrobial peptides and rifampicin in three rat models of Pseudomonas aeruginosa infection. J. Antimicrob. Chemother. 2008;62:1332-1338.

    Not in our library10.1093/jac/dkn393

  363. 363.

    Mwangi J., Yin Y., Wang G., Yang M., Li Y., Zhang Z., Lai R. The antimicrobial peptide ZY4 combats multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii infection. Proc. Natl. Acad. Sci. USA. 2019;116:26516-26522.

    Not in our library10.1073/pnas.1909585117

  364. 364.

    Peschel A. How do bacteria resist human antimicrobial peptides? Trends Microbiol. 2002;10:179-186.

    Not in our library10.1016/s0966-842x(02)02333-8

  365. 365.

    El Shazely B., Yu G., Johnston P.R., Rolff J. Resistance evolution against antimicrobial peptides in Staphylococcus aureus alters pharmacodynamics beyond the MIC. Front. Microbiol. 2020;11:103.

    Not in our library10.3389/fmicb.2020.00103

  366. 366.

    Bowie A.G., Unterholzner L. Viral evasion and subversion of pattern-recognition receptor signalling. Nat. Rev. Immunol. 2008;8:911-922.

    Not in our library10.1038/nri2436

  367. 367.

    Albrecht C., Boutrot F., Segonzac C., Schwessinger B., Gimenez-Ibanez S., Chinchilla D., Rathjen J.P., de Vries S.C., Zipfel C. Brassinosteroids inhibit pathogen-associated molecular pattern–triggered immune signaling independent of the receptor kinase BAK1. Proc. Natl. Acad. Sci. USA. 2012;109:303-308.

    Not in our library10.1073/pnas.1109921108

  368. 368.

    Abramovitch R.B., Anderson J.C., Martin G.B. Bacterial elicitation and evasion of plant innate immunity. Nat. Rev. Mol. Cell Biol. 2006;7:601-611.

    Not in our library10.1038/nrm1984

  369. 369.

    Trdá L., Boutrot F., Claverie J., Brulé D., Dorey S., Poinssot B. Perception of pathogenic or beneficial bacteria and their evasion of host immunity: Pattern recognition receptors in the frontline. Front. Plant Sci. 2015;6:1-11.

    Not in our library10.3389/fpls.2015.00219

  370. 370.

    Taxman D.J., Huang M.T., Ting J.P. Inflammasome inhibition as a pathogenic stealth mechanism. Cell Host Microbe. 2010;8:7-11.

    Not in our library10.1016/j.chom.2010.06.005

  371. 371.

    Kahraman C., Yümün G., Kahraman N.K., Namdar N.D., Cosgun S. Neutrophil-to-lymphocyte ratio in diabetes mellitus patients with and without diabetic foot ulcer. Eur. J. Med. Sci. 2014;1:8-13.

    Not in our library10.12973/ejms.2014.102p

  372. 372.

    Serban D., Papanas N., Dascalu A.M., Kempler P., Raz I., Rizvi A.A., Rizzo M., Tudor C., Silviu Tudosie M., Tanasescu D. Significance of neutrophil to lymphocyte ratio (nlr) and platelet lymphocyte ratio (plr) in diabetic foot ulcer and potential new therapeutic targets. Int. J. Low. Extrem. Wounds. 2021;15347346211057742.

    Not in our library10.1177/15347346211057742

  373. 373.

    Watters C., DeLeon K., Trivedi U., Griswold J.A., Lyte M., Hampel K.J., Wargo M.J., Rumbaugh K.P. Pseudomonas aeruginosa biofilms perturb wound resolution and antibiotic tolerance in diabetic mice. Med. Microbiol. Immunol. 2013;202:131-141.

    Not in our library10.1007/s00430-012-0277-7

  374. 374.
    Bacteriophage therapy against Pseudomonas aeruginosa biofilms: a review · 2020
    No notice
  375. 375.

    Kakasis A., Panitsa G. Bacteriophage therapy as an alternative treatment for human infections. A comprehensive review. Int. J. Antimicrob. Agents. 2019;53:16-21.

    Not in our library10.1016/j.ijantimicag.2018.09.004

  376. 376.

    Kellenberger G., Kellenberger E. Electron microscopical studies of phage multiplication: III. Observation of single cell bursts. Virology. 1957;3:275-285.

    Not in our library10.1016/0042-6822(57)90093-4

  377. 377.

    Ferry T., Kolenda C., Laurent F., Leboucher G., Merabischvilli M., Djebara S., Gustave C.-A., Perpoint T., Barrey C., Pirnay J.-P. Personalized bacteriophage therapy to treat pandrug-resistant spinal Pseudomonas aeruginosa infection. Nat. Commun. 2022;13:4239.

    Not in our library10.1038/s41467-022-31837-9

  378. 378.

    Law N., Logan C., Yung G., Furr C.-L.L., Lehman S.M., Morales S., Rosas F., Gaidamaka A., Bilinsky I., Grint P. Successful adjunctive use of bacteriophage therapy for treatment of multidrug-resistant Pseudomonas aeruginosa infection in a cystic fibrosis patient. Infection. 2019;47:665-668.

    Not in our library10.1007/s15010-019-01319-0

  379. 379.

    McVay C.S., Velásquez M., Fralick J.A. Phage therapy of Pseudomonas aeruginosa infection in a mouse burn wound model. Antimicrob. Agents Chemother. 2007;51:1934-1938.

    Not in our library10.1128/aac.01028-06

  380. 380.
    Phage therapy against Pseudomonas aeruginosa infections in a cystic fibrosis zebrafish model · 2019
    No notice
  381. 381.
    Phage treatment of an aortic graft infected with Pseudomonas aeruginosa · 2018
    No notice
  382. 382.

    Nilsson A.S. Pharmacological limitations of phage therapy. Upsala J. Med. Sci. 2019;124:218-227.

    Not in our library10.1080/03009734.2019.1688433

  383. 383.

    Örmälä A.-M., Jalasvuori M. Phage therapy: Should bacterial resistance to phages be a concern, even in the long run? Bacteriophage. 2013;3:e24219.

    Not in our library10.4161/bact.24219

  384. 384.
    The Safety and Toxicity of Phage Therapy: A Review of Animal and Clinical Studies · 2021
    No notice
  385. 385.
    Pseudomonas aeruginosa: An Audacious Pathogen with an Adaptable Arsenal of Virulence Factors · 2021
    No notice
  386. 386.

    Foulkes D.M., McLean K., Haneef A.S., Fernig D.G., Winstanley C., Berry N., Kaye S.B. Pseudomonas aeruginosa toxin ExoU as a therapeutic target in the treatment of bacterial infections. Microorganisms. 2019;7:707.

    Not in our library10.3390/microorganisms7120707

  387. 387.

    Shaw E., Wuest W.M. Virulence attenuating combination therapy: A potential multi-target synergy approach to treat Pseudomonas aeruginosa infections in cystic fibrosis patients. RSC Med. Chem. 2020;11:358-369.

    Not in our library10.1039/c9md00566h

  388. 388.

    Anantharajah A., Mingeot-Leclercq M.-P., Van Bambeke F. Targeting the type three secretion system in Pseudomonas aeruginosa. Trends Pharmacol. Sci. 2016;37:734-749.

    Not in our library10.1016/j.tips.2016.05.011

  389. 389.

    Warrener P., Varkey R., Bonnell J.C., DiGiandomenico A., Camara M., Cook K., Peng L., Zha J., Chowdury P., Sellman B. A novel anti-PcrV antibody providing enhanced protection against Pseudomonas aeruginosa in multiple animal infection models. Antimicrob. Agents Chemother. 2014;58:4384-4391.

    Not in our library10.1128/aac.02643-14

  390. 390.

    Abbas H.A., Shaldam M.A., Eldamasi D. Curtailing quorum sensing in Pseudomonas aeruginosa by sitagliptin. Curr. Microbiol. 2020;77:1051-1060.

    Not in our library10.1007/s00284-020-01909-4

  391. 391.

    Hendrix H., Zimmermann-Kogadeeva M., Zimmermann M., Sauer U., De Smet J., Muchez L., Lissens M., Staes I., Voet M., Wagemans J. Metabolic reprogramming of Pseudomonas aeruginosa by phage-based quorum sensing modulation. Cell Rep. 2022;38:110372.

    Not in our library10.1016/j.celrep.2022.110372

  392. 392.

    Hauser A.R. The type III secretion system of Pseudomonas aeruginosa: Infection by injection. Nat. Rev. Microbiol. 2009;7:654-665.

    Not in our library10.1038/nrmicro2199

  393. 393.

    Engel J., Balachandran P. Role of Pseudomonas aeruginosa type III effectors in disease. Curr. Opin. Microbiol. 2009;12:61-66.

    Not in our library10.1016/j.mib.2008.12.007

  394. 394.
    Attenuation of Pseudomonas aeruginosa infection by INP0341, a salicylidene acylhydrazide, in a murine model of keratitis · 2020
    Not checked
  395. 395.

    Rumbaugh K.P., Griswold J.A., Hamood A.N. The role of quorum sensing in the in vivo virulence of Pseudomonas aeruginosa. Microbes Infect. 2000;2:1721-1731.

    Not in our library10.1016/s1286-4579(00)01327-7

  396. 396.

    Saqr A.A., Aldawsari M.F., Khafagy E.-S., Shaldam M.A., Hegazy W.A., Abbas H.A. A novel use of Allopurinol as a quorum-sensing inhibitor in Pseudomonas aeruginosa. Antibiotics. 2021;10:1385.

    Not in our library10.3390/antibiotics10111385

  397. 397.

    Haque S., Ahmad F., Dar S.A., Jawed A., Mandal R.K., Wahid M., Lohani M., Khan S., Singh V., Akhter N. Developments in strategies for Quorum Sensing virulence factor inhibition to combat bacterial drug resistance. Microb. Pathog. 2018;121:293-302.

    Not in our library10.1016/j.micpath.2018.05.046

  398. 398.

    Sandri A., Ortombina A., Boschi F., Cremonini E., Boaretti M., Sorio C., Melotti P., Bergamini G., Lleo M. Inhibition of Pseudomonas aeruginosa secreted virulence factors reduces lung inflammation in CF mice. Virulence. 2018;9:1008-1018.

    Not in our library10.1080/21505594.2018.1489198

  399. 399.

    Shao X., Xie Y., Zhang Y., Liu J., Ding Y., Wu M., Wang X., Deng X. Novel therapeutic strategies for treating Pseudomonas aeruginosa infection. Expert Opin. Drug Discov. 2020;15:1403-1423.

    Not in our library10.1080/17460441.2020.1803274

  400. 400.

    Pier G.B. Promises and pitfalls of Pseudomonas aeruginosa lipopolysaccharide as a vaccine antigen. Carbohydr. Res. 2003;338:2549-2556.

    Not in our library10.1016/s0008-6215(03)00312-4

  401. 401.

    Göcke K., Baumann U., Hagemann H., Gabelsberger J., Hahn H., Freihorst J., von Specht B.U. Mucosal vaccination with a recombinant OprF-I vaccine of Pseudomonas aeruginosa in healthy volunteers: Comparison of a systemic vs. a mucosal booster schedule. FEMS Immunol. Med. Microbiol. 2003;37:167-171.

    Not in our library10.1016/s0928-8244(03)00094-4

  402. 402.

    Baumann U., Mansouri E., Von Specht B.-U. Recombinant OprF–OprI as a vaccine against Pseudomonas aeruginosa infections. Vaccine. 2004;22:840-847.

    Not in our library10.1016/j.vaccine.2003.11.029

  403. 403.

    Sawa T., Yahr T.L., Ohara M., Kurahashi K., Gropper M.A., Wiener-Kronish J.P., Frank D.W. Active and passive immunization with the Pseudomonas V antigen protects against type III intoxication and lung injury. Nat. Med. 1999;5:392-398.

    Not in our library10.1038/7391

  404. 404.

    Rello J., Krenn C.-G., Locker G., Pilger E., Madl C., Balica L., Dugernier T., Laterre P.-F., Spapen H., Depuydt P. A randomized placebo-controlled phase II study of a Pseudomonas vaccine in ventilated ICU patients. Crit. Care. 2017;21:22.

    Not in our library10.1186/s13054-017-1601-9

  405. 405.

    Wang Y., Cheng X., Wan C., Wei J., Gao C., Zhang Y., Zeng H., Peng L., Luo P., Lu D. Development of a chimeric vaccine against Pseudomonas aeruginosa based on the Th17-stimulating epitopes of PcrV and AmpC. Front. Immunol. 2021;11:601601.

    Not in our library10.3389/fimmu.2020.601601

  406. 406.

    DiGiandomenico A., Rao J., Goldberg J.B. Oral vaccination of BALB/c mice with Salmonella enterica serovar Typhimurium expressing Pseudomonas aeruginosa O antigen promotes increased survival in an acute fatal pneumonia model. Infect. Immun. 2004;72:7012-7021.

    Not in our library10.1128/iai.72.12.7012-7021.2004

  407. 407.

    Kamei A., Coutinho-Sledge Y.S., Goldberg J.B., Priebe G.P., Pier G.B. Mucosal vaccination with a multivalent, live-attenuated vaccine induces multifactorial immunity against Pseudomonas aeruginosa acute lung infection. Infect. Immun. 2011;79:1289-1299.

    Not in our library10.1128/iai.01139-10

  408. 408.

    Zhang X., Yang F., Zou J., Wu W., Jing H., Gou Q., Li H., Gu J., Zou Q., Zhang J. Immunization with Pseudomonas aeruginosa outer membrane vesicles stimulates protective immunity in mice. Vaccine. 2018;36:1047-1054.

    Not in our library10.1016/j.vaccine.2018.01.034

  409. 409.
    Enhanced annotations and features for comparing thousands of Pseudomonas genomes in the Pseudomonas genome database · 2015
    No notice
  410. 410.

    Boukerb A.M., Marti R., Cournoyer B. Genome sequences of three strains of the Pseudomonas aeruginosa PA7 clade. Genome Announc. 2015;3:e01366-15.

    Not in our library10.1128/genomea.01366-15

  411. 411.

    Elsen S., Huber P., Bouillot S., Couté Y., Fournier P., Dubois Y., Timsit J.-F., Maurin M., Attrée I. A type III secretion negative clinical strain of Pseudomonas aeruginosa employs a two-partner secreted exolysin to induce hemorrhagic pneumonia. Cell Host Microbe. 2014;15:164-176.

    Not in our library10.1016/j.chom.2014.01.003

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    Bumann D., Behre C., Behre K., Herz S., Gewecke B., Gessner J.E., von Specht B.U., Baumann U. Systemic, nasal and oral live vaccines against Pseudomonas aeruginosa: A clinical trial of immunogenicity in lower airways of human volunteers. Vaccine. 2010;28:707-713.

    Not in our library10.1016/j.vaccine.2009.10.080

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    Killough M., Rodgers A.M., Ingram R.J. Pseudomonas aeruginosa: Recent Advances in Vaccine Development. Vaccines. 2022;10:1100.

    Not in our library10.3390/vaccines10071100

  414. 414.
    Antibacterial Silver · 1994
    No notice
  415. 415.

    Yin I.X., Zhang J., Zhao I.S., Mei M.L., Li Q., Chu C.H. The antibacterial mechanism of silver nanoparticles and its application in dentistry. Int. J. Nanomed. 2020;15:2555.

    Not in our library10.2147/ijn.s246764

  416. 416.

    Bjarnsholt T., KIRKETERP-MØLLER K., Kristiansen S., Phipps R., Nielsen A.K., Jensen P.Ø., Høiby N., Givskov M. Silver against Pseudomonas aeruginosa biofilms. Acta Pathol. Microbiol. Immunol. Scand. 2007;115:921-928.

    Not in our library10.1111/j.1600-0463.2007.apm_646.x

  417. 417.

    Ahmadi M., Adibhesami M. The effect of silver nanoparticles on wounds contaminated with Pseudomonas aeruginosa in mice: An experimental study. Iran. J. Pharm. Res. 2017;16:661.

    Not in our library

  418. 418.

    Wan B., Zhu Y., Tao J., Zhu F., Chen J., Li L., Zhao J., Wang L., Sun S., Yang Y. Alginate lyase guided silver nanocomposites for eradicating Pseudomonas aeruginosa from lungs. ACS Appl. Mater. Interfaces. 2020;12:9050-9061.

    Not in our library10.1021/acsami.9b21815

  419. 419.

    Kuwabara M., Sato Y., Ishihara M., Takayama T., Nakamura S., Fukuda K., Murakami K., Yokoe H., Kiyosawa T. Healing of Pseudomonas aeruginosa-infected wounds in diabetic db/db mice by weakly acidic hypochlorous acid cleansing and silver nanoparticle/chitin-nanofiber sheet covering. Wound Med. 2020;28:100183.

    Not in our library10.1016/j.wndm.2020.100183

  420. 420.

    Khansa I., Schoenbrunner A.R., Kraft C.T., Janis J.E. Silver in wound care—Friend or foe?: A comprehensive review. Plast. Reconstr. Surg. Glob. Open. 2019;7:e2390.

    Not in our library10.1097/gox.0000000000002390

  421. 421.

    Riley D.K., Classen D.C., Stevens L.E., Burke J.P. A large randomized clinical trial of a silver-impregnated urinary catheter: Lack of efficacy and staphylococcal superinfection. Am. J. Med. 1995;98:349-356.

    Not in our library10.1016/s0002-9343(99)80313-1

  422. 422.

    Majno G. The Healing Hand: Man and Wound in the Ancient World. 1991.

    Not in our library

  423. 423.
    Antibacterial Potency of Honey · 2019
    No notice
  424. 424.

    Yupanqui Mieles J., Vyas C., Aslan E., Humphreys G., Diver C., Bartolo P. Honey: An Advanced Antimicrobial and Wound Healing Biomaterial for Tissue Engineering Applications. Pharmaceutics. 2022;14:1663.

    Not in our library10.3390/pharmaceutics14081663

  425. 425.

    Lusby P.E., Coombes A.L., Wilkinson J.M. Bactericidal activity of different honeys against pathogenic bacteria. Arch. Med. Res. 2005;36:464-467.

    Not in our library10.1016/j.arcmed.2005.03.038

  426. 426.

    Lu J., Cokcetin N.N., Burke C.M., Turnbull L., Liu M., Carter D.A., Whitchurch C.B., Harry E.J. Honey can inhibit and eliminate biofilms produced by Pseudomonas aeruginosa. Sci. Rep. 2019;9:18160.

    Not in our library10.1038/s41598-019-54576-2

  427. 427.
    Characterizing the Mechanism of Action of an Ancient Antimicrobial, Manuka Honey, against Pseudomonas aeruginosa Using Modern Transcriptomics · 2020
    Not checked
  428. 428.

    Robson V., Dodd S., Thomas S. Standardized antibacterial honey (Medihoney™) with standard therapy in wound care: Randomized clinical trial. J. Adv. Nurs. 2009;65:565-575.

    Not in our library10.1111/j.1365-2648.2008.04923.x

  429. 429.

    Memar M.Y., Yekani M., Alizadeh N., Baghi H.B. Hyperbaric oxygen therapy: Antimicrobial mechanisms and clinical application for infections. Biomed. Pharmacother. 2019;109:440-447.

    Not in our library10.1016/j.biopha.2018.10.142

  430. 430.

    Çimşit M., Uzun G., Yıldız Ş. Hyperbaric oxygen therapy as an anti-infective agent. Expert Rev. Anti-Infect. Ther. 2009;7:1015-1026.

    Not in our library10.1586/eri.09.76

  431. 431.

    Møller S.A., Jensen P.Ø., Høiby N., Ciofu O., Kragh K.N., Bjarnsholt T., Kolpen M. Hyperbaric oxygen treatment increases killing of aggregating Pseudomonas aeruginosa isolates from cystic fibrosis patients. J. Cyst. Fibros. 2019;18:657-664.

    Not in our library10.1016/j.jcf.2019.01.005

  432. 432.

    Luongo C., Imperatore F., Matera M., Mangoni G. Effect of hyperbaric oxygen therapy in experimental subcutaneous and pulmonary infections due to Pseudomonas aeruginosa. Undersea Hyperb. Med. 1999;26:21.

    Not in our library

  433. 433.

    Kranke P., Bennett M.H., Martyn-St James M., Schnabel A., Debus S.E., Weibel S. Hyperbaric oxygen therapy for chronic wounds. Cochrane Database Syst. Rev. 2015;2015:CD004123.

    Not in our library10.1002/14651858.cd004123.pub4

  434. 434.

    Dauwe P.B., Pulikkottil B.J., Lavery L., Stuzin J.M., Rohrich R.J. Does hyperbaric oxygen therapy work in facilitating acute wound healing: A systematic review. Plast. Reconstr. Surg. 2014;133:208e-215e.

    Not in our library10.1097/01.prs.0000436849.79161.a4

  435. 435.

    Gupta R., Darby G.C., Imagawa D.K. Efficacy of negative pressure wound treatment in preventing surgical site infections after Whipple procedures. Am. Surg. 2017;83:1166-1169.

    Not in our library10.1177/000313481708301031

  436. 436.

    Burkhart R.A., Javed A.A., Ronnekleiv-Kelly S., Wright M.J., Poruk K.E., Eckhauser F., Makary M.A., Cameron J.L., Wolfgang C.L., He J. The use of negative pressure wound therapy to prevent post-operative surgical site infections following pancreaticoduodenectomy. HPB. 2017;19:825-831.

    Not in our library10.1016/j.hpb.2017.05.004

  437. 437.

    Liu Y., Zhou Q., Wang Y., Liu Z., Dong M., Wang Y., Li X., Hu D. Negative pressure wound therapy decreases mortality in a murine model of burn-wound sepsis involving Pseudomonas aeruginosa infection. PLoS ONE. 2014;9:e90494.

    Not in our library10.1371/journal.pone.0090494

  438. 438.

    Wang G., Li Z., Li T., Wang S., Zhang L., Zhang L., Tang P. Negative-pressure wound therapy in a Pseudomonas aeruginosa infection model. BioMed Res. Int. 2018;2018:9496183.

    Not in our library10.1155/2018/9496183

  439. 439.

    Guoqi W., Zhirui L., Song W., Tongtong L., Lihai Z., Licheng Z., Peifu T. Negative pressure wound therapy reduces the motility of Pseudomonas aeruginosa and enhances wound healing in a rabbit ear biofilm infection model. Antonie Leeuwenhoek. 2018;111:1557-1570.

    Not in our library10.1007/s10482-018-1045-5

  440. 440.

    Comolli J., Hauser A., Waite L., Whitchurch C., Mattick J., Engel J. PilU and PilT are required for cytotoxicity and virulence of Pseudomonas aeruginosa. Infect. Immun. 1999;67:3625-3630.

    Not in our library10.1128/iai.67.7.3625-3630.1999

  441. 441.

    Pliska N.N. Pseudomonas aeruginosa as the main causative agent of osteomyelitis and its susceptibility to antibiotics. Drug Res. 2020;70:280-285.

    Not in our library10.1055/a-1150-2372

  442. 442.

    Cerioli M., Batailler C., Conrad A., Roux S., Perpoint T., Becker A., Triffault-Fillit C., Lustig S., Fessy M.-H., Laurent F. Pseudomonas aeruginosa implant-associated bone and joint infections: Experience in a regional reference center in France. Front. Med. 2020;7:513242.

    Not in our library10.3389/fmed.2020.513242

  443. 443.

    Norden C.W., Keleti E. Experimental osteomyelitis caused by Pseudomonas aeruginosa. J. Infect. Dis. 1980;141:71-75.

    Not in our library10.1093/infdis/141.1.71

  444. 444.

    Gürtler N., Osthoff M., Rueter F., Wüthrich D., Zimmerli L., Egli A., Bassetti S. Prosthetic valve endocarditis caused by Pseudomonas aeruginosa with variable antibacterial resistance profiles: A diagnostic challenge. BMC Infect. Dis. 2019;19:530.

    Not in our library10.1186/s12879-019-4164-3

  445. 445.

    Razvi S., Quittell L., Sewall A., Quinton H., Marshall B., Saiman L. Respiratory microbiology of patients with cystic fibrosis in the United States, 1995 to 2005. Chest. 2009;136:1554-1560.

    Not in our library10.1378/chest.09-0132

  446. 446.
    Epidemiology of Burkholderia cepacia Complex in Patients with Cystic Fibrosis, Canada · 2002
    No notice
  447. 447.

    Salsgiver E.L., Fink A.K., Knapp E.A., LiPuma J.J., Olivier K.N., Marshall B.C., Saiman L. Changing epidemiology of the respiratory bacteriology of patients with cystic fibrosis. Chest. 2016;149:390-400.

    Not in our library10.1378/chest.15-0676

  448. 448.
    Evaluation of the bacterial diversity in the feces of cattle using 16S rDNA bacterial tag-encoded FLX amplicon pyrosequencing (bTEFAP) · 2008
    No notice
  449. 449.

    Uçkay I., Lebowitz D., Kressmann B., von Dach E., Lipsky B.A., Gariani K. Pseudomonal Diabetic Foot Infections: Vive la Différence? Mayo Clin. Proc. Innov. Qual. Outcomes. 2022;6:250-256.

    Not in our library10.1016/j.mayocpiqo.2022.04.005

  450. 450.

    Sivanmaliappan T.S., Sevanan M. Antimicrobial susceptibility patterns of Pseudomonas aeruginosa from diabetes patients with foot ulcers. Int. J. Microbiol. 2011;2011:605195.

    Not in our library10.1155/2011/605195

  451. 451.

    Dhanasekaran G., Sastry G., Viswanathan M. Microbial pattern of soft tissue infections in diabetic patients in South India. Asian J. Diabet. 2003;5:8-10.

    Not in our library

  452. 452.

    Koo D.S., Sun Z., Shi X.W., Xiang S.J. Assessment of topical therapy of the burn wound with silver sulphadiazine after its use for 15 years in a burn unit. Burns. 1989;15:193-196.

    Not in our library10.1016/0305-4179(89)90182-4

  453. 453.
    Epidemiology of burn wound bacterial infections at a Meknes hospital, Morocco · 2020
    Not checked
  454. 454.

    Emami A., Pirbonyeh N., Keshavarzi A., Javanmardi F., Moradi Ghermezi S., Ghadimi T. Three year study of infection profile and antimicrobial resistance pattern from burn patients in southwest Iran. Infect. Drug Resist. 2020;13:1499-1506.

    Not in our library10.2147/idr.s249160

  455. 455.

    Rolston K.V., Hauser A.R., Rello J. Pseudomonas aeruginosa infections in cancer patients. Severe infections caused by Pseudomonas aeruginosa. 2003;Volume 7:113-125.

    Not in our library

  456. 456.

    Lima L.M., da Silva B.N.M., Barbosa G., Barreiro E.J. β-lactam antibiotics: An overview from a medicinal chemistry perspective. Eur. J. Med. Chem. 2020;208:112829.

    Not in our library10.1016/j.ejmech.2020.112829

  457. 457.

    Ezelarab H.A., Abbas S.H., Hassan H.A., Abuo-Rahma G.E.D.A. Recent updates of fluoroquinolones as antibacterial agents. Arch. Pharm. 2018;351:1800141.

    Not in our library10.1002/ardp.201800141

  458. 458.

    Grossman T.H. Tetracycline antibiotics and resistance. Cold Spring Harb. Perspect. Med. 2016;6:a025387.

    Not in our library10.1101/cshperspect.a025387

  459. 459.

    Nguyen F., Starosta A.L., Arenz S., Sohmen D., Dönhöfer A., Wilson D.N. Tetracycline antibiotics and resistance mechanisms. Biol. Chem. 2014;395:559-575.

    Not in our library10.1515/hsz-2013-0292

  460. 460.

    Lambert P. Mechanisms of antibiotic resistance in Pseudomonas aeruginosa. J. R. Soc. Med. 2002;95:22.

    Not in our library

  461. 461.

    Steyger P.S. Mechanisms of aminoglycoside-and cisplatin-induced ototoxicity. Am. J. Audiol. 2021;30:887-900.

    Not in our library10.1044/2021_aja-21-00006

  462. 462.

    Arnold T.M., Forrest G.N., Messmer K.J. Polymyxin antibiotics for gram-negative infections. Am. J. Health-Syst. Pharm. 2007;64:819-826.

    Not in our library10.2146/ajhp060473

  463. 463.

    Trimble M.J., Mlynárčik P., Kolář M., Hancock R.E. Polymyxin: Alternative mechanisms of action and resistance. Cold Spring Harb. Perspect. Med. 2016;6:a025288.

    Not in our library10.1101/cshperspect.a025288

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