Publications by authors named "Andreas Widmer"

219 Publications

Antibiotic prescription monitoring and feedback in primary care in Switzerland: Design and rationale of a nationwide pragmatic randomized controlled trial.

Contemp Clin Trials Commun 2021 Mar 20;21:100712. Epub 2021 Jan 20.

Basel Institute for Clinical Epidemiology and Biostatistics, Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland.

Introduction: Antibiotic consumption is highest in primary care, and antibiotic overuse furthers antimicrobial resistance. In our recently published pilot-RCT, we used monthly aggregated claims data to provide personalized antibiotic prescription feedback to general practitioners (GPs). The pilot-RCT has shown that personalized prescription feedback is a feasible and promising low-cost intervention to reduce antibiotic prescribing. Here, we describe the rationale and design of the follow-up RCT with 3426 GPs in Switzerland. We now have access to pseudonymized patient-level data from routinely collected health insurance data of the three largest health insurers in Switzerland.

Methods And Analysis: 1713 GPs randomized to the intervention group received once evidence-based treatment guidelines at the beginning, including region-specific antibiotic resistance information from the community and personalized feedback of their antibiotic prescribing, followed by quarterly personalized prescription feedback for two years. The first and the last mailings were sent out in December 2017 and September 2019, respectively. The 1713 GPs randomized to the control group were not notified about the study and they received no guidelines and no prescription feedback. The personalized prescription feedbacks and the analyses of the primary and secondary outcomes are entirely based on pseudonymized patient-level data from routinely collected health insurance data. The primary outcome is prescribed antibiotics per 100 patient consultations during the second year of intervention. The secondary outcomes include antibiotic use during the entire two-year trial period, use of broad-spectrum antibiotics, hospitalization rates (all-cause and infection-related), and antibiotic use in different age groups. If the feedback intervention proves to be efficacious, the intervention could be continued systemwide.

Ethics And Dissemination: The trial is publicly funded by the Swiss National Science Foundation (SNSF, grant number 407240_167066). The trial was approved by the ethics committee "Ethikkommission Nordwest-und Zentralschweiz" (EKNZ Project-ID 2017-00888). Results will be disseminated in peer-reviewed journals and international conferences.
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http://dx.doi.org/10.1016/j.conctc.2021.100712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897989PMC
March 2021

Systematic screening on admission for SARS-CoV-2 to detect asymptomatic infections.

Antimicrob Resist Infect Control 2021 02 27;10(1):44. Epub 2021 Feb 27.

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, University of Basel, Petersgraben 4, 4031, Basel, Switzerland.

The proportion of asymptomatic carriers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains elusive and the potential benefit of systematic screening during the SARS-CoV-2-pandemic is controversial. We investigated the proportion of asymptomatic inpatients who were identified by systematic screening for SARS-CoV-2 upon hospital admission. Our analysis revealed that systematic screening of asymptomatic inpatients detects a low total number of SARS-CoV-2 infections (0.1%), questioning the cost-benefit ratio of this intervention. Even when the population-wide prevalence was low, the proportion of asymptomatic carriers remained stable, supporting the need for universal infection prevention and control strategies to avoid onward transmission by undetected SARS-CoV-2-carriers during the pandemic.
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http://dx.doi.org/10.1186/s13756-021-00912-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912536PMC
February 2021

Cohort profile: SARS-CoV-2/COVID-19 hospitalised patients in Switzerland.

Swiss Med Wkly 2021 02 15;151:w20475. Epub 2021 Feb 15.

Institut de Santé Globale, Faculté de Médecine de l'Université de Genève, Geneva, Switzerland.

Background: SARS-CoV-2/COVID-19, which emerged in China in late 2019, rapidly spread across the world with several million victims in 213 countries. Switzerland was severely hit by the virus, with 43,000 confirmed cases as of 1 September 2020.

Aim: In cooperation with the Federal Office of Public Health, we set up a surveillance database in February 2020 to monitor hospitalised patients with COVID-19, in addition to their mandatory reporting system.

Methods: Patients hospitalised for more than 24 hours with a positive polymerase chain-reaction test, from 20 Swiss hospitals, are included. Data were collected in a customised case report form based on World Health Organisation recommendations and adapted to local needs. Nosocomial infections were defined as infections for which the onset of symptoms was more than 5 days after the patient’s admission date.

Results: As of 1 September 2020, 3645 patients were included. Most patients were male (2168, 59.5%), and aged between 50 and 89 years (2778, 76.2%), with a median age of 68 (interquartile range 54–79). Community infections dominated with 3249 (89.0%) reports. Comorbidities were frequently reported, with hypertension (1481, 61.7%), cardiovascular diseases (948, 39.5%) and diabetes (660, 27.5%) being the most frequent in adults; respiratory diseases and asthma (4, 21.1%), haematological and oncological diseases (3, 15.8%) were the most frequent in children. Complications occurred in 2679 (73.4%) episodes, mostly respiratory diseases (2470, 93.2% in adults; 16, 55.2% in children), and renal (681, 25.7%) and cardiac (631, 23.8%) complications for adults. The second and third most frequent complications in children affected the digestive system and the liver (7, 24.1%). A targeted treatment was given in 1299 (35.6%) episodes, mostly with hydroxychloroquine (989, 76.1%). Intensive care units stays were reported in 578 (15.8%) episodes. A total of 527 (14.5%) deaths were registered, all among adults.

Conclusion: The surveillance system has been successfully initiated and provides a robust set of data for Switzerland by including about 80% (compared with official statistics) of SARS-CoV-2/COVID-19 hospitalised patients, with similar age and comorbidity distributions. It adds detailed information on the epidemiology, risk factors and clinical course of these cases and, therefore, is a valuable addition to the existing mandatory reporting.
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http://dx.doi.org/10.4414/smw.2021.20475DOI Listing
February 2021

The Detection of Vancomycin in Sweat: A Next-Generation Digital Surrogate Marker for Antibiotic Tissue Penetration: A Pilot Study.

Digit Biomark 2021 Jan-Apr;5(1):24-28. Epub 2021 Jan 14.

CMIO Research Group, Department of Digitalization and ICT, University Hospital Basel, Basel, Switzerland.

Background: Assuring adequate antibiotic tissue concentrations at the point of infection, especially in skin and soft tissue infections, is pivotal for an effective treatment and cure. Despite the global issue, a reliable AB monitoring test is missing. Inadequate antibiotic treatment leads to the development of antimicrobial resistances and toxic side effects. β-lactam antibiotics were already detected in sweat of patients treated with the respective antibiotics intravenously before. With the emergence of smartphone-based biosensors to analyse sweat on the spot of need, next-generation molecular digital biomarkers will be increasingly available for a non-invasive pharmacotherapy monitoring.

Objective: Here, we investigated if the glycopeptide antibiotic vancomycin is detectable in sweat samples of in-patients treated with intravenous vancomycin.

Methods: Eccrine sweat samples were collected using the Macroduct Sweat Collector®. Along every sweat sample, a blood sample was taken. Bio-fluid analysis was performed by Ultra-high Pressure Liquid Chromatograph-Tandem Quadrupole Mass Spectrometry coupled with tandem mass spectrometry.

Results: A total of 5 patients were included. Results demonstrate that vancomycin was detected in 5 out of 5 sweat samples. Specifically, vancomycin concentrations ranged from 0.011 to 0.118 mg/L in sweat and from 4.7 to 8.5 mg/L in blood.

Conclusion: Our results serve as proof-of-concept that vancomycin is detectable in eccrine sweat and may serve as a surrogate marker for antibiotic tissue penetration. A targeted vancomycin treatment is crucial in patients with repetitive need for antibiotics and a variable antibiotic distribution such as in peripheral artery disease to optimize treatment effectiveness. If combined with on-skin smartphone-based biosensors and smartphone applications, the detection of antibiotic concentrations in sweat might enable a first digital, on-spot, lab-independent and non-invasive therapeutic drug monitoring in skin and soft tissue infections.
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http://dx.doi.org/10.1159/000512947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879282PMC
January 2021

Nosocomial transmission of a carbapenemase integron between isolates of two different species.

Infect Control Hosp Epidemiol 2021 Feb 19:1-3. Epub 2021 Feb 19.

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland.

We report the first documented in-hospital patient-to-patient-transmission of a blaVIM-2 integron between isolates of Pseudomonas alcaligenes and P. aeruginosa. Molecular typing looking only for difference within species may fail to detect nosocomial transmission of resistance genes.
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http://dx.doi.org/10.1017/ice.2021.39DOI Listing
February 2021

Surveillance quality correlates with surgical site infection rates in knee and hip arthroplasty and colorectal surgeries: A call to action to adjust reporting of SSI rates.

Infect Control Hosp Epidemiol 2021 Feb 18:1-7. Epub 2021 Feb 18.

Department of Infectious Diseases, Bern University Hospital, Inselspital, University of Bern, Bern, Switzerland.

Objective: The incidence of surgical site infections may be underreported if the data are not routinely validated for accuracy. Our goal was to investigate the communicated SSI rate from a large network of Swiss hospitals compared with the results from on-site surveillance quality audits.

Design: Retrospective cohort study.

Patients: In total, 81,957 knee and hip prosthetic arthroplasties from 125 hospitals and 33,315 colorectal surgeries from 110 hospitals were included in the study.

Methods: Hospitals had at least 2 external audits to assess the surveillance quality. The 50-point standardized score per audit summarizes quantitative and qualitative information from both structured interviews and a random selection of patient records. We calculated the mean National Healthcare Safety Network (NHSN) risk index adjusted infection rates in both surgery groups.

Results: The median NHSN adjusted infection rate per hospital was 1.0% (interquartile range [IQR], 0.6%-1.5%) with median audit score of 37 (IQR, 33-42) for knee and hip arthroplasty, and 12.7% (IQR, 9.0%-16.6%), with median audit score 38 (IQR, 35-42) for colorectal surgeries. We observed a wide range of SSI rates and surveillance quality, with discernible clustering for public and private hospitals, and both lower infection rates and audit scores for private hospitals. Infection rates increased with audit scores for knee and hip arthroplasty (P value for the slope = .002), and this was also the case for planned (P = .002), and unplanned (P = .02) colorectal surgeries.

Conclusions: Surveillance systems without routine evaluation of validity may underestimate the true incidence of SSIs. Audit quality should be taken into account when interpreting SSI rates, perhaps by adjusting infection rates for those hospitals with lower audit scores.
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http://dx.doi.org/10.1017/ice.2021.14DOI Listing
February 2021

Preventive measures for accompanying caregivers of children in paediatric health care during the COVID-19 pandemic-walking an ethical tightrope.

Clin Microbiol Infect 2021 Feb 2. Epub 2021 Feb 2.

Department of Infectious Diseases and Vaccinology, University of Basel Children's Hospital, Basel, Switzerland; Swissnoso, the National Centre for Infection Control, Bern, Switzerland.

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http://dx.doi.org/10.1016/j.cmi.2021.01.023DOI Listing
February 2021

Reply by Authors.

J Urol 2021 Feb 3:101097JU000000000000151303. Epub 2021 Feb 3.

Department of Urology, University Hospital Basel, Basel, Switzerland.

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http://dx.doi.org/10.1097/JU.0000000000001513.03DOI Listing
February 2021

Evaluating antimicrobial effectiveness in environmental microbiology.

Clin Infect Dis 2021 Jan 10. Epub 2021 Jan 10.

Division of Infectious diseases & hospital epidemiology, University of Basel Hospitals & Clinics, Basel, Switzerland.

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http://dx.doi.org/10.1093/cid/ciab013DOI Listing
January 2021

Antimicrobial prophylaxis administration after umbilical cord clamping in cesarean section and the risk of surgical site infection: a cohort study with 55,901 patients.

Antimicrob Resist Infect Control 2020 12 22;9(1):201. Epub 2020 Dec 22.

Swissnoso, National Center for Infection Control, Bern, Switzerland.

Background: The World Health Organization (WHO) recommends administration of surgical antimicrobial prophylaxis (SAP) in cesarean section prior to incision to prevent surgical site infections (SSI). This study aimed to determine whether SAP administration following cord clamping confers an increased SSI risk to the mother.

Methods: Study design: Cohort.

Setting: 75 participating Swiss hospitals, from 2009 to 2018.

Participants: A total of 55,901 patients were analyzed.

Main Outcome Measures: We assessed the association between SAP administration relative to incision and clamping and the SSI rate, using generalized linear multilevel models, adjusted for patient characteristics, procedural variables, and health-care system factors.

Results: SAP was administered before incision in 26'405 patients (47.2%) and after clamping in 29,496 patients (52.8%). Overall 846 SSIs were documented, of which 379 (1.6% [95% CI, 1.4-1.8%]) occurred before incision and 449 (1.7% [1.5-1.9%]) after clamping (p = 0.759). The adjusted odds ratio for SAP administration after clamping was not significantly associated with an increased SSI rate (1.14, 95% CI 0.96-1.36; p = 0.144) when compared to before incision. Supplementary and subgroup analyses supported these main results.

Conclusions: This study did not confirm an increased SSI risk for the mother in cesarean section if SAP is given after umbilical cord clamping compared to before incision.
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http://dx.doi.org/10.1186/s13756-020-00860-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754587PMC
December 2020

Effect of COVID-19 on acute treatment of ST-segment elevation and Non-ST-segment elevation acute coronary syndrome in northwestern Switzerland.

Int J Cardiol Heart Vasc 2021 Feb 4;32:100686. Epub 2020 Dec 4.

Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, University of Basel, Switzerland.

Background: To investigate the effect of the corona virus disease 2019 (COVID-19) pandemic on the acute treatment of patients with ST-segment elevation (STEMI) and Non-ST-segment elevation acute coronary syndrome (NSTE-ACS).

Methods: We retrospectively identified patients presenting to the emergency department (ED) with suspected ACS. We evaluated the number of percutaneous coronary interventions (PCIs) for STEMI, NSTE-ACS, and elective PCI cases. In STEMI patients, we assessed the time from chest pain onset (cpo) to ED presentation, post-infarction left ventricular ejection fraction (LVEF), and time from ED presentation to PCI. We directly compared cases from two time intervals: January/February 2020 versus March/April 2020 (defined as 2 months before and after the COVID-19 outbreak). In a secondary analysis, we directly compared cases from March/April 2020 with patients from the same time interval in 2019.

Results: From January to April 2020, 765 patients presented with acute chest pain to the ED. A dramatic reduction of ED presentations after compared to before the COVID-19 outbreak (31% relative reduction) was observed. Overall, 398 PCIs were performed, 220/398 PCIs (55.3%) before versus 178/398 PCIs (44.7%) after the outbreak. While numbers for NSTE-ACS and elective interventions declined by 21% and 31%, respectively, the number of STEMI cases remained stable. Time from cpo to ED presentation, post-infarction LVEF, and median door-to-balloon time remained unchanged.

Conclusions: In contrast to previous reports, our findings do not confirm the dramatic drop in STEMI cases and interventions in northwestern Switzerland as observed in other regions and hospitals around the world.
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http://dx.doi.org/10.1016/j.ijcha.2020.100686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734221PMC
February 2021

Epidemiology and precision of SARS-CoV-2 detection following lockdown and relaxation measures.

J Med Virol 2021 04 29;93(4):2374-2384. Epub 2020 Dec 29.

Clinical Virology, Laboratory Medicine, University Hospital Basel, Basel, Switzerland.

Objectives: Detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is key to the clinical and epidemiological assessment of CoVID-19. We cross-validated manual and automated high-throughput testing for SARS-CoV-2-RNA, evaluated SARS-CoV-2 loads in nasopharyngeal-oropharyngeal swabs (NOPS), lower respiratory fluids, and plasma, and analyzed detection rates after lockdown and relaxation measures.

Methods: Basel-S-gene, Roche-E-gene, and Roche-cobas®6800-Target1 and Target2 were prospectively validated in 1344 NOPS submitted during the first pandemic peak (Week 13). Follow-up cohort (FUP) 1, 2, and 3 comprised 10,999, 10,147, and 19,389 NOPS submitted during a 10-week period until Weeks 23, 33, and 43, respectively.

Results: Concordant results were obtained in 1308 cases (97%), including 97 (9%) SARS-CoV-2-positives showing high quantitative correlations (Spearman's r > .95; p < .001) for all assays and high precision by Bland-Altman analysis. Discordant samples (N = 36, 3%) had significantly lower SARS-CoV-2 loads (p < .001). Following lockdown, detection rates declined to <1% in FUP-1, reducing single-test positive predictive values from 99.3% to 85.1%. Following relaxation, rates flared up to 4% and 12% in FUP-2 and -3, but infected patients were younger than during lockdown (34 vs. 52 years, p < .001). In 261 patients providing 936 NOPS, SARS-CoV-2 loads declined by three orders of magnitude within 10 days postdiagnosis (p < .001). SARS-CoV-2 loads in NOPS correlated with those in time-matched lower respiratory fluids or in plasma but remained detectable in some cases with negative follow-up NOPS, respectively.

Conclusion: Manual and automated assays significantly correlated qualitatively and quantitatively. Following a successful lockdown, declining positive predictive values require independent dual-target confirmation for reliable assessment. Confirmatory and quantitative follow-up testing should be obtained within <5 days and consider lower respiratory fluids in symptomatic patients with SARS-CoV-2-negative NOPS.
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http://dx.doi.org/10.1002/jmv.26731DOI Listing
April 2021

Antimicrobial Prophylaxis for Postoperative Urinary Tract Infections in Transurethral Resection of Bladder Tumors: A Systematic Review and Meta-analysis.

J Urol 2020 Dec 7:101097JU0000000000001513. Epub 2020 Dec 7.

Department of Urology, University Hospital Basel, Basel, Switzerland.

Purpose: The administration of antimicrobial prophylaxis for postoperative urinary tract infections following transurethral resection of bladder tumors is controversial. We aimed to systematically review evidence on the potential effect of antimicrobial prophylaxis on postoperative urinary tract infections and asymptomatic bacteriuria.

Materials And Methods: We conducted a systematic search in Embase, Medline and the Cochrane Central Register of Controlled Trials. Randomized controlled trials and nonrandomized controlled trials assessing the effect of any form of antimicrobial prophylaxis in patients with transurethral resection of bladder tumors on postoperative urinary tract infections or asymptomatic bacteriuria were included. Risk of bias was assessed using RoB 2.0 or the Newcastle-Ottawa Scale. Fixed and random effects meta-analyses were conducted. As a potential basis for a scoping review, we exploratorily searched Medline for risk factors for urinary tract infections after transurethral resection of bladder tumors. The protocol was registered on PROSPERO (CRD42019131733).

Results: Of 986 screened publications, 7 studies with 1,725 participants were included; the reported effect sizes varied considerably. We found no significant effect of antimicrobial prophylaxis on urinary tract infections: the pooled odds ratio of the random effects model was 1.55 (95% CI 0.73-3.31). The random effects meta-analysis examining the effect of antimicrobial prophylaxis on asymptomatic bacteriuria showed an OR of 0.43 (0.18-1.04). Risk of bias was moderate. Our exploratory search identified three studies reporting age, preoperative pelvic radiation, preoperative hospital-stay, duration of operation, tumor size, preoperative asymptomatic bacteriuria and pyuria as risk factors for urinary tract infections following transurethral resection of bladder tumors.

Conclusions: We observed insufficient evidence supporting routine antimicrobial prophylaxis in patients undergoing transurethral resection of bladder tumors for the prevention of postoperative urinary tract infections; our findings may inform harmonization of international guidelines.
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http://dx.doi.org/10.1097/JU.0000000000001513DOI Listing
December 2020

Education and training programmes for infection prevention and control professionals: mapping the current opportunities and local needs in European countries.

Antimicrob Resist Infect Control 2020 11 9;9(1):183. Epub 2020 Nov 9.

European Committee On Infection Control (EUCIC), Basel, Switzerland.

Background: Studies have repeatedly highlighted the need for homogenisation of training content and opportunities in infection prevention and control (IPC) across European countries.

Objectives: To map current training opportunities for IPC professionals, define local needs and highlight differences, across 11 European countries (Cyprus, France, England, Germany, Greece, Italy, Netherlands, Poland, Romania, Spain, Switzerland).

Sources: From July 2018 to February 2019, IPC experts directly involved in IPC training and education in their countries and/or internationally were invited to complete a prespecified set of questions in order to provide a detailed description of IPC training opportunities and needs in their country.

Conclusions: IPC training among nurses and doctors varies greatly across countries, with differences in content and type of training (e.g., standardised curriculum, educational programme, clinical experience) duration, as well as in assessment and recognition/accreditation. The observed heterogeneity in IPC training between European countries can be eliminated through establishment of interdisciplinary region-wide training programmes, with common learning objectives, shared know-how and supported by national and international professional bodies.
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http://dx.doi.org/10.1186/s13756-020-00835-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652580PMC
November 2020

COVID-19 Triage and Test Center: Safety, Feasibility, and Outcomes of Low-Threshold Testing.

J Clin Med 2020 Oct 7;9(10). Epub 2020 Oct 7.

Emergency Department, University Hospital Basel, University of Basel, CH-4031 Basel, Switzerland.

This prospective observational study evaluated the safety and feasibility of a low threshold testing process in a Triage and Test Center (TTC) during the early course of the coronavirus disease 19 (COVID-19) pandemic. In addition, we aimed to identify clinical predictors for a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) swab result. Patients underwent informal triage, standardized history taking, and physician evaluation, only where indicated. Patients were observed for 30 days. Safety was the primary outcome and was defined as a COVID-19-related 30 day re-presentation rate <5% and mortality rate <1% in patients presenting to the TTC. Feasibility was defined as an overruling of informal triage <5%. Among 4815 presentations, 572 (11.9%) were tested positive for SARS-CoV-2, and 4774 were discharged. Mortality at 30-days was 0.04% (2 patients, one of which related to COVID-19). Fever (OR 2.03 [95% CI 1.70;2.42]), myalgia (OR 1.94 [1.63;2.31]), chills (OR 1.77 [1.44;2.16]), headache (OR 1.61 [1.34;1.94]), cough (OR 1.50 [1.24;1.83]), weakness (OR 1.46 [1.21;1.76]), and confusion (OR 1.39 [1.06;1.80]) were associated with test positivity. Re-presentation rate was 8% overall and 1.4% in COVID-19 related re-presentation (69 of 4774). The overruling rate of informal triage was 1.5%. According to our study, a low-threshold testing process in a TTC appeared to be safe (low re-presentation and low mortality) and is feasible (low overruling of informal triage). A COVID-19 diagnosis based on clinical parameters only does not appear possible.
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http://dx.doi.org/10.3390/jcm9103217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601442PMC
October 2020

Non-invasive Drug Monitoring of β-Lactam Antibiotics Using Sweat Analysis-A Pilot Study.

Front Med (Lausanne) 2020 25;7:476. Epub 2020 Aug 25.

CMIO Research Group, University Hospital Basel, Basel, Switzerland.

Antimicrobial resistance is a major challenge in treating infectious diseases. Therapeutic drug monitoring (TDM) can optimize and personalize antibiotic treatment. Previously, antibiotic concentrations in tissues were extrapolated from skin blister studies, but sweat analyses for TDM have not been conducted. To investigate the potential of sweat analysis as a non-invasive, rapid, and potential bedside TDM method. We analyzed sweat and blood samples from 13 in-house patients treated with intravenous cefepime, imipenem, or flucloxacillin. For cefepime treatment, full pharmacokinetic sampling was performed (five subsequent sweat samples every 2 h) using ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry. The ClinicalTrials.gov registration number is NCT03678142. In this study, we demonstrated for the first time that flucloxacillin, imipenem, and cefepime are detectable in sweat. Antibiotic concentration changes over time demonstrated comparable (age-adjusted) dynamics in the blood and sweat of patients treated with cefepime. Patients treated with standard flucloxacillin dosage showed the highest mean antibiotic concentration in sweat. Our results provide a proof-of-concept that sweat analysis could potentially serve as a non-invasive, rapid, and reliable method to measure antibiotic concentration and as a surrogate marker for tissue penetration. If combined with smart biosensors, sweat analysis may potentially serve as the first lab-independent, non-invasive antibiotic TDM method.
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http://dx.doi.org/10.3389/fmed.2020.00476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477313PMC
August 2020

Candida auris - recommendations on infection prevention and control measures in Switzerland.

Swiss Med Wkly 2020 Sep 25;150:w20297. Epub 2020 Sep 25.

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, University of Basel, Switzerland.

Candida auris, a globally emerging pathogen, has been repeatedly introduced into European healthcare settings, leading to large and long-lasting nosocomial outbreaks. The pathogen has already been isolated in Switzerland, requiring clinicians and microbiologists to become alert. This is the first comprehensive guidance document on prevention and control of C. auris in Swiss acute care hospitals. It brings to light the most recent evidence from published original articles and reviews. We emphasise the importance of quickly identifying this yeast by means of screening in order to prevent an outbreak that could be difficult to contain. Key containment strategies include reinforcing early detection, hand hygiene, application of strict contact precautions for colonised and infected patients, and thorough specific environmental cleaning and disinfection.
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http://dx.doi.org/10.4414/smw.2020.20297DOI Listing
September 2020

Multicenter Prevalence Study Comparing Molecular and Toxin Assays for Clostridioides difficile Surveillance, Switzerland.

Emerg Infect Dis 2020 10;26(10):2370-2377

Public health authorities in the United States and Europe recommend surveillance for Clostridioides difficile infections among hospitalized patients, but differing diagnostic algorithms can hamper comparisons between institutions and countries. We compared surveillance based on detection of C. difficile by PCR or enzyme immunoassay (EIA) in a nationwide C. difficile prevalence study in Switzerland. We included all routinely collected stool samples from hospitalized patients with diarrhea in 76 hospitals in Switzerland on 2 days, 1 in winter and 1 in summer, in 2015. EIA C. difficile detection rates were 6.4 cases/10,000 patient bed-days in winter and 5.7 cases/10,000 patient bed-days in summer. PCR detection rates were 11.4 cases/10,000 patient bed-days in winter and 7.1 cases/10,000 patient bed-days in summer. We found PCR used alone increased reported C. difficile prevalence rates by <80% compared with a 2-stage EIA-based algorithm.
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http://dx.doi.org/10.3201/eid2610.190804DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510716PMC
October 2020

Are three antiseptic paints needed for safe preparation of the surgical field? A prospective cohort study with 239 patients.

Antimicrob Resist Infect Control 2020 07 31;9(1):120. Epub 2020 Jul 31.

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland.

Background: Preoperative skin antisepsis is an essential component of safe surgery. However, it is unclear how many antiseptic paints are needed to eliminate bacteria prior to incision. This study compared microbial skin counts after two and three antiseptic paints.

Methods: We conducted a prospective cohort study in non-emergency patients receiving a cardiac/abdominal surgery with standardized, preoperative skin antisepsis consisting of an alcoholic compound and either povidone iodine (PI) or chlorhexidine (CHX). We obtained three skin swabs from the participant's thorax/abdomen using a sterile template with a 25 cm window: After collection of the first swab prior to skin antisepsis, and once the second and third application of PI/CHX had dried out, we obtained a second and third swab, respectively. Our primary outcome was the reduction in microbial skin counts after two and three paints of PI/CHX.

Results: Among the 239 enrolled patients, there was no significant difference in the reduction of mean square root-transformed microbial skin counts with three versus two paints (P = 0.2). But distributions of colony forming units (CFUs) decreased from paint 2 to 3 in a predefined analysis (P = 0.002). There was strong evidence of an increased proportion of patients with zero CFU after paint 3 versus paint 2 (P = 0.003). We did not identify risk factors for insufficient reduction of microbial skin counts after two paints, defined as the detection of > 5 CFUs and/or ≥ 1 pathogens.

Conclusions: In non-emergency surgical patients, three antiseptic paints may be superior to two paints in reducing microbial skin colonization prior to surgery.
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http://dx.doi.org/10.1186/s13756-020-00780-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393917PMC
July 2020

Epidemiology of Severe Acute Respiratory Syndrome Coronavirus 2 Emergence Amidst Community-Acquired Respiratory Viruses.

J Infect Dis 2020 09;222(8):1270-1279

Clinical Virology, Laboratory Medicine, University Hospital Basel, Basel, Switzerland.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China as the cause of coronavirus disease 2019 in December 2019 and reached Europe by late January 2020, when community-acquired respiratory viruses (CARVs) are at their annual peak. We validated the World Health Organization (WHO)-recommended SARS-CoV-2 assay and analyzed the epidemiology of SARS-CoV-2 and CARVs.

Methods: Nasopharyngeal/oropharyngeal swabs (NOPS) from 7663 patients were prospectively tested by the Basel S-gene and WHO-based E-gene (Roche) assays in parallel using the Basel N-gene assay for confirmation. CARVs were prospectively tested in 2394 NOPS by multiplex nucleic acid testing, including 1816 (75%) simultaneously for SARS-CoV-2.

Results: The Basel S-gene and Roche E-gene assays were concordant in 7475 cases (97.5%) including 825 (11%) SARS-CoV-2 positives. In 188 (2.5%) discordant cases, SARS-CoV-2 loads were significantly lower than in concordant positive ones and confirmed in 105 (1.4%). Adults were more frequently SARS-CoV-2 positive, whereas children tested more frequently CARV positive. CARV coinfections with SARS-CoV-2 occurred in 1.8%. SARS-CoV-2 replaced CARVs within 3 weeks, reaching 48% of all detected respiratory viruses followed by rhinovirus/enterovirus (13%), influenza virus (12%), coronavirus (9%), respiratory syncytial virus (6%), and metapneumovirus (6%).

Conclusions: Winter CARVs were dominant during the early SARS-CoV-2 pandemic, impacting infection control and treatment decisions, but were rapidly replaced, suggesting competitive infection. We hypothesize that preexisting immune memory and innate immune interference contribute to the different SARS-CoV-2 epidemiology among adults and children.
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http://dx.doi.org/10.1093/infdis/jiaa464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454752PMC
September 2020

Perceived challenges of COVID-19 infection prevention and control preparedness: A multinational survey.

J Glob Antimicrob Resist 2020 09 11;22:779-781. Epub 2020 Jul 11.

Radboudumc Center for Infectious Diseases, Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Medical Microbiology and Infectious Diseases, Canisius-Wilhelmina Hospital (CWZ), Nijmegen, The Netherlands; REshape Center for Innovation, Radboudumc, Nijmegen, The Netherlands. Electronic address:

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http://dx.doi.org/10.1016/j.jgar.2020.07.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351656PMC
September 2020

Risk of SARS-CoV-2 transmission by aerosols, the rational use of masks, and protection of healthcare workers from COVID-19.

Antimicrob Resist Infect Control 2020 07 6;9(1):100. Epub 2020 Jul 6.

Swissnoso, the National Center for Infection Control, Bern, Switzerland.

Objectives: To determine the risk of SARS-CoV-2 transmission by aerosols, to provide evidence on the rational use of masks, and to discuss additional measures important for the protection of healthcare workers from COVID-19.

Methods: Literature review and expert opinion.

Short Conclusion: SARS-CoV-2, the pathogen causing COVID-19, is considered to be transmitted via droplets rather than aerosols, but droplets with strong directional airflow support may spread further than 2 m. High rates of COVID-19 infections in healthcare-workers (HCWs) have been reported from several countries. Respirators such as filtering face piece (FFP) 2 masks were designed to protect HCWs, while surgical masks were originally intended to protect patients (e.g., during surgery). Nevertheless, high quality standard surgical masks (type II/IIR according to European Norm EN 14683) appear to be as effective as FFP2 masks in preventing droplet-associated viral infections of HCWs as reported from influenza or SARS. So far, no head-to-head trials with these masks have been published for COVID-19. Neither mask type completely prevents transmission, which may be due to inappropriate handling and alternative transmission pathways. Therefore, compliance with a bundle of infection control measures including thorough hand hygiene is key. During high-risk procedures, both droplets and aerosols may be produced, reason why respirators are indicated for these interventions.
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http://dx.doi.org/10.1186/s13756-020-00763-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336106PMC
July 2020

Parvimonas micra as a rare cause of spondylodiscitis - case series from a single centre.

Swiss Med Wkly 2020 Jun 16;150:w20272. Epub 2020 Jun 16.

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, University of Basel, Switzerland.

Background: The anaerobe Parvimonas micra is usually recovered as part of the normal flora or in polymicrobial infections of odontogenic or gastrointestinal origin. P. micra has rarely been described as the causative organism of pyogenic spondylodiscitis. Here we report multiple cases of spondylodiscitis caused by this organism and compare their clinical features with the published literature.

Methods: We performed a retrospective review of all institutional cases with P. micra spondylodiscitis between 01 June 2012 and 31 May 2019. For comparison, the literature was searched for studies reporting vertebral infections with P. micra in adult patients.

Results: Over 7 years, six cases were identified: one with a polymicrobial infection (with P. micra and Fusobacterium nucleatum) and five with P. micra as the only pathogen isolated. The six patients with P. micra infections were between 63 and 82 years old (median 72 years) and presented with persistent lower back pain. Common findings were infection of the lumbar spine region (in 6/6 cases) and recent dental inflammation (4/6 cases). 3/6 patients had previously undergone decompressive spinal surgery due to spinal stenosis (2 to 11 years before). In 4/6 cases the organism was detected in blood cultures drawn at admission. Treatment consisted of antibiotics for all patients and additional decompressive surgery due to abscess formation in half the cases. Outcomes were mostly favourable, but persistent pain was a common complaint after resolution of infection.

Conclusions: P. micra is a rare cause of spondylodiscitis. Nevertheless, recent dental procedures with subsequent back pain should lead to the consideration of possible anaerobic causes of spondylodiscitis. Heightened awareness of this pathogen and improvements in diagnostic methods might lead to higher detection rates.
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http://dx.doi.org/10.4414/smw.2020.20272DOI Listing
June 2020

Infective Endocarditis After Transcatheter Aortic Valve Replacement.

J Am Coll Cardiol 2020 06;75(24):3020-3030

Department of Infectious Diseases and Hospital Hygiene, Kantonsspital Aarau, Aarau, Switzerland.

Background: Infective endocarditis may affect patients after transcatheter aortic valve replacement (TAVR).

Objectives: The purpose of this study was to provide detailed information on incidence rates, types of microorganisms, and outcomes of infective endocarditis after TAVR.

Methods: Between February 2011 and July 2018, consecutive patients from the SwissTAVI Registry were eligible. Infective endocarditis was classified into early (peri-procedural [<100 days] and delayed-early [100 days to 1 year]) and late (>1 year) endocarditis. Clinical events were adjudicated according to the Valve Academic Research Consortium-2 endpoint definitions.

Results: During the observational period, 7,203 patients underwent TAVR at 15 hospitals in Switzerland. During follow-up of 14,832 patient-years, endocarditis occurred in 149 patients. The incidence for peri-procedural, delayed-early, and late endocarditis after TAVR was 2.59, 0.71, and 0.40 events per 100 person-years, respectively. Among patients with early endocarditis, Enterococcus species were the most frequently isolated microorganisms (30.1%). Among those with peri-procedural endocarditis, 47.9% of patients had a pathogen that was not susceptible to the peri-procedural antibiotic prophylaxis. Younger age (subhazard ratio [SHR]: 0.969; 95% confidence interval [CI]: 0.944 to 0.994), male sex (SHR: 1.989; 95% CI: 1.403 to 2.818), lack of pre-dilatation (SHR: 1.485; 95% CI: 1.065 to 2.069), and treatment in a catheterization laboratory as opposed to hybrid operating room (SHR: 1.648; 95% CI: 1.187 to 2.287) were independently associated with endocarditis. In a case-control matched analysis, patients with endocarditis were at increased risk of mortality (hazard ratio: 6.55; 95% CI: 4.44 to 9.67) and stroke (hazard ratio: 4.03; 95% CI: 1.54 to 10.52).

Conclusions: Infective endocarditis after TAVR most frequently occurs during the early period, is commonly caused by Enterococcus species, and results in considerable risks of mortality and stroke. (NCT01368250).
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http://dx.doi.org/10.1016/j.jacc.2020.04.044DOI Listing
June 2020

Proposal for a EN 149 acceptable reprocessing method for FFP2 respirators in times of severe shortage.

Antimicrob Resist Infect Control 2020 06 17;9(1):88. Epub 2020 Jun 17.

Federal Office for Civil Protection FOCP, Spiez Laboratory, Spiez, Switzerland.

Introduction: Transmission of SARS-CoV-2 to health care workers (HCW) poses a major burden in the current COVID-19 pandemic. Unprotected exposure to a COVID-19 patient is a key risk factor for HCWs. Transmission mainly occurs by droplet transmission, or by aerosol generating procedures. Respirators such as filtering face piece masks (FFP2), also called respirators, are required to prevent transmission during aerosol generating procedures, as part of the personal protective equipment (PPE) for HCWs. However, many HCW were infected due to lack of PPE, or failure to use them. Therefore, the worldwide shortage of respirators triggered the development of reprocessing used FFP2 respirators or N95 respirators as standard in the US. Our proposal with HO plasma sterilization for decontamination allows to reprocess FFP2, while they still meet the filtration efficiency required by EN 149. The protocol is simple, uses available resources in hospitals and can be rapidly implemented to decrease the shortage of respirators during this crisis. The goal of the study was the evaluate if respirators can be reprocessed and still fulfill the requirements for filtration efficiency outlined by EN 149.

Methods: Used FFP2 respirators - Model 3 M Aura™ 1862+ - were sterilized using a low temperature process hydrogen peroxide (HO), V-PRO® maX Low Temperature, a FDA (Food and Drug Administration) approved method to decontaminate FFP2 respirators. Decontaminated respirators were further checked for residual peroxide by a single-gas detector for HO. The total inward leakage of the protective respirators was quantitatively tested with 10 test persons in an atmosphere charged with paraffin aerosol according to the European Standard EN 149. The fit factor was calculated as the inverse of the total inward leakage.

Results: Ten new and ten decontaminated FFP2 respirators were tested for filtration efficiency. None of the respirators exceeded the maximum acceptable concentration of peroxide. More than 4000 respirators have been reprocessed so far, at cost of approximately 0.3 Euro/piece.

Conclusions: FFP2 respirators can be safely reprocessed once after decontamination with plasma peroxide sterilization, whereafter they still fulfill EN 149 requirements. This allows to almost double the current number of available FFP2 respirators.
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http://dx.doi.org/10.1186/s13756-020-00744-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7298450PMC
June 2020

Cefiderocol for Extensively Drug-Resistant Gram-Negative Bacterial Infections: Real-world Experience From a Case Series and Review of the Literature.

Open Forum Infect Dis 2020 Jun 21;7(6):ofaa185. Epub 2020 May 21.

Division of Infectious Diseases & Hospital Epidemiology, University Hospital Basel and University of Basel, Basel, Switzerland.

Cefiderocol is a new siderophore cephalosporin with activity against carbapenem-resistant gram-negative bacteria. Data on its clinical efficacy are limited to complicated urinary tract infections. We present a series of 3 patients successfully treated with cefiderocol for complicated health care-associated infections and review published case reports.
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http://dx.doi.org/10.1093/ofid/ofaa185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284008PMC
June 2020

Not sick enough to worry? "Influenza-like" symptoms and work-related behavior among healthcare workers and other professionals: Results of a global survey.

PLoS One 2020 13;15(5):e0232168. Epub 2020 May 13.

Department of Medical Microbiology and Infectious Diseases, Canisius-Wilhelmina Hospital (CWZ), Nijmegen, The Netherlands.

Background: Healthcare workers (HCWs) and non-HCWs may contribute to the transmission of influenza-like illness (ILI) to colleagues and susceptible patients by working while sick (presenteeism). The present study aimed to explore the views and behavior of HCWs and non-HCWs towards the phenomenon of working while experiencing ILI.

Methods: The study was a cross-sectional online survey conducted between October 2018 and January 2019 to explore sickness presenteeism and the behaviour of HCWs and non-HCWs when experiencing ILI. The survey questionnaire was distributed to the members and international networks of the International Society of Antimicrobial Chemotherapy (ISAC) Infection Prevention and Control (IPC) Working Group, as well as via social media platforms, including LinkedIn, Twitter and IPC Blog.

Results: In total, 533 respondents from 49 countries participated (Europe 69.2%, Asia-Pacific 19.1%, the Americas 10.9%, and Africa 0.8%) representing 249 HCWs (46.7%) and 284 non-HCWs (53.2%). Overall, 312 (58.5%; 95% confidence interval [CI], 56.2-64.6) would continue to work when sick with ILI, with no variation between the two categories. Sixty-seven (26.9%) HCWs and forty-six (16.2%) non-HCWs would work with fever alone (p<0 .01) Most HCWs (89.2-99.2%) and non-HCWs (80%-96.5%) would work with "minor" ILI symptoms, such as sore throat, sinus cold, fatigue, sneezing, runny nose, mild cough and reduced appetite.

Conclusion: A future strategy to successfully prevent the transmission of ILI in healthcare settings should address sick-leave policy management, in addition to encouraging the uptake of influenza vaccine.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0232168PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7219706PMC
July 2020

The potential negative impact of antibiotic pack on antibiotic stewardship in primary care in Switzerland: a modelling study.

Antimicrob Resist Infect Control 2020 05 8;9(1):60. Epub 2020 May 8.

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland.

Background: In Switzerland, oral antibiotics are dispensed in packs rather than by exact pill-count. We investigated whether available packs support compliance with recommended primary care treatment regimens for common infections in children and adults.

Methods: Hospital-based guidelines for oral community -based treatment of acute otitis media, sinusitis, tonsillopharyngitis, community-acquired pneumonia and afebrile urinary tract infection were identified in 2017 in an iterative process by contacting hospital pharmacists and infectious diseases specialists. Furthermore, newly available national guidelines published in 2019 were reviewed. Available pack sizes for recommended solid, dispersible and liquid antibiotic formulations were retrieved from the Swiss pharmaceutical register and compared with recommended regimens to determine optimal (no leftovers) and adequate (optimal +/- one dose) matches.

Results: A large variety of recommended regimens were identified. For adults, optimal and adequate packs were available for 25/70 (36%) and 8/70 (11%) regimens, respectively. Pack-regimen matching was better for WHO Watch (optimal: 15/24, 63%) than Access antibiotics (optimal: 7/39, 18%). For the four paediatric weight-examples and 42 regimens involving child-appropriate formulations, optimal and adequate packs were available for only 14/168 (8%) and 27/168 (16%), respectively. Matching was better for older children with higher body and for longer treatment courses > 7 days.

Conclusions: Fixed antibiotic packs often do not match recommended treatment regimens, especially for children, potentially resulting in longer than necessary treatments and leftover doses in the community. As part of national stewardship, a move to an exact pill-count system, including for child-appropriate solid formulations, should be considered.
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http://dx.doi.org/10.1186/s13756-020-00724-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7206713PMC
May 2020

Reproductive number of the COVID-19 epidemic in Switzerland with a focus on the Cantons of Basel-Stadt and Basel-Landschaft.

Swiss Med Wkly 2020 05 4;150:w20271. Epub 2020 May 4.

Department of Biosystems Science and Engineering, ETH Zürich, Switzerland / Swiss Institute of Bioinformatics, Basel, Switzerland.

The reproductive number in Switzerland was between 1.5 and 2 during the first third of March, and has consistently decreased to around 1. After the announcement of the latest strict measure on 20 March 2020, namely that gatherings of more than five people in public spaces are prohibited, the reproductive number dropped significantly below 1; the authors of this study estimate the reproductive number to be between 0.6 and 0.8 in the first third of April.
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http://dx.doi.org/10.4414/smw.2020.20271DOI Listing
May 2020