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BackgroundWhen comparing the periods of time during and after the first wave of the ongoing SARS-CoV-2/COVID-19 pandemic in Europe, the associated COVID-19 mortality seems to have decreased substantially. Various factors could explain this trend, including changes in demographic characteristics of infected persons, and the improvement of case management. To date, no study has been performed to investigate the evolution of COVID-19 in-hospital mortality in Switzerland, while also accounting for risk factors.MethodsWe investigated the trends in COVID-19 related mortality (in-hospital and in-intermediate/intensive-care) over time in Switzerland, from February 2020 to May 2021, comparing in particular the first and the second wave. We used data from the COVID-19 Hospital-based Surveillance (CH-SUR) database. We performed survival analyses adjusting for well-known risk factors of COVID-19 mortality (age, sex and comorbidities) and accounting for competing risk.ResultsOur analysis included 16,030 episodes recorded in CH-SUR, with 2,320 reported deaths due to COVID-19 (13.0% of included episodes). We found that overall in-hospital mortality was lower during the second wave of COVID-19 compared to the first wave (HR 0.71, 95% CI 0.69 – 0.72, p-value < 0.001), a decrease apparently not explained by changes in demographic characteristics of patients. In contrast, mortality in intermediate and intensive care significantly increased in the second wave compared to the first wave (HR 1.48, 95% CI 1.42 – 1.55, p-value < 0.001), with significant changes in the course of hospitalisation between the first and the second wave.ConclusionWe found that, in Switzerland, COVID-19 mortality decreased among hospitalised persons, whereas it increased among patients admitted to intermediate or intensive care, when comparing the second wave to the first wave. We put our findings in perspective with changes over time in case management, treatment strategy, hospital burden and non-pharmaceutical interventions. Further analyses of the potential effect of virus variants and of vaccination on mortality would be crucial to have a complete overview of COVID-19 mortality trends throughout the different phases of the pandemic.

Background: Elastomeric pumps can be used for the continuous administration of antimicrobials in the outpatient setting. A potentially limiting factor in their use is the stability of antimicrobials. Objectives: To investigate under real-life conditions the temperature variations of antibiotic solutions contained in elastomeric pumps, and to examine under such conditions the stability of five antibiotics. Methods: Healthy volunteers carried the elastomeric pumps in carry pouches during their daily activities. A thermologger measured the temperatures every 15 min over 24 h. Antibiotic concentrations were measured by HPLC coupled to tandem MS. Results: During daytime, the temperature of solutions in the pumps increased steadily, warming to >30°C. During the night, when the pumps were kept attached to the waist, the temperatures reached up to 33°C. The use of white carry pouches avoided excessive temperature increases. Over seven experiments, cefazolin, cefepime, piperacillin and tazobactam were found to be stable over 24 h. Flucloxacillin showed a mean decrease in concentration of 11% (P = 0.001). Conclusions: Real-life situations can cause significant temperature rises in elastomeric pumps, thereby potentially increasing the risk of antibiotic degradation. Patients should be instructed to avoid situations causing excessive temperature increases. Despite these temperature variations, cefazolin, cefepime, piperacillin and tazobactam were found to be stable over 24 h. A moderate degradation was noticed for flucloxacillin, albeit most probably not to an extent that might impair anti-infective efficacy.

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.

BackgroundSARS-CoV-2/COVID-19, which emerged in China in late 2019, rapidly spread across the world causing several million victims in 213 countries. Switzerland was severely hit by the virus, with 43’000 confirmed cases as of September 1st, 2020.AimIn 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.MethodsPatients hospitalised for more than 24 hours with a positive PCR test, from 20 Swiss hospitals, are included. Data collection follows a custom Case Report Form based on WHO recommendations and adapted to local needs. Nosocomial infections were defined as infections for which the onset of symptoms started more than 5 days after the patient’s admission date.ResultsAs of September 1st, 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 (IQR 54-79). Community infections dominated with 3249 (89.0%) reports. Comorbidities were frequently reported: 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%) being the most frequent in children. Complications occurred in 2679 (73.4%) episodes, mostly for respiratory diseases (2470 - 93.2% in adults, 16 – 55.2% in children), renal (681 – 25.7%) and cardiac (631 – 23.8%) complication 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. 527 (14.5%) deaths were registered, all among adults.ConclusionThe surveillance system has been successfully initiated and provides a very representative set of data for Switzerland. We therefore consider it to be a valuable addition to the existing mandatory reporting, providing more precise information on the epidemiology, risk factors, and clinical course of these cases.

BackgroundBlastocystis sp. is a protist with a worldwide distribution and able to colonise the gut of humans and of a great variety of animals. It is unclear whether it is just a commensal of a healthy gut microbiota or an infectious parasite that needs to be eradicated. Currently no treatment has proven its usefulness for patients complaining of gastro-intestinal symptoms and found to have Blastocystis sp.The primary objective of this study was to evaluate the usefulness of metronidazole in patients with gastrointestinal symptoms harbouring only Blastocystis sp. In addition, we explored whether Blastocystis subtype or concomitant parasitic infection detected by polymerase chain reaction (PCR) may influence treatment outcome.MethodsAdults with persistent gastrointestinal symptoms (> 14 days) visiting a primary care physician and in whom stool microscopy revealed only Blastocystis sp. were included. Eligible patients were randomised to receive ten days of metronidazole or placebo, followed by a crossover if still symptomatic. Stool samples were tested for 11 other protozoa with an in-house PCR and Blastocystis subtypes were determined by PCR and sequencing.ResultsWe screened 474 outpatients for inclusion; 50 met the eligibility criteria. In the metronidazole group, 48% (12/25) reported an improvement of symptoms compared to 44% (11/25) in the placebo group (p = 0.78). After the crossover, again no differences in improvement of symptoms were seen between groups (placebo: 53% (8/15); metronidazole: 50% (8/16)). The in-house PCR was positive for other protozoa in 25% (10/40) of the patients. The protozoa identified were Dientamoeba fragilis (5), Entamoeba dispar (3) and Cyclospora cayetanensis (2). The most frequent Blastocystis subtypes were ST4 (11/36) and ST2 (10/36). Stratified analysis according to subtype or the presence of other protozoa showed no significant difference in treatment outcome with metronidazole or placebo.Conclusion Among patients infected with Blastocystis sp., metronidazole did not improve gastrointestinal symptoms, irrespective of subtype or microscopically undetected coinfection with other protozoa.Trial registrationClinicalTrials.gov: NTC01521403, 06-Nov-2012.

Objectives This study aimed to evaluate the efficacy and safety of continuous antimicrobial infusion using elastomeric pumps in an outpatient setting, while simultaneously documenting circulating antibiotic concentration exposure achieved with this mode of administration. Methods Clinical outcomes, adverse events and antibiotic plasma concentrations were recorded for all patients treated by continuous infusion with elastomeric pumps at the outpatient parenteral antimicrobial therapy (OPAT) unit of the University Hospital of Lausanne between December 2013 and January 2017. The study was registered under ClinicalTrials.gov identifier NCT03221140. Results One hundred and fifty outpatients were treated by continuous intravenous infusions using flucloxacillin (70 patients), cefepime (36), vancomycin (32) and piperacillin/tazobactam (12). The calculated free fractions of each antibiotic were above the epidemiological cut-off values for resistance (ECOFF) of the treated microorganisms in 92% of measurements. Cure was achieved in 143 patients (95%) 3 months after the end of treatment. Four patients needed unexpected readmission and three had a relapse. In none of the patients with unsuccessful treatment was the ratio of free antibiotic plasma concentration/ECOFF

Background A point prevalence survey (PPS) on healthcare-associated infections (HAI) and antimicrobial use was conducted in Swiss acute care hospitals in 2017. Aim Our objective was to assess antimicrobial use in Swiss acute care hospitals. Methods All patients hospitalised in any acute care hospital in Switzerland were eligible. We used the most recent version of the PPS protocol of the European Centre for Disease Prevention and Control. Results Data from 12,931 patients of 96 hospitals were collected. Of these, 4,265 (33%; 95% confidence interval (CI): 32.2–33.8) were on 5,354 antimicrobials for 4,487 indications. Most of the 2,808 therapeutic indications addressed 1,886 community-acquired infections (67.2%; 95% CI: 65.4–68.9). Of the 1,176 surgical prophylaxes, 350 (29.8%; 95% CI: 27.1–32.4) exceeded the duration of 1 day. Of the 1,090 antimicrobial regimens that were changed, 309 (28.3%; 95% CI: 25.7–31.0) were escalated and 337 (30.9%; 95% CI: 28.2–33.7) were de-escalated. Amoxicillin/clavulanic acid was the most frequent antimicrobial (18.8%; 95% CI: 17.7–19.8), prescribed mainly for therapeutic indications (76.0%; 95% CI: 73.3–78.7). A total of 1,931 (37.4%; 95% CI: 36.1–38.8) of the 5,158 antimicrobials for systemic use were broad-spectrum antibiotics, most frequently third- and fourth-generation cephalosporins (35.9%; 95% CI: 33.8–38.1). Conclusions Antimicrobial consumption was at European average, the use of broad-spectrum antibiotics in the lower third. Swiss acute care hospitals should invest in antimicrobial stewardship, particularly in reducing the use of broad-spectrum antibiotics.

This nation-wide survey on the epidemiology of vancomycin-resistant enterococci (VRE) included 142 healthcare institutions and showed an increasing number of VRE colonizations and infections in Switzerland, probably for the most part due to nosocomial dissemination. The introduction and spread of a new clone, gaps in VRE screening policies as well as heterogeneity regarding the management of VRE clusters may be possible explanations. Electronic supplementary material The online version of this article (10.1186/s13756-019-0466-x) contains supplementary material, which is available to authorized users.

BACKGROUND The overall burden of healthcare-associated infections (HAIs) remains high, even in high-income countries. However, the current burden of HAI in Switzerland is unknown. Prevalence surveys have a long tradition in the field of infection prevention and control for measuring both HAI and antimicrobial use. The objective of this survey was to test the point prevalence survey (PPS) methodology of the European Centre for Disease Prevention and Control (ECDC) in acute-care hospitals in Switzerland. METHODS Two tertiary care hospitals and one secondary care hospital in central and western Switzerland participated in the survey. Patients from all wards except for emergency departments and psychiatric wards were included. Data were collected on a single day for every ward with a maximum time frame of 2 weeks for completing data collection. Methodology and definitions were based on the most recent ECDC PPS protocol. RESULTS Data on a total of 2421 patients were analysed. One hundred thirty-six patients had 153 HAIs, corresponding to a prevalence of 5.6% (95% confidence interval [CI] 4.7-6.5%). Rapidly fatal McCabe score, hospitalisation in the intensive care unit (ICU), and having a medical device in place were independent risk factors for HAI. Lower respiratory tract infection was the most frequent HAI type (24.8%), followed by surgical site infection (22.2%), bloodstream infection (17.0%) and urinary tract infection (13.7%). The highest HAI prevalence (26.2%) was observed in the ICU. In total, 60.8% of all HAIs were microbiologically confirmed. The most common microorganism was Escherichia coli (21.1%). Six hundred sixty-nine patients (27.6%, 95% CI 25.9-29.4%) received 893 antimicrobials for 705 indications. Community-acquired infections (39.0%) were the most common indication for antimicrobial use and amoxicillin-clavulanate was the most commonly prescribed antimicrobial (18.4%). CONCLUSIONS HAI prevalence and antimicrobial use in this survey were similar to findings of the past ECDC PPS. The ECDC methodology proved applicable to Swiss acute-care hospitals.

Self-administration of antibiotics using elastomeric pumps has become the most frequently used treatment modality at the outpatient parenteral antimicrobial therapy (OPAT) unit of the University Hospital of Lausanne. However, it remains unknown how comfortable patients feel using this mode of treatment. A questionnaire was offered to all patients treated at the OPAT unit between June 2014 and December 2015. The questionnaire was distributed to 188 patients and 112 questionnaires were returned. Seventy-one patients were treated by self-administration, 21 attended the OPAT unit on a daily basis, and 20 received their antibiotics from home-care nurses. Overall, 83-97% of the patients gave the highest possible scores to the four items evaluating their global satisfaction. Subjects treated by self-administration gave a significantly better rating to 6 of the 17 semi-quantitative questions than the patients treated at the OPAT unit or by home-care nurses. There was no item which was more poorly rated by patients treated by self-administered OPAT than by the other treatment groups. In conclusion satisfaction was high in all patients treated by OPAT. The particularly high satisfaction of patients treated by self-administration of antibiotics with elastomeric pumps suggests that a significant number of patients are happy to take over some responsibility for their treatment. Patients' capacity to appropriate their care themselves should not be underestimated by health care professionals.

Die intravenose Antibiotikatherapie ist fur die Behandlung zahlreicher Infektionen erforderlich. Die ambulante parenterale Antibiotikatherapie ermoglicht es, Patienten, die eine intravenose Behandlung benotigen, bei gleicher Wirksamkeit und Sicherheit ausserhalb des Spitals zu versorgen. Die Versorgung kann in unterschiedlichen Settings stattfinden. Alle stabilen Patienten, die abgesehen von der Antibiotika­therapie nicht mehr im Spital bleiben mussten, konnen ambulant behandelt werden.

Colistin is a last resort's antibacterial treatment in critically ill patients with multi-drug resistant Gram-negative infections. As appropriate colistin exposure is the key for maximizing efficacy while minimizing toxicity, individualized dosing optimization guided by therapeutic drug monitoring is a top clinical priority. Objective of the present work was to develop a rapid and robust HPLC-MS/MS assay for quantification of colistin plasma concentrations. This novel methodology validated according to international standards simultaneously quantifies the microbiologically active compounds colistin A and B, plus the pro-drug colistin methanesulfonate (colistimethate, CMS). 96-well micro-Elution SPE on Oasis Hydrophilic-Lipophilic-Balanced (HLB) followed by direct analysis by Hydrophilic Interaction Liquid Chromatography (HILIC) with Ethylene Bridged Hybrid--BEH--Amide phase column coupled to tandem mass spectrometry allows a high-throughput with no significant matrix effect. The technique is highly sensitive (limit of quantification 0.014 and 0.006 μg/mL for colistin A and B), precise (intra-/inter-assay CV 0.6-8.4%) and accurate (intra-/inter-assay deviation from nominal concentrations -4.4 to +6.3%) over the clinically relevant analytical range 0.05-20 μg/mL. Colistin A and B in plasma and whole blood samples are reliably quantified over 48 h at room temperature and at +4°C (6% deviation from nominal values) and after three freeze-thaw cycles. Colistimethate acidic hydrolysis (1M H2SO4) to colistin A and B in plasma was completed in vitro after 15 min of sonication while the pro-drug hydrolyzed spontaneously in plasma ex vivo after 4 h at room temperature: this information is of utmost importance for interpretation of analytical results. Quantification is precise and accurate when using serum, citrated or EDTA plasma as biological matrix, while use of heparin plasma is not appropriate. This new analytical technique providing optimized quantification in real-life conditions of the microbiologically active compounds colistin A and B offers a highly efficient tool for routine therapeutic drug monitoring aimed at individualizing drug dosing against life-threatening infections.

The risk of contracting a sexually transmitted infection while traveling abroad is increased in certain populations. Pre-travel consultation should include the education of travelers on the prevalence of HIV in the countries visited and on appropriate prevention measures. In patients infected with HIV (PHIV), combined antiretroviral therapy (cART) improves immunity, enabling them to travel with less risk for their health. Pre-travel consultation of PVIH has the following objectives: to determine immune status, to update immunization and to decide on anti-malaria drug prophylaxis, taking into account potential drug interactions with antiretroviral therapy. Vaccine response and duration of protection is shorter-lived in PVIH, especially if the CD4 count is below 200 cells/mm3 and the HIV viral load is detectable. Therefore cART is a cornerstone for disease prevention among patients infected with HIV who travel.