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Background: Preoperative antimicrobial prophylaxis is widely used in pediatric patients undergoing appendectomy, but evidence showing a reduction of postoperative infectious complications is lacking. Methods: A prospective consecutive cohort study on changing from preoperative antimicrobial prophylaxis to no prophylaxis in children undergoing urgent appendectomy was undertaken. The impact of this change in management on postoperative infectious complications was evaluated by comparing the outcome in 100 patients receiving (group A) and a subsequent 100 patients not receiving prophylaxis (group B), which consisted of a preoperative single dose of intravenous metronidazole (10 mg/kg body weight). Results: Histology confirmed acute appendicitis in 92 patients of group A and 95 patients of group B. In patients with histological simple appendicitis, postoperative infectious complications were noted in 2 (3.0 %) of 69 patients from group A and in none of 70 patients from group B, and in patients with histological perforated appendicitis in 5 (22 %) of 23 and 4 (16 %) of 25 patients from groups A and B, respectively. Postoperative infectious complications were more frequent ( p < 0.05) in perforated than in simple appendicitis. These infectious complications included in simple appendicitis two wound infections in group A, and in perforated appendicitis four intraabdominal abscesses and one wound infection in group A and two intraabdominal abscesses and two wound infections in group B. Conclusion: Postoperative infectious complications were seen more often in patients with perforated appendicitis than in those with simple appendicitis. Preoperative antimicrobial prophylaxis with metronidazole did not reduce the rates of postoperative infectious complications. [ABSTRACT FROM AUTHOR]

Clin Microbiol Infect 2010; 16: 1414–1420 Nasal carriage of Staphylococcus aureus contributes to an increased risk of developing an infection with the same bacterial strain. Genetic regulatory elements and toxin-expressing genes are virulence factors associated with the pathogenic potential of S. aureus. We undertook an extensive molecular characterization of methicillin-susceptible S. aureus (MSSA) carried by children. MSSA were recovered from the nostrils of children. The presence of Panton-Valentine leukocidin (PVL), exfoliatins A and B (exfoA and exfoB), and the toxic-shock staphylococcal toxin (TSST-1) and agr group typing were determined by quantitative PCR. A multiple-locus variable-number of tandem repeat analysis (MLVA) assay was also performed for genotyping. Five hundred and seventy-two strains of MSSA were analysed. Overall, 30% were positive for toxin-expressing genes: 29% contained one toxin and 1.6% two toxins. The most commonly detected toxin gene was tst, which was present in 145 (25%) strains. The TSST-1 gene was significantly associated with the agr group 3 (OR 56.8, 95% CI 32.0–100.8). MLVA analysis revealed a large diversity of genetic content and no clonal relationship was demonstrated among the analysed MSSA strains. Multilocus sequence typing confirmed this observation of diversity and identified ST45 as a frequent colonizer. This broad diversity in MSSA carriage strains suggests a limited selection pressure in our geographical area. [ABSTRACT FROM AUTHOR]

Background: The rising prevalence of acute ischemic stroke (AIS) in young adults, particularly with undetermined pathogenesis, is a growing concern. This study assessed risk factors, treatments, and outcomes between young AIS patients with undetermined and determined pathogeneses., Methods and Results: This was a retrospective cohort study including AIS patients aged 18 to 55 years in Switzerland, treated between 2014 and 2022. Stroke pathogeneses were classified using a modified TOAST (Trial of ORG 10172 in Acute Stroke Treatment) classification, with undetermined pathogenesis defined as no identified cause (including patent foramen ovale and cervical artery dissection). We examined vascular risk factors, acute treatments, 3-month functional outcomes, and AIS recurrence within 3 months using logistic regression and Fine-Gray proportional hazards models. Of 3995 patients, 863 (22%) had undetermined pathogenesis. Compared with patients with determined pathogenesis, those with undetermined pathogenesis had a higher prevalence of dyslipidemia (54% versus 59%, P =0.007) and smoking (37% versus 43%, P =0.001), and were more likely to receive intravenous thrombolysis (27% versus 31%, P =0.046). Despite higher 3-month AIS recurrence risk for the undetermined group (adjusted hazard ratio, 1.72 [95% CI, 1.01-2.94]), favorable functional outcomes at 3 months were more frequent (modified Rankin Scale score, 0-2: 90% versus 87%, P =0.033). Patients aged 46 to 55 years with undetermined pathogenesis had better outcomes than those with determined pathogenesis (modified Rankin Scale score, 0-1: 70% versus 64%, P =0.013; modified Rankin Scale score, 0-2: 89% versus 85%, P =0.023), while those aged 18 to 45 years showed higher recurrence rates (4.5% versus 1.8%, P <0.05) but similar functional outcomes., Conclusions: Young adults with AIS exhibit a considerable vascular risk burden. Those with undetermined pathogenesis displayed age-related outcome disparities, with better short-term outcomes in older and higher recurrence rates in younger patients.

In Switzerland and other high-income countries, one out of 3000 to 5000 term and late preterm neonates develops early onset sepsis (EOS) associated with a mortality of around 3%, while incidence and mortality of EOS in very preterm infants are substantially higher. Exposure to antibiotics for suspected EOS is disproportionally high compared to the incidence of EOS with consequences for future health and antimicrobial resistance (AMR). A safe reduction of unnecessary antibiotic treatment has to be a major goal of new management strategies and guidelines. Antibiotics should be administered immediately in situations with clinical signs of septic shock. Group B streptococcus (GBS) and Escherichia coli (E. coli) are the leading pathogens of EOS. Amoxicillin combined with an aminoglycoside remains the first choice for empirical treatment. Serial physical examinations are recommended for all neonates with risk factors for EOS. Neonates without any clinical signs suggestive of EOS should not be treated with antibiotics. In Switzerland, we do not recommend the use of the EOS calculator, a risk stratification tool, due to its unclear impact in a population with an observed antibiotic exposure below 3%. Not all neonates with respiratory distress should be empirically treated with antibiotics. Isolated tachypnea or respiratory distress starting immediately after delivery by elective caesarean section or a clearly assessed alternative explanation than EOS for clinical signs may point towards a low probability of sepsis. On the other hand, unexplained prematurity with risk factors has an inherent higher risk of EOS. Before the start of antibiotic therapy, blood cultures should be drawn with a minimum volume of 1 ml in a single aerobic blood culture bottle. This standard procedure allows antibiotics to be stopped after 24 to 36 h if no pathogen is detected in blood cultures. Current data do not support the use of PCR-based pathogen detection in blood as a standard method. Lumbar puncture is recommended in blood culture-proven EOS, critical illness, or in the presence of neurological symptoms such as seizures or altered consciousness. The accuracy of a single biomarker measurement to distinguish inflammation from infection is low in neonates. Therefore, biomarker guidance is not a standard part of decision-making regarding the start or stop of antibiotic therapy but may be used as part of an algorithm and after appropriate education of health care teams. Every newborn started on antibiotics should be assessed for organ dysfunction with prompt initiation of respiratory and hemodynamic support if needed. An elevated lactate may be a sign of poor perfusion and requires a comprehensive assessment of the clinical condition. Interventions to restore perfusion include fluid boli with crystalloids and catecholamines. Neonates in critical condition should be cared for in a specialized unit. In situations with a low probability of EOS, antibiotics should be stopped as early as possible within the first 24 h after the start of therapy. In cases with microbiologically proven EOS, reassessment and streamlining of antibiotic therapy in neonates is an important step to minimize AMR., Conclusion:  This guideline, developed through a critical review of the literature, facilitates a probability-based approach to the management of neonates at risk of early onset sepsis., What Is Known: • Neonatal exposure to antibiotics is disproportionally high compared with the incidence of early onset sepsis with implications for future health and antimicrobial resistance., What Is New: • A probability-based approach may facilitate a more balanced management of neonatal sepsis and antibiotic stewardship., (© 2024. The Author(s).)

Background: Mycoplasma pneumoniae is a major cause of community-acquired pneumonia (CAP) in school-aged children. Macrolides are the first-line treatment for this infection. However, it is unclear whether macrolides are effective in treating M. pneumoniae CAP, mainly due to limitations in microbiological diagnosis of previous studies. The extensive global use of macrolides has led to increasing antimicrobial resistance. The overall objective of this trial is to produce efficacy data for macrolide treatment in children with M. pneumoniae CAP., Methods: The MYTHIC Study is a randomized, double-blind, placebo-controlled, multicenter, non-inferiority trial in 13 Swiss pediatric centers. Previously healthy ambulatory and hospitalized children aged 3-17 years with clinically diagnosed CAP will be screened with a sensitive and commercially available M. pneumoniae-specific IgM lateral flow assay from capillary blood. Mycoplasma pneumoniae infection in screened patients will be verified retrospectively by respiratory PCR (reference test) and IgM antibody-secreting cell enzyme-linked immunospot (ELISpot) assay (confirmatory test for distinguishing between carriage and infection). Patients will be randomized 1:1 to receive a 5-day treatment of macrolides (azithromycin) or placebo. The co-primary endpoints are (1) time to normalization of all vital signs, including body temperature, respiratory rate, heart rate, and saturation of peripheral oxygen (efficacy), and (2) CAP-related change in patient care status (i.e., admission, re-admission, or intensive care unit transfer) within 28 days (safety). Secondary outcomes include adverse events (AEs), as well as antimicrobial and anti-inflammatory effects. For both co-primary endpoints, we aim to show non-inferiority of placebo compared to macrolide treatment. We expect no macrolide effect (hazard ratio of 1, absolute risk difference of 0) and set the corresponding non-inferiority margins to 0.7 and -7.5%. The "at least one" success criterion is used to handle multiplicity with the two co-primary endpoints. With a power of 80% to reject at least one null hypothesis at a one-sided significance level of 1.25%, 376 patients will be required., Discussion: This trial will produce efficacy data for macrolide treatment in children with M. pneumoniae CAP that might help to reduce the prescription of antibiotics and therefore contribute to the global efforts toward reducing antimicrobial resistance., Trial Registration: ClinicalTrials.gov, NCT06325293. Registered on 24 April 2024., (© 2024. The Author(s).)

Principles to guide and inform population-based screening decisions cover a wide range of aspects beyond the screening test. Colorectal cancer (CRC) meets these requirements for individuals at moderate risk aged 50 to 69. In Switzerland, screening using a biennial faecal occult blood test or colonoscopy every 10 years is reimbursed free of deductible in 12 programs covering 15 cantons. This article assesses the appropriateness of systematic screening from age 45 in the Swiss context. Prioritizing measures to raise awareness among healthcare professionals and high-risk subjects rather than lowering the age of eligibility would not only be more sensible but would also benefit to the population over 50 years old., Competing Interests: Les auteur-trices n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Background: A considerable proportion of drugs administered to children are not authorised for this purpose, and consequently off-label use is common in paediatric care. Our aims were to quantify systematically the number of drugs authorised in Switzerland for use in children based on their current summary of product characteristics (SmPC) and to assess the quality of this information., Methods: We used natural language processing to screen all Swiss SmPCs, available in German language in the open-source drug database, for information about use in children. Based on the SmPCs of the most frequently used drugs in Swiss children's hospitals, 10 search terms were defined to retrieve this information., Results: Of the analysed 4214 drugs corresponding to 1553 active substances, 2322 (55.1%) drugs were authorised for use in children. In only 639 (15.2%) SmPCs, information about authorisation for children was found in the section 'Therapeutic indications'. 320 (13.8%) SmPCs of drugs authorised for use in children contained only verbal age indications such as 'children' and 'adolescents' without a clear definition of the age or an age range., Conclusions: Most Swiss SmPCs contain information about children, but only a minority refer to an official indication. Even if some SmPCs clearly indicate that use in children is authorised, a clear statement of the age at which the drug may be administered is missing. Standardisation of information about use in children in SmPCs is needed., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: In the initial phase of the SARS-CoV-2 pandemic, masking has been widely accepted in healthcare institutions to mitigate the risk of healthcare-associated infection. Evidence, however, is still scant and the role of masks in preventing healthcare-associated SARS-CoV-2 acquisition remains unclear.We investigated the association of variation in institutional mask policies with healthcare-associated SARS-CoV-2 infections in acute care hospitals in Switzerland during the BA.4/5 2022 wave., Methods: SARS-CoV-2 infections in hospitalized patients between June 1 and September 5, 2022, were obtained from the "Hospital-based surveillance of COVID-19 in Switzerland"-database and classified as healthcare- or community-associated based on time of disease onset. Institutions provided information regarding institutional masking policies for healthcare workers and other prevention policies. The percentage of healthcare-associated SARS-CoV-2 infections was calculated per institution and per type of mask policy. The association of healthcare-associated SARS-CoV-2 infections with mask policies was tested using a negative binominal mixed-effect model., Results: We included 2'980 SARS-CoV-2 infections from 13 institutions, 444 (15%) were classified as healthcare-associated. Between June 20 and June 30, 2022, six (46%) institutions switched to a more stringent mask policy. The percentage of healthcare-associated infections subsequently declined in institutions with policy switch but not in the others. In particular, the switch from situative masking (standard precautions) to general masking of HCW in contact with patients was followed by a strong reduction of healthcare-associated infections (rate ratio 0.39, 95% CI 0.30-0.49). In contrast, when compared across hospitals, the percentage of health-care associated infections was not related to mask policies., Conclusions: Our findings suggest switching to a more stringent mask policy may be beneficial during increases of healthcare-associated SARS-CoV-2 infections at an institutional level., (© 2024. The Author(s).)

Background: The immunogenicity of the standard influenza vaccine is reduced in solid-organ transplant (SOT) recipients, so new vaccination strategies are needed in this population., Methods: Adult SOT recipients from 9 transplant clinics in Switzerland and Spain were enrolled if they were >3 months after transplantation. Patients were randomized (1:1:1) to a MF59-adjuvanted or a high-dose vaccine (intervention), or a standard vaccine (control), with stratification by organ and time from transplant. The primary outcome was vaccine response rate, defined as a ≥4-fold increase of hemagglutination-inhibition titers to at least 1 vaccine strain at 28 days postvaccination. Secondary outcomes included polymerase chain reaction-confirmed influenza and vaccine reactogenicity., Results: A total of 619 patients were randomized, 616 received the assigned vaccines, and 598 had serum available for analysis of the primary endpoint (standard, n = 198; MF59-adjuvanted, n = 205; high-dose, n = 195 patients). Vaccine response rates were 42% (84/198) in the standard vaccine group, 60% (122/205) in the MF59-adjuvanted vaccine group, and 66% (129/195) in the high-dose vaccine group (difference in intervention vaccines vs standard vaccine, 0.20; 97.5% confidence interval [CI], .12-1); P < .001; difference in high-dose vs standard vaccine, 0.24 [95% CI, .16-1]; P < .001; difference in MF59-adjuvanted vs standard vaccine, 0.17 [97.5% CI, .08-1]; P < .001). Influenza occurred in 6% of the standard, 5% in the MF59-adjuvanted, and 7% in the high-dose vaccine groups. Vaccine-related adverse events occurred more frequently in the intervention vaccine groups, but most of the events were mild., Conclusions: In SOT recipients, use of an MF59-adjuvanted or a high-dose influenza vaccine was safe and resulted in a higher vaccine response rate., Clinical Trials Registration: Clinicaltrials.gov NCT03699839., Competing Interests: Potential conflicts of interest. O. M. reports receiving grants from Lophius Bioscience and participated in advisory boards of Takeda and MSD. N. J. M. reports receiving grants from the Swiss Transplant Cohort Study, receiving support for attending a meeting by Biotest, and participating in the board of the Swiss Society for Infectious Diseases. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Aims of the Study: We previously reported a re-emergence of syphilis from 2006 to 2009 with detection of congenital syphilis in Switzerland. This study aimed to reassess the incidence of children exposed to maternal syphilis during pregnancy and congenital syphilis in a following 10-year period in the canton of Zurich, the most populous canton in Switzerland with the highest incidences of syphilis., Methods: Children were identified both by reviewing medical records at the four major neonatal and paediatric hospitals providing acute care in the canton of Zurich and by the serological database of the syphilis reference laboratory. Inclusion criteria for children were (a) date of birth in the period 2010-2019, (b) place of birth in the canton of Zurich, (c) evaluation for syphilis due to positive syphilis pregnancy screening and (d) age <1 year at diagnosis. Results were compared with epidemiological data provided by the Federal Office of Public Health (FOPH)., Results: We identified and evaluated 17 children after potential exposure to maternal syphilis. Residual antibodies of a past infection were found in 11 mothers. Six children were identified as having had real exposure to asymptomatic maternal syphilis. From an epidemiological perspective, the distribution of the cases followed a similar pattern as confirmed syphilis cases in women of childbearing age reported to the FOPH. No cases of congenital syphilis were observed., Conclusions: In contrast to the rise in syphilis infections, this study identified no cases of congenital syphilis in the canton of Zurich, Switzerland, in the period 2010-2019. Syphilis pregnancy screening may have prevented congenital syphilis by diagnosing and allowing adequate treatment of asymptomatic maternal syphilis.

Objective: We aimed to evaluate the association between post-appendectomy SSI rates and the two most commonly used regimens for perioperative antimicrobial prophylaxis in Swiss children., Methods: We conducted a retrospective cohort study, analysing data from the Swiss national SSI surveillance database with a study period from 2014 to 2018. All hospitals undertaking paediatric appendectomies in Switzerland participate in the surveillance. We compared the cumulative incidence and odds of post-appendectomy SSI within 30 days of surgery in children ≤ 16 years of age undergoing appendectomy for uncomplicated appendicitis and receiving perioperative antimicrobial prophylaxis with cefuroxime plus metronidazole or with amoxicillin/clavulanic acid using multivariable adjusted logistic regression and propensity-score matching., Results: A total of 6207 cases were recorded in the study time frame. Overall SSI cumulative incidence was 1.9% (n = 119). 4256 children (54.9% male, median (IQR) age 12 [10, 14] years) received either cefuroxime plus metronidazole (n = 2348, 53.8% male) or amoxicillin/clavulanic acid (n = 1491, 57.0% male). SSI cumulative incidence was 1.1% (25/2348) among children receiving cefuroxime plus metronidazole and 2.8% (42/1491, p < 0.001) when receiving amoxicillin/clavulanic acid. The administration of cefuroxime plus metronidazole was associated with statistically significantly lower SSI odds compared to amoxicillin/clavulanic acid (aOR 0.35, 95%CI [0.20, 0.61], p < 0.001), and this was confirmed upon propensity-score matching., Conclusion: We found lower odds of post-appendectomy SSI in children receiving cefuroxime plus metronidazole compared to amoxicillin/clavulanic acid. Treating amoxicillin/clavulanic acid as the baseline, only 55 children need to receive cefuroxime plus metronidazole perioperative prophylaxis to avert one SSI. Existing guidelines recommending amoxicillin/clavulanic acid may need to be revised. Trial registration ISRCTN47727811, registered retrospectively., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Importance: Vaccine responses are decreased in solid organ transplant (SOT) recipients, and given the complexity of implementation, vaccination programs may be suboptimal. The actual burden of vaccine-preventable infections (VPIs) among SOT recipients remains unclear., Objectives: To assess the incidence rate of VPIs among SOT recipients and to evaluate whether SOT recipients are at increased risk for specific VPIs compared with the general population., Design, Setting, and Participants: This nationwide cohort study used data from the Swiss Transplant Cohort Study on VPIs in individuals who underwent SOT from May 2008 to June 2019 (follow-up until December 2019) and data from the Swiss Federal Office of Public Health on notifiable VPIs in the general population in the same period. Data were analyzed from January 2021 to June 2022., Exposures: Solid organ transplant., Main Outcomes and Measures: The main outcomes were the incidence rate of the following VPIs in SOT recipients: hepatitis A and B, diphtheria, Haemophilus influenzae infection, influenza, measles, mumps, pertussis, pneumococcal disease, poliomyelitis, meningococcal disease, rubella, tetanus, tick-borne encephalitis, and varicella zoster virus infection. Age-adjusted standardized incidence ratios were used to assess whether VPIs occurred more frequently in SOT recipients compared with the general population. For SOT recipients, factors associated with occurrence of VPIs were explored and the associated morbidity and mortality assessed., Results: Of 4967 SOT recipients enrolled (median age, 54 years [IQR, 42-62 years]; 3191 [64.2%] male), 593 (11.9%) experienced at least 1 VPI. The overall VPI incidence rate was higher in the population that underwent SOT (30.57 per 1000 person-years [PY]; 95% CI, 28.24-33.10 per 1000 PY) compared with the general population (0.71 per 1000 PY). The standardized age-adjusted incidence ratio for notifiable VPIs in SOT recipients was higher compared with the general population (27.84; 95% CI, 25.00-31.00). In SOT recipients, influenza and varicella zoster virus infection accounted for most VPI episodes (16.55 per 1000 PY [95% CI, 14.85-18.46 per 1000 PY] and 12.83 per 1000 PY [95% CI, 11.40-14.44 per 1000 PY], respectively). A total of 198 of 575 VPI episodes in the population that underwent SOT (34.4%) led to hospital admission, and the occurrence of a VPI was associated with an increased risk for death and/or graft loss (hazard ratio, 2.44; 95% CI, 1.50-3.99; P = .002). In multivariable analysis, age 65 years or older at the time of transplant (incidence rate ratio [IRR], 1.29; 95% CI, 1.02-1.62) and receipt of a lung (IRR, 1.77; 95% CI, 1.38-2.26) or a heart (IRR, 1.40; 95% CI, 1.05-1.88) transplant were associated with an increased risk of VPI occurrence., Conclusions and Relevance: In this study, 11.9% of SOT recipients experienced VPIs, and the incidence rate was higher than in the general population. There was significant morbidity and mortality associated with these infections in the population that underwent SOT, which highlights the need for optimizing immunization strategies.

At our tertiary children's hospital, infections with newly detected methicillin-resistant Staphylococcus aureus (MRSA) among children attending primary (age 6-12 years) and secondary school (age 13-16 years) nearly doubled in 2018 compared to previous years. This observation initiated an epidemiological outbreak investigation including phenotypic (susceptibility testing) and genotypic (whole genome sequencing) characterization of the isolates. In addition, a cross-sectional study was conducted to determine source of the outbreak, colonization frequency and to identify risk factors for transmission using a questionnaire. As a result, 49 individuals were detected with 57 corresponding isolates. Based on the case definition combined with whole genome sequencing, a core cluster was identified that shared common genetic features and a similar antimicrobial susceptibility pattern (efflux-mediated macrolide resistance, tetracycline susceptibility along with presence of Panton-Valentine leukocidin). Epidemiologic evaluation identified a distinct school as a common risk factor. However, the source of the clustered infections within that school could not be further specified. No further cases could be detected after decolonization of infected and colonized children., (© 2022. The Author(s).)

Infection following surgical procedures leads to significant morbidity and mortality in all age groups. Sterile techniques, antibiotic prophylaxis and improved postoperative wound care have contributed to the decline of surgical site infections since the early days of surgery. Recommendations on the use of perioperative antimicrobial prophylaxis exist for adults, but are rare for the paediatric population. Here, we provide a standardised approach to the effective use of antimicrobial agents for the prevention of surgical site infections in children contributing to a targeted and rational perioperative use of antibiotics in Switzerland.

Objective: Although medical providers are a trusted vaccination information source for parents, they do not universally support vaccination. Complementary medicine (CM) providers are particularly likely to hold vaccine hesitant (VH) views, and VH parents often consult with them. Little research compares VH of parents and providers, and if and how each is associated with uptake of recommended childhood vaccines., Methods: We defined non-timely receipt as recommended vaccines given > 1 month later than officially recommended, based on vaccination records. We administered versions of the Parent Attitudes about Childhood Vaccines (PACV) 5-item survey instrument to 1256 parents and their children's pediatricians (N = 112, 40 CM-oriented, 72 biomedical [not CM-oriented]) to identify moderately (PACV-score 5-6) and highly (PACV-score 7+) hesitant providers/parents. We obtained multivariable adjusted odds ratios to test relationships between parental VH and provider type/VH, and between non-timely receipt of selected childhood vaccines and parental VH and provider type/VH., Results: No biomedical providers were VH, 9 CM providers were moderately VH, and 17 were highly VH. Parents seeing moderately and highly hesitant providers had adjusted odds ratio (AOR) for being VH = 6.6 (95% confidence interval (CI), 3.1-14.0) and AOR = 31.3 (95% CI 16.8-58.3), respectively. Across all vaccine uptake endpoints, children of moderately and highly hesitant parents had 1.9-3.8 and 7.1-12.3 higher odds of non-timely vaccination, and children seeing highly hesitant CM providers had 4.9-9.4 higher odds. Children seeing moderately hesitant CM providers had 3.3 higher odds of non-timely vaccination for the 1st dose of measles and 3.5 higher odds for 1st dose of polio/pertussis/tetanus., Conclusion: VH by both parents and providers each is associated with non-timely childhood vaccination. As VH parents are more likely to consult with VH providers, interventions aimed at increasing timely vaccination need to primarily target VH providers and their clients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

In daily paediatrics, drugs are commonly used off-label, as they are not approved for children. Approval is lacking because the required clinical studies were limited to adults in the past. Without clinical studies, evidence-based recommendations for drug use in children are limited. Information on off-label drug dosing in children can be found in different handbooks, databases and scientific publications but the dosing recommendations can differ considerably. To improve safety and efficacy of drugs prescribed to children and to assist the prescribers, stakeholders in Swiss paediatrics started a pilot project, supported by the Federal Office of Public Health, with the aim to create a database, providing healthcare professionals with so called "harmonised" dosage recommendations based on the latest available scientific evidence and best clinical practice. A standardised process for dosage harmonisation between paediatric experts was defined, guided and documented in an electronic tool, developed for this purpose. As proof of principle, a total of 102 dosage recommendations for 30 different drugs have been nationally harmonised in the pilot phase considering the current scientific literature and the approval of the most experienced national experts in the field.Conclusion: This approach paved the way for unified national dosage recommendations for children. Reaching the project's milestones fulfilled the prerequisites for funding and starting regular operation of SwissPedDose in 2018. Since then, the database was extended with recommendations for 100 additional drugs. What is Known: • Prescribing off-label is a common practice among paediatricians, as many drugs are still not authorised for use in children. • Some countries developed national drug formularies providing off-label dosage recommendations. What is New: • Comparison of published dosage recommendations in known drug handbooks and online databases show substantial differences and heterogeneity, revealing the need for harmonisation. • The design of a tool for standardised harmonisation of dosage recommendations, based on information collected on currently applied dosages, latest scientific evidence and the approval of experts., (© 2021. The Author(s).)

Background and Purpose: In Switzerland, the COVID-19 incidence during the first pandemic wave was high. Our aim was to assess the association of the outbreak with acute stroke care in Switzerland in spring 2020., Methods: This was a retrospective analysis based on the Swiss Stroke Registry, which includes consecutive patients with acute cerebrovascular events admitted to Swiss Stroke Units and Stroke Centers. A linear model was fitted to the weekly admission from 2018 and 2019 and was used to quantify deviations from the expected weekly admissions from 13 March to 26 April 2020 (the "lockdown period"). Characteristics and 3-month outcome of patients admitted during the lockdown period were compared with patients admitted during the same calendar period of 2018 and 2019., Results: In all, 28,310 patients admitted between 1 January 2018 and 26 April 2020 were included. Of these, 4491 (15.9%) were admitted in the periods March 13-April 26 of the years 2018-2020. During the lockdown in 2020, the weekly admissions dropped by up to 22% compared to rates expected from 2018 and 2019. During three consecutive weeks, weekly admissions fell below the 5% quantile (likelihood 0.38%). The proportion of intracerebral hemorrhage amongst all registered admissions increased from 7.1% to 9.3% (p = 0.006), and numerically less severe strokes were observed (median National Institutes of Health Stroke Scale from 3 to 2, p = 0.07)., Conclusions: Admissions and clinical severity of acute cerebrovascular events decreased substantially during the lockdown in Switzerland. Delivery and quality of acute stroke care were maintained., (© 2021 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: Most case series of patients with ischemic stroke (IS) and COVID-19 are limited to selected centers or lack 3-month outcomes. The aim of this study was to describe the frequency, clinical and radiological features, and 3-month outcomes of patients with IS and COVID-19 in a nationwide stroke registry., Methods: From the Swiss Stroke Registry (SSR), we included all consecutive IS patients ≥18 years admitted to Swiss Stroke Centers or Stroke Units during the first wave of COVID-19 (25 February to 8 June 2020). We compared baseline features, etiology, and 3-month outcome of SARS-CoV-2 polymerase chain reaction-positive (PCR+) IS patients to SARS-CoV-2 PCR- and/or asymptomatic non-tested IS patients., Results: Of the 2341 IS patients registered in the SSR during the study period, 36 (1.5%) had confirmed COVID-19 infection, of which 33 were within 1 month before or after stroke onset. In multivariate analysis, COVID+ patients had more lesions in multiple vascular territories (OR 2.35, 95% CI 1.08-5.14, p = 0.032) and fewer cryptogenic strokes (OR 0.37, 95% CI 0.14-0.99, p = 0.049). COVID-19 was judged the likely principal cause of stroke in 8 patients (24%), a contributing/triggering factor in 12 (36%), and likely not contributing to stroke in 13 patients (40%). There was a strong trend towards worse functional outcome in COVID+ patients after propensity score (PS) adjustment for age, stroke severity, and revascularization treatments (PS-adjusted common OR for shift towards higher modified Rankin Scale (mRS) = 1.85, 95% CI 0.96-3.58, p = 0.07)., Conclusions: In this nationwide analysis of consecutive ischemic strokes, concomitant COVID-19 was relatively rare. COVID+ patients more often had multi-territory stroke and less often cryptogenic stroke, and their 3-month functional outcome tended to be worse., (© 2021 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: Syrian refugees in Switzerland face several barriers in accessing mental health care. Cost-effective psychological interventions are urgently needed to meet the mental health needs of refugees. Problem Management Plus (PM+) is an evidence-based, psychological intervention delivered by trained non-specialist 'helpers'., Objective: To assess the feasibility and acceptability of PM+ among Syrian refugees in Switzerland., Methods: We conducted a single-blind pilot randomized controlled trial (RCT) with Syrian refugees impaired by psychological distress (K10 > 15 and WHODAS 2.0 > 16). Participants were randomized to PM+ or Enhanced Treatment As Usual (ETAU). Participants were assessed at baseline, and 1 week and 3 months after the intervention, and completed measures indexing mental health problems and health care usage. Semi-structured interviews were conducted with different stakeholders., Results: N = 59 individuals were randomized into PM+ ( n = 31) or ETAU ( n = 28). N = 18 stakeholders were interviewed about facilitators and barriers for the implementation of PM+. Retention rates in the trial (67.8%) and mean intervention attendance ( M = 3.94 sessions, SD  = 1.97) were high. No severe events related to the study were reported. These findings indicate that the trial procedures and PM+ were feasible, acceptable and safe., Conclusions: The findings support the conduct of a definitive RCT and show that PM+ might have the potential to be scaled-up in Switzerland. The importance, as well as the challenges, of implementing and scaling-up PM+ in high-income countries, such as Switzerland, are discussed., Competing Interests: No potential conflict of interest was reported by the author (s)., (© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Clinical trials have been performed mainly in adults and accordingly the necessary information is lacking for pediatric patients, especially regarding dosage recommendation for approved drugs. This gap in information could be filled with results from pharmacokinetic (PK) modeling, based on data collected in daily clinical routine. In order to make this data accessible and usable for research, the Swiss Pharmacokinetics Clinical Data Warehouse (SwissPK cdw ) project has been set up, including a clinical data warehouse (CDW) and the regulatory framework for data transfer and use within. Embedded into the secure BioMedIT network, the CDW can connect to various data providers and researchers in order to collaborate on the data securely. Due to its modularity, partially containerized deployment and open-source software, each of the components can be extended, modified, and re-used for similar projects that require integrated data management, data analysis, and web tools in a secure scientific data and information technology (IT) environment. Here, we describe a collaborative and interprofessional effort to implement the aforementioned infrastructure between several partners from medical health care and academia. Furthermore, we describe a real-world use case where blood samples from pediatric patients were analyzed for the presence of genetic polymorphisms and the results were aggregated and further analyzed together with the health-related patient data in the SwissPK cdw ., (© 2021 The Authors. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: When the periods of time during and after the first wave of the ongoing SARS-CoV-2/COVID-19 pandemic in Europe are compared, 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., Methods: We investigated the trends in COVID-19-related mortality (in-hospital and in-intermediate/intensive-care) over time in Switzerland, from February 2020 to June 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., Results: Our analysis included 16,984 patients recorded in CH-SUR, with 2201 reported deaths due to COVID-19 (13.0%). We found that overall in-hospital mortality was lower during the second wave of COVID-19 than in the first wave (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.63- 0.78; p <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 with the first wave (HR 1.25, 95% CI 1.05-1.49; p = 0.029), with significant changes in the course of hospitalisation between the first and the second wave., Conclusion: We 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.

In anticipation of an interseasonal respiratory syncytial virus (RSV) epidemic, a clinician-led reporting system was rapidly established to capture RSV infections in Swiss hospitals, starting in January 2021. Here, we present details of the reporting system and first results to June 2021. An unusual epidemiology was observed with an interseasonal surge of RSV infections associated with COVID-19-related non-pharmacological interventions. These data allowed real-time adjustment of RSV prophylaxis guidelines and consequently underscore the need for and continuation of systematic nationwide RSV surveillance.

Objectives: To determine the variation in SARS-CoV-2 seroprevalence in school children and the relationship with self-reported symptoms., Design: Baseline measurements of a longitudinal cohort study ( Ciao Corona ) from June to July 2020., Setting: 55 schools stratified by district in the canton of Zurich, Switzerland., Participants: 2585 children (1339 girls; median age: 11 years, age range: 6-16 years), attending grades 1-2, 4-5 and 7-8., Main Outcome Measures: Variation in seroprevalence of SARS-CoV-2 in children across 12 cantonal districts, schools and grades, assessed using Luminex-based test of four epitopes for IgG, IgA and IgM (Antibody Coronavirus Assay,ABCORA 2.0). Clustering of cases within classes. Association of seropositivity and symptoms. Comparison with seroprevalence in adult population, assessed using Luminex-based test of IgG and IgA (Sensitive Anti-SARS-CoV-2 Spike Trimer Immunoglobulin Serological test)., Results: Overall seroprevalence was 2.8% (95% CI 1.5% to 4.1%), ranging from 1.0% to 4.5% across districts. Seroprevalence in grades 1-2 was 3.8% (95% CI 2.0% to 6.1%), in grades 4-5 was 2.4% (95% CI 1.1% to 4.2%) and in grades 7-8 was 1.5% (95% CI 0.5% to 3.0%). At least one seropositive child was present in 36 of 55 (65%) schools and in 44 (34%) of 131 classes where ≥5 children and ≥50% of children within the class were tested. 73% of children reported COVID-19-compatible symptoms since January 2020, with the same frequency in seropositive and seronegative children for all symptoms. Seroprevalence of children and adults was similar (3.2%, 95% credible interval (CrI) 1.7% to 5.0% vs 3.6%, 95% CrI 1.7% to 5.4%). The ratio of confirmed SARS-CoV-2 cumulative incidence-to-seropositive cases was 1:89 in children and 1:12 in adults., Conclusions: SARS-CoV-2 seroprevalence was low in children and similar to that in adults by the end of June 2020. Very low ratio of diagnosed-to-seropositive children was observed. We did not detect clustering of SARS-CoV-2-seropositive children within classes, but the follow-up of this study will shed more light on transmission within schools., Trial Registration Number: NCT04448717., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Solid organ transplant (SOT) recipients are exposed to respiratory viral infection (RVI) during seasonal epidemics; however, the associated burden of disease has not been fully characterized. We describe the epidemiology and outcomes of RVI in a cohort enrolling 3294 consecutive patients undergoing SOT from May 2008 to December 2015 in Switzerland. Patient and allograft outcomes, and RVI diagnosed during routine clinical practice were prospectively collected. Median follow-up was 3.4 years (interquartile range 1.61-5.56). Six hundred ninety-six RVIs were diagnosed in 151/334 (45%) lung and 265/2960 (9%) non-lung transplant recipients. Cumulative incidence was 60% (95% confidence interval [CI] 53%-69%) in lung and 12% (95% CI 11%-14%) in non-lung transplant recipients. RVI led to 17.9 (95% CI 15.7-20.5) hospital admissions per 1000 patient-years. Intensive care unit admission was required in 4% (27/691) of cases. Thirty-day all-cause case fatality rate was 0.9% (6/696). Using proportional hazard models we found that RVI (adjusted hazard ratio [aHR] 2.45; 95% CI 1.62-3.73), lower respiratory tract RVI (aHR 3.45; 95% CI 2.15-5.52), and influenza (aHR 3.57; 95% CI 1.75-7.26) were associated with graft failure or death. In this cohort of SOT recipients, RVI caused important morbidity and may affect long-term outcomes, underlying the need for improved preventive strategies., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

The kidneys and the urinary tract are a common source of infection in children of all ages, especially infants and young children. The main risk factors for sequelae after urinary tract infections (UTI) are congenital anomalies of the kidney and urinary tract (CAKUT) and bladder-bowel dysfunction. UTI should be considered in every child with fever without a source. The differentiation between upper and lower UTI is crucial for appropriate management. Method of urine collection should be based on age and risk factors. The diagnosis of UTI requires urine analysis and significant growth of a pathogen in culture. Treatment of UTI should be based on practical considerations regarding age and presentation with adjustment of the initial antimicrobial treatment according to antimicrobial sensitivity testing. All children, regardless of age, should have an ultrasound of the urinary tract performed after pyelonephritis. In general, antibiotic prophylaxis is not recommended.Conclusion: Based on recent data and in line with international guidelines, multidisciplinary Swiss consensus recommendations were developed by members of Swiss pediatric infectious diseases, nephrology, and urology societies giving the clinician clear recommendations in regard to diagnosis, type and duration of therapy, antimicrobial treatment options, indication for imaging, and antibiotic prophylaxis. What is Known: • Urinary tract infections (UTI) are a common and important clinical problem in childhood. Although children with pyelonephritis tend to present with fever, it can be difficult on clinical grounds to distinguish cystitis from pyelonephritis, particularly in young children less than 2 years of age. • Method of urine collection is based on age and risk factors. The diagnosis of UTI requires urine analysis and significant growth of a pathogen in culture. What is New: • Vesicoureteric reflux (VUR) remains a risk factor for UTI but per se is neither necessary nor sufficient for the development of renal scars. Congenital anomalies of the kidney and urinary tract (CAKUT) and bladder-bowel dysfunction play a more important role as causes of long-term sequelae. In general, antibiotic prophylaxis is not recommended. • A switch to oral antibiotics should be considered already in young infants. Indications for invasive imaging are more restrictive and reserved for patients with abnormal renal ultrasound, complicated UTI, and infections with pathogens other than E. coli.

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&rsquo;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&ndash;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.

Objectives: This longitudinal cohort study aims to assess the extent and patterns of seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in school-attending children, and their parents and school personnel. It will examine risk factors for infection, the relationship between seropositivity and symptoms, and temporal persistence of antibodies., Methods: The study (Ciao Corona) will enroll a regionally representative, random sample of schools in the canton of Zurich, where 18% of the Swiss population live. Children aged 5-16 years, attending primary and secondary schools, and their parents and school personnel are invited. Venous blood and saliva samples are collected for serological testing in June/July 2020, in October/November 2020, and in March/April 2021. Bi-monthly questionnaires will cover SARS-CoV-2 symptoms and tests, health, preventive behavior, and lifestyle information. Hierarchical Bayesian logistic regression models will account for sensitivity and specificity of the serological tests in the analyses and complex sampling structure, i.e., clustering within classes and schools., Results and Conclusions: This unique school-based study will allow describing temporal trends of immunity, evaluate effects of preventive measures and will inform goal-oriented policy decisions during subsequent outbreaks. Trial registration ClinicalTrials.gov Identifier: NCT04448717, registered June 26, 2020. https://clinicaltrials.gov/ct2/show/NCT04448717 .

Background: The burden and timeline of posttransplant infections are not comprehensively documented in the current era of immunosuppression and prophylaxis., Methods: In this prospective study nested within the Swiss Transplant Cohort Study (STCS), all clinically relevant infections were identified by transplant-infectious diseases physicians in persons receiving solid organ transplant (SOT) between May 2008 and December 2014 with ≥12 months of follow-up., Results: Among 3541 SOT recipients, 2761 (1612 kidney, 577 liver, 286 lung, 213 heart, and 73 kidney-pancreas) had ≥12 months of follow-up; 1520 patients (55%) suffered 3520 infections during the first year posttransplantation. Burden and timelines of clinically relevant infections differed between transplantations. Bacteria were responsible for 2202 infections (63%) prevailing throughout the year, with a predominance of Enterobacteriaceae (54%) as urinary pathogens in heart, lung, and kidney transplant recipients, and as digestive tract pathogens in liver transplant recipients. Enterococcus spp (20%) occurred as urinary tract pathogens in kidney transplant recipients and as digestive tract pathogens in liver transplant recipients, and Pseudomonas aeruginosa (9%) in lung transplant recipients. Among 1039 viral infections, herpesviruses predominated (51%) in kidney, liver, and heart transplant recipients. Among 263 fungal infections, Candida spp (60%) prevailed as digestive tract pathogens in liver transplant recipients. Opportunistic pathogens, including Aspergillus fumigatus (1.4%) and cytomegalovirus (6%), were rare, scattering over 12 months across all SOT recipients., Conclusions: In the current era of immunosuppression and prophylaxis, SOT recipients experience a high burden of infections throughout the first year posttransplantation, with rare opportunistic pathogens and a predominance of bacteria., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

The recent introduction of newborn screening for severe primary T and B cell deficiencies in Switzerland allows rapid identification of patients with severe combined immunodeficiency (SCID). Outcomes for SCID are greatly improved by early diagnosis and treatment with allogeneic haematopoietic stem cell transplantation or, in selected cases, gene therapy. National centralised newborn screening is performed in Switzerland since January 2019 using a combined T cell receptor excision circles (TREC) / &kappa;-deleting recombination excision circles (KREC) assay, also revealing infants with non-SCID severe T and B cell disorders, who are often diagnosed with a substantial delay. Here, we outline the screening procedure currently performed in Switzerland and give recommendations for diagnostic evaluations and precautionary measures against infection in children with abnormal screening test results.

Background: We recently demonstrated that the measurement of Mycoplasma pneumoniae (Mp)-specific immunoglobulin (Ig)M antibody-secreting cells (ASCs) improved diagnosis of Mp infection. Here, we aimed to describe Mp ASC kinetics and duration in comparison to conventional measures such as pharyngeal Mp deoxyribonucleic acid (DNA) and serum antibodies., Methods: This is a prospective longitudinal study of 63 community-acquired pneumonia (CAP) patients and 21 healthy controls (HCs), 3-18 years of age, from 2016 to 2017. Mycoplasma pneumoniae ASCs measured by enzyme-linked immunospot assay were assessed alongside Mp DNA and antibodies during 6-month follow-up., Results: Mycoplasma pneumoniae ASCs of the isotype IgM were found in 29 (46%), IgG were found in 27 (43%), and IgA were found in 27 (43%) CAP patients. Mycoplasma pneumoniae ASCs were detected from 2 days to a maximum of 6 weeks after symptom onset, whereas Mp DNA and antibodies persisted until 4 months (P = .03) and 6 months (P < .01). Mycoplasma pneumoniae ASCs were undetectable in HCs, in contrast to detection of Mp DNA in 10 (48%) or antibodies in 6 (29%) controls for a prolonged time. The Mp ASC response correlated with clinical disease, but it did not differ between patients treated with or without antibiotics against Mp., Conclusions: Mycoplasma pneumoniae-specific ASCs are short-lived and associated with clinical disease, making it an optimal resource for determining Mp pneumonia etiology., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

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.

Background: Typhoid fever usually manifests as an acute disease. However, asymptomatic carriage with Salmonella Typhi may occur. This study investigated a family setting of severe typhoid fever in Switzerland months after return from Bangladesh., Method: Standard microbiological procedures were performed. Testing for S. Typhi IgM antibodies was done using a novel immunochromographic lateral flow assay. Whole genome sequencing (WGS) followed by comparative core genome multilocus sequence typing (cgMLST) was performed on the S. Typhi isolates., Results: Four months after returning from a visit to Bangladesh sibling 1 (9 months) was diagnosed with a S. Typhi meningitis and sibling 3 (8 years) was identified as asymptomatic S. Typhi carrier. Sibling 2 (2 years) was retrospectively diagnosed with typhoid fever by IgM serology at the time point of admission to the hospital. Parents were asymptomatic and culture-negative. WGS analysis of family S. Typhi isolates showed clonality and strongest homology with S. Typhi strains occurring in Bangladesh. The S. Typhi strain showed resistance against fluoroquinolones. A 4-week course of ceftriaxone resulted in full recovery of sibling 1. S. Typhi was eradicated from sibling 3 following azithromycin treatment for 14 days., Conclusion: S. Typhi, acquired from a visit to Bangladesh, was most likely transmitted within the family from one brother as asymptomatic shedder to his 9-month-old brother who manifested S. Typhi meningitis as a very rare and life-threatening presentation of typhoid fever. S. Typhi infection should be considered even in case of uncommon manifestations and irrespective of the interval between disease presentation and travel to an endemic area., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Sapovirus (SaV) and astrovirus (AstV) increasingly are recognized as cause of acute viral gastroenteritis (AGE). We evaluated the real-time RT-PCR assays RIDA®GENE SaV and viral stool panel II (RGN RT-PCR) for detection of SaV, AstV, adenovirus (AdV) F40/41 and rotavirus (RoV) in clinical stool samples (n = 69). Results were compared with reference singleplex RT-PCRs. The sensitivity for SaV, AstV and RoV are 100%, the specificity ranges from 98.1% to 100%. In 10 out of 11 AdV (all types) samples, the RGN RT-PCR for AdV F40/41 displayed negative results. Retrospectively, 196 stool specimens from adult patients previously tested negative for norovirus (NoV) were analyzed. In about 10% of NoV-negative stool samples, AdV (n = 9), RoV (n = 6), AstV (n = 3) or SaV (n = 3) were found. The RGN RT-PCR assays are useful for detection of enteric viruses other than NoV. This study emphasizes the need for further testing of NoV-negative stool samples in patients with AGE., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Crime scene samples originating from domestic dogs such as hair, blood, or saliva can be probative as possible transfer evidence in human crime and in dog attack cases. In the majority of such cases canine DNA identification using short tandem repeat (STR) analysis is the method of choice, which demands, among others, a systematic survey of allele frequency data in the relevant dog populations. A set of 13 highly polymorphic canine STR markers was used to analyze samples of 1,184 dogs (including 967 purebred dogs) from the so-called DACH countries (Germany, Austria, Switzerland). This CaDNAP 13-STR panel has previously been validated for canine identification in a forensic context. Here, we present robust estimates of allele frequencies, which are essential to assess the weight of the evidence by estimating the probability of a matching DNA profile within the dog population under question, e.g. in the form of a random match probability (RMP). The geographical provenance of the tested dogs showed a negligible influence on the observed genotype variation. Therefore, we combined the STR data from all three countries into a single dog population sample (DPS). In contrast, pronounced genetic differentiation between dog breeds was found by principal component analysis and sub-structure analysis with the STRUCTURE software. These findings entailed the need to account for the effects of DPS breed composition on allele frequency estimates. A possible strategy, which was favored here, relies on collecting a DPS that is guided by the breed composition of the relevant dog population. In total, dogs from 166 different breeds were included in our DPS, 64 of them including at least 5 individuals (n = 771 dogs). Sampling reflected the abundance of breeds in the DACH countries with the following being the most common ones: German Shepherds (population frequency: 14.3%), Dachshunds (5.9%), Labrador Retrievers (3.9%), and Golden Retrievers (3.2%). The pedigree listing of the purebred dogs in our DPS ranked German Shepherds (DPS frequency 8.5%) first, followed by Labrador Retrievers (3.9%), Golden Retrievers (3%), and Dachshunds (2.5%). RMP values based on overall allele frequencies and accounting for substructure using F ST between breeds ranged between 10-13 and 10-14 and represent a conservative approach of RMP assessment., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Contemporary, comprehensive data on epidemiology and outcomes of invasive fungal disease (IFD) including breakthrough IFD among allogeneic hematopoietic stem cell transplantation (HSCT) recipients are scarce. We included 479 allogeneic HSCT recipients with 10 invasive candidiasis (IC) and 31 probable/proven invasive mold disease (IMD) from the Swiss Transplant Cohort Study from 01.2009 to 08.2013. Overall cumulative incidence was 2.3% for IC and 8.5% for probable/proven IMI: 6% for invasive aspergillosis (IA) and 2.5% for non-AspergillusIMI. Among 41 IFD, 46% IFD were breakthrough, with an overall incidence of 4.6%, more frequently caused by other-than-Aspergillus fumigatus molds than primary IFD (47.6% (10/21) vs 13% (3/23), P = 0.04). Twelve-week mortality among patients with IC was 20% and 58.6% for probable/proven IMD (60% IA and 54.6% non-Aspergillus). Our results reveal that breakthrough IFD represent a marked burden of probable/proven IFD postallogeneic HSCT and mortality remains above 50% in patients with probable/proven IMD, underscoring the ongoing challenges to prevent and treat IFD in these patients., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To assess the epidemiology of blood culture-proven early- (EOS) and late-onset neonatal sepsis (LOS)., Study Design: All newborn infants admitted to tertiary care neonatal intensive care units in Switzerland and presenting with blood culture-proven sepsis between September 2011 and December 2015 were included in the study. We defined EOS as infection occurring <3 days after birth, and LOS as infection ≥3 days after birth. Infants with LOS were classified as having community-acquired LOS if onset of infection was ≤48 hours after admission, and hospital-acquired LOS, if onset was >48 hours after admission. Incidence was estimated based on the number of livebirths in Switzerland and adjusted for the proportion of admissions at centers participating in the study., Results: We identified 444 episodes of blood culture-proven sepsis in 429 infants; 20% of cases were EOS, 62% hospital-acquired LOS, and 18% community-acquired LOS. The estimated national incidence of EOS, hospital-acquired LOS, and community-acquired LOS was 0.28 (95% CI 0.23-0.35), 0.86 (0.76-0.97), and 0.28 (0.23-0.34) per 1000 livebirths. Compared with EOS, hospital-acquired LOS occurred in infants of lower gestational age and was more frequently associated with comorbidities. Community-acquired LOS was more common in term infants and in male infants. Mortality was 18%, 12%, and 0% in EOS, hospital-acquired LOS, and community-acquired LOS, and was higher in preterm infants, in infants with septic shock, and in those requiring mechanical ventilation., Conclusions: We report a high burden of sepsis in neonates with considerable mortality and morbidity. EOS, hospital-acquired LOS, and community-acquired LOS affect specific patient subgroups and have distinct clinical presentation, pathogens and outcomes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: There is lack of recent multicenter epidemiological data on invasive aspergillosis (IA) among solid organ transplant recipient (SOTr) in the mold-acting antifungal era. We describe the epidemiology and outcomes of IA in a contemporary cohort of SOTr using the Swiss Transplant Cohort Study., Methods: All consecutive SOTr with proven or probable IA between 01.05.2008 and 31.12.2014 were included. A case-control study to identify IA predictors was performed: 1-case was matched with 3-controls based on SOT type, transplant center, and time post-SOT., Results: Among 2868 SOTr, 70 (2.4%) patients were diagnosed with proven (N: 30/70, 42.9%) or probable (N: 40/70, 57.1%) IA. The incidence of IA was 8.3%, 7.1%, 2.6%, 1.3%, and 1.2% in lung, heart, combined, kidney, and liver transplant recipients, respectively, Galactomannan immunoassay was positive in 1/3 of patients tested. Only 33/63 (52.4%) of patients presented with typical pulmonary radiographic findings. Predictors of IA included: renal insufficiency, re-operation, and bacterial and viral infections. 12-week mortality was higher in liver (85.7%, 6/7) compared to other (15.9%, 10/63; P < .001) SOTr., Conclusions: Invasive aspergillosis remains a rare complication post-SOT, with atypical radiographic presentations and low positivity rates of biomarkers posing significant diagnostic challenges. Although overall mortality has decreased in SOTr, it remains high in liver SOTr., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Clostridium difficile infection (CDI) is a leading cause of infectious diarrhea in solid organ transplant recipients (SOT). We aimed to assess incidence, risk factors, and outcome of CDI within the Swiss Transplant Cohort Study (STCS). We performed a case-control study of SOT recipients in the STCS diagnosed with CDI between May 2008 and August 2013. We matched 2 control subjects per case by age at transplantation, sex, and transplanted organ. A multivariable analysis was performed using conditional logistic regression to identify risk factors and evaluate outcome of CDI. Two thousand one hundred fifty-eight SOT recipients, comprising 87 cases of CDI and 174 matched controls were included. The overall CDI rate per 10 000 patient days was 0.47 (95% confidence interval ([CI] 0.38-0.58), with the highest rate in lung (1.48, 95% CI 0.93-2.24). In multivariable analysis, proven infections (hazard ratio [HR] 2.82, 95% CI 1.29-6.19) and antibiotic treatments (HR 4.51, 95% CI 2.03-10.0) during the preceding 3 months were independently associated with the development of CDI. Despite mild clinical presentations, recipients acquiring CDI posttransplantation had an increased risk of graft loss (HR 2.24, 95% CI 1.15-4.37; P = .02). These findings may help to improve the management of SOT recipients., (© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Objective: This study aims to describe complications related to ventricular catheter systems with subcutaneous reservoirs (VCSR) (such as Ommaya reservoirs) in pediatric patients with brain tumors., Methods: Retrospective analysis of consecutive patients with a total of 31 VCSR treated at the Children's University Hospital of Zurich, Switzerland., Results: A total of 20 patients with a median age of 3.3 years at VCSR implantation received 31 VCSR. Overall, 19 complications in 11 patients were recorded: 7 patients had a VCSR-related infection with coagulase-negative staphylococci, 4 of these probably as a surgical complication and 3 probably related to VCSR use. Systemic perioperative prophylaxis was administered in 22 cases, and intraventricular vancomycin and gentamicin were given in 8 cases (none of which subsequently developed an infection). Other complications included wound dehiscence, catheter malplacement, and leakage of cerebrospinal fluid. Overall, 17 VCSR were explanted due to complications., Conclusion: Infections were the most frequent VCSR-related complication. In our own institution, the high rate of complications led to the definition of a bundle of measures as a standard operating procedure for VCSR placement and use. Prospective studies in larger patient collectives are warranted to better identify risk factors and evaluate preventive measures such as the administration of perioperative antibiotics and the use of antimicrobial coating of catheters., (Georg Thieme Verlag KG Stuttgart · New York.)

The establishment of stroke networks is an approach to forward guideline driven stroke care to hospitals without full-time neurological service. Tele- stroke networks are evidence based for remote neurological support of acute stroke patients, administration of thrombolysis safely as well as increasing thrombolysis rates. Since 2011 the district hospital in Grabs was linked to the stroke center at the cantonal hospital St. Gallen which provided teleconsultations with full-scale audiovisual communication and access to brain images 24 hours per day 7 days per week. Regarding quality and safety issues the experiences were promising including the selection of patients for appropriate treatment with allocation to systemic thrombolysis or en dovascular reperfusion therapy. As perspective it may definitely contribute to better supply of rural areas with acute stroke therapy but also other specializations and neurological indications may benefit from telemedical support

Objective: To describe all patients admitted to children's hospitals in Switzerland with a diagnosis of influenza A/H1N1/09 virus infection during the 2009 influenza pandemic, and to analyse their characteristics, predictors of complications, and outcome., Methods: All patients ≤18-years-old hospitalised in eleven children's hospitals in Switzerland between June 2009 and January 2010 with a positive influenza A/H1N1/09 reverse transcriptase polymerase chain reaction (RT-PCR) from a nasopharyngeal specimen were included., Results: There were 326 PCR-confirmed patients of whom 189 (58%) were younger than 5 years of age, and 126 (38.7%) had one or more pre-existing medical condition. Fever (median 39.1 °C) was the most common sign (85.6% of all patients), while feeding problems (p = 0.003) and febrile seizures (p = 0.016) were significantly more frequent in children under 5 years. In 142 (43.6%) patients there was clinical suspicion of a concomitant bacterial infection, which was confirmed in 36 patients (11%). However, severe bacterial infection was observed in 4% of patients. One third (n = 108, 33.1%) of the patients were treated with oseltamivir, 64 (59.3%, or 20% overall) within 48 hours of onset of symptoms. Almost half of the patients (45.1%) received antibiotics for a median of 7 days. Twenty patients (6.1%) required intensive care, mostly for complicated pneumonia (50%) without an underlying medical condition. The median duration of hospitalisation was 2 days (range 0-39) for 304 patients. Two children (<15 months of age with underlying disease) died., Conclusions: Although pandemic influenza A/H1N1/09 virus infection in children is mostly mild, it can be severe, regardless of past history or underlying disease.

Objectives: To assess the effectiveness of implementing guidelines, coupled with individual feedback, on antibiotic prescribing behaviour of primary care physicians in Switzerland., Methods: One hundred and forty general practices from a representative Swiss sentinel network of primary care physicians participated in this cluster-randomized prospective intervention study. The intervention consisted of providing guidelines on treatment of respiratory tract infections (RTIs) and uncomplicated lower urinary tract infections (UTIs), coupled with sustained, regular feedback on individual antibiotic prescription behaviour during 2 years. The main aims were: (i) to increase the percentage of prescriptions of penicillins for all RTIs treated with antibiotics; (ii) to increase the percentage of trimethoprim/sulfamethoxazole prescriptions for all uncomplicated lower UTIs treated with antibiotics; (iii) to decrease the percentage of quinolone prescriptions for all cases of exacerbated COPD (eCOPD) treated with antibiotics; and (iv) to decrease the proportion of sinusitis and other upper RTIs treated with antibiotics. The study was registered at ClinicalTrials.gov (NCT01358916)., Results: While the percentage of antibiotics prescribed for sinusitis or other upper RTIs and the percentage of quinolones prescribed for eCOPD did not differ between the intervention group and the control group, there was a significant increase in the percentage of prescriptions of penicillins for all RTIs treated with antibiotics [57% versus 49%, OR=1.42 (95% CI 1.08-1.89), P=0.01] and in the percentage of trimethoprim/sulfamethoxazole prescriptions for all uncomplicated lower UTIs treated with antibiotics [35% versus 19%, OR=2.16 (95% CI 1.19-3.91), P=0.01] in the intervention group., Conclusions: In our setting, implementing guidelines, coupled with sustained individual feedback, was not able to reduce the proportion of sinusitis and other upper RTIs treated with antibiotics, but increased the use of recommended antibiotics for RTIs and UTIs, as defined by the guidelines., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

The frequency of HIV mother-to-child transmission in Switzerland is nowadays < 1 %, if the pregnant woman receives successful anti-HIV treatment and the newborn apt post-exposure prophylaxis (PEP) and is not breast-fed. The interdisciplinary approach in arranging the maternal anti-HIV treatment, birth mode and PEP for the child is essential. Nevertheless, HIV infection in the child needs to be considered when it presents with compatible signs and symptoms, as HIV infection of the mother may escape diagnosis.

Reptile-associated salmonellosis (RAS) in children has been reported primarily due to direct contact with turtles, but recently also due to indirect contact with more exotic reptiles, causing disease in infants. To evaluate risk factors for RAS, we reviewed the RAS cases published in the literature since 1965. A case was defined as a child ≤18 years of age with an epidemiological link by identification of Salmonella enterica in cultures from both the affected child and the exposed reptile. We identified a total of 177 otherwise healthy children (median age 1.0 years, range 2 days to 17.0 years). RAS manifested mainly with gastrointestinal disease, but 15% presented with invasive RAS, including septicemia, meningitis, and bone and joint infection. The children with invasive RAS were significantly younger than children with noninvasive disease (median age 0.17 and 2.0 years, p<0.0001). RAS is most frequently seen after exposure to turtles (42%). However, children with invasive RAS had been exposed more often (p≤0.001) to reptiles other than turtles, including iguanas, bearded dragons, snakes, chameleons, and geckos. Children exposed to those latter reptiles usually kept indoors were younger than children exposed to turtles mostly kept outdoors (p<0.0001). RAS in children is significantly associated with invasive disease at young age, in particular infants <6 months of age. Exposure to reptiles, other than turtles, kept indoors is associated with RAS at younger age and more invasive disease. This finding is helpful for recognizing or even preventing invasive RAS in young infants that are at highest risk.

Objective: To describe measles vaccination patterns in a cohort of Swiss children aged up to 3 years insured with a single health insurer., Methods: A dynamic cohort study evaluating measles immunizations patterns in children born between 2006 and 2008 was conducted. Time-to-event analysis was used to describe timing of measles immunization. Effective vaccine coverage was calculated by using an area under the curve approach., Results: In the study cohort, 62.6% of 13-month-old children were up-to-date for the first measles immunization (recommended at 12 months of age). Approximately 59% of 25-month-old children were up-to-date for the second measles immunization (recommended at 15-24 months of age). Most doses were delivered during months in a child's life when well-child visits are recommended (eg, 12 months of age). For second measles vaccine dose, accelerations in vaccine delivery occurred at time points for well-child visits during the months 19 and 25 of age but with lower final uptake than for the first measles vaccine dose. Until their second birthday, children in our cohort spent on average 177 days and 89 days susceptible to measles due to policy recommendations and additional delays, respectively. In a group of children aged 6 months to 2 years reflecting the age distribution in our cohort, effective vaccine coverage was only 48.6%., Conclusions: Timing and timeliness of measles immunizations influence effective population vaccine coverage and should be routinely reported in addition to coverage whenever possible. Proposed timing and relation of recommended vaccinations to well-child visits could be relevant aspects in optimizing measles vaccine coverage to reach measles elimination.

Background: The number of families traveling with their children to their country of origin and/or to tropical destinations has increased in Switzerland and includes a changing profile and multinational range of patients. Defining the profile of reported travel-associated illnesses will help to improve the prevention and treatment of such illnesses in children., Methods: This study includes children aged up to 16 years who sought medical advice for a presumed travel-related illness at the emergency room of the University of Zürich Children's Hospital during the period July 2007 to December 2008., Results: We analyzed data on 328 children (58.8% male, mean age: 4.62 y) who presented with travel-associated illness. Our analysis included 155 traditional (mainly tourist) travelers, 162 children who were visiting friends and relatives (VFR), and 11 immigrants. Some 11% were hospitalized. No deaths occurred. The main conditions recorded were diarrheal illness (39%), respiratory (28.7%) and febrile/systemic illness (13.4%). With increasing age, the proportion of children with diarrheal disease increased, while the proportion with respiratory illness declined. There were significant associations between geographic area of exposure and the profile of travel-related disease (p < 0.001). Among 36 children with more serious diseases requiring hospitalization, 12 (3.7% overall) presented with potentially serious diseases: malaria (n = 2), Salmonella typhi (n = 3), Salmonella paratyphi (n = 2), meningococcal meningitis (n = 1), tuberculosis (n = 2), visceral leishmania (n = 1), and hepatitis A (n = 1). Eleven of the 12 children presenting with these potentially serious illnesses were VFR or immigrant children., Conclusion: The main diagnoses for ill-returned Zürich children who presented for emergency care were diarrhea, respiratory, and febrile/systemic illness. A broad spectrum of morbidity was seen including meningococcal meningitis, malaria, tuberculosis, typhoid fever, leishmania, and hepatitis A. Diagnoses varied between geographic regions visited, and VFR child travelers constituted a large proportion of sick-returned children presenting for emergency care., (© 2012 International Society of Travel Medicine.)