The Percentage of Antibiotic Resistance in Uncomplicated Community-Acquired Urinary Tract Infections.

BACKGROUND: Uncomplicated bacterial urinary tract infections(uUTIs) are commonly seen in outpatient practice. They are usuallytreated empirically with antibiotics. The pertinent German ClinicalPractice Guideline contains recommendations on antibiotic selection,with the additional advice that the local resistance situationshould be considered as well. However, up-to-date information onlocal resistance is often unavailable, because microbiological testingis mainly recommended for complicated UTIs. Resistance ratesare often higher in recurrent uUTIs than in single episodes. In thisstudy, we aimed to determine the resistance rates of Escherichiacoli (E. coli) in patients with community-acquired uUTIs and tomake these data available to the treating physicians. METHODS: In a nationwide cross-sectional study in Germany (DRKS00019059), we determined the percentages of resistance to antibioticsrecommended for uUTIs (first choice: fosfomycin, nitro -xoline, mecillinam, nitrofurantoin, trimethoprim; second choice:cefpodoxime, ciprofloxacin, cotrimoxazole, levofloxacin, norfloxacin,ofloxacin) over the period 2019-2021. The data were stratified bysingle episodes vs. recurrent UTIs (rUTIs). RESULTS: Data from 2390 subjects were analyzed. E. coli was foundin 75.4% of the samples with positive urine cultures (1082 out of1435). The resistance rate of E. coli in single episodes (n = 725)was less than 15% for all antibiotics tested. In rUTIs(n = 357), resistance rates were also less than 15%for the most part; the only exceptions were trimethoprim(21.4%) and cotrimoxazole (19.3%). CONCLUSION: For single episodes of uUTI, all of theantibiotics studied can be recommended, at least asfar as their resistance profiles are concerned. Forrecurrent UTI, all but trimethoprim and cotrimoxazolecan be recommended. The second-choice antibioticsexamined do not have a more favorable resistanceprofile than the first-choice antibiotics.

GPs' Perspective on a Multimodal Intervention to Enhance Guideline-Adherence in Uncomplicated Urinary Tract Infections: A Qualitative Process Evaluation of the Multicentric RedAres Cluster-Randomised Controlled Trial.

Urinary tract infections (UTIs) are among the most common reasons patients seeking health care and antibiotics to be prescribed in primary care. However, general practitioners' (GPs) guideline adherence is low. The RedAres randomised controlled trial aims to increase guideline adherence by implementing a multimodal intervention consisting of four elements: information on current UTI guidelines (1) and regional resistance data (2); feedback regarding prescribing behaviour (3); and benchmarking compared to peers (4). The RedAres process evaluation assesses GPs' perception of the multimodal intervention and the potential for implementation into routine care. We carried out 19 semi-structured interviews with GPs (intervention arm). All interviews were carried out online and audio recorded. For transcription and analysis, Mayring's qualitative content analysis was used. Overall, GPs considered the interventions helpful for knowledge gain and confirmation when prescribing. Information material and resistance were used for patient communication and teaching purposes. Feedback was considered to enhance reflection by breaking routines of clinical workup. Implementation into routine practice could be enhanced by integrating feedback loops into patient management systems and conveying targeted information via trusted channels or institutions. The process evaluation of RedAres intervention was considered beneficial by GPs. It confirms the convenience of multimodal interventions to enhance guideline adherence.

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.

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.

REDuction of Antibiotic RESistance (REDARES) in urinary tract infections using treatments according to national clinical guidelines: study protocol for a pragmatic randomized controlled trial with a multimodal intervention in primary care.

BACKGROUND: Urinary tract infections (UTIs) are a common cause of prescribing antibiotics in family medicine. In Germany, about 40% of UTI-related prescriptions are second-line antibiotics, which contributes to emerging resistance rates. To achieve a change in the prescribing behaviour among family physicians (FPs), this trial aims to implement the guideline recommendations in German family medicine. METHODS/DESIGN: In a randomized controlled trial, a multimodal intervention will be developed and tested in family practices in four regions across Germany. The intervention will consist of three elements: information on guideline recommendations, information on regional resistance and feedback of prescribing behaviour for FPs on a quarterly basis. The effect of the intervention will be compared to usual practice. The primary endpoint is the absolute difference in the mean of prescribing rates of second-line antibiotics among the intervention and the control group after 12 months. To detect a 10% absolute difference in the prescribing rate after one year, with a significance level of 5% and a power of 86%, a sample size of 57 practices per group will be needed. Assuming a dropout rate of 10%, an overall number of 128 practices will be required. The accompanying process evaluation will provide information on feasibility and acceptance of the intervention. DISCUSSION: If proven effective and feasible, the components of the intervention can improve adherence to antibiotic prescribing guidelines and contribute to antimicrobial stewardship in ambulatory care.  Trial registration DRKS, DRKS00020389, Registered 30 January 2020, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00020389 .

Intestinal colonization with extended-spectrum beta-lactamase producing Enterobacterales (ESBL-PE) during long distance travel: A cohort study in a German travel clinic (2016-2017).

BACKGROUND: Intercontinental travel contributes to the spread of extended-spectrum beta-lactamase producing Enterobacterales (ESBL-PE). We assessed risk factors for intestinal ESBL-PE colonization in people travelling to low and middle income countries in the tropics and subtropics to better understand how travel affects ESBL-PE spread. METHOD: This prospective cohort study in travellers attending a travel clinic in Leipzig, Germany was conducted in 2016-2017. Information on risk factors related to travel, symptoms, antibiotic use, health care usage, accommodation, destination, diet and hygiene was collected by questionnaire after travel. Stools were phenotypically tested for ESBL-PE before and after travel. Risk factors for ESBL-PE colonization were identified using logistic regression. RESULTS: Of the 230 travellers that were ESBL-PE negative before travelling, 23% (n = 53) travellers returned positive. Multivariable analyses showed that age, type of accommodation and travelling to Asia were associated with ESBL-PE colonization. CONCLUSIONS: Given that a considerable amount of travellers returned with ESBL-PE, we recommend raising awareness in returning high-risk travellers, e.g. those returning from high-risk areas. They should be aware that they may carry antimicrobial-resistant bacteria after travel, and how they can prevent its spread. The role of the type of accommodation as a factor favouring intestinal colonization with ESBL-PE requires further investigation.

Antimicrobial resistance of Escherichia coli isolates from outpatient urinary tract infections in women in six European countries including Russia.

OBJECTIVES: In the Northern Dimension Antibiotic Resistance Study (NoDARS), Finland, Germany, Latvia, Poland, Russia and Sweden collected urine samples from outpatient women (aged 18-65years) with symptoms of uncomplicated urinary tract infection (UTI) to investigate the levels of antimicrobial resistance (AMR) among Escherichia coli isolates. METHODS: A total of 775 E. coli isolates from 1280 clinical urine samples were collected from October 2015 to January 2017. Antimicrobial susceptibility testing was performed and the results were interpreted according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. RESULTS: Overall AMR rates to the commonly used antibiotics nitrofurantoin, fosfomycin and mecillinam (except for Germany that was missing a result for mecillinam) were 1.2%, 1.3% and 4.1%, respectively. The highest overall resistance rates were determined for ampicillin (39.6%), trimethoprim (23.8%), trimethoprim/sulfamethoxazole (22.4%), amoxicillin/clavulanic acid (16.7%) and ciprofloxacin (15.1%), varying significantly between countries. The rate of extended-spectrum ß-lactamase (ESBL) production was 8.7%. None of the isolates showed resistance to meropenem. CONCLUSIONS: In most cases, low AMR rates were detected against the first-line antibiotics recommended in national UTI treatment guidelines, giving support to their future use. These results also support the European Association of Urology guidelines stating that nitrofurantoin, fosfomycin and mecillinam are viable treatment options for uncomplicated UTI.

Antibiotic-Resistant E. coli in Uncomplicated Community-Acquired Urinary Tract Infection.

BACKGROUND: Routine urine culture testing is not recommended for uncomplicated urinary tract infections (UTIs). As a result, the antibiotic resistance patterns or the organisms causing UTIs are not adequately reflected in routine data. We studied the sensitivity of Escherichia coli (E. coli) to trimethoprim (TMP) and to cotrimoxazole (i.e., trimethoprim/sulfamethoxazole, TMP/SMX) in community-acquired UTI and compared the findings with the resistance data of the Antimicrobial Resistance Surveillance System (ARS). METHODS: General practitioners and internists in private practice prospectively recruited all of their adult patients with symptoms of a urinary tract infection from May 2015 to February 2016. Urine specimens from all patients were tested (including urine culture testing and antibiotic susceptibility) and infections were defined as uncomplicated or complicated UTIs. RESULTS: 1245 participants from 58 medical practices were enrolled in the study. Pathogenic organisms were found in the urine of 877 patients, of whom 74.5% had E. coli infections. Among the E.-coli-positive UTIs, 52.4% were classified as uncomplicated and 47.6% as complicated. The prevalence of E. coli that was resistant to TMP and to TMP/SMX in uncomplicated UTIs was 15.2% and 13.0%, respectively, compared to 25.3% and 24.4%, respectively, from all UTIs in ARS in 2015. Study participants who had previously taken antibiotics had the highest prevalence of E. coli resistance (30.9%), followed by those who had two or more UTIs within the past six months (28.9%). CONCLUSION: E. coli with resistance to TMP was significantly less prevalent among the study patients with uncomplicated UTIs than in the routine data of the ARS. Accordingly, TMP should still be considered as an option for the treatment of uncomplicated UTIs. TMP/SMX is considered the agent of second choice because of its side effects. Surveillance systems based on routine data do not yield a representative sample for the evaluation of the resistance situation in patients with uncomplicated UTIs.

Burden of Six Healthcare-Associated Infections on European Population Health: Estimating Incidence-Based Disability-Adjusted Life Years through a Population Prevalence-Based Modelling Study.

BACKGROUND: Estimating the burden of healthcare-associated infections (HAIs) compared to other communicable diseases is an ongoing challenge given the need for good quality data on the incidence of these infections and the involved comorbidities. Based on the methodology of the Burden of Communicable Diseases in Europe (BCoDE) project and 2011-2012 data from the European Centre for Disease Prevention and Control (ECDC) point prevalence survey (PPS) of HAIs and antimicrobial use in European acute care hospitals, we estimated the burden of six common HAIs. METHODS AND FINDINGS: The included HAIs were healthcare-associated pneumonia (HAP), healthcare-associated urinary tract infection (HA UTI), surgical site infection (SSI), healthcare-associated Clostridium difficile infection (HA CDI), healthcare-associated neonatal sepsis, and healthcare-associated primary bloodstream infection (HA primary BSI). The burden of these HAIs was measured in disability-adjusted life years (DALYs). Evidence relating to the disease progression pathway of each type of HAI was collected through systematic literature reviews, in order to estimate the risks attributable to HAIs. For each of the six HAIs, gender and age group prevalence from the ECDC PPS was converted into incidence rates by applying the Rhame and Sudderth formula. We adjusted for reduced life expectancy within the hospital population using three severity groups based on McCabe score data from the ECDC PPS. We estimated that 2,609,911 new cases of HAI occur every year in the European Union and European Economic Area (EU/EEA). The cumulative burden of the six HAIs was estimated at 501 DALYs per 100,000 general population each year in EU/EEA. HAP and HA primary BSI were associated with the highest burden and represented more than 60% of the total burden, with 169 and 145 DALYs per 100,000 total population, respectively. HA UTI, SSI, HA CDI, and HA primary BSI ranked as the third to sixth syndromes in terms of burden of disease. HAP and HA primary BSI were associated with the highest burden because of their high severity. The cumulative burden of the six HAIs was higher than the total burden of all other 32 communicable diseases included in the BCoDE 2009-2013 study. The main limitations of the study are the variability in the parameter estimates, in particular the disease models' case fatalities, and the use of the Rhame and Sudderth formula for estimating incident number of cases from prevalence data. CONCLUSIONS: We estimated the EU/EEA burden of HAIs in DALYs in 2011-2012 using a transparent and evidence-based approach that allows for combining estimates of morbidity and of mortality in order to compare with other diseases and to inform a comprehensive ranking suitable for prioritization. Our results highlight the high burden of HAIs and the need for increased efforts for their prevention and control. Furthermore, our model should allow for estimations of the potential benefit of preventive measures on the burden of HAIs in the EU/EEA.