Effects of a multimodal intervention in primary care to reduce second line antibiotic prescriptions for urinary tract infections in women: parallel, cluster randomised, controlled trial

Abstract Objectives To evaluate whether a multimodal intervention in general practice reduces the proportion of second line antibiotic prescriptions and the overall proportion of antibiotic prescriptions for uncomplicated urinary tract infections in women. Design Parallel, cluster randomised, controlled trial. Setting General practices in five regions in Germany. Data were collected between 1 April 2021 and 31 March 2022. Participants General practitioners from 128 randomly assigned practices. Interventions Multimodal intervention consisting of guideline recommendations for general practitioners and patients, provision of regional data for antibiotic resistance, and quarterly feedback, which included individual first line and second line proportions of antibiotic prescribing, benchmarking with regional or supra-regional practices, and telephone counselling. Participants in the control group received no information on the intervention. Main outcome measures Primary outcome was the proportion of second line antibiotics prescribed by general practices, in relation to all antibiotics prescribed, for uncomplicated urinary tract infections after one year between the intervention and control group. General practices were randomly assigned in blocks (1:1), with a block size of four, into the intervention or control group using SAS version 9.4; randomisation was stratified by region. The secondary outcome was the prescription proportion of all antibiotics, relative within all cases (instances of UTI diagnosis), for the treatment of urinary tract infections after one year between the groups. Adverse events were assessed as exploratory outcomes. Results 110 practices with full datasets identified 10 323 cases during five quarters (ie, 15 months). The mean proportion of second line antibiotics prescribed was 0.19 (standard deviation 0.20) in the intervention group and 0.35 (0.25) in the control group after 12 months. After adjustment for preintervention proportions, the mean difference was −0.13 (95% confidence interval −0.21 to −0.06, P<0.001). The overall proportion of all antibiotic prescriptions for urinary tract infections over 12 months was 0.74 (standard deviation 0.22) in the intervention and 0.80 (0.15) in the control group with a mean difference of −0.08 (95% confidence interval −0.15 to −0.02, P<0.029). No differences were noted in the number of complications (ie, pyelonephritis, admission to hospital, or fever) between the groups. Conclusions The multimodal intervention in general practice significantly reduced the proportion of second line antibiotics and all antibiotic prescriptions for uncomplicated urinary tract infections in women. Trial registration German Clinical Trials Register (DRKS), DRKS00020389

• ALWAYS FILL IN THE CASE PAGES COMPLETELY FIRST! (only then transfer to the tally pages when it is certain that the case is included) • On the "information sheet on inclusion/exclusion criteria" you will find an overview of cases that may not be included • After completing the case pages, place them on the appropriate tally pages so that the outer column is exactly adjacent • Based on what was ticked in the outer (coloured) column of the case pages, draw a tally mark on the tally sheet (use a waterproof pen).If a question is not marked in the outer column, do not draw a mark.For questions 7, 8 and 9, note the name of the antibiotic if "Other antibiotic" was ticked • After transferring the results of all questions, tick off the case on the PVS results list, wipe off the marks on the case pages and start a new case • It is best to use water to wipe the case, and alcohol-based disinfectant in between if necessary.When wiping the case sheets, it is best to take them off the tally sheet so that it does not get wet and smeared • Please cross out cases that are not to be included on the PVS results list (e.g. if it turns out before or during data collection that it was not an uncomplicated UTI) • In unclear cases, note this on the PVS results list and only process the case further or delete it from the list after consulting the doctor • At the beginning of each new quarter, insert a new tally sheet and label it (e.g.

03/2021)
Important: Keep the old tally sheets even after the data transfer at the end of the quarter until the end of the study, as certain questions will only be counted at the end of the year

Counting and transferring the tally sheet to the data extraction sheet and entering it into the RedCap database (quarterly and once after one year)
• When all cases on the PVS results list have been gone through and the cases to be included have been recorded accordingly on the tally sheet, the tally sheet is counted and transferred to a data extraction sheet and to the RedCap database.The RedCap login data is in the envelope used for randomisation at the beginning of the study.For handling RedCap, please refer to the separate instructions for RedCap (screenshots) • Please note: For data protection reasons, some questions are counted every quarter and some only at the end of the study period after one year; there are separate data extraction sheets and separate input masks in RedCap for each of these

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Counting quarterly: Questions 3-11 >> "Data extraction sheet for intervention practice".• Count, transfer to the data extraction sheet and fax to the Institute of General Practice at the University Hospital of Wuerzburg or email.• Open RedCap, enter the results of the counts in the corresponding fields • Ignore questions 1, 2 and 12-17 now, they will be counted only in the end of the study • Counting after one year: Questions 1., 2. and 12.-17.>> "Data extraction sheet for aggregated data after one year".• The results for each question from all collected quarters have to be summed up.• Transfer the respective sums to the data extraction sheet and fax it to the Institute of • General Medicine at the University Hospital of Würzburg or email it • Open RedCap, enter the totals in the corresponding fields.• Supplementary material 2

Reduction in prescribing second-line antibiotics for urinary tract infections: a cluster randomised controlled trial by a multimodal intervention in primary care Supplementary table 1
1 n (%); Mean (SD) 2 Pearson's Chi-squared test; Fisher's exact test; Welch Two Sample t-test; Wilcoxon rank sum test 4 Supplementary

table 2 Absolute and relative antibiotic prescriptions in Control and Intervention group at practice level from Qb to Q4
1 Welch Two Sample t-test 2 Mean (SD = Standard Deviation); Range; Sum 3 Baseline quarter 4 Intervention period 5 The total number (Qb to Q4) is the average frequency of prescribed antibiotics per practices over the quarters 6 Supplementary

Weighted Means for practices with medium number of cases per quarter
*Weighted means and standard deviations are calculated by the inverse variance method using the practice's number of treatment cases as sample sizes to determine the