Table 2Antibiotic treatment studies conducted outside the U.S

S TUDY S ETTING AND TARGET M EASURED P OPULATION AND CONDITION * I NTERVENTION D ESCRIPTION AND Q UALITY I MPROVEMENT S TRATEGIES R ESULTS **
Studies targeting prescribing for children
Smabrekke L, Scandinavian Journal of Infectious Diseases, 2002 Norway Children with otitis media Patient education (distribution of materials), Clinician education (distribution of materials, educational meetings) Absolute effect size: -12.0%
Physicians and nurses at urgent care clinic The intervention consisted of a symposium on evidence-based management of otitis media for physicians and nurses at an acute care clinic. Guidelines on appropriate treatment were distributed. The guideline recommended narrow-spectrum antibiotic use when necessary, and suggested use of delayed prescriptions. Pamphlets for patients were made available in exam rooms; the pamphlets stressed that most patients recover without antibiotic and indiscriminate use of antibiotic leads to resistance. This information was also provided to patients who called the clinic. The percentage of patients receiving antibiotics decreased 16.0% (from 90.0% before the intervention to 74.0% after). In the control group, the prescribing rate decreased 4.0% (from 95.0% to 91.0%). This difference was statistically significant.
Cates C, BMJ, 1999 UK Children with otitis media Patient education (distribution of materials), Delayed prescriptions In the intervention clinic, the number of amoxicillin prescriptions per month decreased from 75 to 47 (a 32% relative reduction.) In the control group, the number of amoxicillin prescriptions decreased from 72 to 66 per month (a 12% relative reduction.) This difference was statistically significant.
General practitioners in outpatient clinics in Hertfordshire Parents of children with acute otitis media who were “not particularly ill” were given a handout summarizing the limited benefit of antibiotics. Parents also received a delayed prescription for antibiotics with instructions to fill the script if the child did not improve in the next “day or two.” The comparison was another nearby clinic that followed usual care.
Little P, BMJ, 2001 UK Children with otitis media Delayed prescriptions In the intervention group, 24.0% of patients used antibiotics, compared to 98.5% of patients in the control group. This difference was statistically significant.
General practices in southwest England Children with otitis media were randomized to receive either immediate antibiotics or delayed treatment. Patients in the delayed treatment group were to receive antibiotics after 72 hours if their symptoms did not improve.
Gonzalez Ochoa E, Bulletin of the Pan American Health Organization, 1996 [comparison 1] Cuba Children with respiratory infections Patient education (group educational sessions, distribution of materials), Clinician education (distribution of materials, educational meetings, educational outreach visits, educational workshops) Absolute effect size: -28.5%
General practitioners in 4 areas of Havana The intervention consisted of education of health care providers and community education components. For education of health care providers, there was a special refresher course for family physicians which included videos and slide presentations on treatment of acute respiratory infections in children. There were also opportunities for provider group discussions. The community education program consisted of group discussions in the participants' homes and talks given to mothers in the clinics. The percentage of patients receiving antibiotics decreased 27.8% (from 36.6% before the intervention to 7.8% after). In the control group, the prescribing rate increased 0.7% (from 19.6% to 20.3%).
Gonzalez Ochoa E, Bulletin of the Pan American Health Organization, 1996 [comparison 2] Cuba Children with respiratory infections Clinician education (distribution of materials, educational meeting) Absolute effect size: -9.6%
General practitioners in 4 areas of Havana This study arm consisted of health care provider education. For education of health care providers, there was a special refresher course for family physicians which included videos and slide presentations on treatment of acute respiratory infections in children. There were also opportunities for provider group discussions. In the intervention group, prescribing decreased 8.9% (from 20.6% before the intervention to 11.7% after the intervention). In the control group, the prescribing rate increased 0.7% (from 19.6% to 20.3%). The investigators did not report if this difference was statistically significant.
Gonzalez Ochoa E, Bulletin of the Pan American Health Organization, 1996 [comparison 3] Cuba Children with respiratory infections Patient education (individual educational sessions, group educational sessions, distribution of materials) Absolute effect size: 0.2%
General practitioners in 4 areas of Havana This study arm consisted of a community education program. The community education program consisted of group discussions in the participants' homes and talks given to mothers in the clinics. In the intervention group, prescribing increased 0.9% (from 11.4% before the intervention to 12.3% after.) In the control group, the prescribing rate increased 0.7% (from 19.6% to 20.3%). The investigators did not report if this difference was statistically significant.
Pshetizky Y, Family Practice, 2003 Israel Children with otitis media Patient education (individual educational sessions), Delayed prescriptions In the intervention group, 37.0% of patients used antibiotics after the intervention. In the comparison group, 63.0% of patients used antibiotics. This difference was statistically significant.
General practitioners The intervention targeted parents of children with acute otitis media. All patients were given an antibiotic prescription. Parents in the intervention group received instruction to only use antibiotics if the child's condition did not improve in 24– 48 hours. The intervention group also received a brief explanation from the physician, stressing that most patients recover regardless of whether antibiotics are used, and that serious complications of acute otitis media are not necessarily prevented by antibiotics.
Wilson EJ, Communicable Diseases Intelligence, 2003 Australia Children with respiratory infections Clinician education (distribution of materials, consensus building sessions), Patient education (distribution of materials), Self-management In the intervention group, prescriptions decreased by 0.78 prescriptions per 100 visits; in the control group, prescribing increased by 0.35 prescriptions per 100 visits. This difference was statistically significant.
General practitioners in Canberra Physicians participated in focus groups with parents of young children and workshops with other GP's; these were used to develop a practice guideline for antibiotic prescribing in upper respiratory infection. All intervention general practitioners then received a packet containing the guideline, information sheets on otitis media and sore throat for patient education, prescription pads for nonprescription medicines, patient self-management advice, and a poster advocating the guideline.
Santoso B, Social Science & Medicine, 1996 [comparison 1] Indonesia Children with diarrhea Clinician education (distribution of materials, educational outreach, educational workshops) Absolute effect size: -13.7%
General practitioners in Yogyakarta and Java provinces The study consisted of a small group intervention designed to reduce antibiotic prescribing in cases of acute diarrhea. The small group meetings consisted of face-to-face, interactive discussions involving 8–12 providers at a health center. Discussions were led by a trained physician moderator, assisted by a pharmacologist or pediatrician. Each lasted approximately two hours. A booklet on appropriate management of diarrhea was also provided. In the intervention group, prescribing rates decreased by 17.0% (from 77.4% before the intervention to 60.4% after the intervention.) In the control group, prescribing rates decreased by 3.3% (from 82.6% before the intervention to 79.3% after the intervention.)
Santoso B, Social Science & Medicine, 1996 [comparison 2] Indonesia Children with diarrhea Clinician education (distribution of materials, educational meetings) Absolute effect size: -6.7%
General practitioners in Yogyakarta and Java provinces The study consisted of a two hour seminar on appropriate prescribing for acute diarrhea targeted at physicians and paramedical personnel. The goal was to reduce antibiotic use and encourage use of oral rehydration solution. The presentation was by two physicians from the district office and the university. Question-and-answer sessions followed the seminar. Written materials on management of diarrhea were also provided. In the intervention group, prescribing rates decreased by 10.0% (from 82.3% to 72.3%.) In the control group, prescribing rates decreased by 3.3% (from 82.6% before the intervention to 79.3% after the intervention.)
Studies targeting prescribing for adults
McIsaac WJ, Medical Decision Making 1998 Canada Adults with sore throat Clinician reminder In the intervention group, 27.8% of patients received antibiotics, compared to 35.7% in the comparison group. This difference was not statistically significant.
Family physicians in Ontario Physicians received a mailing containing both a modified scoring system to help guide antibiotic prescribing and management recommendations. The intervention group also received an encounter form for a specific patient visit with the scoring system and recommendations for testing or treating based on the score. The control group received a similar encounter form without the scoring system or treatment recommendations.
Coenen SJ, Antimicrobial Agents and Chemotherapy, 2004 Belgium Adults with respiratory infections Clinician education (distribution of materials, educational outreach) Absolute effect size: 6.5%
General practitioners Physicians received a mailed guideline for treatment of patients with acute cough, which was followed by a reminder phone call. Provides also received an educational outreach visit from a pharmacist and “former medical representative”, which focused on guideline adherence and dialogue with the provider to overcome barriers to appropriate prescribing. Following this, the providers received a mailing with the key messages from the guideline. The percentage of patients receiving antibiotics decreased 15.6% (from 43.0% before the intervention to 27.4% after). In the control group, the prescribing rate decreased 9.1% (from 37.8% to 28.7%). This difference was statistically significant.
Macfarlane J, BMJ, 2002 UK Adults with acute bronchitis Patient education (distribution of materials), Delayed prescriptions Patients in the intervention group used antibiotics in 47.0% of cases, compared to 62.0% in the comparison group. This difference was statistically significant.
General practices Patients with acute bronchitis not requiring immediate treatment received a delayed prescription for antibiotics. They also were given a patient information leaflet about symptoms and the advantages/disadvantages of antibiotic use. The leaflet described when to fill the prescription and methods of self-treatment.
Studies targeting prescribing for patients of all ages
McNulty CA, Journal of Antimicrobial Chemotherapy, 2000 UK All patients Clinician education (educational workshops), Audit and feedback In the intervention group, the number of antibiotic prescriptions per provider per year declined from 395.9 before the intervention to 382.3 after the intervention. In the control group, prescriptions declined from 356.7 per provider per year to 348.7. This difference was not statistically significant.
General practices in Gloucestershire General practitioners received twelve antibiotic educational workshops, which were delivered over a seven week period. Workshops focused on promoting antibiotic guidelines, reducing antibiotic use for unnecessary conditions and making better prescribing decisions.
Melander E, Scandinavian Journal of Primary Health Care, 1999 [comparison 1] Sweden All patients with respiratory infections Clinician education (educational workshops), Audit and feedback Absolute effect size: -2.0%
General practitioners The intervention consisted of an audit of physician's antibiotic prescribing behavior. Based on the results of this audit, group discussions on appropriate management of ARIs were held, and an educational program was developed using local opinion leaders. Prescribing data was fed back to the individual physicians. The percentage of patients receiving antibiotics for ARIs decreased 4.0% (from 13.0% before the intervention to 9.0% after). In the control group, the prescribing rate decreased 2.0% (from 37.0% to 35.0%). The investigators did not report if this difference was statistically significant.
Molstad S, Family Practice, 1989 Sweden All patients with respiratory infections Clinician education (consensus building sessions) Absolute effect size: -23.3%
General practitioners at community health centers Physicians designed and administered an educational program consisting of developing indications for antibiotic treatment and reviewing regional resistance patterns. Physicians were encouraged to use rapid streptococcal assays when warranted. The percentage of patients receiving antibiotics decreased 23.7% (from 67.6% before the intervention to 43.9% after). In the control group, the prescribing rate decreased 0.4% (from 71.5% to 71.1%). The investigators did not report if this difference was statistically significant.
Zwar N, Family Practice, 1999 Australia All patients with respiratory infections Clinician education (distribution of materials, educational outreach, other), Audit and feedback Absolute effect size: -15.0%
General practitioner trainees in New South Wales The intervention consisted of a mailed packet of individualized feedback to providers, management guidelines, and patient handouts. Providers who exceeded thresholds for inappropriate prescriptions based on feedback data also received an academic detailing session, in person or over the telephone. The percentage of patients receiving antibiotics decreased 5.3% (from 25.0% before the intervention to 19.7% after). In the control group, the prescribing rate increased 9.7% (from 22.0% to 31.7%). This difference was statistically significant.
Angunawela I, International Journal of Epidemiology, 1991 [comparison 1] Sri Lanka All patients Clinician education (distribution of materials) Absolute effect size: -7.0%
General practitioners at rural primary care clinics The intervention consisted of newsletters mailed fortnightly to providers, which covered topics about treatment of common infections, encouraged use of penicillin, discouraged use of antibiotics in viral infections and tetracycline to children. The percentage of patients receiving antibiotics decreased 7.4% (from 31.5% before the intervention to 24.1% after). In the control group, the prescribing rate decreased 0.4% (from 32.2% to 31.8%). This difference was not statistically significant.
Angunawela I, International Journal of Epidemiology, 1991 [comparison 2] Sri Lanka All patients Clinician education (distribution of materials, educational meetings) Absolute effect size: -6.9%
General practitioners at rural primary care clinics In addition to the newsletters described above, providers participated in a seminar conducted by two clinical pharmacologists, one microbiologist, and one general physician. The seminar reinforced the information in the newsletter. The percentage of patients receiving antibiotics decreased 7.3% (from 38.8% before the intervention to 31.5% after). In the control group, the prescribing rate decreased 0.4% (from 32.2% to 31.8%). This difference was not statistically significant.
Arroll B, Journal of Family Practice, 2002 New Zealand All patients with common cold Delayed prescriptions In the intervention group, 48% of patients used antibiotics; in the comparison group, 89% of patients used them. This difference was statistically significant.
General practitioners Patients with the common cold who requested antibiotics were given a prescription with instructions to fill it only if their symptoms did not improve after 3 days. The comparison group was given antibiotics immediately.
Bexell A, Journal of Clinical Epidemiology, 1996 Zambia All patients with diarrhea and respiratory infections Clinician education (educational meetings) Absolute effect size: -8.1%
General practices in The intervention consisted of three 2-day seminars for providers on rational drug prescribing. Educational content consisted of standardized guidelines for managing “common conditions seen in primary care.” Seminars were led by pharmacists, clinical officers, medical officers, and a nurse. Specific diseases discussed included diarrheal diseases and acute respiratory infections. The percentage of patients receiving antibiotics decreased 7.0% (from 41.2% before the intervention to 34.2% after). In the control group, the prescribing rate increased 1.1% (from 41.0% to 42.1%). This difference was statistically significant.
Flottorp S, BMJ, 2002 Norway All patients with sore throat Patient education (distribution of materials, other), Clinician education (distribution of materials, other), Clinician Reminders, Organizational change, Regulatory changes for providers, Financial or regulatory incentives for patients Absolute effect size: -3.0%
142 General practices The investigators conducted a multifaceted intervention to improve management of sore throat. Providers received guidelines on sore throat management, in electronic and poster format. Computer based decision support, reminders, and interactive courses were offered to providers. Patients received electronic and paper-based educational materials. Patients had to pay an increased fee for a telephone consult (but not for office visit.) Only practices using an electronic medical records system were eligible. The percentage of patients receiving antibiotics decreased 4.3% (from 48.1% before the intervention to 43.8% after). In the control group, the prescribing rate decreased 1.3% (from 50.8% to 49.5%). This difference was statistically significant.
Gutierrez G, Medical Care, 1994 Mexico All patients with diarrhea Clinician education (distribution of materials, educational workshops, consensus building session), Audit and feedback After the intervention, the prescribing rate in the intervention group was 20.2%, compared to 35.4% before the intervention. Corresponding comparison group values were not provided.
General practitioners at health care clinics of the Mexican Social Security Institute Physicians received an educational workshop on treatment of acute diarrhea for physicians. They received literature and had group discussions to develop a treatment algorithm and discuss management of simulated cases. Five months after the workshops, physicians' practice habits were audited and reviewed by a committee including study physicians.
McIsaac WJ, Journal of Family Practice, 2002 Canada All patients with sore throat Clinician reminder The prescribing rate in the intervention group was 28.1%, compared to 27.9% in the comparison group. This difference was not statistically significant.
Family physicians in Ontario Physicians received a sample encounter form for patients with sore throat, which explicitly described a scoring system (to help guide antibiotic prescribing) and provided management recommendations. The form also had space to record the score. The control group did not receive the sticker, and the encounter form did not have the prompt to record the score.
Meyer JC, Medical Education, 2001 South Africa All patients with diarrhea Clinician education (educational workshops) Absolute effect size: -28.6%
Nurses at primary health clinics Nurses in primary health care centers received training focused on teaching rational drug prescribing, conducted during a 4-day workshop. A World Health Organization manual was used as the framework for the training course. The target was reducing antibiotic prescribing for ARIs. The percentage of patients receiving antibiotics decreased 36.9% (from 66.3% before the intervention to 29.4% after). In the control group, the prescribing rate decreased 8.3% (from 53.9% to 45.6%). This difference was statistically significant.
O'Connell DL, BMJ, 1999 Australia All patients Clinician education (distribution of materials), Audit and feedback In the intervention group, median antibiotic prescribing rates changed from 10.7 prescriptions per 100 patients before the intervention to 10.5 prescriptions per 100 patients after the intervention. Corresponding comparison group values were 10.7 prescriptions per 100 patients before the intervention and 10.1 after the intervention. This difference was not statistically significant.
General practitioners in rural area Physicians received a graphical display of their level of prescribing of five different drug groups (including oral antibiotics) over the past eight quarters. These data were provided as graphs displaying the individual physician's prescribing in comparison to all physicians. This intervention was repeated twice, six months apart. The first intervention was accompanied by a general prescribing educational letter. The second was accompanied by a letter with specific antibiotic prescribing information.
Welschen I, BMJ, 2004 The Netherlands All patients with respiratory infections Patient education (distribution of materials), Clinician education (distribution of materials, educational meetings, educational workshops, consensus building sessions), Audit and feedback Absolute effect size: -12.0%
General practitioners in Utrecht Physicians attended a group educational meeting, at which feedback data on antibiotic prescribing was provided, evidence on the effectiveness of antibiotic for upper respiratory infections was presented, and used to develop consensus on indications for antibiotic use and choice. These were formalized into guidelines that were mailed to participations. Six months later physicians received repeat feedback on their prescribing. Physician assistants and pharmacists also received a 2 hour session on antibiotic prescribing guidelines. Physicians, assistants, and pharmacists also received communication skills training. Patient education materials, consisting of brochures and posters, were provided in offices, pharmacies, and municipal health services. The percentage of patients receiving antibiotics decreased 4.0% (from 27.0% before the intervention to 23.0% after). In the control group, the prescribing rate increased 8.0% (from 29.0% to 37.0%).
*

The measured population refers to the patient population in which prescribing data was measured. This population is the group to which the study results are most generalizable.

**

The Absolute effect size is provided for studies that were used in the median effects analysis. These studies reported data as the percentage of visits at which patients received an antibiotic prescription. The individual study Absolute effect size was calculated as: [(Intervention) post - (Intervention) pre ] - [(Control) post - (Control) pre ]. A negative effect size means an overall reduction in the rate of antibiotic prescribing. The % sign refers to the percent of patients with a particular diagnosis.

From: Appendix B, Summaries of Included Studies, Grouped by Setting and Measured Population

Cover of Closing the Quality Gap: A Critical Analysis of Quality Improvement Strategies (Vol. 4: Antibiotic Prescribing Behavior)
Closing the Quality Gap: A Critical Analysis of Quality Improvement Strategies (Vol. 4: Antibiotic Prescribing Behavior).
Technical Reviews, No. 9.4.
Ranji SR, Steinman MA, Shojania KG, et al.

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