Cost-effectiveness analysis of procalcitonin and lung ultrasonography guided antibiotic prescriptions in primary care.

Antimicrobial resistance comes with high morbidity and mortality burden, and ultimately high impact on healthcare and social costs. Efficient strategies are needed to limit antibiotic overuse. This paper investigates the cost-effectiveness of testing patients with lower respiratory tract infection with procalcitonin, either at the point-of-care only or combined with lung ultrasonography. These diagnostic tools help detect the presence of bacterial pneumonia, guiding prescription decisions. The clinical responses of these strategies were studied in the primary care setting. Evidence is needed on their cost-effectiveness. We used data from a cluster-randomized bi-centric clinical trial conducted in Switzerland and estimated patient-level costs using data on resource use to which we applied Swiss tariffs. Combining the incremental costs of the two strategies and the reduction in the 28-days antibiotic prescription rate (APR) compared to usual care, we calculated Incremental Cost-Effectiveness Ratios (ICER). We also used the Cost-Effectiveness Acceptability Curve as an analytical decision-making tool. The robustness of the findings is ensured by Probabilistic Sensitivity Analysis and scenario analysis. In the base case scenario, the ICER compared to usual care is $2.3 per percentage point (pp) reduction in APR for the procalcitonin group, and $4.4 for procalcitonin-ultrasound combined. Furthermore, we found that for a willingness to pay per patient of more than $2 per pp reduction in the APR, procalcitonin is the strategy with the highest probability to be cost-effective. Our findings suggest that testing patients with respiratory symptoms with procalcitonin to guide antibiotic prescription in the primary care setting represents good value for money.

Pseudomonasaeruginosa antimicrobial susceptibility profiles, resistance mechanisms and international clonal lineages: update from ESGARS-ESCMID/ISARPAE Group.

SCOPE: Pseudomonas aeruginosa, a ubiquitous opportunistic pathogen considered one of the paradigms of antimicrobial resistance, is among the main causes of hospital-acquired and chronic infections associated with significant morbidity and mortality. This growing threat results from the extraordinary capacity of P. aeruginosa to develop antimicrobial resistance through chromosomal mutations, the increasing prevalence of transferable resistance determinants (such as the carbapenemases and the extended-spectrum ß-lactamases), and the global expansion of epidemic lineages. The general objective of this initiative is to provide a comprehensive update of P. aeruginosa resistance mechanisms, especially for the extensively drug-resistant (XDR)/difficult-to-treat resistance (DTR) international high-risk epidemic lineages, and how the recently approved ß-lactams and ß-lactam/ß-lactamase inhibitor combinations may affect resistance mechanisms and the definition of susceptibility profiles. METHODS: To address this challenge, the European Study Group for Antimicrobial Resistance Surveillance (ESGARS) from the European Society of Clinical Microbiology and Infectious Diseases launched the 'Improving Surveillance of Antibiotic-Resistant Pseudomonas aeruginosa in Europe (ISARPAE)' initiative in 2022, supported by the Joint programming initiative on antimicrobial resistance network call and included a panel of over 40 researchers from 18 European Countries. Thus, a ESGARS-ISARPAE position paper was designed and the final version agreed after four rounds of revision and discussion by all panel members. QUESTIONS ADDRESSED IN THE POSITION PAPER: To provide an update on (a) the emerging resistance mechanisms to classical and novel anti-pseudomonal agents, with a particular focus on ß-lactams, (b) the susceptibility profiles associated with the most relevant ß-lactam resistance mechanisms, (c) the impact of the novel agents and resistance mechanisms on the definitions of resistance profiles, and (d) the globally expanding XDR/DTR high-risk lineages and their association with transferable resistance mechanisms. IMPLICATION: The evidence presented herein can be used for coordinated epidemiological surveillance and decision making at the European and global level.

Exploration of the Acceptance of the Use of Procalcitonin Point-of-Care Testing and Lung Ultrasonography by General Practitioners to Decide on Antibiotic Prescriptions for Lower Respiratory Infections: A Qualitative Study.

OBJECTIVES: We aimed to explore the acceptance and opinions of general practitioners (GPs) on the use of procalcitonin point-of-care and lung ultrasonography for managing patients with lower respiratory tract infections in primary care. We suppose that there are several factors that can influence the physician's antibiotic prescribing decision, and the implementation of a new tool will only be possible when it can be inserted into the physician's daily practice, helping him/her in the decision-making process. DESIGN: Semistructured interviews; data analysis using the grounded theory method. SETTING: Lausanne, Switzerland. PARTICIPANTS: 12 GPs who participated in the randomised clinical trial UltraPro, which evaluated the impact of the use of procalcitonin only or an algorithm combining procalcitonin and lung ultrasonography on antibiotic prescription. RESULTS: GPs had mostly positive attitudes towards the use of point-of-care procalcitonin in lower respiratory tract infections and uncertainties regarding the usefulness of ultrasonography. Physicians' prescribing decisions result from interactions between three kinds of TrustS (core category): 'self-confidence', 'trust in the results' and 'trust in the doctor-patient relationship'. Procalcitonin reinforced the three levels of trust, while ultrasonography only strengthened the physician-patient relationship. To facilitate implementation of procalcitonin, physicians pointed out the need of coverage by insurance and of clear guidelines describing the targeted patient population. CONCLUSIONS: Our data show that there is a preference for the implementation of procalcitonin rather than lung ultrasonography for the management of patients with lower respiratory tract infections in primary care. Coverage by insurance plans and updated guidelines are prerequisite to the successful implementation of procalcitonin testing in primary care. TRIAL REGISTRATION NUMBER: NCT03191071.

Estimating antibiotic coverage from linked microbiological and clinical data from the Swiss Paediatric Sepsis Study to support empiric antibiotic regimen selection.

In light of rising antibiotic resistance, better methods for selection of empiric antibiotic treatment based on clinical and microbiological data are needed. Most guidelines target specific clinical infections, and variably adjust empiric antibiotic selection by certain patient characteristics. Coverage estimates reflect the probability that an antibiotic regimen will be active against the causative pathogen once confirmed and can provide an objective basis for empiric regimen selection. Coverage can be estimated for specific infections using a weighted incidence syndromic combination antibiograms (WISCAs) framework. However, no comprehensive data combining clinical and microbiological data for specific clinical syndromes are available in Switzerland. We therefore describe estimating coverage from semi-deterministically linked routine microbiological and cohort data of hospitalised children with sepsis. Coverage estimates were generated for each hospital and separately pooling data across ten contributing hospitals for five pre-defined patient risk groups. Data from 1,082 patients collected during the Swiss Paediatric Sepsis Study (SPSS) 2011-2015 were included. Preterm neonates were the most commonly represented group, and half of infants and children had a comorbidity. 67% of neonatal sepsis cases were hospital-acquired late-onset whereas in children 76% of infections were community-acquired. Escherichia coli, Coagulase-negative staphylococci (CoNS) and Staphylococcus aureus were the most common pathogens. At all hospitals, ceftazidime plus amikacin regimen had the lowest coverage, and coverage of amoxicillin plus gentamicin and meropenem were generally comparable. Coverage was improved when vancomycin was included in the regimen, reflecting uncertainty about the empirically targeted pathogen spectrum. Children with community-acquired infections had high coverage overall. It is feasible to estimate coverage of common empiric antibiotic regimens from linked data. Pooling data by patient risk groups with similar expected pathogen and susceptibility profiles may improve coverage estimate precision, supporting better differentiation of coverage between regimens. Identification of data sources, selection of regimens and consideration of pathogens to target for improved empiric coverage is important.

Associated deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in Switzerland, 2010 to 2019.

BackgroundCassini et al. (2019) estimated that, in 2015, infections with 16 different antibiotic-resistant bacteria resulted in ca 170 disability-adjusted life-years (DALYs) per 100,000 population in the European Union and European Economic area (EU/EEA). The corresponding estimate for Switzerland was about half of this (87.8 DALYs per 100,000 population) but still higher than that of several EU/EEA countries (e.g. neighbouring Austria (77.2)).AimIn this study, the burden caused by the same infections due to antibiotic-resistant bacteria ('AMR burden') in Switzerland from 2010 to 2019 was estimated and the effect of the factors 'linguistic region' and 'hospital type' on this estimate was examined.MethodsNumber of infections, DALYs and deaths were estimated according to Cassini et al. (2019) whereas separate models were built for each linguistic region/hospital type combination.ResultsDALYs increased significantly from 3,995 (95% uncertainty interval (UI): 3;327-4,805) in 2010 to 6,805 (95% UI: 5,820-7,949) in 2019. Linguistic region and hospital type stratifications significantly affected the absolute values and the slope of the total AMR burden estimates. DALYs per population were higher in the Latin part of Switzerland (98 DALYs per 100,000 population; 95% UI: 83-115) compared with the German part (57 DALYs per 100,000 population; 95% UI: 49-66) and in university hospitals (165 DALYs per 100,000 hospitalisation days; 95% UI: 140-194) compared with non-university hospitals (62 DALYs per 100,000 hospitalisation days; 95% UI: 53-72).ConclusionsThe AMR burden estimate in Switzerland has increased significantly between 2010 and 2019. Considerable differences depending on the linguistic region and the hospital type were identified - a finding which affects the nationwide burden estimation.

Carbonates and intermediate-depth seismicity: Stable and unstable shear in altered subducting plates and overlying mantle.

A model for intermediate-depth earthquakes of subduction zones is evaluated based on shear localization, shear heating, and runaway creep within thin carbonate layers in an altered downgoing oceanic plate and the overlying mantle wedge. Thermal shear instabilities in carbonate lenses add to potential mechanisms for intermediate-depth seismicity, which are based on serpentine dehydration and embrittlement of altered slabs or viscous shear instabilities in narrow fine-grained olivine shear zones. Peridotites in subducting plates and the overlying mantle wedge may be altered by reactions with CO2-bearing fluids sourced from seawater or the deep mantle, to form carbonate minerals, in addition to hydrous silicates. Effective viscosities of magnesian carbonates are higher than those for antigorite serpentine and they are markedly lower than those for H2O-saturated olivine. However, magnesian carbonates may extend to greater mantle depths than hydrous silicates at temperatures and pressures of subduction zones. Strain rates within altered downgoing mantle peridotites may be localized within carbonated layers following slab dehydration. A simple model of shear heating and temperature-sensitive creep of carbonate horizons, based on experimentally determined creep laws, predicts conditions of stable and unstable shear with strain rates up to 10/s, comparable to seismic velocities of frictional fault surfaces. Applied to intermediate-depth earthquakes of the Tonga subduction zone and the double Wadati-Benioff zone of NE Japan, this mechanism provides an alternative to the generation of earthquakes by dehydration embrittlement, beyond the stability of antigorite serpentine in subduction zones.

Pulse Oximetry as an Aid to Rule Out Pneumonia among Patients with a Lower Respiratory Tract Infection in Primary Care.

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.

Bacterial species and antimicrobial resistance differ between catheter and non-catheter-associated urinary tract infections: Data from a national surveillance network.

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 ß-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.

Effect of Antibiotic Prescription Audit and Feedback on Antibiotic Prescribing in Primary Care: A Randomized Clinical Trial.

Importance: Antibiotics are commonly prescribed in primary care, increasing the risk of antimicrobial resistance in the population. Objective: To investigate the effect of quarterly audit and feedback on antibiotic prescribing among primary care physicians in Switzerland with medium to high antibiotic prescription rates. Design, Setting, and Participants: This pragmatic randomized clinical trial was conducted from January 1, 2018, to December 31, 2019, among 3426 registered primary care physicians and pediatricians in single or small practices in Switzerland who were among the top 75% prescribers of antibiotics. Intention-to-treat analysis was performed using analysis of covariance models and conducted from September 1, 2021, to January 31, 2022. Interventions: Primary care physicians were randomized in a 1:1 fashion to undergo quarterly antibiotic prescribing audit and feedback with peer benchmarking vs no intervention for 2 years, with 2017 used as the baseline year. Anonymized patient-level claims data from 3 health insurers serving roughly 50% of insurees in Switzerland were used for audit and feedback. The intervention group also received evidence-based guidelines for respiratory tract and urinary tract infection management and community antibiotic resistance information. Physicians in the intervention group were blinded regarding the nature of the trial, and physicians in the control group were not informed of the trial. Main Outcomes and Measures: The claims data used for audit and feedback were analyzed to assess outcomes. Primary outcome was the antibiotic prescribing rate per 100 consultations during the second year of the intervention. Secondary end points included overall antibiotic use in the first year and over 2 years, use of quinolones and oral cephalosporins, all-cause hospitalizations, and antibiotic use in 3 age groups. Results: A total of 3426 physicians were randomized to the intervention (n = 1713) and control groups (n = 1713) serving 629 825 and 622 344 patients, respectively, with a total of 4 790 525 consultations in the baseline year of 2017. In the entire cohort, a 4.2% (95% CI, 3.9%-4.6%) relative increase in the antibiotic prescribing rate was noted during the second year of the intervention compared with 2017. In the intervention group, the median annual antibiotic prescribing rate per 100 consultations was 8.2 (IQR, 6.1-11.4) in the second year of the intervention and was 8.4 (IQR, 6.0-11.8) in the control group. Relative to the overall increase, a -0.1% (95% CI, -1.2% to 1.0%) lower antibiotic prescribing rate per 100 consultations was found in the intervention group compared with the control group. No relevant reductions in specific antibiotic prescribing rates were noted between groups except for quinolones in the second year of the intervention (-0.9% [95% CI, -1.5% to -0.4%]). Conclusions and Relevance: This randomized clinical trial found that quarterly personalized antibiotic prescribing audit and feedback with peer benchmarking did not reduce antibiotic prescribing among primary care physicians in Switzerland with medium to high antibiotic prescription rates. Trial Registration: ClinicalTrials.gov Identifier: NCT03379194.

Overruling of Procalcitonin-Guided Antibiotics for Lower Respiratory Tract Infections in Primary Care: Ancillary Study of a Randomized Controlled Trial.

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.

Increase in methicillin-susceptible Staphylococcus aureus bloodstream infections in Switzerland: a nationwide surveillance study (2008-2021).

PURPOSE: An increasing burden of Staphylococcus aureus bloodstream infections (BSI), despite a decrease in the percentage of methicillin-resistant S. aureus (MRSA), was described recently in other European countries. The main aim of this study was to analyse recent temporal trends of S. aureus, methicillin-susceptible S. aureus (MSSA) and MRSA BSI for Switzerland as well as the different linguistic regions within Switzerland. An additional aim was to estimate potential differences among patient-based and epidemiological risk factors. METHODS: A retrospective observational study was conducted in Switzerland over a period of 14 years (2008-2021). Trends in S. aureus, MSSA and MRSA BSI were analysed by applying linear regression models. RESULTS: Staphylococcus aureus BSI increased by + 30% from 19.7 to 25.6 cases per 100,000 inhabitants between 2008 and 2021 (P < 0.01) in Switzerland. Thereof, MSSA increased by + 37% from 17.8 to 24.4 cases per 100,000 inhabitants (P < 0.01). MRSA decreased from 1.9 to 1.2 cases per 100,000 inhabitants (P < 0.01), which was driven by decreasing incidence in the French-speaking region. MSSA BSI increased significantly (P < 0.01) in both linguistic regions. A further stratification revealed that incidence increased the most in male patients of the age group ≥ 80 years of the German-speaking region. CONCLUSION: The increasing health burden of MSSA BSI in Switzerland indicates that not only proportions of resistant microorganisms but also total BSI incidences should be monitored. In addition, data stratification revealed that the increase was mainly driven by an increasing incidence in elderly males of the German-speaking region.

Antibiotic resistance surveillance of Klebsiella pneumoniae complex is affected by refined MALDI-TOF identification, Swiss data, 2017 to 2022.

BackgroundModern laboratory methods such as next generation sequencing and MALDI-TOF allow identification of novel bacterial species. This can affect surveillance of infections and antimicrobial resistance. From 2017, increasing numbers of medical microbiology laboratories in Switzerland differentiated Klebsiella variicola from Klebsiella pneumoniae complex using updated MALDI-TOF databases, whereas many laboratories still report them as K. pneumoniae or K. pneumoniae complex.AimOur study explored whether separate reporting of K. variicola and the Klebsiella pneumoniae complex affected the ANRESIS surveillance database.MethodsWe analysed antibiotic susceptibility rates and specimen types of K. variicola and non-K. variicola-K. pneumoniae complex isolates reported by Swiss medical laboratories to the ANRESIS database (Swiss Centre for Antibiotic Resistance) from January 2017 to June 2022.ResultsAnalysis of Swiss antimicrobial resistance data revealed increased susceptibility rates of K. variicola compared with species of the K. pneumoniae complex other than K. variicola in all six antibiotic classes tested. This can lead to underestimated resistance rates of K. pneumoniae complex in laboratories that do not specifically identify K. variicola. Furthermore, K. variicola strains were significantly more often reported from blood and primarily sterile specimens than isolates of the K. pneumoniae complex other than K. variicola, indicating increased invasiveness of K. variicola.ConclusionOur data suggest that refined differentiation of the K. pneumoniae complex can improve our understanding of its taxonomy, susceptibility, epidemiology and clinical significance, thus providing more precise information to clinicians and epidemiologists.

Air temperature and incidence of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae.

BACKGROUND: Higher outdoor temperature may be related to an increase in antibiotic resistant bacteria. We investigated the association between local outdoor air temperature and the incidence of extended-spectrum betalactamase (ESBL)-producing Enterobacteriaceae (ESBL-PE) correcting for known drivers of antibiotic resistance. METHODS: We performed a time-series regression study using prospectively collected weekly surveillance data on all ESBL-PE isolated from in- and outpatients of the University Hospital Basel, a tertiary care center in Switzerland, between 01/2008-12/2017. Temperature was measured hourly at the meteorological institute of the University Basel next to our institution over this time period. A time-series approach using a Poisson regression model and different lag terms for delayed exposure effects was performed to assess associations between minimal, mean and maximal weekly temperature and the number of ESBL-PE recovered. RESULTS: Over 10 years, recovery of ESBL-PE increased (annual incidence rate ratio [IRR] 1.14, 95%CI 1.13-1.16), while mean weekly temperature measures remained stable. In multivariable analyses, increasing temperature was associated with higher recovery rates of ESBL-PE after three to four weeks, correcting for potential confounders, such as the number of admissions, proportion of long-term nursing facility- and ICU-admissions, age, Charlson comorbidity index and consumption of antimicrobials (IRRs per 10 °C ranging from 1.14 to 1.22, 95%CIs 1.07-1.33). These trends remained when analyzing correlations between temperature with the proportion of extended spectrum cephalosporin resistance of all recovered Enterobacteriaceae. CONCLUSIONS: Higher outdoor temperature may be associated with an increase of ESBL-PE-incidence, independent of important confounders, such as antimicrobial consumption and thus should be considered for future resistance-trajectories.

Reducing antibiotic use in uncomplicated urinary tract infections in adult women: a systematic review and individual participant data meta-analysis.

BACKGROUND: Randomised controlled trials (RCTs) investigated analgesics, herbal formulations, delayed prescription of antibiotics, and placebo to prevent overprescription of antibiotics in women with uncomplicated urinary tract infections (uUTI). OBJECTIVES: To estimate the effect of these strategies and to identify symptoms, signs, or other factors that indicate a benefit from these strategies. DATA SOURCES: MEDLINE, EMBASE, Web of Science, LILACS, Cochrane Database of Systematic Reviews and of Controlled Trials, and ClinicalTrials. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS AND INTERVENTIONS: RCTs investigating any strategies to reduce antibiotics vs. immediate antibiotics in adult women with uUTI in primary care. METHODS: We extracted individual participant data (IPD) if available, otherwise aggregate data (AD). Bayesian random-effects meta-analysis of the AD was used for pairwise comparisons. Candidate moderators and prognostic indicators of treatment effects were investigated using generalised linear mixed models based on IPD. RESULTS: We analysed IPD of 3524 patients from eight RCTs and AD of 78 patients. Non-antibiotic strategies increased the rates of incomplete recovery (OR 3.0; 95% credible interval (CrI), 1.7-5.5; Bayesian p-value (pB) = 0.0017; τ = 0.6), subsequent antibiotic treatment (OR 3.5; 95% CrI, 2.1-5.8; pB = 0.0003) and pyelonephritis (OR 5.6; 95% CrI, 2.3-13.9; pB = 0.0003). Conversely, they decreased overall antibiotic use by 63%. Patients positive for urinary erythrocytes and urine culture were at increased risk for incomplete recovery (OR 4.7; 95% CrI, 2.1-10.8; pB = 0.0010), but no difference was apparent where both were negative (OR 0.8; 95% CrI, 0.3-2.0; pB = 0.667). In patients treated using non-antibiotic strategies, urinary erythrocytes and positive urine culture were independent prognostic indicators for subsequent antibiotic treatment and pyelonephritis. CONCLUSIONS: Compared to immediate antibiotics, non-antibiotic strategies reduce overall antibiotic use but result in poorer clinical outcomes. The presence of erythrocytes and tests to confirm bacteria in urine could be used to target antibiotic prescribing.

Retrospective data analysis for definition of multidrug resistance in gram-negative bacteria - a consensus proposal.

AIM OF THE STUDY: The main objective of this study was to propose a common definition of multidrug-resistant gram-negative organisms (GN-MDRO), which may be used for epidemiological surveillance and benchmarking. METHODS: In this retrospective data analysis, we used interpreted qualitative susceptibility data (SIR) from blood culture isolates of different gram-negative microorganisms from the ANRESIS database from 2017-2021. We first analysed testing algorithms used by different Swiss laboratories and investigated cross-resistance patterns within antibiotic groups. Comparing these data with existing international definitions, we developed two different GN-MDRO definitions, an extended one for surveillance purposes (ANRESIS-extended) and a more stringent one for clinical purposes, aimed primarily at the identification of difficult-to-treat GN-MDRO (ANRESIS-restricted). Using these novel algorithms, the rates of invasive GN-MDRO identified in our national dataset were compared with international and national definitions: the European Centre for Disease Prevention and Control (ECDC) definition, the Commission for Hospital Hygiene and Infection (KRINKO) definition and the definition proposed by the University Hospital Zurich. RESULTS: SIR data of a total of 41,785 Enterobacterales, 2,919 , and 419 spp. isolates were used for the analyses. Five antibiotic categories were used for our MDRO definition: aminoglycosides, piperacillin-tazobactam, third- and fourth-generation cephalosporins, carbapenems and fluoroquinolones. Large differences were found between the testing algorithms of the different laboratories. Cross-resistance analysis within an antibiotic group revealed that the substance most likely to be effective against a particular gram-negative bacterium was not preferentially tested (e.g. amikacin for the aminoglycosides). For all bacterial species tested, the highest rates of multidrug-resistant isolates were found using the ECDC-MDR definition, followed by the ANRESIS-extended definition. The number of MDR-Enterobacterales identified using the ANRESIS-restricted definition (n = 627) was comparable to those identified using the KRINKO (n = 622) and UHZ definitions (n = 437). However, the isolates classified as MDR-Enterobacterales according to the KRINKO, UHZ and ANRESIS-restricted definitions (total n = 870) differed considerably. Only 242 of the isolates (27.8%) were uniformly classified as MDRO according to the KRINKO, UHZ and ANRESIS-restricted definitions. Comparable findings were made for Klebsiella spp. and Pseudomonas aeruginosa. CONCLUSIONS: The application of different MDRO definitions leads to significant differences in not only MDRO rates but also the isolates that are eventually classified as MDRO. Therefore, defining a nationwide MDRO algorithm is crucial if data are compared between hospitals. The definition of a minimal antibiotic susceptibility testing panel would improve comparability further.

Impact of the COVID-19 Pandemic on Inpatient Antibiotic Consumption in Switzerland.

The aim of this study was to analyze inpatient antibiotic consumption during the first 16 months of the COVID-19 pandemic in Switzerland. The entire period (January 2018−June 2021) was divided into the prepandemic period, the first and second waves, and the intermediate period. In the first year of the pandemic, total overall inpatient antibiotic consumption measured in defined daily doses (DDD) per 100 bed-days remained stable (+1.7%), with a slight increase in ICUs of +4.2%. The increase in consumption of broad-spectrum antibiotics was +12.3% overall and 17.3% in ICUs. The segmented regression model of monthly data revealed an increase in overall antibiotic consumption during the first wave but not during the second wave. In the correlation analysis performed in a subset of the data, a significant positive association was found between broad-spectrum antibiotic consumption and an increasing number of hospitalized COVID-19 patients (p = 0.018). Restricting this dataset to ICUs, we found significant positive correlations between the number of hospitalized COVID-19 patients and total antibiotic consumption (p = 0.007) and broad-spectrum antibiotic consumption (p < 0.001). In conclusion, inpatient antibiotic use during the different periods of the COVID-19 pandemic varied greatly and was predominantly notable for broad-spectrum antibiotics.

The impact of public health interventions on the future prevalence of ESBL-producing Klebsiella pneumoniae: a population based mathematical modelling study.

BACKGROUND: Future prevalence of colonization with extended-spectrum betalactamase (ESBL-) producing K. pneumoniae in humans and the potential of public health interventions against the spread of these resistant bacteria remain uncertain. METHODS: Based on antimicrobial consumption and susceptibility data recorded during > 13 years in a Swiss region, we developed a mathematical model to assess the comparative effect of different interventions on the prevalence of colonization. RESULTS: Simulated prevalence stabilized in the near future when rates of antimicrobial consumption and in-hospital transmission were assumed to remain stable (2025 prevalence: 6.8% (95CI%:5.4-8.8%) in hospitals, 3.5% (2.5-5.0%) in the community versus 6.1% (5.0-7.5%) and 3.2% (2.3-4.2%) in 2019, respectively). When overall antimicrobial consumption was set to decrease by 50%, 2025 prevalence declined by 75% in hospitals and by 64% in the community. A 50% decline in in-hospital transmission rate led to a reduction in 2025 prevalence of 31% in hospitals and no reduction in the community. The best model fit estimated that 49% (6-100%) of observed colonizations could be attributable to sources other than human-to-human transmission within the geographical setting. CONCLUSIONS: Projections suggests that overall antimicrobial consumption will be, by far, the most powerful driver of prevalence and that a large fraction of colonizations could be attributed to non-local transmissions.

Agrobacterium species bacteraemia, Switzerland, 2008 to 2019: a molecular epidemiological study.

BACKGROUND: Agrobacterium spp. are infrequent agents of bloodstream infections linked to healthcare-associated outbreaks. However, it is unclear if outbreaks also occur across larger geographic areas. Triggered by two local clusters from putative point sources, our aim was to detect potential additional clusters in Switzerland. METHODS: We performed a nationwide descriptive study of cases in Switzerland based on a prospective surveillance system (Swiss Centre for Antibiotic Resistance, anresis.ch), from 2008 to 2019. We identified patients with Agrobacterium spp. isolated from blood cultures and used a survey to collect clinical-epidemiological information and susceptibility testing results. We performed whole genome sequencing (WGS) of available clinical isolates and determined their relatedness by single nucleotide polymorphism (SNP) variant calling analysis. RESULTS: We identified a total of 36 cases of Agrobacterium spp. from blood samples over 10 years. Beyond previously known local clusters, no new ones were identified. WGS-based typing was performed on 22 available isolates and showed no clonal relationships between newly identified isolates or to those from the known clusters, with all isolates outside these clusters being at least 50 SNPs apart. CONCLUSION AND RELEVANCE: Agrobacterium spp. bacteraemia is infrequently detected and, given that it may be healthcare-associated and stem from a point source, occurrence of multiple episodes should entail an outbreak investigation. With the help of the national antimicrobial resistance surveillance system we identified multiple clinical cases of this rare pathogen but found no evidence by WGS that suggested a nation-wide outbreak.

High adherence to national IPC guidelines as key to sustainable VRE control in Swiss hospitals: a cross-sectional survey.

BACKGROUND: Vancomycin resistant enterococci (VRE) are on the rise in many European hospitals. In 2018, Switzerland experienced its largest nosocomial VRE outbreak. The national center for infection prevention (Swissnoso) elaborated recommendations for controlling this outbreak and published guidelines to prevent epidemic and endemic VRE spread. The primary goal of this study was to evaluate adherence to this new guideline and its potential impact on the VRE epidemiology in Swiss acute care hospitals. METHODS: In March 2020, Swissnoso distributed a survey among all Swiss acute care hospitals. The level of adherence as well as changes of infection prevention and control (IPC) strategies in the years 2018 and 2019 after publication of the national guidelines were asked along with an inventory on VRE surveillance and outbreaks. RESULTS: Data of 97/146 (66%) participants were available, representing 81.6% of all acute care beds operated in Switzerland in 2019. The vast majority-72/81 (88%) responding hospitals-have entirely or largely adopted our new national guideline. 38/51 (74.5%) hospitals which experienced VRE cases were significantly more likely to have changed their IPC strategies than those 19/38 (50%) hospitals without VRE cases p = 0.017). The new IPC guidelines included (1) introduction of targeted admission screening in 89.5%, (2) screening of close contacts of VRE cases in 56%, and (3) contact precaution for suspected VRE cases 58% of these hospitals. 52 (54%) hospitals reported 569 new VRE cases in 2018 including 14 bacteremia, and 472 new cases in 2019 with 10 bacteremia. The ten largest outbreaks encountered between 2018 and 2019 included 671 VRE cases, of which most (93.4%) consisted of colonization events, 29 (4.3%) infections and 15 (2.2%) bacteremia. CONCLUSION: Wide adoption of this VRE control guideline seemed to have a positive effect on VRE containment in Swiss acute care hospitals over two years, even if its long-term impact on the VRE epidemiology remains to be evaluated. Broad dissemination and strict implementation of a uniform national guideline may therefore serve as model for other countries to fight VRE epidemics on a national level.