Long-term effect of a practice-based intervention (HAPPY AUDIT) aimed at reducing antibiotic prescribing in patients with respiratory tract infections

Long-term effect of a practice-based intervention (HAPPY AUDIT) aimed at reducing antibiotic... Abstract Objectives Few studies have evaluated the long-term effects of educational interventions on antibiotic prescription and the results are controversial. This study was aimed at assessing the effect of a multifaceted practice-based intervention carried out 6 years earlier on current antibiotic prescription for respiratory tract infections (RTIs). Methods The 210 general practitioners (GPs) who completed the first two registrations in 2008 and 2009 were invited to participate in a third registration. The intervention held before the second registration consisted of discussion about the first registration of results, appropriate use of antibiotics for RTIs, patient brochures, a workshop and the provision of rapid tests. As in the previous registrations, GPs were instructed to complete a template for all the patients with RTIs during 15 working days in 2015. A new group of GPs from the same areas was also invited to participate and acted as controls. A multilevel logistic regression analysis was performed considering the prescription of antibiotics as the dependent variable. Results A total of 121 GPs included in the 2009 intervention (57.6%) and 117 control GPs registered 22 247 RTIs. On adjustment for covariables, compared with the antibiotic prescription observed just after the intervention, GPs assigned to intervention prescribed slightly more antibiotics 6 years later albeit without statistically significant differences (OR 1.08, 95% CI 0.89–1.31, P = 0.46), while GPs in the control group prescribed significantly more antibiotics (OR 2.74, 95% CI 2.09–3.59, P < 0.001). Conclusions This study shows that a single multifaceted intervention continues to reduce antibiotic prescribing 6 years later. Introduction Overuse of antibiotics has contributed to the development of antimicrobial resistance.1 As most antibiotics are prescribed in primary care and many of these prescriptions for mainly respiratory tract infections (RTIs) are of questionable value, reducing inappropriate prescribing in this setting is paramount.2–4 Spain is one of the EU countries with the highest rates of antibiotic prescribing, with a slight increase having been observed over recent years.5,6 According to the Agencia Española del Medicamento y Productos Sanitarios, the overall antibiotic consumption in 2016 was slightly over 33 defined daily doses per 1000 inhabitants per day, of which one-third corresponded to non-reimbursed sales.6 This finding is also supported by the results of the latest Eurobarometer on antibiotic use carried out in 2016, in which 47% of the Spanish respondents admitted having taken an antibiotic in the previous year.7 Several strategies have been developed to reduce unnecessary antibiotic prescribing in RTIs in the community with little success.8,9 A systematic Cochrane review, which included 39 studies of outpatient antibiotic prescriptions for several infectious conditions, found that printed educational materials for general practitioners (GPs), audits and feedback alone resulted in little or no change in prescription practices.8 A more recent review, including 58 studies, found similar results, but in general, interventions based on multiple initiatives have been found to be more effective than those focused on only one initiative.9 However, most studies included in these reviews assessed the short-term effect of interventions, and few studies have evaluated the long-term effect of a single intervention, and these have also shown controversial results.10–14 The HAPPY AUDIT project was a study financed by the European Commission aimed at strengthening the surveillance of RTIs through the development of intervention programmes targeting GPs and changing people’s habits towards prudent use of antimicrobial agents.15 The results of this study demonstrated a 50% reduction of antibiotic prescription 1–3 months after the intervention.16 This follow-up study aimed to examine if there continued to be a reduction in antibiotic prescribing in the intervention group of the original study 6 years later. Methods Ethics approval Ethics approval was granted by the Institut d’Investigació en Atenció Primària Jordi Gol i Gurina, Barcelona, reference number 14/106. Study design GPs who had participated in a before-and-after audit-based study in 2008 and 2009 in eight different autonomous regions in Spain were invited to participate in a new registration study in 2015. Patient registration took place during 3 week periods in the winter months—January to February—in 2008 (first registration), 2009 (second registration) and from January to March in 2015 (third registration) covering a total of 15 working days in each of these registrations. Shortly after the first registration, the GPs were invited to follow-up meetings where they received individual prescriber feedback and identified potential quality problems from the first registration. These results were discussed at 2 h follow-up meetings in each of the different areas and were run by the local co-ordinators of the study. One to three months before the second registration (November and December 2008) the participating GPs received the following: (i) a training course on the appropriate use of antibiotics for RTIs; (ii) clinical guidelines with recommendations for diagnosis and treatment of RTIs; (iii) brochures and handouts to patients about prudent use of antibiotics; (iv) posters for waiting rooms, focusing on the appropriate use of antibiotics; (v) access to point-of-care tests (POCTs)—rapid antigen detection tests (RADTs) and C-reactive protein rapid testing (CRP); and (vi) training in the use and interpretation of POCTs. This intervention was done during two different 2 h meetings with all the GPs in each of these areas, led by the local co-ordinators. GPs were then advised to use a POCT in cases of doubt and not as a stand-alone test: RADT only in patients with suspected streptococcal pharyngitis (two or more Centor criteria) and CRP in patients with lower RTI with uncertain aetiology. They were also instructed to withhold antibiotic therapy for CRP values <20 mg/L and to prescribe an antibiotic for values >100 mg/L. As the availability of rapid tests is scarce in Spain, we again provided these POCTs to the consultation offices of the GPs allocated to the intervention group in 2015. The tests provided were the Clearview Strep A Exact II Dipstick, which takes ∼5 min to obtain a result, and the Alere Afinion CRP, for which a result is available in <4 min. The co-ordinators in each area explained how to perform the procedures with these devices, but they did not give any further explanation on when to perform and how to interpret the results of these rapid tests in the third registration. Neither did they give any other information about guidelines and appropriate utilization of antibiotics to avoid any further intervention. A new group of GPs from the same regions who had never participated in courses on the rational use of antibiotics with comparable age, gender, type of job and number of years working to the GPs assigned to intervention were also invited to participate by the local co-ordinators and acted as controls. Measurements and data The GPs were requested to register adults with RTIs by means of a specific template providing relevant information about the infectious disease. On this sheet, the physician attending the patient noted different specific parameters of medical care, including the age and gender of the patient, the number of days with symptoms, presenting symptoms and signs, rapid tests used along with their results, performance of chest radiography, main diagnosis, antibiotic treatment or not, whether the patient requested an antibiotic, and referral to another healthcare setting. Three new variables were added to the template used in 2015: infection severity on a five-item scale, pulse oximetry and significant comorbidities. Only first-time contacts for the current disease were registered. Statistical analyses The data were analysed with the Stata v0.13 statistical program. Data analysed in a hierarchical multilevel logistic regression model were estimated at two levels: contacts with RTIs and GPs. Antibiotic prescription was considered as the dependent variable (yes/no). The random variation at level 2 (physicians) was accounted for with random intercepts (systematic differences among physicians in the propensity to prescribe) and a random slope for the dummy of the intervention group in 2015, which was assumed to have a non-zero correlation with the random intercept. The model was also adjusted for the covariables of age and gender, number of days with symptoms, symptoms and signs presented, diagnosis and patient demand for antibiotics. The goodness of fit was assessed using the Wald test of the model, with the deviance test to compare alternative models. Statistical significance was considered with P < 0.05. Results A total of 123 GPs of the 210 GPs who had participated in the first and second registrations in 2008 and 2009 agreed to participate in the third registration; however, one did not send the templates and another was rejected due to confirmed fraudulent data completion. No statistical differences were observed in terms of age, gender, years working and previous antibiotic prescribing rate between those who completed the third registration and those who discontinued. Valid data were obtained from 121 GPs (57.6% of all the GPs who underwent the intervention in 2008). The control group consisted of 117 new GPs who never had been exposed to interventions on antibiotic prescribing. Figure 1 shows the general scheme of the study. Figure 1. View largeDownload slide General scheme of the study. Figure 1. View largeDownload slide General scheme of the study. GPs assigned to the intervention group were slightly older than those allocated to the control group were (mean age of 50.6 years versus 48.9 years, P = 0.04) and there were slightly more men in the former group (57.8% versus 42.7%, P = 0.21). No statistically significant differences were observed in the number of years of professional activity between the two GP groups (21.4 versus 18.9 years, respectively, P = 0.06). The 238 GPs included a total of 22 247 patients with RTIs, with a mean age of 47.5 years (SD 20.3), and 59.8% were female. The infection most frequently registered was the common cold (9136 cases; 41.1%), followed by acute pharyngitis (4347 cases; 19.5%) and acute bronchitis (3172 cases; 14.3%). As shown in Table 1, the utilization of POCTs was significantly higher among physicians assigned to intervention in 2009 and 2015, while GPs in the control group used the pulse oximetry significantly more frequently than their counterparts (25.5% versus 17.3%, respectively). Table 1. Baseline characteristics of the contacts with RTIs according to the group of physicians Variable Intervention group in 2008, before the intervention (121 GPs; 6089 RTIs) Intervention group in 2009, just after the intervention (121 GPs; 5199 RTIs) Intervention group in 2015, 6 years after the intervention (121 GPs; 5381 RTIs) Control group, 2015 (117 GPs; 5578 RTIs) Demographics and characteristics of the RTI  age (years), mean (SD) 46.5 (19.7) 46.0 (20.4) 48.9 (20.4) 48.6 (20.5)  female, n (%) 3601 (59.1) 3081 (59.3) 3228 (60.0) 3383 (60.6)  prior duration of symptoms (days), mean (SD) 4.3 (4.5) 4.5 (4.6) 4.7 (5.2) 4.7 (5.1)  severity of the infection (score), mean (SD) NC NC 1.4 (0.7) 1.4 (0.6)  significant comorbidities, n (%) NC NC 739 (13.7) 970 (17.4) Symptoms and signs, n (%)  fever 1914 (31.4) 1610 (31.0) 1462 (27.2) 1554 (27.9)  cough 4779 (78.5) 3958 (76.1) 4290 (79.7) 4429 (79.4)  purulent ear discharge 91 (1.5) 78 (1.5) 93 (1.7) 114 (2.0)  odynophagia 2623 (43.1) 2376 (45.7) 2317 (43.1) 2326 (41.7)  tonsillar exudate 265 (4.4) 314 (6.0) 246 (4.6) 185 (3.3)  tender cervical nodes 321 (5.3) 420 (8.1) 328 (6.1) 188 (3.4)  dyspnoea 508 (8.3) 455 (8.8) 542 (10.1) 655 (11.7)  increase in sputum 1135 (18.6) 1011 (19.4) 1076 (20.0) 1037 (18.6)  purulence of sputum 618 (10.1) 431 (8.3) 519 (9.6) 565 (10.1) Tests performed/ordered, n (%)  RADTs 52 (0.9) 865 (16.6) 663 (12.3) 90 (1.6)  CRP 2 (0.0) 597 (11.5) 565 (10.5) 15 (0.3)  pulse oximetry NC NC 930 (17.3) 1421 (25.5)  chest X-ray 140 (2.3) 147 (2.8) 118 (2.2) 142 (2.5) Diagnosis, n (%)  common cold 2417 (39.7) 2031 (39.1) 2356 (43.8) 2332 (41.8)  acute otitis media 124 (2.0) 91 (1.8) 127 (2.4) 167 (3.0)  acute sinusitis 160 (2.6) 172 (3.3) 183 (3.4) 185 (3.3)  acute pharyngitis 1231 (20.2) 1210 (23.3) 953 (17.7) 953 (17.1)  acute bronchitis 721 (11.8) 593 (11.4) 859 (16.0) 999 (17.9)  pneumonia 75 (1.2) 71 (1.4) 54 (1.0) 58 (1.0)  acute exacerbations of CB/COPD 271 (4.5) 195 (3.8) 204 (3.8) 233 (4.2)  influenza 658 (10.8) 420 (8.1) 511 (9.5) 517 (9.3)  other RTIs 321 (5.3) 332 (6.4) 134 (2.5) 134 (2.4) Management of the infection  antibiotic prescribed 1545 (25.4) 872 (16.8) 1201 (22.3) 1707 (30.6)  patient demands antibiotics 110 (1.8) 78 (1.5) 115 (2.1) 93 (1.7)  referral of the patient to hospital 33 (0.5) 30 (0.3) 38 (0.7) 57 (1.0) Variable Intervention group in 2008, before the intervention (121 GPs; 6089 RTIs) Intervention group in 2009, just after the intervention (121 GPs; 5199 RTIs) Intervention group in 2015, 6 years after the intervention (121 GPs; 5381 RTIs) Control group, 2015 (117 GPs; 5578 RTIs) Demographics and characteristics of the RTI  age (years), mean (SD) 46.5 (19.7) 46.0 (20.4) 48.9 (20.4) 48.6 (20.5)  female, n (%) 3601 (59.1) 3081 (59.3) 3228 (60.0) 3383 (60.6)  prior duration of symptoms (days), mean (SD) 4.3 (4.5) 4.5 (4.6) 4.7 (5.2) 4.7 (5.1)  severity of the infection (score), mean (SD) NC NC 1.4 (0.7) 1.4 (0.6)  significant comorbidities, n (%) NC NC 739 (13.7) 970 (17.4) Symptoms and signs, n (%)  fever 1914 (31.4) 1610 (31.0) 1462 (27.2) 1554 (27.9)  cough 4779 (78.5) 3958 (76.1) 4290 (79.7) 4429 (79.4)  purulent ear discharge 91 (1.5) 78 (1.5) 93 (1.7) 114 (2.0)  odynophagia 2623 (43.1) 2376 (45.7) 2317 (43.1) 2326 (41.7)  tonsillar exudate 265 (4.4) 314 (6.0) 246 (4.6) 185 (3.3)  tender cervical nodes 321 (5.3) 420 (8.1) 328 (6.1) 188 (3.4)  dyspnoea 508 (8.3) 455 (8.8) 542 (10.1) 655 (11.7)  increase in sputum 1135 (18.6) 1011 (19.4) 1076 (20.0) 1037 (18.6)  purulence of sputum 618 (10.1) 431 (8.3) 519 (9.6) 565 (10.1) Tests performed/ordered, n (%)  RADTs 52 (0.9) 865 (16.6) 663 (12.3) 90 (1.6)  CRP 2 (0.0) 597 (11.5) 565 (10.5) 15 (0.3)  pulse oximetry NC NC 930 (17.3) 1421 (25.5)  chest X-ray 140 (2.3) 147 (2.8) 118 (2.2) 142 (2.5) Diagnosis, n (%)  common cold 2417 (39.7) 2031 (39.1) 2356 (43.8) 2332 (41.8)  acute otitis media 124 (2.0) 91 (1.8) 127 (2.4) 167 (3.0)  acute sinusitis 160 (2.6) 172 (3.3) 183 (3.4) 185 (3.3)  acute pharyngitis 1231 (20.2) 1210 (23.3) 953 (17.7) 953 (17.1)  acute bronchitis 721 (11.8) 593 (11.4) 859 (16.0) 999 (17.9)  pneumonia 75 (1.2) 71 (1.4) 54 (1.0) 58 (1.0)  acute exacerbations of CB/COPD 271 (4.5) 195 (3.8) 204 (3.8) 233 (4.2)  influenza 658 (10.8) 420 (8.1) 511 (9.5) 517 (9.3)  other RTIs 321 (5.3) 332 (6.4) 134 (2.5) 134 (2.4) Management of the infection  antibiotic prescribed 1545 (25.4) 872 (16.8) 1201 (22.3) 1707 (30.6)  patient demands antibiotics 110 (1.8) 78 (1.5) 115 (2.1) 93 (1.7)  referral of the patient to hospital 33 (0.5) 30 (0.3) 38 (0.7) 57 (1.0) CB, chronic bronchitis; NC, not collected. Table 1. Baseline characteristics of the contacts with RTIs according to the group of physicians Variable Intervention group in 2008, before the intervention (121 GPs; 6089 RTIs) Intervention group in 2009, just after the intervention (121 GPs; 5199 RTIs) Intervention group in 2015, 6 years after the intervention (121 GPs; 5381 RTIs) Control group, 2015 (117 GPs; 5578 RTIs) Demographics and characteristics of the RTI  age (years), mean (SD) 46.5 (19.7) 46.0 (20.4) 48.9 (20.4) 48.6 (20.5)  female, n (%) 3601 (59.1) 3081 (59.3) 3228 (60.0) 3383 (60.6)  prior duration of symptoms (days), mean (SD) 4.3 (4.5) 4.5 (4.6) 4.7 (5.2) 4.7 (5.1)  severity of the infection (score), mean (SD) NC NC 1.4 (0.7) 1.4 (0.6)  significant comorbidities, n (%) NC NC 739 (13.7) 970 (17.4) Symptoms and signs, n (%)  fever 1914 (31.4) 1610 (31.0) 1462 (27.2) 1554 (27.9)  cough 4779 (78.5) 3958 (76.1) 4290 (79.7) 4429 (79.4)  purulent ear discharge 91 (1.5) 78 (1.5) 93 (1.7) 114 (2.0)  odynophagia 2623 (43.1) 2376 (45.7) 2317 (43.1) 2326 (41.7)  tonsillar exudate 265 (4.4) 314 (6.0) 246 (4.6) 185 (3.3)  tender cervical nodes 321 (5.3) 420 (8.1) 328 (6.1) 188 (3.4)  dyspnoea 508 (8.3) 455 (8.8) 542 (10.1) 655 (11.7)  increase in sputum 1135 (18.6) 1011 (19.4) 1076 (20.0) 1037 (18.6)  purulence of sputum 618 (10.1) 431 (8.3) 519 (9.6) 565 (10.1) Tests performed/ordered, n (%)  RADTs 52 (0.9) 865 (16.6) 663 (12.3) 90 (1.6)  CRP 2 (0.0) 597 (11.5) 565 (10.5) 15 (0.3)  pulse oximetry NC NC 930 (17.3) 1421 (25.5)  chest X-ray 140 (2.3) 147 (2.8) 118 (2.2) 142 (2.5) Diagnosis, n (%)  common cold 2417 (39.7) 2031 (39.1) 2356 (43.8) 2332 (41.8)  acute otitis media 124 (2.0) 91 (1.8) 127 (2.4) 167 (3.0)  acute sinusitis 160 (2.6) 172 (3.3) 183 (3.4) 185 (3.3)  acute pharyngitis 1231 (20.2) 1210 (23.3) 953 (17.7) 953 (17.1)  acute bronchitis 721 (11.8) 593 (11.4) 859 (16.0) 999 (17.9)  pneumonia 75 (1.2) 71 (1.4) 54 (1.0) 58 (1.0)  acute exacerbations of CB/COPD 271 (4.5) 195 (3.8) 204 (3.8) 233 (4.2)  influenza 658 (10.8) 420 (8.1) 511 (9.5) 517 (9.3)  other RTIs 321 (5.3) 332 (6.4) 134 (2.5) 134 (2.4) Management of the infection  antibiotic prescribed 1545 (25.4) 872 (16.8) 1201 (22.3) 1707 (30.6)  patient demands antibiotics 110 (1.8) 78 (1.5) 115 (2.1) 93 (1.7)  referral of the patient to hospital 33 (0.5) 30 (0.3) 38 (0.7) 57 (1.0) Variable Intervention group in 2008, before the intervention (121 GPs; 6089 RTIs) Intervention group in 2009, just after the intervention (121 GPs; 5199 RTIs) Intervention group in 2015, 6 years after the intervention (121 GPs; 5381 RTIs) Control group, 2015 (117 GPs; 5578 RTIs) Demographics and characteristics of the RTI  age (years), mean (SD) 46.5 (19.7) 46.0 (20.4) 48.9 (20.4) 48.6 (20.5)  female, n (%) 3601 (59.1) 3081 (59.3) 3228 (60.0) 3383 (60.6)  prior duration of symptoms (days), mean (SD) 4.3 (4.5) 4.5 (4.6) 4.7 (5.2) 4.7 (5.1)  severity of the infection (score), mean (SD) NC NC 1.4 (0.7) 1.4 (0.6)  significant comorbidities, n (%) NC NC 739 (13.7) 970 (17.4) Symptoms and signs, n (%)  fever 1914 (31.4) 1610 (31.0) 1462 (27.2) 1554 (27.9)  cough 4779 (78.5) 3958 (76.1) 4290 (79.7) 4429 (79.4)  purulent ear discharge 91 (1.5) 78 (1.5) 93 (1.7) 114 (2.0)  odynophagia 2623 (43.1) 2376 (45.7) 2317 (43.1) 2326 (41.7)  tonsillar exudate 265 (4.4) 314 (6.0) 246 (4.6) 185 (3.3)  tender cervical nodes 321 (5.3) 420 (8.1) 328 (6.1) 188 (3.4)  dyspnoea 508 (8.3) 455 (8.8) 542 (10.1) 655 (11.7)  increase in sputum 1135 (18.6) 1011 (19.4) 1076 (20.0) 1037 (18.6)  purulence of sputum 618 (10.1) 431 (8.3) 519 (9.6) 565 (10.1) Tests performed/ordered, n (%)  RADTs 52 (0.9) 865 (16.6) 663 (12.3) 90 (1.6)  CRP 2 (0.0) 597 (11.5) 565 (10.5) 15 (0.3)  pulse oximetry NC NC 930 (17.3) 1421 (25.5)  chest X-ray 140 (2.3) 147 (2.8) 118 (2.2) 142 (2.5) Diagnosis, n (%)  common cold 2417 (39.7) 2031 (39.1) 2356 (43.8) 2332 (41.8)  acute otitis media 124 (2.0) 91 (1.8) 127 (2.4) 167 (3.0)  acute sinusitis 160 (2.6) 172 (3.3) 183 (3.4) 185 (3.3)  acute pharyngitis 1231 (20.2) 1210 (23.3) 953 (17.7) 953 (17.1)  acute bronchitis 721 (11.8) 593 (11.4) 859 (16.0) 999 (17.9)  pneumonia 75 (1.2) 71 (1.4) 54 (1.0) 58 (1.0)  acute exacerbations of CB/COPD 271 (4.5) 195 (3.8) 204 (3.8) 233 (4.2)  influenza 658 (10.8) 420 (8.1) 511 (9.5) 517 (9.3)  other RTIs 321 (5.3) 332 (6.4) 134 (2.5) 134 (2.4) Management of the infection  antibiotic prescribed 1545 (25.4) 872 (16.8) 1201 (22.3) 1707 (30.6)  patient demands antibiotics 110 (1.8) 78 (1.5) 115 (2.1) 93 (1.7)  referral of the patient to hospital 33 (0.5) 30 (0.3) 38 (0.7) 57 (1.0) CB, chronic bronchitis; NC, not collected. Antibiotics were given to 5325 patients (23.9%), but this percentage was significantly lower among the GPs assigned to intervention just after the intervention took place and was highest among the new GPs allocated to the control group (16.8% versus 30.6%), whereas the percentage of antibiotics prescribed by the GPs 6 years after the intervention was 22.3%. The highest antibiotic prescription was observed in pneumonia, acute otitis media and acute exacerbations of chronic bronchitis and COPD (Table 2). Table 2. Antibiotic prescription for the different RTIs according to the group of physicians Variable Intervention group in 2008, before the intervention (N = 6089) Intervention group in 2009, just after the intervention (N = 5199) Intervention group in 2015, 6 years after the intervention (N = 5381) Control group, 2015 (N = 5578) Common cold, n (%) 46 (1.9) 22 (1.1) 51 (2.2) 58 (2.5) Acute otitis media, n (%) 107 (86.3) 74 (81.3) 90 (70.9) 133 (79.6) Acute rhinosinusitis, n (%) 135 (84.4) 99 (57.6) 113 (61.7) 147 (79.5) Acute pharyngitis, n (%) 476 (38.7) 258 (21.3) 344 (36.1) 457 (48.0) Acute bronchitis, n (%) 396 (54.9) 174 (29.3) 358 (41.7) 628 (62.9) Pneumonia, n (%) 68 (90.7) 62 (87.3) 46 (85.2) 44 (75.9) Acute exacerbations of CB/COPD, n (%) 212 (78.2) 133 (68.2) 160 (78.4) 181 (77.7) Influenza, n (%) 20 (3.0) 1 (0.2) 18 (33.5) 24 (4.6) Other RTIs, n (%) 60 (18.7) 42 (12.7) 21 (15.7) 35 (26.1) Total, n (%) 1545 (25.4) 872 (16.8) 1201 (22.3) 1707 (30.6) Variable Intervention group in 2008, before the intervention (N = 6089) Intervention group in 2009, just after the intervention (N = 5199) Intervention group in 2015, 6 years after the intervention (N = 5381) Control group, 2015 (N = 5578) Common cold, n (%) 46 (1.9) 22 (1.1) 51 (2.2) 58 (2.5) Acute otitis media, n (%) 107 (86.3) 74 (81.3) 90 (70.9) 133 (79.6) Acute rhinosinusitis, n (%) 135 (84.4) 99 (57.6) 113 (61.7) 147 (79.5) Acute pharyngitis, n (%) 476 (38.7) 258 (21.3) 344 (36.1) 457 (48.0) Acute bronchitis, n (%) 396 (54.9) 174 (29.3) 358 (41.7) 628 (62.9) Pneumonia, n (%) 68 (90.7) 62 (87.3) 46 (85.2) 44 (75.9) Acute exacerbations of CB/COPD, n (%) 212 (78.2) 133 (68.2) 160 (78.4) 181 (77.7) Influenza, n (%) 20 (3.0) 1 (0.2) 18 (33.5) 24 (4.6) Other RTIs, n (%) 60 (18.7) 42 (12.7) 21 (15.7) 35 (26.1) Total, n (%) 1545 (25.4) 872 (16.8) 1201 (22.3) 1707 (30.6) CB, chronic bronchitis. Table 2. Antibiotic prescription for the different RTIs according to the group of physicians Variable Intervention group in 2008, before the intervention (N = 6089) Intervention group in 2009, just after the intervention (N = 5199) Intervention group in 2015, 6 years after the intervention (N = 5381) Control group, 2015 (N = 5578) Common cold, n (%) 46 (1.9) 22 (1.1) 51 (2.2) 58 (2.5) Acute otitis media, n (%) 107 (86.3) 74 (81.3) 90 (70.9) 133 (79.6) Acute rhinosinusitis, n (%) 135 (84.4) 99 (57.6) 113 (61.7) 147 (79.5) Acute pharyngitis, n (%) 476 (38.7) 258 (21.3) 344 (36.1) 457 (48.0) Acute bronchitis, n (%) 396 (54.9) 174 (29.3) 358 (41.7) 628 (62.9) Pneumonia, n (%) 68 (90.7) 62 (87.3) 46 (85.2) 44 (75.9) Acute exacerbations of CB/COPD, n (%) 212 (78.2) 133 (68.2) 160 (78.4) 181 (77.7) Influenza, n (%) 20 (3.0) 1 (0.2) 18 (33.5) 24 (4.6) Other RTIs, n (%) 60 (18.7) 42 (12.7) 21 (15.7) 35 (26.1) Total, n (%) 1545 (25.4) 872 (16.8) 1201 (22.3) 1707 (30.6) Variable Intervention group in 2008, before the intervention (N = 6089) Intervention group in 2009, just after the intervention (N = 5199) Intervention group in 2015, 6 years after the intervention (N = 5381) Control group, 2015 (N = 5578) Common cold, n (%) 46 (1.9) 22 (1.1) 51 (2.2) 58 (2.5) Acute otitis media, n (%) 107 (86.3) 74 (81.3) 90 (70.9) 133 (79.6) Acute rhinosinusitis, n (%) 135 (84.4) 99 (57.6) 113 (61.7) 147 (79.5) Acute pharyngitis, n (%) 476 (38.7) 258 (21.3) 344 (36.1) 457 (48.0) Acute bronchitis, n (%) 396 (54.9) 174 (29.3) 358 (41.7) 628 (62.9) Pneumonia, n (%) 68 (90.7) 62 (87.3) 46 (85.2) 44 (75.9) Acute exacerbations of CB/COPD, n (%) 212 (78.2) 133 (68.2) 160 (78.4) 181 (77.7) Influenza, n (%) 20 (3.0) 1 (0.2) 18 (33.5) 24 (4.6) Other RTIs, n (%) 60 (18.7) 42 (12.7) 21 (15.7) 35 (26.1) Total, n (%) 1545 (25.4) 872 (16.8) 1201 (22.3) 1707 (30.6) CB, chronic bronchitis. Data were analysed in a two-level logistic regression model with patients (n = 22 247) allocated to level 1 and GPs (n = 238) to level 2. The Wald test of the model was 912.1 (P < 0.001). Tonsillar exudate (OR 9.17) and sputum purulence (OR 6.23) were significantly associated with antibiotic prescribing. Conversely, cough (OR 0.73) was associated with low antibiotic prescribing (Table 3). On adjustment for covariables, compared with the antibiotic prescription observed just after the intervention, GPs assigned to the intervention group prescribed slightly more antibiotics in 2015, albeit without statistical significance (OR 1.08, 95% CI 0.89–1.31), while GPs allocated to the control group prescribed significantly more antibiotics (OR 2.74, 95% CI 2.09–3.59). Table 3. Effect of an intervention 6 years later; multivariable predictors of antibiotic prescription in RTIs Variable OR SE 95% CI P Age 1.01 0.00 1.01–1.01 <0.001 Female 0.92 0.46 0.83–1.01 0.08 Prior duration of symptoms 1.03 0.01 1.02–1.04 <0.001 Fever 3.83 0.23 3.41–4.30 <0.001 Cough 0.73 0.05 0.65–0.84 <0.001 Purulent ear discharge 1.76 0.36 1.18–2.62 0.01 Odynophagia 1.08 0.07 0.94–1.23 0.28 Tonsillar exudate 9.17 0.93 7.52–11.18 <0.001 Tender cervical nodes 2.83 0.28 2.34–3.42 <0.001 Dyspnoea 1.52 0.12 1.30–1.78 <0.001 Increase in sputum 2.02 0.14 1.77–2.31 <0.001 Purulence of sputum 6.23 0.49 5.35–7.27 <0.001 Common cold 0.09 0.02 0.05–0.15 <0.001 Acute otitis media 34.36 9.70 19.76–59.76 <0.001 Acute sinusitis 17.77 4.54 10.77–29.32 <0.001 Acute pharyngitis 1.72 0.41 1.07–2.75 0.03 Acute bronchitis 3.69 0.88 2.31–5.89 <0.001 Pneumonia 19.82 6.23 10.71–36.69 <0.001 Acute exacerbations of CB/COPD 8.49 2.18 5.12–14.05 <0.001 Influenza 0.06 0.02 0.03–0.11 <0.001 Other RTIs 1.06 0.27 0.64–1.75 0.82 Patient demands antibiotics 4.36 0.71 3.17–6.00 <0.001 Intervention group in 2015 1.08 0.11 0.89–1.31 0.46 Control group in 2015 2.74 0.38 2.09–3.59 <0.001 Variable OR SE 95% CI P Age 1.01 0.00 1.01–1.01 <0.001 Female 0.92 0.46 0.83–1.01 0.08 Prior duration of symptoms 1.03 0.01 1.02–1.04 <0.001 Fever 3.83 0.23 3.41–4.30 <0.001 Cough 0.73 0.05 0.65–0.84 <0.001 Purulent ear discharge 1.76 0.36 1.18–2.62 0.01 Odynophagia 1.08 0.07 0.94–1.23 0.28 Tonsillar exudate 9.17 0.93 7.52–11.18 <0.001 Tender cervical nodes 2.83 0.28 2.34–3.42 <0.001 Dyspnoea 1.52 0.12 1.30–1.78 <0.001 Increase in sputum 2.02 0.14 1.77–2.31 <0.001 Purulence of sputum 6.23 0.49 5.35–7.27 <0.001 Common cold 0.09 0.02 0.05–0.15 <0.001 Acute otitis media 34.36 9.70 19.76–59.76 <0.001 Acute sinusitis 17.77 4.54 10.77–29.32 <0.001 Acute pharyngitis 1.72 0.41 1.07–2.75 0.03 Acute bronchitis 3.69 0.88 2.31–5.89 <0.001 Pneumonia 19.82 6.23 10.71–36.69 <0.001 Acute exacerbations of CB/COPD 8.49 2.18 5.12–14.05 <0.001 Influenza 0.06 0.02 0.03–0.11 <0.001 Other RTIs 1.06 0.27 0.64–1.75 0.82 Patient demands antibiotics 4.36 0.71 3.17–6.00 <0.001 Intervention group in 2015 1.08 0.11 0.89–1.31 0.46 Control group in 2015 2.74 0.38 2.09–3.59 <0.001 CB, chronic bronchitis; SE, standard error. Table 3. Effect of an intervention 6 years later; multivariable predictors of antibiotic prescription in RTIs Variable OR SE 95% CI P Age 1.01 0.00 1.01–1.01 <0.001 Female 0.92 0.46 0.83–1.01 0.08 Prior duration of symptoms 1.03 0.01 1.02–1.04 <0.001 Fever 3.83 0.23 3.41–4.30 <0.001 Cough 0.73 0.05 0.65–0.84 <0.001 Purulent ear discharge 1.76 0.36 1.18–2.62 0.01 Odynophagia 1.08 0.07 0.94–1.23 0.28 Tonsillar exudate 9.17 0.93 7.52–11.18 <0.001 Tender cervical nodes 2.83 0.28 2.34–3.42 <0.001 Dyspnoea 1.52 0.12 1.30–1.78 <0.001 Increase in sputum 2.02 0.14 1.77–2.31 <0.001 Purulence of sputum 6.23 0.49 5.35–7.27 <0.001 Common cold 0.09 0.02 0.05–0.15 <0.001 Acute otitis media 34.36 9.70 19.76–59.76 <0.001 Acute sinusitis 17.77 4.54 10.77–29.32 <0.001 Acute pharyngitis 1.72 0.41 1.07–2.75 0.03 Acute bronchitis 3.69 0.88 2.31–5.89 <0.001 Pneumonia 19.82 6.23 10.71–36.69 <0.001 Acute exacerbations of CB/COPD 8.49 2.18 5.12–14.05 <0.001 Influenza 0.06 0.02 0.03–0.11 <0.001 Other RTIs 1.06 0.27 0.64–1.75 0.82 Patient demands antibiotics 4.36 0.71 3.17–6.00 <0.001 Intervention group in 2015 1.08 0.11 0.89–1.31 0.46 Control group in 2015 2.74 0.38 2.09–3.59 <0.001 Variable OR SE 95% CI P Age 1.01 0.00 1.01–1.01 <0.001 Female 0.92 0.46 0.83–1.01 0.08 Prior duration of symptoms 1.03 0.01 1.02–1.04 <0.001 Fever 3.83 0.23 3.41–4.30 <0.001 Cough 0.73 0.05 0.65–0.84 <0.001 Purulent ear discharge 1.76 0.36 1.18–2.62 0.01 Odynophagia 1.08 0.07 0.94–1.23 0.28 Tonsillar exudate 9.17 0.93 7.52–11.18 <0.001 Tender cervical nodes 2.83 0.28 2.34–3.42 <0.001 Dyspnoea 1.52 0.12 1.30–1.78 <0.001 Increase in sputum 2.02 0.14 1.77–2.31 <0.001 Purulence of sputum 6.23 0.49 5.35–7.27 <0.001 Common cold 0.09 0.02 0.05–0.15 <0.001 Acute otitis media 34.36 9.70 19.76–59.76 <0.001 Acute sinusitis 17.77 4.54 10.77–29.32 <0.001 Acute pharyngitis 1.72 0.41 1.07–2.75 0.03 Acute bronchitis 3.69 0.88 2.31–5.89 <0.001 Pneumonia 19.82 6.23 10.71–36.69 <0.001 Acute exacerbations of CB/COPD 8.49 2.18 5.12–14.05 <0.001 Influenza 0.06 0.02 0.03–0.11 <0.001 Other RTIs 1.06 0.27 0.64–1.75 0.82 Patient demands antibiotics 4.36 0.71 3.17–6.00 <0.001 Intervention group in 2015 1.08 0.11 0.89–1.31 0.46 Control group in 2015 2.74 0.38 2.09–3.59 <0.001 CB, chronic bronchitis; SE, standard error. Discussion To the best of our knowledge, this is the first study to report the longest effect of an intervention carried out in the community with the use of a control group. A single multifaceted intervention including feedback results of a previous registration, interactive seminars on RTIs, guideline discussion and workshop on rapid tests was associated with a slight increase in antibiotic prescribing 6 years later compared with antibiotic prescription observed just after the intervention, although no statistically significant differences were observed. Notwithstanding, GPs who had never participated in an intervention on the appropriate use of antibiotics and acted as the control group prescribed significantly more antibiotics. Strengths and limitations Our study has several limitations. As in other studies, in the present study, GPs participated voluntarily and probably their prescribing habits were not representative of all GPs and this may have limited the extrapolation of the results obtained. It is possible that the participating GPs were more prone to interventions aimed at behaviour change than their colleagues who did not participate.17 One of the striking results of this paper is the considerable difference in antibiotic prescribing observed in the GPs assigned to intervention before this took place and the control group recruited in 2015, which was 5.2% higher among the latter physicians. Although the GPs allocated to the intervention group could have been more motivated than their control counterparts, this phenomenon could also reflect the slight albeit steady increase in antibiotic consumption observed over recent years in Spain.5,6 It is a limitation that we did not register clinical outcomes or complications. However, some important variables not included in the first two registrations that might have influenced whether an antibiotic was prescribed or not such as significant comorbidities, severity of the infection according to GP judgement or the use of pulse oximetry were added to the 2015 template. For all patients included, GPs registered the first reason for encounter when a patient with suspected RTI was seen in their practice and the pattern of RTI infections was most probably equal for the different groups of patients. Other potential confounders not taken into account in our analysis, such as physician motivation and local campaigns to promote appropriate use of antibiotics, were probably evenly distributed between the groups. In all the groups of patients GPs used the same type of registration sheet and a potential influence of GP behaviour caused by the registration was most likely similar in the two groups of GPs.18 Two different nationwide campaigns regarding antibiotic use were launched in 2007 and 2008, but the results of these campaigns have never been studied. However, public campaigns on antibiotic awareness in other European countries have not been associated with significant reductions in antibiotic prescribing in primary care.19 GPs allocated to the control group had never participated in courses on the rational use of antibiotics, but we cannot rule out the possibility that some may have been particularly concerned about the problem of antimicrobial resistance. Despite the fact that POCTs are seldom used in primary care in Spain, we found that 1.6% of all the contacts with RTIs by GPs assigned to the control group used rapid tests, particularly RADTs. Another potential limitation is the Hawthorne effect, which may have introduced bias because GPs in both the intervention and the control group, but more importantly in the latter as they were not familiar with this audit-based registration, may have altered their prescription habits. To reduce this risk, GPs in the control group were specifically instructed to follow their usual care. Theoretically, the decision to treat should be taken after a diagnosis has been established. In general practice, however, the diagnostic procedures and the decision to treat are intricately intertwined. The GP may decide whether or not to prescribe an antibiotic at the same time, or even before. After making the decision to prescribe, the GP may thus then adjust the diagnosis to fit the decision about treatment. This may lead to a diagnostic misclassification bias. However, this potential bias might have affected the validity of the diagnosis both before and after the intervention and in both groups of GPs (intervention and control groups) and it is very unlikely to have influenced the effect of the intervention.15 The data corresponding to all the registrations completed in 2015 were entered by only one of the authors of this paper (A. M.), who is both a GP and a researcher. She raised concern of alleged fraudulent completion of some data by three GPs allocated to the intervention group on noticing a digit preference in some numerical variables.20 Owing to budget constraints we were unable to double-check the information contained in all the templates with the electronic records, but after checking the information provided by these three suspected cases one of these GPs was excluded from the final analysis due to confirmed fraud and all the data entered by this researcher in the three registration periods were rejected. Conversely, the suspicion of scientific misconduct observed in the other two cases was finally dismissed, as the information provided on the templates was veracious. Therefore, on concluding the investigation of possible data fraud and implementing the necessary actions to ensure data validity, we can confidently state that all the data entered in the study are valid and reliable. This was not a clinical trial, because GPs were not randomly assigned to the different groups. This might explain why the new GPs assigned to the control group were slightly younger than their counterparts, with more female doctors. However, the differences observed were not clinically relevant and we do not consider that this difference could have any effect on the results obtained. A total of 10 trainees who were included in the control group in one of the areas were finally excluded to make both groups of GPs more comparable. The greatest strength of this study was the large number of physicians included. In addition, >50% of the GPs who had participated in the first and second registrations and had participated in the intervention accepted to participate in this new registration 6 years later. Comparison with other studies Several randomized controlled trials conducted in primary care demonstrated a significant effect of various educational interventions on antibiotic prescriptions for RTIs over the subsequent year,21,22 but few studies aimed at assessing the long-term effect of interventions have been published. Indeed, studies assessing effects on antibiotic prescription in primary care after 3 years wrought conflicting results.10–14 In general, a reduction of the antibiotic prescribing rate is still observed in the long term as four of these studies found a decrease in the proportion of patients with RTIs who were prescribed antibiotics, but this mainly depends on the number and type of strategies used in the intervention.10–13 In a 3.5 year follow-up of a randomized controlled trial carried out in the Netherlands, an intervention that consisted of the provision of CRP in the consultations was associated with a 5% reduction of antibiotic prescribing for patients with acute cough, but the intervention was continuously delivered along the study period.12 In a French randomized clinical trial, a 2 day interactive educational intervention was associated with a significant reduction of antimicrobials prescribed 30 months after this intervention,23 and continued showing a lower antibiotic prescribing rate compared with the control group after 4.5 years of follow-up.13 In contrast, a 5 year Finnish study showed that guideline dissemination through local interactive discussion groups failed to decrease significantly the antibiotic prescriptions, but these results were not compared with a control group.14 Changing clinicians’ prescribing behaviour is a complex matter. Several strategies such as the provision of guidelines, poster display in the waiting rooms and even leaflets have limited effect. When active strategies are added to these passive educational sessions, such as the feedback and discussion of previous results, training in enhancing communication skills in the consultation and the provision of POCTs, the effect is much greater. The different active strategies used in the present study, which required the attendance to 2 h courses and workshops on three different days, might explain the continued reduction in antibiotic prescribing observed 6 years after the intervention. Conclusions To the best of our knowledge, no study has evaluated the effect of a single complex intervention more than 5 years later. However, in this observational prospective study, a single multifaceted intervention carried out 6 years earlier consisting of the discussion of the first registration results, a training course on appropriate use of antibiotics and clinical guidelines for RTIs, patients’ brochures, posters for waiting rooms, workshop on rapid tests and provision of these POCTs in the consultation, continued to reduce antibiotic prescription for RTIs. Acknowledgements We wish to acknowledge the GPs who voluntarily participated in the study. Other members of the HAPPY AUDIT 3 Study Team Andalucía: Idoioa Arrillaga Ocampo, Francisco Atienza Martín, Eduardo Ávila Amat, Marta Bernal Raya, Pablo Cabezas Saura, Pilar Carretero Castaño, Carmen Dastís Bendala, Irene V. de Tena Roger, Pedro Fernández-Nieto Fernández, Amalia Filella Sierpes, M. Isabel González Rodríguez, Antonio Hernández Alonso, Guillermo Largaespada Pallaviccini, Beatriz López Fernández, Inés M. López Huerta, Beatriz Luque López, Yanina Maldonado, M. Luisa Manzanares Torné, Leonor Marín Pérez, M. Mercedes Martínez Granero, Rocío Martínez Pérez, M. Antonia Máximo Torres, Ainhoa Mestraitua Vázquez, Mercedes Moreno Labrado, M. Luisa Moya Rodríguez, José Oropesa de Cáceres, Irene Padial Reyes, Antonio Paniagua Galisteo, Vanessa Parra García, M. Encarnación Peláez Gálvez, Juan J. Quero Perabá, M. Jesús Remesal Barrachina, Miguel Sagristá González, Consuelo Sampedro Abascal, Jesús C. Sánchez Vázquez, Auxiliadora Sanchís Osuna, J. Cristóbal Sendín González, Rosario Serrano Ortega, Miguel Silva Cueto, Guillermo Velázquez de Cisneros. Baleares: Ester Adelantado Pozuelo, Daniel Bestard Marín, Aberlado Corrales Nadal, M. Teresa Corredor Ibáñez, Esther Domínguez Padilla, Alberto Eek Comas, Margarita Fornés Homar, Maria E. Garau Miquel, Prado García Servera, Salvador J. Gestoso Gaya, María J. González-Bals González, Mercedes Gutiérrez García, Antoni J. Jover Palmer, Magdalena Llinàs Suau, Marian Llorente Sanmartín, Blanca Martínez Andión, Adriano Mayrata Vicens, David Medina i Bombardó, Gabriel Moragues Sbert, Joana M. Oliver Gornals, Etel Oliver Roset, J. Francisco Palmer Simó, Juana Pérez Galmés, Susana Pons Vives, Lourdes Quintana Torres, José Alfonso Ramón Bauzá, F. Javier Rezola Gambón, Jaime Ripoll Sánchez, Miguel Román Rodríguez, Natalia Serrano Gomila, Magdalena Servera Trias, Isabel M. Socias Buades, M. Mar Sureda Barbosa, Joana Tortella Morro, Lucia Ugarriza Hierro, Silvia Vega García. Canarias: Pilar Aguilar Utrilla, M. Carmen Artiles Ruano, M. Isabel Cardenes Romero, Jonás de la Cruz Cabrera, Margarita García García, M. Carmen Guerra, Ricardo Koch, M. Huertas Llamas Martínez, M. Elena Martín Santana, Alicia Monzón Guerra, Marta Moreno Ramos, Caridad Sánchez Artiles, Lucía Tejera Pulido, José M. Toscano, Carlos Prieto, Aurelia Perdomo. Galicia: Francisco Castrillo Villar, Pilar Cobas Pacín, M. Jesús Colas Martínez, Coral Díez Pérez, Peregrina Eiroa Patiño, Ana Fernández Álvarez, Luis Fuciños Cebreiro, J. Antonio Gómez Villalobos, M. Esther González García-Mayor, Ricardo M. Héctor Sanz, Susana Hernáiz Valero, Esther López Carbajales, J. Luis López Vilar, Elena Lorenzo Llauger, Elisa Mosquera Gayoso, Concepción Nogueiras Santas, M. Pilar Pintos Martínez, M. Teresa Ríos Rey, Lucía Rodríguez Nieto, Santiago Santidrián Arias, Jesús Sueiro Justel. Madrid: Raquel Baños Morras, José M. Casanova Colominas, Santiago Castellanos Redondo, M. Teresa Cobos Hinojal, José Corral Brihuega, M. Canto de Hoyos Alonso, Belén de la Fuente Martín, Silvia de las Heras Loa, Angélica Fajardo Alcántara, M. Jesús Ferrer Signes, Antonia García del Val, M. Mar García Rabanal, Gema García Sacristán, Álvaro García Vega, M. Elena Gerez Sánchez-Escribano, Paloma González Escobar, Rosa M. González San Segundo, M. Elena Hermida López, Paloma Hernández Almarza, Ana Ibarra Sánchez, Ángeles Lagos Aguilar, Ascensión Lázaro Damas, M. Eugenia López Delgado, Guillermina López Fernández, Rosario López Morell, M. José Lucena Martín, Jaime Marín Cañada, Rosa Martín de Cabo, Blanca Matilla Pardo, Teresa Mazarro Enrique, Cristina Moral Moraleda, Adela Moreno Mateos, Joaquín Morera Montes, Renata Muñoz Bieber, Javier Muñoz Gutiérrez, Alicia Muñoz Núñez, M. Arantzazu Murciano Antón, Patricia Navarro Gil, Lourdes Pulido Izquierdo, Carmen Rodríguez Fernández, Ana Rodríguez Nebreda, M. Elena Rodríguez Quiroga, M. Asunción Rosado López, Ana Ruíz Molina, Rocío Susana Ruiz Vargas, Irmina Saldaña Alonso, Mar Sánchez Martín, Laura Santos Larregola, Juana M. Torres Martínez, Gema Val Morales, Amalia Velázquez García, Lourdes Visedo Campillo, Antonio Yagüe Hernando. Rioja: Ascensión Aicua Sadia, M. Carmen Aurensanz Sánchez, Carmen Babace Isturiz, Diego Beni Ruiz, Nieves Calavia Rueda, M. Mar Díez Casado, M. Ángeles Espeso Fernández Valderrama, Francisco García Marín, Tomás García Martínez, Ana M. Gómez Ruiz, Elvira Moreno Hernández, Sabino Ornia Rodríguez, M. José Palomo Larrieta, Olga Revilla González, Rosa Ruiz De Austri Fuente, J. Luis Torres Baile, Antonio Trueba Castillo, Ana M. Vázquez Medrano. Asturias: Carmen Alonso Alonso, Fernando Álvarez Guisasola, Pablo Belderraín Belderraín, J. Carlos Bango Melcón, Teresa Díaz Mujica, Deopatria Azucena Esteban Fresno, Rocío Fernández Collar, Leonor Fuentes Martin, Alfonso García Viejo, Ramón Macía Pérez, Carmen Martín López, Ernesto Martínez Estrada, Herminia Menéndez Fernández, Covadonga Monte Llavona, M. Amor Paredes González, Cristina Pérez Canal, Javier Pérez Fernández, M. Mar Pizarro López, Rosa Rodríguez, J. Ignacio Rodríguez-Arias Palomo, Alicia Rodríguez Fernández, Felipe J. Rodríguez Gordaliza, Celia T. Tamargo García, Salvador Tranche Iparraguirre, M. Raimunda Vázquez Aira, Rubén Villa Estébanez. Valencia: Juan Alamar Provecho, M. Teresa Amorós Barber, Miguel Antón Sánchez, Manuel Batalla Sales, Lourdes Bermejo Mora, Núria Bosch Girona, M. Pilar Carceller Sales, Rosa Carrión Villanueva, Teresa Chirivella Raga, Manuela Domingo Orduña, Concepción García Domingo, Carmen Hernández Espinosa, Blanca Folch Marín, Carmen Gandía Moya, Amparo Haya Guaita, Eva M. Izquierdo Hidalgo, Engracia López González, Nuria Mallén Navarro, Pilar Marín Lluch, Amparo Meneu Ferrer, Helena Molina Raga, Adela Moreno Fernández, Ángeles Pérez Campos, Belén Persiva Saura, Gloria Rabanaque Mallén, Remei Raga Marí, Jazmín Ripoll Perelló, Pilar Roca Navarro, M. Luisa Tregón Moliner. Funding This study was funded by TRACE (Translational Research on Antimicrobial resistance and Community-acquired infections in Europe). The funding source had no role in study design, data collection, data analysis, data interpretation or writing the report. Transparency declarations C. L. and A. M. report receiving research grants from the European Commission (Sixth & Seventh Programme Frameworks and Horizon 2020), the Catalan Society of Family Medicine, Instituto de Salud Carlos III and Alere. All other authors: none to declare. Author contributions The initial idea for this study was proposed by C. L. and L. B.; all authors contributed to the development of the protocol and to the management of the study. A. M. entered all the data. C. L., L. B., A. M. and J. M. C. led the funding application and provided overall co-ordination of the TRANCE consortium. B. G. L.-V. analysed the data; all authors contributed to the interpretation of the data and the write-up. C. L., L. B., B. G. L.-V., A. M. and J. M. C. had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. References 1 Goossens H , Ferech M , Vander Stichele R et al. ; ESAC Project Group . 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Scand J Prim Health Care 1999 ; 17 : 185 – 90 . Google Scholar CrossRef Search ADS PubMed 19 Huttner B , Goossens H , Verheij T et al. Characteristics and outcomes of public campaigns aimed at improving the use of antibiotics in outpatients in high-income countries . Lancet Infect Dis 2010 ; 10 : 17 – 31 . Google Scholar CrossRef Search ADS PubMed 20 Al-Marzouki S , Evans S , Marshall T et al. Are these data real? Statistical methods for the detection of data fabrication in clinical trials . BMJ 2005 ; 331 : 267 – 70 . Google Scholar CrossRef Search ADS PubMed 21 Gjelstad S , Høye S , Straand J et al. Improving antibiotic prescribing in acute respiratory tract infections: cluster randomised trial from Norwegian general practice (prescription peer academic detailing (Rx-PAD) study) . BMJ 2013 ; 347 : f4403. Google Scholar CrossRef Search ADS PubMed 22 Butler CC , Simpson SA , Dunstan F et al. Effectiveness of multifaceted educational programme to reduce antibiotic dispensing in primary care: practice based randomised controlled trial . BMJ 2012 ; 344 : d8173. Google Scholar CrossRef Search ADS PubMed 23 Le Corvoisier P , Renard V , Roudot-Thoraval F et al. Long-term effects of an educational seminar on antibiotic prescribing by GPs: a randomised controlled trial . Br J Gen Pract 2013 ; 63 : e455 – 64 . Google Scholar CrossRef Search ADS PubMed © The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Antimicrobial Chemotherapy Oxford University Press

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© The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.
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Abstract

Abstract Objectives Few studies have evaluated the long-term effects of educational interventions on antibiotic prescription and the results are controversial. This study was aimed at assessing the effect of a multifaceted practice-based intervention carried out 6 years earlier on current antibiotic prescription for respiratory tract infections (RTIs). Methods The 210 general practitioners (GPs) who completed the first two registrations in 2008 and 2009 were invited to participate in a third registration. The intervention held before the second registration consisted of discussion about the first registration of results, appropriate use of antibiotics for RTIs, patient brochures, a workshop and the provision of rapid tests. As in the previous registrations, GPs were instructed to complete a template for all the patients with RTIs during 15 working days in 2015. A new group of GPs from the same areas was also invited to participate and acted as controls. A multilevel logistic regression analysis was performed considering the prescription of antibiotics as the dependent variable. Results A total of 121 GPs included in the 2009 intervention (57.6%) and 117 control GPs registered 22 247 RTIs. On adjustment for covariables, compared with the antibiotic prescription observed just after the intervention, GPs assigned to intervention prescribed slightly more antibiotics 6 years later albeit without statistically significant differences (OR 1.08, 95% CI 0.89–1.31, P = 0.46), while GPs in the control group prescribed significantly more antibiotics (OR 2.74, 95% CI 2.09–3.59, P < 0.001). Conclusions This study shows that a single multifaceted intervention continues to reduce antibiotic prescribing 6 years later. Introduction Overuse of antibiotics has contributed to the development of antimicrobial resistance.1 As most antibiotics are prescribed in primary care and many of these prescriptions for mainly respiratory tract infections (RTIs) are of questionable value, reducing inappropriate prescribing in this setting is paramount.2–4 Spain is one of the EU countries with the highest rates of antibiotic prescribing, with a slight increase having been observed over recent years.5,6 According to the Agencia Española del Medicamento y Productos Sanitarios, the overall antibiotic consumption in 2016 was slightly over 33 defined daily doses per 1000 inhabitants per day, of which one-third corresponded to non-reimbursed sales.6 This finding is also supported by the results of the latest Eurobarometer on antibiotic use carried out in 2016, in which 47% of the Spanish respondents admitted having taken an antibiotic in the previous year.7 Several strategies have been developed to reduce unnecessary antibiotic prescribing in RTIs in the community with little success.8,9 A systematic Cochrane review, which included 39 studies of outpatient antibiotic prescriptions for several infectious conditions, found that printed educational materials for general practitioners (GPs), audits and feedback alone resulted in little or no change in prescription practices.8 A more recent review, including 58 studies, found similar results, but in general, interventions based on multiple initiatives have been found to be more effective than those focused on only one initiative.9 However, most studies included in these reviews assessed the short-term effect of interventions, and few studies have evaluated the long-term effect of a single intervention, and these have also shown controversial results.10–14 The HAPPY AUDIT project was a study financed by the European Commission aimed at strengthening the surveillance of RTIs through the development of intervention programmes targeting GPs and changing people’s habits towards prudent use of antimicrobial agents.15 The results of this study demonstrated a 50% reduction of antibiotic prescription 1–3 months after the intervention.16 This follow-up study aimed to examine if there continued to be a reduction in antibiotic prescribing in the intervention group of the original study 6 years later. Methods Ethics approval Ethics approval was granted by the Institut d’Investigació en Atenció Primària Jordi Gol i Gurina, Barcelona, reference number 14/106. Study design GPs who had participated in a before-and-after audit-based study in 2008 and 2009 in eight different autonomous regions in Spain were invited to participate in a new registration study in 2015. Patient registration took place during 3 week periods in the winter months—January to February—in 2008 (first registration), 2009 (second registration) and from January to March in 2015 (third registration) covering a total of 15 working days in each of these registrations. Shortly after the first registration, the GPs were invited to follow-up meetings where they received individual prescriber feedback and identified potential quality problems from the first registration. These results were discussed at 2 h follow-up meetings in each of the different areas and were run by the local co-ordinators of the study. One to three months before the second registration (November and December 2008) the participating GPs received the following: (i) a training course on the appropriate use of antibiotics for RTIs; (ii) clinical guidelines with recommendations for diagnosis and treatment of RTIs; (iii) brochures and handouts to patients about prudent use of antibiotics; (iv) posters for waiting rooms, focusing on the appropriate use of antibiotics; (v) access to point-of-care tests (POCTs)—rapid antigen detection tests (RADTs) and C-reactive protein rapid testing (CRP); and (vi) training in the use and interpretation of POCTs. This intervention was done during two different 2 h meetings with all the GPs in each of these areas, led by the local co-ordinators. GPs were then advised to use a POCT in cases of doubt and not as a stand-alone test: RADT only in patients with suspected streptococcal pharyngitis (two or more Centor criteria) and CRP in patients with lower RTI with uncertain aetiology. They were also instructed to withhold antibiotic therapy for CRP values <20 mg/L and to prescribe an antibiotic for values >100 mg/L. As the availability of rapid tests is scarce in Spain, we again provided these POCTs to the consultation offices of the GPs allocated to the intervention group in 2015. The tests provided were the Clearview Strep A Exact II Dipstick, which takes ∼5 min to obtain a result, and the Alere Afinion CRP, for which a result is available in <4 min. The co-ordinators in each area explained how to perform the procedures with these devices, but they did not give any further explanation on when to perform and how to interpret the results of these rapid tests in the third registration. Neither did they give any other information about guidelines and appropriate utilization of antibiotics to avoid any further intervention. A new group of GPs from the same regions who had never participated in courses on the rational use of antibiotics with comparable age, gender, type of job and number of years working to the GPs assigned to intervention were also invited to participate by the local co-ordinators and acted as controls. Measurements and data The GPs were requested to register adults with RTIs by means of a specific template providing relevant information about the infectious disease. On this sheet, the physician attending the patient noted different specific parameters of medical care, including the age and gender of the patient, the number of days with symptoms, presenting symptoms and signs, rapid tests used along with their results, performance of chest radiography, main diagnosis, antibiotic treatment or not, whether the patient requested an antibiotic, and referral to another healthcare setting. Three new variables were added to the template used in 2015: infection severity on a five-item scale, pulse oximetry and significant comorbidities. Only first-time contacts for the current disease were registered. Statistical analyses The data were analysed with the Stata v0.13 statistical program. Data analysed in a hierarchical multilevel logistic regression model were estimated at two levels: contacts with RTIs and GPs. Antibiotic prescription was considered as the dependent variable (yes/no). The random variation at level 2 (physicians) was accounted for with random intercepts (systematic differences among physicians in the propensity to prescribe) and a random slope for the dummy of the intervention group in 2015, which was assumed to have a non-zero correlation with the random intercept. The model was also adjusted for the covariables of age and gender, number of days with symptoms, symptoms and signs presented, diagnosis and patient demand for antibiotics. The goodness of fit was assessed using the Wald test of the model, with the deviance test to compare alternative models. Statistical significance was considered with P < 0.05. Results A total of 123 GPs of the 210 GPs who had participated in the first and second registrations in 2008 and 2009 agreed to participate in the third registration; however, one did not send the templates and another was rejected due to confirmed fraudulent data completion. No statistical differences were observed in terms of age, gender, years working and previous antibiotic prescribing rate between those who completed the third registration and those who discontinued. Valid data were obtained from 121 GPs (57.6% of all the GPs who underwent the intervention in 2008). The control group consisted of 117 new GPs who never had been exposed to interventions on antibiotic prescribing. Figure 1 shows the general scheme of the study. Figure 1. View largeDownload slide General scheme of the study. Figure 1. View largeDownload slide General scheme of the study. GPs assigned to the intervention group were slightly older than those allocated to the control group were (mean age of 50.6 years versus 48.9 years, P = 0.04) and there were slightly more men in the former group (57.8% versus 42.7%, P = 0.21). No statistically significant differences were observed in the number of years of professional activity between the two GP groups (21.4 versus 18.9 years, respectively, P = 0.06). The 238 GPs included a total of 22 247 patients with RTIs, with a mean age of 47.5 years (SD 20.3), and 59.8% were female. The infection most frequently registered was the common cold (9136 cases; 41.1%), followed by acute pharyngitis (4347 cases; 19.5%) and acute bronchitis (3172 cases; 14.3%). As shown in Table 1, the utilization of POCTs was significantly higher among physicians assigned to intervention in 2009 and 2015, while GPs in the control group used the pulse oximetry significantly more frequently than their counterparts (25.5% versus 17.3%, respectively). Table 1. Baseline characteristics of the contacts with RTIs according to the group of physicians Variable Intervention group in 2008, before the intervention (121 GPs; 6089 RTIs) Intervention group in 2009, just after the intervention (121 GPs; 5199 RTIs) Intervention group in 2015, 6 years after the intervention (121 GPs; 5381 RTIs) Control group, 2015 (117 GPs; 5578 RTIs) Demographics and characteristics of the RTI  age (years), mean (SD) 46.5 (19.7) 46.0 (20.4) 48.9 (20.4) 48.6 (20.5)  female, n (%) 3601 (59.1) 3081 (59.3) 3228 (60.0) 3383 (60.6)  prior duration of symptoms (days), mean (SD) 4.3 (4.5) 4.5 (4.6) 4.7 (5.2) 4.7 (5.1)  severity of the infection (score), mean (SD) NC NC 1.4 (0.7) 1.4 (0.6)  significant comorbidities, n (%) NC NC 739 (13.7) 970 (17.4) Symptoms and signs, n (%)  fever 1914 (31.4) 1610 (31.0) 1462 (27.2) 1554 (27.9)  cough 4779 (78.5) 3958 (76.1) 4290 (79.7) 4429 (79.4)  purulent ear discharge 91 (1.5) 78 (1.5) 93 (1.7) 114 (2.0)  odynophagia 2623 (43.1) 2376 (45.7) 2317 (43.1) 2326 (41.7)  tonsillar exudate 265 (4.4) 314 (6.0) 246 (4.6) 185 (3.3)  tender cervical nodes 321 (5.3) 420 (8.1) 328 (6.1) 188 (3.4)  dyspnoea 508 (8.3) 455 (8.8) 542 (10.1) 655 (11.7)  increase in sputum 1135 (18.6) 1011 (19.4) 1076 (20.0) 1037 (18.6)  purulence of sputum 618 (10.1) 431 (8.3) 519 (9.6) 565 (10.1) Tests performed/ordered, n (%)  RADTs 52 (0.9) 865 (16.6) 663 (12.3) 90 (1.6)  CRP 2 (0.0) 597 (11.5) 565 (10.5) 15 (0.3)  pulse oximetry NC NC 930 (17.3) 1421 (25.5)  chest X-ray 140 (2.3) 147 (2.8) 118 (2.2) 142 (2.5) Diagnosis, n (%)  common cold 2417 (39.7) 2031 (39.1) 2356 (43.8) 2332 (41.8)  acute otitis media 124 (2.0) 91 (1.8) 127 (2.4) 167 (3.0)  acute sinusitis 160 (2.6) 172 (3.3) 183 (3.4) 185 (3.3)  acute pharyngitis 1231 (20.2) 1210 (23.3) 953 (17.7) 953 (17.1)  acute bronchitis 721 (11.8) 593 (11.4) 859 (16.0) 999 (17.9)  pneumonia 75 (1.2) 71 (1.4) 54 (1.0) 58 (1.0)  acute exacerbations of CB/COPD 271 (4.5) 195 (3.8) 204 (3.8) 233 (4.2)  influenza 658 (10.8) 420 (8.1) 511 (9.5) 517 (9.3)  other RTIs 321 (5.3) 332 (6.4) 134 (2.5) 134 (2.4) Management of the infection  antibiotic prescribed 1545 (25.4) 872 (16.8) 1201 (22.3) 1707 (30.6)  patient demands antibiotics 110 (1.8) 78 (1.5) 115 (2.1) 93 (1.7)  referral of the patient to hospital 33 (0.5) 30 (0.3) 38 (0.7) 57 (1.0) Variable Intervention group in 2008, before the intervention (121 GPs; 6089 RTIs) Intervention group in 2009, just after the intervention (121 GPs; 5199 RTIs) Intervention group in 2015, 6 years after the intervention (121 GPs; 5381 RTIs) Control group, 2015 (117 GPs; 5578 RTIs) Demographics and characteristics of the RTI  age (years), mean (SD) 46.5 (19.7) 46.0 (20.4) 48.9 (20.4) 48.6 (20.5)  female, n (%) 3601 (59.1) 3081 (59.3) 3228 (60.0) 3383 (60.6)  prior duration of symptoms (days), mean (SD) 4.3 (4.5) 4.5 (4.6) 4.7 (5.2) 4.7 (5.1)  severity of the infection (score), mean (SD) NC NC 1.4 (0.7) 1.4 (0.6)  significant comorbidities, n (%) NC NC 739 (13.7) 970 (17.4) Symptoms and signs, n (%)  fever 1914 (31.4) 1610 (31.0) 1462 (27.2) 1554 (27.9)  cough 4779 (78.5) 3958 (76.1) 4290 (79.7) 4429 (79.4)  purulent ear discharge 91 (1.5) 78 (1.5) 93 (1.7) 114 (2.0)  odynophagia 2623 (43.1) 2376 (45.7) 2317 (43.1) 2326 (41.7)  tonsillar exudate 265 (4.4) 314 (6.0) 246 (4.6) 185 (3.3)  tender cervical nodes 321 (5.3) 420 (8.1) 328 (6.1) 188 (3.4)  dyspnoea 508 (8.3) 455 (8.8) 542 (10.1) 655 (11.7)  increase in sputum 1135 (18.6) 1011 (19.4) 1076 (20.0) 1037 (18.6)  purulence of sputum 618 (10.1) 431 (8.3) 519 (9.6) 565 (10.1) Tests performed/ordered, n (%)  RADTs 52 (0.9) 865 (16.6) 663 (12.3) 90 (1.6)  CRP 2 (0.0) 597 (11.5) 565 (10.5) 15 (0.3)  pulse oximetry NC NC 930 (17.3) 1421 (25.5)  chest X-ray 140 (2.3) 147 (2.8) 118 (2.2) 142 (2.5) Diagnosis, n (%)  common cold 2417 (39.7) 2031 (39.1) 2356 (43.8) 2332 (41.8)  acute otitis media 124 (2.0) 91 (1.8) 127 (2.4) 167 (3.0)  acute sinusitis 160 (2.6) 172 (3.3) 183 (3.4) 185 (3.3)  acute pharyngitis 1231 (20.2) 1210 (23.3) 953 (17.7) 953 (17.1)  acute bronchitis 721 (11.8) 593 (11.4) 859 (16.0) 999 (17.9)  pneumonia 75 (1.2) 71 (1.4) 54 (1.0) 58 (1.0)  acute exacerbations of CB/COPD 271 (4.5) 195 (3.8) 204 (3.8) 233 (4.2)  influenza 658 (10.8) 420 (8.1) 511 (9.5) 517 (9.3)  other RTIs 321 (5.3) 332 (6.4) 134 (2.5) 134 (2.4) Management of the infection  antibiotic prescribed 1545 (25.4) 872 (16.8) 1201 (22.3) 1707 (30.6)  patient demands antibiotics 110 (1.8) 78 (1.5) 115 (2.1) 93 (1.7)  referral of the patient to hospital 33 (0.5) 30 (0.3) 38 (0.7) 57 (1.0) CB, chronic bronchitis; NC, not collected. Table 1. Baseline characteristics of the contacts with RTIs according to the group of physicians Variable Intervention group in 2008, before the intervention (121 GPs; 6089 RTIs) Intervention group in 2009, just after the intervention (121 GPs; 5199 RTIs) Intervention group in 2015, 6 years after the intervention (121 GPs; 5381 RTIs) Control group, 2015 (117 GPs; 5578 RTIs) Demographics and characteristics of the RTI  age (years), mean (SD) 46.5 (19.7) 46.0 (20.4) 48.9 (20.4) 48.6 (20.5)  female, n (%) 3601 (59.1) 3081 (59.3) 3228 (60.0) 3383 (60.6)  prior duration of symptoms (days), mean (SD) 4.3 (4.5) 4.5 (4.6) 4.7 (5.2) 4.7 (5.1)  severity of the infection (score), mean (SD) NC NC 1.4 (0.7) 1.4 (0.6)  significant comorbidities, n (%) NC NC 739 (13.7) 970 (17.4) Symptoms and signs, n (%)  fever 1914 (31.4) 1610 (31.0) 1462 (27.2) 1554 (27.9)  cough 4779 (78.5) 3958 (76.1) 4290 (79.7) 4429 (79.4)  purulent ear discharge 91 (1.5) 78 (1.5) 93 (1.7) 114 (2.0)  odynophagia 2623 (43.1) 2376 (45.7) 2317 (43.1) 2326 (41.7)  tonsillar exudate 265 (4.4) 314 (6.0) 246 (4.6) 185 (3.3)  tender cervical nodes 321 (5.3) 420 (8.1) 328 (6.1) 188 (3.4)  dyspnoea 508 (8.3) 455 (8.8) 542 (10.1) 655 (11.7)  increase in sputum 1135 (18.6) 1011 (19.4) 1076 (20.0) 1037 (18.6)  purulence of sputum 618 (10.1) 431 (8.3) 519 (9.6) 565 (10.1) Tests performed/ordered, n (%)  RADTs 52 (0.9) 865 (16.6) 663 (12.3) 90 (1.6)  CRP 2 (0.0) 597 (11.5) 565 (10.5) 15 (0.3)  pulse oximetry NC NC 930 (17.3) 1421 (25.5)  chest X-ray 140 (2.3) 147 (2.8) 118 (2.2) 142 (2.5) Diagnosis, n (%)  common cold 2417 (39.7) 2031 (39.1) 2356 (43.8) 2332 (41.8)  acute otitis media 124 (2.0) 91 (1.8) 127 (2.4) 167 (3.0)  acute sinusitis 160 (2.6) 172 (3.3) 183 (3.4) 185 (3.3)  acute pharyngitis 1231 (20.2) 1210 (23.3) 953 (17.7) 953 (17.1)  acute bronchitis 721 (11.8) 593 (11.4) 859 (16.0) 999 (17.9)  pneumonia 75 (1.2) 71 (1.4) 54 (1.0) 58 (1.0)  acute exacerbations of CB/COPD 271 (4.5) 195 (3.8) 204 (3.8) 233 (4.2)  influenza 658 (10.8) 420 (8.1) 511 (9.5) 517 (9.3)  other RTIs 321 (5.3) 332 (6.4) 134 (2.5) 134 (2.4) Management of the infection  antibiotic prescribed 1545 (25.4) 872 (16.8) 1201 (22.3) 1707 (30.6)  patient demands antibiotics 110 (1.8) 78 (1.5) 115 (2.1) 93 (1.7)  referral of the patient to hospital 33 (0.5) 30 (0.3) 38 (0.7) 57 (1.0) Variable Intervention group in 2008, before the intervention (121 GPs; 6089 RTIs) Intervention group in 2009, just after the intervention (121 GPs; 5199 RTIs) Intervention group in 2015, 6 years after the intervention (121 GPs; 5381 RTIs) Control group, 2015 (117 GPs; 5578 RTIs) Demographics and characteristics of the RTI  age (years), mean (SD) 46.5 (19.7) 46.0 (20.4) 48.9 (20.4) 48.6 (20.5)  female, n (%) 3601 (59.1) 3081 (59.3) 3228 (60.0) 3383 (60.6)  prior duration of symptoms (days), mean (SD) 4.3 (4.5) 4.5 (4.6) 4.7 (5.2) 4.7 (5.1)  severity of the infection (score), mean (SD) NC NC 1.4 (0.7) 1.4 (0.6)  significant comorbidities, n (%) NC NC 739 (13.7) 970 (17.4) Symptoms and signs, n (%)  fever 1914 (31.4) 1610 (31.0) 1462 (27.2) 1554 (27.9)  cough 4779 (78.5) 3958 (76.1) 4290 (79.7) 4429 (79.4)  purulent ear discharge 91 (1.5) 78 (1.5) 93 (1.7) 114 (2.0)  odynophagia 2623 (43.1) 2376 (45.7) 2317 (43.1) 2326 (41.7)  tonsillar exudate 265 (4.4) 314 (6.0) 246 (4.6) 185 (3.3)  tender cervical nodes 321 (5.3) 420 (8.1) 328 (6.1) 188 (3.4)  dyspnoea 508 (8.3) 455 (8.8) 542 (10.1) 655 (11.7)  increase in sputum 1135 (18.6) 1011 (19.4) 1076 (20.0) 1037 (18.6)  purulence of sputum 618 (10.1) 431 (8.3) 519 (9.6) 565 (10.1) Tests performed/ordered, n (%)  RADTs 52 (0.9) 865 (16.6) 663 (12.3) 90 (1.6)  CRP 2 (0.0) 597 (11.5) 565 (10.5) 15 (0.3)  pulse oximetry NC NC 930 (17.3) 1421 (25.5)  chest X-ray 140 (2.3) 147 (2.8) 118 (2.2) 142 (2.5) Diagnosis, n (%)  common cold 2417 (39.7) 2031 (39.1) 2356 (43.8) 2332 (41.8)  acute otitis media 124 (2.0) 91 (1.8) 127 (2.4) 167 (3.0)  acute sinusitis 160 (2.6) 172 (3.3) 183 (3.4) 185 (3.3)  acute pharyngitis 1231 (20.2) 1210 (23.3) 953 (17.7) 953 (17.1)  acute bronchitis 721 (11.8) 593 (11.4) 859 (16.0) 999 (17.9)  pneumonia 75 (1.2) 71 (1.4) 54 (1.0) 58 (1.0)  acute exacerbations of CB/COPD 271 (4.5) 195 (3.8) 204 (3.8) 233 (4.2)  influenza 658 (10.8) 420 (8.1) 511 (9.5) 517 (9.3)  other RTIs 321 (5.3) 332 (6.4) 134 (2.5) 134 (2.4) Management of the infection  antibiotic prescribed 1545 (25.4) 872 (16.8) 1201 (22.3) 1707 (30.6)  patient demands antibiotics 110 (1.8) 78 (1.5) 115 (2.1) 93 (1.7)  referral of the patient to hospital 33 (0.5) 30 (0.3) 38 (0.7) 57 (1.0) CB, chronic bronchitis; NC, not collected. Antibiotics were given to 5325 patients (23.9%), but this percentage was significantly lower among the GPs assigned to intervention just after the intervention took place and was highest among the new GPs allocated to the control group (16.8% versus 30.6%), whereas the percentage of antibiotics prescribed by the GPs 6 years after the intervention was 22.3%. The highest antibiotic prescription was observed in pneumonia, acute otitis media and acute exacerbations of chronic bronchitis and COPD (Table 2). Table 2. Antibiotic prescription for the different RTIs according to the group of physicians Variable Intervention group in 2008, before the intervention (N = 6089) Intervention group in 2009, just after the intervention (N = 5199) Intervention group in 2015, 6 years after the intervention (N = 5381) Control group, 2015 (N = 5578) Common cold, n (%) 46 (1.9) 22 (1.1) 51 (2.2) 58 (2.5) Acute otitis media, n (%) 107 (86.3) 74 (81.3) 90 (70.9) 133 (79.6) Acute rhinosinusitis, n (%) 135 (84.4) 99 (57.6) 113 (61.7) 147 (79.5) Acute pharyngitis, n (%) 476 (38.7) 258 (21.3) 344 (36.1) 457 (48.0) Acute bronchitis, n (%) 396 (54.9) 174 (29.3) 358 (41.7) 628 (62.9) Pneumonia, n (%) 68 (90.7) 62 (87.3) 46 (85.2) 44 (75.9) Acute exacerbations of CB/COPD, n (%) 212 (78.2) 133 (68.2) 160 (78.4) 181 (77.7) Influenza, n (%) 20 (3.0) 1 (0.2) 18 (33.5) 24 (4.6) Other RTIs, n (%) 60 (18.7) 42 (12.7) 21 (15.7) 35 (26.1) Total, n (%) 1545 (25.4) 872 (16.8) 1201 (22.3) 1707 (30.6) Variable Intervention group in 2008, before the intervention (N = 6089) Intervention group in 2009, just after the intervention (N = 5199) Intervention group in 2015, 6 years after the intervention (N = 5381) Control group, 2015 (N = 5578) Common cold, n (%) 46 (1.9) 22 (1.1) 51 (2.2) 58 (2.5) Acute otitis media, n (%) 107 (86.3) 74 (81.3) 90 (70.9) 133 (79.6) Acute rhinosinusitis, n (%) 135 (84.4) 99 (57.6) 113 (61.7) 147 (79.5) Acute pharyngitis, n (%) 476 (38.7) 258 (21.3) 344 (36.1) 457 (48.0) Acute bronchitis, n (%) 396 (54.9) 174 (29.3) 358 (41.7) 628 (62.9) Pneumonia, n (%) 68 (90.7) 62 (87.3) 46 (85.2) 44 (75.9) Acute exacerbations of CB/COPD, n (%) 212 (78.2) 133 (68.2) 160 (78.4) 181 (77.7) Influenza, n (%) 20 (3.0) 1 (0.2) 18 (33.5) 24 (4.6) Other RTIs, n (%) 60 (18.7) 42 (12.7) 21 (15.7) 35 (26.1) Total, n (%) 1545 (25.4) 872 (16.8) 1201 (22.3) 1707 (30.6) CB, chronic bronchitis. Table 2. Antibiotic prescription for the different RTIs according to the group of physicians Variable Intervention group in 2008, before the intervention (N = 6089) Intervention group in 2009, just after the intervention (N = 5199) Intervention group in 2015, 6 years after the intervention (N = 5381) Control group, 2015 (N = 5578) Common cold, n (%) 46 (1.9) 22 (1.1) 51 (2.2) 58 (2.5) Acute otitis media, n (%) 107 (86.3) 74 (81.3) 90 (70.9) 133 (79.6) Acute rhinosinusitis, n (%) 135 (84.4) 99 (57.6) 113 (61.7) 147 (79.5) Acute pharyngitis, n (%) 476 (38.7) 258 (21.3) 344 (36.1) 457 (48.0) Acute bronchitis, n (%) 396 (54.9) 174 (29.3) 358 (41.7) 628 (62.9) Pneumonia, n (%) 68 (90.7) 62 (87.3) 46 (85.2) 44 (75.9) Acute exacerbations of CB/COPD, n (%) 212 (78.2) 133 (68.2) 160 (78.4) 181 (77.7) Influenza, n (%) 20 (3.0) 1 (0.2) 18 (33.5) 24 (4.6) Other RTIs, n (%) 60 (18.7) 42 (12.7) 21 (15.7) 35 (26.1) Total, n (%) 1545 (25.4) 872 (16.8) 1201 (22.3) 1707 (30.6) Variable Intervention group in 2008, before the intervention (N = 6089) Intervention group in 2009, just after the intervention (N = 5199) Intervention group in 2015, 6 years after the intervention (N = 5381) Control group, 2015 (N = 5578) Common cold, n (%) 46 (1.9) 22 (1.1) 51 (2.2) 58 (2.5) Acute otitis media, n (%) 107 (86.3) 74 (81.3) 90 (70.9) 133 (79.6) Acute rhinosinusitis, n (%) 135 (84.4) 99 (57.6) 113 (61.7) 147 (79.5) Acute pharyngitis, n (%) 476 (38.7) 258 (21.3) 344 (36.1) 457 (48.0) Acute bronchitis, n (%) 396 (54.9) 174 (29.3) 358 (41.7) 628 (62.9) Pneumonia, n (%) 68 (90.7) 62 (87.3) 46 (85.2) 44 (75.9) Acute exacerbations of CB/COPD, n (%) 212 (78.2) 133 (68.2) 160 (78.4) 181 (77.7) Influenza, n (%) 20 (3.0) 1 (0.2) 18 (33.5) 24 (4.6) Other RTIs, n (%) 60 (18.7) 42 (12.7) 21 (15.7) 35 (26.1) Total, n (%) 1545 (25.4) 872 (16.8) 1201 (22.3) 1707 (30.6) CB, chronic bronchitis. Data were analysed in a two-level logistic regression model with patients (n = 22 247) allocated to level 1 and GPs (n = 238) to level 2. The Wald test of the model was 912.1 (P < 0.001). Tonsillar exudate (OR 9.17) and sputum purulence (OR 6.23) were significantly associated with antibiotic prescribing. Conversely, cough (OR 0.73) was associated with low antibiotic prescribing (Table 3). On adjustment for covariables, compared with the antibiotic prescription observed just after the intervention, GPs assigned to the intervention group prescribed slightly more antibiotics in 2015, albeit without statistical significance (OR 1.08, 95% CI 0.89–1.31), while GPs allocated to the control group prescribed significantly more antibiotics (OR 2.74, 95% CI 2.09–3.59). Table 3. Effect of an intervention 6 years later; multivariable predictors of antibiotic prescription in RTIs Variable OR SE 95% CI P Age 1.01 0.00 1.01–1.01 <0.001 Female 0.92 0.46 0.83–1.01 0.08 Prior duration of symptoms 1.03 0.01 1.02–1.04 <0.001 Fever 3.83 0.23 3.41–4.30 <0.001 Cough 0.73 0.05 0.65–0.84 <0.001 Purulent ear discharge 1.76 0.36 1.18–2.62 0.01 Odynophagia 1.08 0.07 0.94–1.23 0.28 Tonsillar exudate 9.17 0.93 7.52–11.18 <0.001 Tender cervical nodes 2.83 0.28 2.34–3.42 <0.001 Dyspnoea 1.52 0.12 1.30–1.78 <0.001 Increase in sputum 2.02 0.14 1.77–2.31 <0.001 Purulence of sputum 6.23 0.49 5.35–7.27 <0.001 Common cold 0.09 0.02 0.05–0.15 <0.001 Acute otitis media 34.36 9.70 19.76–59.76 <0.001 Acute sinusitis 17.77 4.54 10.77–29.32 <0.001 Acute pharyngitis 1.72 0.41 1.07–2.75 0.03 Acute bronchitis 3.69 0.88 2.31–5.89 <0.001 Pneumonia 19.82 6.23 10.71–36.69 <0.001 Acute exacerbations of CB/COPD 8.49 2.18 5.12–14.05 <0.001 Influenza 0.06 0.02 0.03–0.11 <0.001 Other RTIs 1.06 0.27 0.64–1.75 0.82 Patient demands antibiotics 4.36 0.71 3.17–6.00 <0.001 Intervention group in 2015 1.08 0.11 0.89–1.31 0.46 Control group in 2015 2.74 0.38 2.09–3.59 <0.001 Variable OR SE 95% CI P Age 1.01 0.00 1.01–1.01 <0.001 Female 0.92 0.46 0.83–1.01 0.08 Prior duration of symptoms 1.03 0.01 1.02–1.04 <0.001 Fever 3.83 0.23 3.41–4.30 <0.001 Cough 0.73 0.05 0.65–0.84 <0.001 Purulent ear discharge 1.76 0.36 1.18–2.62 0.01 Odynophagia 1.08 0.07 0.94–1.23 0.28 Tonsillar exudate 9.17 0.93 7.52–11.18 <0.001 Tender cervical nodes 2.83 0.28 2.34–3.42 <0.001 Dyspnoea 1.52 0.12 1.30–1.78 <0.001 Increase in sputum 2.02 0.14 1.77–2.31 <0.001 Purulence of sputum 6.23 0.49 5.35–7.27 <0.001 Common cold 0.09 0.02 0.05–0.15 <0.001 Acute otitis media 34.36 9.70 19.76–59.76 <0.001 Acute sinusitis 17.77 4.54 10.77–29.32 <0.001 Acute pharyngitis 1.72 0.41 1.07–2.75 0.03 Acute bronchitis 3.69 0.88 2.31–5.89 <0.001 Pneumonia 19.82 6.23 10.71–36.69 <0.001 Acute exacerbations of CB/COPD 8.49 2.18 5.12–14.05 <0.001 Influenza 0.06 0.02 0.03–0.11 <0.001 Other RTIs 1.06 0.27 0.64–1.75 0.82 Patient demands antibiotics 4.36 0.71 3.17–6.00 <0.001 Intervention group in 2015 1.08 0.11 0.89–1.31 0.46 Control group in 2015 2.74 0.38 2.09–3.59 <0.001 CB, chronic bronchitis; SE, standard error. Table 3. Effect of an intervention 6 years later; multivariable predictors of antibiotic prescription in RTIs Variable OR SE 95% CI P Age 1.01 0.00 1.01–1.01 <0.001 Female 0.92 0.46 0.83–1.01 0.08 Prior duration of symptoms 1.03 0.01 1.02–1.04 <0.001 Fever 3.83 0.23 3.41–4.30 <0.001 Cough 0.73 0.05 0.65–0.84 <0.001 Purulent ear discharge 1.76 0.36 1.18–2.62 0.01 Odynophagia 1.08 0.07 0.94–1.23 0.28 Tonsillar exudate 9.17 0.93 7.52–11.18 <0.001 Tender cervical nodes 2.83 0.28 2.34–3.42 <0.001 Dyspnoea 1.52 0.12 1.30–1.78 <0.001 Increase in sputum 2.02 0.14 1.77–2.31 <0.001 Purulence of sputum 6.23 0.49 5.35–7.27 <0.001 Common cold 0.09 0.02 0.05–0.15 <0.001 Acute otitis media 34.36 9.70 19.76–59.76 <0.001 Acute sinusitis 17.77 4.54 10.77–29.32 <0.001 Acute pharyngitis 1.72 0.41 1.07–2.75 0.03 Acute bronchitis 3.69 0.88 2.31–5.89 <0.001 Pneumonia 19.82 6.23 10.71–36.69 <0.001 Acute exacerbations of CB/COPD 8.49 2.18 5.12–14.05 <0.001 Influenza 0.06 0.02 0.03–0.11 <0.001 Other RTIs 1.06 0.27 0.64–1.75 0.82 Patient demands antibiotics 4.36 0.71 3.17–6.00 <0.001 Intervention group in 2015 1.08 0.11 0.89–1.31 0.46 Control group in 2015 2.74 0.38 2.09–3.59 <0.001 Variable OR SE 95% CI P Age 1.01 0.00 1.01–1.01 <0.001 Female 0.92 0.46 0.83–1.01 0.08 Prior duration of symptoms 1.03 0.01 1.02–1.04 <0.001 Fever 3.83 0.23 3.41–4.30 <0.001 Cough 0.73 0.05 0.65–0.84 <0.001 Purulent ear discharge 1.76 0.36 1.18–2.62 0.01 Odynophagia 1.08 0.07 0.94–1.23 0.28 Tonsillar exudate 9.17 0.93 7.52–11.18 <0.001 Tender cervical nodes 2.83 0.28 2.34–3.42 <0.001 Dyspnoea 1.52 0.12 1.30–1.78 <0.001 Increase in sputum 2.02 0.14 1.77–2.31 <0.001 Purulence of sputum 6.23 0.49 5.35–7.27 <0.001 Common cold 0.09 0.02 0.05–0.15 <0.001 Acute otitis media 34.36 9.70 19.76–59.76 <0.001 Acute sinusitis 17.77 4.54 10.77–29.32 <0.001 Acute pharyngitis 1.72 0.41 1.07–2.75 0.03 Acute bronchitis 3.69 0.88 2.31–5.89 <0.001 Pneumonia 19.82 6.23 10.71–36.69 <0.001 Acute exacerbations of CB/COPD 8.49 2.18 5.12–14.05 <0.001 Influenza 0.06 0.02 0.03–0.11 <0.001 Other RTIs 1.06 0.27 0.64–1.75 0.82 Patient demands antibiotics 4.36 0.71 3.17–6.00 <0.001 Intervention group in 2015 1.08 0.11 0.89–1.31 0.46 Control group in 2015 2.74 0.38 2.09–3.59 <0.001 CB, chronic bronchitis; SE, standard error. Discussion To the best of our knowledge, this is the first study to report the longest effect of an intervention carried out in the community with the use of a control group. A single multifaceted intervention including feedback results of a previous registration, interactive seminars on RTIs, guideline discussion and workshop on rapid tests was associated with a slight increase in antibiotic prescribing 6 years later compared with antibiotic prescription observed just after the intervention, although no statistically significant differences were observed. Notwithstanding, GPs who had never participated in an intervention on the appropriate use of antibiotics and acted as the control group prescribed significantly more antibiotics. Strengths and limitations Our study has several limitations. As in other studies, in the present study, GPs participated voluntarily and probably their prescribing habits were not representative of all GPs and this may have limited the extrapolation of the results obtained. It is possible that the participating GPs were more prone to interventions aimed at behaviour change than their colleagues who did not participate.17 One of the striking results of this paper is the considerable difference in antibiotic prescribing observed in the GPs assigned to intervention before this took place and the control group recruited in 2015, which was 5.2% higher among the latter physicians. Although the GPs allocated to the intervention group could have been more motivated than their control counterparts, this phenomenon could also reflect the slight albeit steady increase in antibiotic consumption observed over recent years in Spain.5,6 It is a limitation that we did not register clinical outcomes or complications. However, some important variables not included in the first two registrations that might have influenced whether an antibiotic was prescribed or not such as significant comorbidities, severity of the infection according to GP judgement or the use of pulse oximetry were added to the 2015 template. For all patients included, GPs registered the first reason for encounter when a patient with suspected RTI was seen in their practice and the pattern of RTI infections was most probably equal for the different groups of patients. Other potential confounders not taken into account in our analysis, such as physician motivation and local campaigns to promote appropriate use of antibiotics, were probably evenly distributed between the groups. In all the groups of patients GPs used the same type of registration sheet and a potential influence of GP behaviour caused by the registration was most likely similar in the two groups of GPs.18 Two different nationwide campaigns regarding antibiotic use were launched in 2007 and 2008, but the results of these campaigns have never been studied. However, public campaigns on antibiotic awareness in other European countries have not been associated with significant reductions in antibiotic prescribing in primary care.19 GPs allocated to the control group had never participated in courses on the rational use of antibiotics, but we cannot rule out the possibility that some may have been particularly concerned about the problem of antimicrobial resistance. Despite the fact that POCTs are seldom used in primary care in Spain, we found that 1.6% of all the contacts with RTIs by GPs assigned to the control group used rapid tests, particularly RADTs. Another potential limitation is the Hawthorne effect, which may have introduced bias because GPs in both the intervention and the control group, but more importantly in the latter as they were not familiar with this audit-based registration, may have altered their prescription habits. To reduce this risk, GPs in the control group were specifically instructed to follow their usual care. Theoretically, the decision to treat should be taken after a diagnosis has been established. In general practice, however, the diagnostic procedures and the decision to treat are intricately intertwined. The GP may decide whether or not to prescribe an antibiotic at the same time, or even before. After making the decision to prescribe, the GP may thus then adjust the diagnosis to fit the decision about treatment. This may lead to a diagnostic misclassification bias. However, this potential bias might have affected the validity of the diagnosis both before and after the intervention and in both groups of GPs (intervention and control groups) and it is very unlikely to have influenced the effect of the intervention.15 The data corresponding to all the registrations completed in 2015 were entered by only one of the authors of this paper (A. M.), who is both a GP and a researcher. She raised concern of alleged fraudulent completion of some data by three GPs allocated to the intervention group on noticing a digit preference in some numerical variables.20 Owing to budget constraints we were unable to double-check the information contained in all the templates with the electronic records, but after checking the information provided by these three suspected cases one of these GPs was excluded from the final analysis due to confirmed fraud and all the data entered by this researcher in the three registration periods were rejected. Conversely, the suspicion of scientific misconduct observed in the other two cases was finally dismissed, as the information provided on the templates was veracious. Therefore, on concluding the investigation of possible data fraud and implementing the necessary actions to ensure data validity, we can confidently state that all the data entered in the study are valid and reliable. This was not a clinical trial, because GPs were not randomly assigned to the different groups. This might explain why the new GPs assigned to the control group were slightly younger than their counterparts, with more female doctors. However, the differences observed were not clinically relevant and we do not consider that this difference could have any effect on the results obtained. A total of 10 trainees who were included in the control group in one of the areas were finally excluded to make both groups of GPs more comparable. The greatest strength of this study was the large number of physicians included. In addition, >50% of the GPs who had participated in the first and second registrations and had participated in the intervention accepted to participate in this new registration 6 years later. Comparison with other studies Several randomized controlled trials conducted in primary care demonstrated a significant effect of various educational interventions on antibiotic prescriptions for RTIs over the subsequent year,21,22 but few studies aimed at assessing the long-term effect of interventions have been published. Indeed, studies assessing effects on antibiotic prescription in primary care after 3 years wrought conflicting results.10–14 In general, a reduction of the antibiotic prescribing rate is still observed in the long term as four of these studies found a decrease in the proportion of patients with RTIs who were prescribed antibiotics, but this mainly depends on the number and type of strategies used in the intervention.10–13 In a 3.5 year follow-up of a randomized controlled trial carried out in the Netherlands, an intervention that consisted of the provision of CRP in the consultations was associated with a 5% reduction of antibiotic prescribing for patients with acute cough, but the intervention was continuously delivered along the study period.12 In a French randomized clinical trial, a 2 day interactive educational intervention was associated with a significant reduction of antimicrobials prescribed 30 months after this intervention,23 and continued showing a lower antibiotic prescribing rate compared with the control group after 4.5 years of follow-up.13 In contrast, a 5 year Finnish study showed that guideline dissemination through local interactive discussion groups failed to decrease significantly the antibiotic prescriptions, but these results were not compared with a control group.14 Changing clinicians’ prescribing behaviour is a complex matter. Several strategies such as the provision of guidelines, poster display in the waiting rooms and even leaflets have limited effect. When active strategies are added to these passive educational sessions, such as the feedback and discussion of previous results, training in enhancing communication skills in the consultation and the provision of POCTs, the effect is much greater. The different active strategies used in the present study, which required the attendance to 2 h courses and workshops on three different days, might explain the continued reduction in antibiotic prescribing observed 6 years after the intervention. Conclusions To the best of our knowledge, no study has evaluated the effect of a single complex intervention more than 5 years later. However, in this observational prospective study, a single multifaceted intervention carried out 6 years earlier consisting of the discussion of the first registration results, a training course on appropriate use of antibiotics and clinical guidelines for RTIs, patients’ brochures, posters for waiting rooms, workshop on rapid tests and provision of these POCTs in the consultation, continued to reduce antibiotic prescription for RTIs. Acknowledgements We wish to acknowledge the GPs who voluntarily participated in the study. Other members of the HAPPY AUDIT 3 Study Team Andalucía: Idoioa Arrillaga Ocampo, Francisco Atienza Martín, Eduardo Ávila Amat, Marta Bernal Raya, Pablo Cabezas Saura, Pilar Carretero Castaño, Carmen Dastís Bendala, Irene V. de Tena Roger, Pedro Fernández-Nieto Fernández, Amalia Filella Sierpes, M. Isabel González Rodríguez, Antonio Hernández Alonso, Guillermo Largaespada Pallaviccini, Beatriz López Fernández, Inés M. López Huerta, Beatriz Luque López, Yanina Maldonado, M. Luisa Manzanares Torné, Leonor Marín Pérez, M. Mercedes Martínez Granero, Rocío Martínez Pérez, M. Antonia Máximo Torres, Ainhoa Mestraitua Vázquez, Mercedes Moreno Labrado, M. Luisa Moya Rodríguez, José Oropesa de Cáceres, Irene Padial Reyes, Antonio Paniagua Galisteo, Vanessa Parra García, M. Encarnación Peláez Gálvez, Juan J. Quero Perabá, M. Jesús Remesal Barrachina, Miguel Sagristá González, Consuelo Sampedro Abascal, Jesús C. Sánchez Vázquez, Auxiliadora Sanchís Osuna, J. Cristóbal Sendín González, Rosario Serrano Ortega, Miguel Silva Cueto, Guillermo Velázquez de Cisneros. Baleares: Ester Adelantado Pozuelo, Daniel Bestard Marín, Aberlado Corrales Nadal, M. Teresa Corredor Ibáñez, Esther Domínguez Padilla, Alberto Eek Comas, Margarita Fornés Homar, Maria E. Garau Miquel, Prado García Servera, Salvador J. Gestoso Gaya, María J. González-Bals González, Mercedes Gutiérrez García, Antoni J. Jover Palmer, Magdalena Llinàs Suau, Marian Llorente Sanmartín, Blanca Martínez Andión, Adriano Mayrata Vicens, David Medina i Bombardó, Gabriel Moragues Sbert, Joana M. Oliver Gornals, Etel Oliver Roset, J. Francisco Palmer Simó, Juana Pérez Galmés, Susana Pons Vives, Lourdes Quintana Torres, José Alfonso Ramón Bauzá, F. Javier Rezola Gambón, Jaime Ripoll Sánchez, Miguel Román Rodríguez, Natalia Serrano Gomila, Magdalena Servera Trias, Isabel M. Socias Buades, M. Mar Sureda Barbosa, Joana Tortella Morro, Lucia Ugarriza Hierro, Silvia Vega García. Canarias: Pilar Aguilar Utrilla, M. Carmen Artiles Ruano, M. Isabel Cardenes Romero, Jonás de la Cruz Cabrera, Margarita García García, M. Carmen Guerra, Ricardo Koch, M. Huertas Llamas Martínez, M. Elena Martín Santana, Alicia Monzón Guerra, Marta Moreno Ramos, Caridad Sánchez Artiles, Lucía Tejera Pulido, José M. Toscano, Carlos Prieto, Aurelia Perdomo. Galicia: Francisco Castrillo Villar, Pilar Cobas Pacín, M. Jesús Colas Martínez, Coral Díez Pérez, Peregrina Eiroa Patiño, Ana Fernández Álvarez, Luis Fuciños Cebreiro, J. Antonio Gómez Villalobos, M. Esther González García-Mayor, Ricardo M. Héctor Sanz, Susana Hernáiz Valero, Esther López Carbajales, J. Luis López Vilar, Elena Lorenzo Llauger, Elisa Mosquera Gayoso, Concepción Nogueiras Santas, M. Pilar Pintos Martínez, M. Teresa Ríos Rey, Lucía Rodríguez Nieto, Santiago Santidrián Arias, Jesús Sueiro Justel. Madrid: Raquel Baños Morras, José M. Casanova Colominas, Santiago Castellanos Redondo, M. Teresa Cobos Hinojal, José Corral Brihuega, M. Canto de Hoyos Alonso, Belén de la Fuente Martín, Silvia de las Heras Loa, Angélica Fajardo Alcántara, M. Jesús Ferrer Signes, Antonia García del Val, M. Mar García Rabanal, Gema García Sacristán, Álvaro García Vega, M. Elena Gerez Sánchez-Escribano, Paloma González Escobar, Rosa M. González San Segundo, M. Elena Hermida López, Paloma Hernández Almarza, Ana Ibarra Sánchez, Ángeles Lagos Aguilar, Ascensión Lázaro Damas, M. Eugenia López Delgado, Guillermina López Fernández, Rosario López Morell, M. José Lucena Martín, Jaime Marín Cañada, Rosa Martín de Cabo, Blanca Matilla Pardo, Teresa Mazarro Enrique, Cristina Moral Moraleda, Adela Moreno Mateos, Joaquín Morera Montes, Renata Muñoz Bieber, Javier Muñoz Gutiérrez, Alicia Muñoz Núñez, M. Arantzazu Murciano Antón, Patricia Navarro Gil, Lourdes Pulido Izquierdo, Carmen Rodríguez Fernández, Ana Rodríguez Nebreda, M. Elena Rodríguez Quiroga, M. Asunción Rosado López, Ana Ruíz Molina, Rocío Susana Ruiz Vargas, Irmina Saldaña Alonso, Mar Sánchez Martín, Laura Santos Larregola, Juana M. Torres Martínez, Gema Val Morales, Amalia Velázquez García, Lourdes Visedo Campillo, Antonio Yagüe Hernando. Rioja: Ascensión Aicua Sadia, M. Carmen Aurensanz Sánchez, Carmen Babace Isturiz, Diego Beni Ruiz, Nieves Calavia Rueda, M. Mar Díez Casado, M. Ángeles Espeso Fernández Valderrama, Francisco García Marín, Tomás García Martínez, Ana M. Gómez Ruiz, Elvira Moreno Hernández, Sabino Ornia Rodríguez, M. José Palomo Larrieta, Olga Revilla González, Rosa Ruiz De Austri Fuente, J. Luis Torres Baile, Antonio Trueba Castillo, Ana M. Vázquez Medrano. Asturias: Carmen Alonso Alonso, Fernando Álvarez Guisasola, Pablo Belderraín Belderraín, J. Carlos Bango Melcón, Teresa Díaz Mujica, Deopatria Azucena Esteban Fresno, Rocío Fernández Collar, Leonor Fuentes Martin, Alfonso García Viejo, Ramón Macía Pérez, Carmen Martín López, Ernesto Martínez Estrada, Herminia Menéndez Fernández, Covadonga Monte Llavona, M. Amor Paredes González, Cristina Pérez Canal, Javier Pérez Fernández, M. Mar Pizarro López, Rosa Rodríguez, J. Ignacio Rodríguez-Arias Palomo, Alicia Rodríguez Fernández, Felipe J. Rodríguez Gordaliza, Celia T. Tamargo García, Salvador Tranche Iparraguirre, M. Raimunda Vázquez Aira, Rubén Villa Estébanez. Valencia: Juan Alamar Provecho, M. Teresa Amorós Barber, Miguel Antón Sánchez, Manuel Batalla Sales, Lourdes Bermejo Mora, Núria Bosch Girona, M. Pilar Carceller Sales, Rosa Carrión Villanueva, Teresa Chirivella Raga, Manuela Domingo Orduña, Concepción García Domingo, Carmen Hernández Espinosa, Blanca Folch Marín, Carmen Gandía Moya, Amparo Haya Guaita, Eva M. Izquierdo Hidalgo, Engracia López González, Nuria Mallén Navarro, Pilar Marín Lluch, Amparo Meneu Ferrer, Helena Molina Raga, Adela Moreno Fernández, Ángeles Pérez Campos, Belén Persiva Saura, Gloria Rabanaque Mallén, Remei Raga Marí, Jazmín Ripoll Perelló, Pilar Roca Navarro, M. Luisa Tregón Moliner. Funding This study was funded by TRACE (Translational Research on Antimicrobial resistance and Community-acquired infections in Europe). The funding source had no role in study design, data collection, data analysis, data interpretation or writing the report. Transparency declarations C. L. and A. M. report receiving research grants from the European Commission (Sixth & Seventh Programme Frameworks and Horizon 2020), the Catalan Society of Family Medicine, Instituto de Salud Carlos III and Alere. All other authors: none to declare. Author contributions The initial idea for this study was proposed by C. L. and L. B.; all authors contributed to the development of the protocol and to the management of the study. A. M. entered all the data. C. L., L. B., A. M. and J. M. C. led the funding application and provided overall co-ordination of the TRANCE consortium. B. G. L.-V. analysed the data; all authors contributed to the interpretation of the data and the write-up. C. L., L. B., B. G. L.-V., A. M. and J. M. C. had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. References 1 Goossens H , Ferech M , Vander Stichele R et al. ; ESAC Project Group . 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Effectiveness of multifaceted educational programme to reduce antibiotic dispensing in primary care: practice based randomised controlled trial . BMJ 2012 ; 344 : d8173. Google Scholar CrossRef Search ADS PubMed 23 Le Corvoisier P , Renard V , Roudot-Thoraval F et al. Long-term effects of an educational seminar on antibiotic prescribing by GPs: a randomised controlled trial . Br J Gen Pract 2013 ; 63 : e455 – 64 . Google Scholar CrossRef Search ADS PubMed © The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

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Journal of Antimicrobial ChemotherapyOxford University Press

Published: Apr 27, 2018

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