Educational interventions to improve prescription and dispensing of antibiotics: a systematic review

1Antibiotic resistance is an important public-health issue, which is aggravated by the lack of new antimicrobial agents. Inappropriate use of antibiotics is the main factor underlying microbial resistance. Ecological studies in Europe suggest that there is a clear association between extent of antibiotic use and rate of resistance. Excessive and inappropriate use of antibiotics is attributed to misprescription and to self-medication with “leftovers” from previous courses or with antibiotics dispensed in pharmacies without prescription. In countries with a high incidence of self-medication with antibiotics, prescription of antibiotics is also high, suggesting that both practices are subject to the same cultural factors. Physicians and pharmacists are the health professionals who exert most influence on patients’ medication-related behavior. Many educational interventions to improve antibiotic-prescribing and/or dispensing have targeted those health professionals. Previous systematic reviews of the topic include Steinman’s, which covered reports published prior to 2004 and on interventions directed at physicians. Other more recent reviews have targeted specific areas, namely, respiratory tract infections, critical care, and acute care. Therefore, there has been no general reviews, of the topic, including interventions on physicians a pharmacists to improve antibiotic prescription and dispensing. To close this gap, we carried out a critical review of educational programs aimed at improving antibiotic-prescribing by physicians and/or antibiotic-dispensing by pharmacists, in both primary-care and hospital settings.

2For review purposes, we conducted a search of the MEDLINE-PubMED scientific database from January 2001 through December 2011. In addition, other papers were located by manual searches targeting journals, particularly those less likely to be indexed, and references cited by papers retrieved.

3The search strategy was designed to identify relevant studies addressing antibiotic resistance and the prescribing/dispensing habits of health care providers (physicians and pharmacists) pre- and post-educational interventions. The following search terms and their equivalents were used in PubMed: (“intervention” OR “program” OR “health promotion” OR “education”) AND (“pharmacists” OR “pharmacy” OR “physician” OR “health professionals” OR “clinician” OR “clinic” OR “practitioner” OR “general practitioner” OR “doctor”) AND (“antibiotics” OR “antimicrobial”).

4Based on previous reviews, we apply this selection criteria: (i) language: papers had to be published in English, French, Spanish or Portuguese; (ii) type of intervention: studies had to describe educational interventions; (iii) target population: educational interventions had to target physicians (general practitioners and all specialties) and/or pharmacists (population studies were included only if they also included interventions on pharmacists and/or physicians); and (iv) outcome measures: studies had to measure the effect of educational interventions on the prescribing behavior of physicians and/or dispensing behavior of pharmacists. Insofar as study design was concerned, no inclusion or exclusion criteria were stipulated because our aim was to use quality methodology to conduct a critical review of all published studies.

5Adapted from Figueiras, study designs were classified as follows: (1) before/after study; (2) non-randomized controlled study without cross-contamination control; (3) non-randomized controlled study with cross-contamination control; (4) randomized controlled study without cross-contamination control; and (5) randomized controlled study without cross-contamination control. Where authors reported the different groups as being in workplaces that were geographically far apart, the study was deemed to have cross-contamination control; and where no mention was made of distance between groups or specific implementation of cross-contamination control, the study was deemed to be without such control.

6In cases where studies identified specific diseases in which interventions were made to improve antibiotic use, this was recorded.

7Educational interventions include any attempt to persuade physicians to modify their practice performance by communicating clinical information strategies and by communication skills training. Strategies that were purely administrative or applied incentives or coercion were excluded from this definition of educational interventions. In our review, we only included studies that assessed educational interventions. However, in studies in which these types of interventions were associated with others, we extracted data on all strategies. Consequently, interventions were classified into the following categories, adapted from Davis and Figueiras: (1) dissemination of printed/audiovisual educational materials (mailed printed matter; protocols and guidelines; self-instruction materials; drug bulletins); (2) group education, including group-session rounds, conferences, lectures, seminars, and tutorials; (3) feedback of physician prescribing patterns (individually, or including a comparison between these patterns and peer behavior and/or accepted standards), or feedback of patient-specific lists of prescribed medication; (4) individual outreach visits; (5) reminders at the time of prescribing; (6) computer-assisted decision-making systems; (7) formulary control/restrictive formulary process; (8) patient education (pamphlets); (9) patient education (videotapes); (10) workshops on rapid tests/introduction of Rapid Antigen Detection Testing (RADT) in consulting offices; (11) enforcement of regulations; (12) prescription feedback, with recommendations to modify it made by pharmacists and/or infectious-disease physicians; (13) financial incentives.

8Under this head, we included the period during which outcomes were measured (baseline, intervention period and follow-up).

9Studies were classified into different categories, namely: (1) comparison of post-intervention values between groups; (2) comparison of pre- and post-intervention values within each group; (3) comparison of pre- and post-intervention values between groups; (4) comparison of follow-up values between groups; (5) comparison of pre-, post, and follow-up values within each group; and, (6) comparison of pre-, post- and follow-up values between groups.

10We collected data yielded by statistical tests used to assess the effectiveness of interventions.

11The results extracted from studies consisted of changes in: total antibiotics prescribed/dispensed (T); choice of appropriate antibiotics/adherence to antibiotic guidance according to guideline algorithms, including dosages and administration routes (Ga); attitudes and behavior (At/Bh); quality of pharmacy practice (Qph).

12Study results were classified as: positive (+), if reported as positive or if changes in outcomes measured were statistically significant; partially positive (±), if reported as positive for some variables and negative for others; and negative (−), if reported as negative.

13The search yielded a total of 90,350 Abstracts, 47,535 of which were potentially eligible for inclusion. A reading of the titles and abstracts led to an initial selection of 571 papers for full-text analysis; of these, 65 were then selected, made up of 40 primary- and 25 hospital-care studies. After a search of the references cited, 7 papers were added to the primary-care and 6 to the hospital-care studies. A total of 78 papers were included, 47 primary- and 31 hospital-care interventions (Figure 1)

14In the studies analyzed (Table 1), educational interventions in primary care mainly targeted physicians, and outcomes were assessed by reference to the total antibiotic prescription or appropriate antibiotic prescription rates. Educational interventions in pharmacists occurred in 8 studies, though in 6 cases the interventions covered both pharmacists and physicians. In 21 studies, the interventions were extended to patients and their caregivers or general population.

15In primary care (table 2), 33 studies (70%) focused on the use of antibiotics in respiratory infections, and one focused on the use of antibiotics in infectious diseases and other infections (urinary infections, skin and soft tissue infections and septicemia); the remaining 30% failed to identify any target disease. Of the 47 papers, 27 (57%) studied the efficacy/effectiveness of one or more interventions versus non-intervention, using a control group that received the intervention in four studies, dissemination of guideline information in three and educational sessions on diagnosis of otitis media in one. In this last study, the educational session in the intervention group included diagnosis of otitis media and information on recommendations for antibiotic use.

16Only two studies, evaluated the efficacy of passive interventions in physicians and in one of them interventions was in combination with educational campaigns directed at patients and their caregivers. All the other studies included active interventions in health professionals (whether or not associated with passive interventions). Three studies, involved active interventions in patients and health professionals, and in four studies the interventions included improvement of doctor-patient communication skills.

17Twenty-nine studies (62%) reported positive results for all outcomes measured; fourteen studies (30%) reported positive results for some outcomes, and results that were not statistically influenced by the intervention for others; only four studies failed to report significant post-intervention improvements for all outcomes.

18While some studies conducted no post-intervention follow-up of participants, others followed up their participants for different periods, ranging from two months to three, six, twelve and twenty-four months.

19Interventions that included improving diagnostic procedures to help physicians distinguish bacterial from viral infections led to very positive results.

20Whereas most interventions concentrated on physicians (Table 1), some included a multidisciplinary intervention targeting physicians and nurses, patients, and in one case, solely pharmacists. Some studies identified the patients targeted, with these being elderly in five instances children in three. Table 3 summarizes the studies retrieved containing interventions for improving antibiotic use in hospital care. The diseases targeted were as follows: pneumonia in four cases; urinary infections in two; urinary and upper respiratory tract infections in one; pneumonia, meningitis and urinary infection in one study, and bronchitis, community acquired pneumonia and chronic obstructive pulmonary disease in other. Of the thirty-one papers, 6 (20%) studied the efficacy/effectiveness of one or more interventions versus no intervention, using a control group. Naughton compared two strategies, a multidisciplinary intervention in physicians and nurses, and a physician-only intervention in ten skilled nursing facilities randomized into two groups, and reported no statistically significant differences between the two groups. Most of the reported hospital-based interventions coincided with the implementation of protocols or new computer systems, with the result that post-intervention were compared with pre-intervention outcomes without the use of control groups.

21While some studies used passive interventions, all the others used active interventions or passive and active simultaneously. Twenty-four papers (78%) reported positive results for all outcome measures; 6 papers (20%) reported some outcomes as positive and others as positive statistically non-significant; and Naughton reported negative results.

22In contrast to primary care in which only three studies analyzed clinical outcomes, in hospital care some studies compared outcomes pre- and post-intervention to assess whether a reduction in antibiotic use might cause clinical alterations, and no influences were observed, namely, to length of hospital stay, and mortality, morbidity and/or readmission rates.

23Many of the hospital-care studies highlighted the important role of clinical pharmacists in drawing up and implementing guidelines and policies for antibiotic use in hospital settings.

24While 25 papers (53%) reported randomized controlled studies in the case of primary care, a far lower number, i.e., 8 (26%), reported this type of study in the case of hospital care, and only one of these included cross-contamination control. Cross-contamination can occur when the participants of different intervention or control groups have close working relationships and might share information about the intervention, and this is important because differences in the results between the intervention and the control group may be influenced by this factor. In some studies physicians participated on a voluntary basis (they were invited to participate in the study), and their prescribing habits recorded during the intervention may not represent their real use of antibiotics.

25There were many differences in the analytical approaches adopted by the different studies: while some compared the results of the intervention with the situation at baseline, and some compared the results between groups pre- and post-intervention, others focused exclusively on the position post-intervention. There were few studies that conducted a follow-up after the intervention had ended, and those which did reported that the majority of positive results observed in the post-intervention period were lost over time.

26No studies were found in which the interventions had been designed on the basis of the attitudes and behavior responsible for antibiotic prescribing or dispensing habits, despite the fact that many authors contend that this knowledge contributes to the success of educational interventions in health professionals. In some studies, however, interventions addressed barriers facing the individual prescriber, particularly when it came to dealing with diagnostic uncertainty, and were tailored to: overcoming any identified barriers and enable general practitioners (GPs) to reflect on their own prescribing; helping decrease uncertainty about appropriate disease management and appropriate prescribing; facilitating more patient-centered care; and being beneficial to implementation in practice. One study assessed the impact of interventions on the knowledge, beliefs, and decision-making of primary care physicians, and two others, used workshops and focus-group discussions to determine the possible motivating factors underlying observed prescribing practices. The importance of interventions being acceptable to physicians was highlighted by a recent systematic review.

27All the studies underlined the importance of appropriate use of antibiotics to prevent the problem of microbial resistance, and stated that the most important aim of interventions to improve antibiotic use was to reduce this important public health problem. Even so, only one primary-care and eight hospital-care studies analyzed improvement in bacterial susceptibility during the intervention. While some studies reported the reduction in the cost of antibiotic use, only five studies analyzed the effectiveness of intervention in terms of the cost of the intervention versus the cost of reducing antibiotic use.

28We found only two studies that addressed interventions (undertaken in Thailand and Vietnam, respectively) specifically designed to improve pharmacists’ to combat the dispensing of antibiotics without prescription, despite there were studies which established that the sale of antibiotics without a prescription are a reality in some European countries. Although some of the studies reviewed -mainly those pertaining to hospital care- reported the important role played by pharmacists in developing interventions to be undertaken in physicians and implementing antibiotic treatment guidelines and protocols in hospital settings, there were few studies with interventions targeted at pharmacists. Some authors stressed the usefulness of including pharmacists in teams tasked with drawing up recommendations and making decisions about antibiotic use in certain countries.

29Results obtained by our search showed that the majority of published studies about educational interventions describe active and multifaceted interventions. This finding is in accordance with a number of systematic meta-analyses of randomized controlled trials to improve health care practice, which conclude that highly interactive learning methods, such as educational outreach visits workshops, small discussion groups, individualized training sessions, practice-based interventions and case-based learning, are the most effective strategies.

30Some recent review papers on interventions to improve antibiotic prescribing (Table 4) focus on a limited set of intervention targets, such as acute outpatient infections, and more specifically on clinical knowledge and decision-making processes, specific populations (children), specific diseases (upper respiratory tract infections) or purpose-designed noneducational (stewardship) interventions in specific hospital divisions, such as critical care and acute care. One paper reviewed studies that evaluated GPs’ perceptions about antibiotic prescribing and interventions aimed at prudent prescribing. Our study only analyzed educational interventions but was more extensive, in that it included interventions aimed at physicians and/or pharmacists in both primary-care and hospital settings, and focused on any disease with antibiotic prescribing for child, adult or geriatric patients. In contrast to Steinman, who made a quantitative analyses of quality-improvement strategies, our review, like those of Boonacker, Kaki and Charani, was a qualitative analysis.

31As in the case of any systematic review, ours suffers from the limitation of publication bias. The inclusion criteria allowed for the review to cover a wide range of studies with different designs, something hindered us in making comparisons and performing a meta-analysis. Identification of the design proved a complex task, and it is therefore possible that some study may have been misclassified as regards design, due to an incomplete description of the methodology used. In many cases, deficiencies in the design and description of the intervention and identification of the sample made tabulating the study characteristics difficult.

32The results yielded by our search show that there are many more papers on educational interventions in physicians than pharmacists. Respiratory disorders were the disease targeted by most studies, mainly in primary care. Published studies varied widely in terms of study design, outcome measures, outcome period, and definition of sample. Most studies used active or a mix of active and passive interventions, and reported that active interventions were more effective. Notwithstanding these heterogeneity, it can be concluded from the above: first, that educational interventions to improve antibiotic use are essential; and second, that in many studies such interventions are active and multifaceted, some of them include both physicians and pharmacists, and were designed taking these health professionals’ attitudes and knowledge into account, in order to focus on the barriers so identified.