Andreas Kronenberg

Antimicrobial resistance (AMR) surveillance requires approaches that monitor both clinical and community-level dynamics. We monitored antibiotic-resistant bacteria in Swiss wastewater and compared these results with human resistance and antibiotic consumption data from the national surveillance network ANRESIS. Between 2021 and 2024, 772 samples from six wastewater treatment plants were analyzed for Escherichia coli , extended-spectrum β-lactamase-producing (ESBL)- E.coli , carbapenem-resistant E. coli (CR- E.coli ), Enterococcus faecium/faecalis , and vancomycin-resistant enterococci (VRE). The rank order of the proportion of resistance was conserved between wastewater and clinical data. Mean (±standard deviation) wastewater resistance percentages were 2.2±0.8 for ESBL- E.coli , 0.4±0.6 for VRE, and 0.1±0.1 for CR- E.coli . Clinical resistance percentages were 9.8±0.8 for ESBL- E.coli , 2.9±1.4 for VRE, and 0.3±0.1 for CR- E.coli . Both datasets showed similar rising trends for ESBL- E. coli and VRE, while CR- E. coli remained stable in wastewater but increased slightly in clinics. No consistent lead-lag relationships were observed between wastewater resistance, clinical resistance, or antibiotic use, indicating independent short-term dynamics. Resistance percentages in wastewater were not associated with antibiotic use data for either the antibiotics used for treatment or the ones that are selective for the target. These results suggest that wastewater monitoring reflects long-term population-level AMR dynamics, aligning with clinical trends over years but not months. Graphical Synopsis: Antibiotic-resistant bacteria in Swiss wastewater alongside hospital resistance and antibiotic use data reveal increasing community resistance and show how environmental surveillance can complement clinical surveillance in understanding antibiotic resistance spread.

We describe the emergence of vancomycin-resistant Enterococcus faecium (VREfm) vanA ST612 in Switzerland from 2018 to 2024 that resulted in a national outbreak investigation. This clone has predisposing genetic alterations associated with reduced daptomycin susceptibility. The National Nosocomial Outbreak Investigation Center was commissioned to assess the temporospatial distribution of this clone in Switzerland and evaluate its clinical impact. Core genome multi-locus sequence typing (cgMLST) revealed five separate VREfm van A ST612 clusters of different sizes across different healthcare regions, but predominantly in the German-speaking part. The broad geographic dissemination and temporal variation in detection suggests multiple introductions to the healthcare system. One of these cgMLST clusters (n = 79 cases) with an infection rate of 12.8% was ongoing, mainly affecting patients with extensive contact to the Swiss healthcare system or prior antibiotic exposure. The detection of daptomycin non-susceptibility in patients without prior daptomycin exposure suggests ongoing E. faecium adaptation due to external pressures. Future prevention efforts should emphasise assessing barriers for active surveillance cultures, developing a national standard for cost-effective sequencing methods and promoting the sharing of sequencing results together with epidemiological metadata. Our report intends to raise awareness as this sequence type might already be spreading undetected in European countries.

To reduce antimicrobial resistance (AMR), pathogen-specific AMR burden data are crucial to guide target selection for research and development of vaccines and monoclonal antibodies (mAbs). We identified knowledge gaps through previously conducted systematic reviews, which informed a Delphi expert consultation on future AMR research priorities and harmonisation strategies to support data-driven decision-making. Consensus (≥80% agreement) on importance and feasibility of research topics was achieved in two rounds, involving 24 of 39 and 19 of 24 invited experts, respectively. Priority pathogens and resistance profiles for future research were identified: third generation cephalosporin-resistant Klebsiella pneumoniae and Escherichia coli, for bloodstream and urinary tract infections, respectively, and meticillin-resistant Staphylococcus aureus for surgical-site infections. Prioritised high-risk populations included surgical, haemato-oncological and transplant patients. Mortality and resource use were prioritised as health-economic outcomes. The importance of age-stratified data and inclusion of a non-infected comparator group were highlighted. This agenda provides guidance for future research to fill knowledge gaps and support data-driven selection of target pathogens and populations for new preventive and treatment strategies, specifically vaccines and mAbs, to effectively address the AMR burden in Europe. These research priorities are also relevant to improve the evidence base for future AMR burden estimates.

Background: Measuring the appropriateness of antibiotic use is crucial for antibiotic stewardship (ABS) programmes to identify targets for interventions. Objectives: To assess the technical feasibility of converting electronic medical record (EMR) data into ABS indicators. Methods: In this observational feasibility study covering a period of 2 years, the EMRs of patients hospitalized at a large non-university hospital network and receiving at least one dose of a systemic antibiotic were included. ABS indicators measuring steps in the process of antibiotic prescription proposed by the literature were collected and rephrased or defined more specifically to be calculable if needed. Algorithms were programmed in R to convert EMR data into ABS indicators. The indicators were visualized in an interactive dashboard and the plausibility of each output value was assessed. Results: In total, data from 25 337 hospitalizations from 20 723 individual patients were analysed and visualized in an interactive dashboard. Algorithms could be programmed to compute 89% (25/28) of all pre-selected indicators assessing treatment decisions automatically out of EMR data, with good data quality for 46% (13/28) of these indicators. According to the data quality observed, the most important issues were (i) missing or meaningless information on indication (e.g. ‘mild infection’) and (ii) data processing issues such as insufficiently categorized metadata. Conclusions: The calculation of indicators assessing treatment decisions from EMRs was feasible. However, better data structure and processing within EMR systems are crucial for improving the validity of the results.

Objective: To investigate clinically relevant microbiological characteristics of uropathogens and to compare patients with catheter-associated urinary tract infections (CAUTIs) to those with non-CAUTIs. Methods: All urine cultures from the calendar year 2019 of the Swiss Centre for Antibiotic Resistance database were analyzed. Group differences in the proportions of bacterial species and antibiotic-resistant isolates from CAUTI and non-CAUTI samples were investigated. Results: Data from 27,158 urine cultures met the inclusion criteria. Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Proteus mirabilis together represented 70% and 85% of pathogens identified in CAUTI and non-CAUTI samples, respectively. Pseudomonas aeruginosa was significantly more often detected in CAUTI samples. The overall resistance rate for the empirically often-prescribed antibiotics ciprofloxacin (CIP), norfloxacin (NOR), and trimethoprim-sulfamethoxazole (TMP-SMX) was between 13% and 31%. Except for nitrofurantoin, E. coli from CAUTI samples were more often resistant (P ≤ .048) to all classes of antibiotics analyzed, including third-generation cephalosporines used as surrogate for extended-spectrum β-lactamase (ESBL). Significanty higher resistance proportions in CAUTI samples versus non-CAUTI samples were observed for CIP (P = .001) and NOR (P = .033) in K. pneumoniae, for NOR (P = .011) in P. mirabilis, and for cefepime (P = .015), and piperacillin-tazobactam (P = .043) in P. aeruginosa. Conclusion: CAUTI pathogens were more often resistant to recommended empirical antibiotics than non-CAUTI pathogens. This finding emphasizes the need for urine sampling for culturing before initiating therapy for CAUTI and the importance of considering therapeutic alternatives.

Guidelines recommend chest X-rays (CXRs) to diagnose pneumonia and guide antibiotic treatment. This study aimed to identify clinical predictors of pneumonia that are visible on a chest X-ray (CXR+) which could support ruling out pneumonia and avoiding unnecessary CXRs, including oxygen saturation. A secondary analysis was performed in a clinical trial that included patients with suspected pneumonia in Swiss primary care. CXRs were reviewed by two radiologists. We evaluated the association between clinical signs (heart rate > 100/min, respiratory rate ≥ 24/min, temperature ≥ 37.8 °C, abnormal auscultation, and oxygen saturation < 95%) and CXR+ using multivariate analysis. We also calculated the diagnostic performance of the associated clinical signs combined in a clinical decision rule (CDR), as well as a CDR derived from a large meta-analysis (at least one of the following: heart rate > 100/min, respiratory rate ≥ 24/min, temperature ≥ 37.8 °C, or abnormal auscultation). Out of 469 patients from the initial trial, 107 had a CXR and were included in this study. Of these, 26 (24%) had a CXR+. We found that temperature and oxygen saturation were associated with CXR+. A CDR based on the presence of either temperature ≥ 37.8 °C and/or an oxygen saturation level < 95% had a sensitivity of 69% and a negative likelihood ratio (LR−) of 0.45. The CDR from the meta-analysis had a sensitivity of 92% and an LR− of 0.37. The addition of saturation < 95% to this CDR increased the sensitivity (96%) and decreased the LR− (0.21). In conclusion, this study suggests that pulse oximetry could be added to a simple CDR to decrease the probability of pneumonia to an acceptable level and avoid unnecessary CXRs.

Background: Lower respiratory tract infections (LRTIs) in primary care are a promising target for antibiotic stewardship. A clinical trial in Switzerland showed a large decrease in antibiotic prescriptions with procalcitonin guidance (cut-off < 0.25 µg/L) compared with usual care. However, one-third of patients with low procalcitonin at baseline received antibiotics by day 28. Aim: To explore the factors associated with the overruling of initial procalcitonin guidance. Design and Setting: Secondary analysis of a cluster randomized trial in which patients with an LRTI were included. Method: Using the characteristics of patients, their disease, and general practitioners (GPs), we conducted a multivariate logistic regression, adjusted for clustering. Results: Ninety-five out of 301 (32%) patients with low procalcitonin received antibiotics by day 28. Factors associated with an overruling of procalcitonin guidance were: a history of chest pain (adjusted OR [aOR] 1.81, 95% confidence interval 1.03–3.17); a prescription of chest X-ray by the GP (aOR 4.65, 2.32–9.34); a C-reactive protein measured retrospectively above 100 mg/L (aOR 7.48, 2.34–23.93, reference ≤ 20 mg/L); the location of the GP practice in an urban setting (aOR 2.27, 1.18–4.37); and the GP’s number of years of experience (aOR per year 1.05, 1.01–1.09). Conclusions: Overruling of procalcitonin guidance was associated with GPs’ socio-demographic characteristics, pointing to the general behavioral problem of overprescription by physicians. Continuous medical education and communication training might support the successful implementation of procalcitonin point-of-care tests aimed at antibiotic stewardship.