Trends in preterm birth in women living with HIV in Switzerland over the last three decades: A multicentric, prospective, cohort study.

BACKGROUND: HIV infection and its management during pregnancy to reduce perinatal transmission has been associated with preterm birth (PTB). This management has drastically changed. We aimed to evaluate changes in rates of PTB over 34 years in women living with HIV (WLWH) in Switzerland, and to identify factors and interventions associated with these changes. METHODS: We analysed data from 1238 singleton pregnancies, prospectively collected by the Swiss Mother and Child HIV Cohort Study (MoCHiV) and the Swiss HIV Cohort Study (SHCS) between 1986 and 2020. Rates of PTB in this cohort were compared with that of the general Swiss population for three time periods according to changing treatment strategies recommended at the time. We evaluated the association of PTB with sociodemographic, HIV infection and obstetric variables in uni- and multivariate logistic regression. RESULTS: Rate of PTB in WLWH was highest prior to 2010 (mean 20.4%), and progressively decreased since then (mean 11.3%), but always remained higher than in the general population (5%). Older maternal age, lower CD4 count and detectable viraemia at third trimester (T3), drug consumption and mode of delivery were all significantly associated with both PTB and period of study in univariate analysis. There was no association between PTB and type of antiretroviral regimen. No difference was found in the rate of spontaneous labor between PTB and term delivery groups. Only higher CD4 count at T3 and vaginal delivery were significantly associated with a decrease in PTB over time in multivariate analysis. CONCLUSIONS: Preterm birth in WLWH in Switzerland has drastically decreased over the last three decades, but remains twice the rate of that in the general population. Improved viral control and changes in mode of delivery (vaginal birth recommended if viral loads are low near birth) have led to this progress.

Pharmacometric in silico studies used to facilitate a national dose standardisation process in neonatology - application to amikacin.

BACKGROUND AND AIMS: Pharmacometric in silico approaches are frequently applied to guide decisions concerning dosage regimes during the development of new medicines. We aimed to demonstrate how such pharmacometric modelling and simulation can provide a scientific rationale for optimising drug doses in the context of the Swiss national dose standardisation project in paediatrics using amikacin as a case study. METHODS: Amikacin neonatal dosage is stratified by post-menstrual age (PMA) and post-natal age (PNA) in Switzerland and many other countries. Clinical concerns have been raised for the subpopulation of neonates with a post-menstrual age of 30-35 weeks and a post-natal age of 0-14 days ("subpopulation of clinical concern"), as potentially oto-/nephrotoxic trough concentrations (Ctrough >5 mg/l) were observed with a once-daily dose of 15 mg/kg. We applied a two-compartmental population pharmacokinetic model (amikacin clearance depending on birth weight and post-natal age) to real-world demographic data from 1563 neonates receiving anti-infectives (median birth weight 2.3 kg, median post-natal age six days) and performed pharmacometric dose-exposure simulations to identify extended dosing intervals that would ensure non-toxic Ctrough (Ctrough <5 mg/l) dosages in most neonates. RESULTS: In the subpopulation of clinical concern, Ctrough <5 mg/l was predicted in 59% versus 79-99% of cases in all other subpopulations following the current recommendations. Elevated Ctrough values were associated with a post-natal age of less than seven days. Simulations showed that extending the dosing interval to ≥36 h in the subpopulation of clinical concern increased the frequency of a desirable Ctrough below 5 mg/l to >80%. CONCLUSION: Pharmacometric in silico studies using high-quality real-world demographic data can provide a scientific rationale for national paediatric dose optimisation. This may increase clinical acceptance of fine-tuned standardised dosing recommendations and support their implementation, including in vulnerable subpopulations.

Viral suppression and retention in HIV care during the postpartum period among women living with HIV: a longitudinal multicenter cohort study.

Background: Low rates of postnatal retention in HIV care and viral suppression have been reported in women living with HIV (WLWH) despite viral suppression at delivery. At the same time, postpartum follow-up is of crucial importance in light of the increasing support offered in many resource-rich countries including Switzerland to WLWH choosing to breastfeed their infant, if optimal scenario criteria are met. Methods: We longitudinally investigated retention in HIV care, viral suppression, and infant follow-up in a prospective multicentre HIV cohort study of WLWH in the optimal scenario who had a live birth between January 2000 and December 2018. Risk factors for adverse outcomes in the first year postpartum were assessed using logistic and proportional hazard models. Findings: Overall, WLWH were retained in HIV care for at least six months after 94.2% of the deliveries (694/737). Late start of combination antiretroviral therapy (cART) during the third trimester was found to be the main risk factor for failure of retention in HIV care (crude odds ratio [OR] 3.91; 95% confidence interval [CI], 1.50-10.22; p = 0.005). Among mothers on cART until at least one year after delivery, 4.4% (26/591) experienced viral failure, with illicit drugs use being the most important risk factor (hazard ratio [HR], 13.2; 95% CI, 2.35-73.6; p = 0.003). The main risk factors for not following the recommendations regarding infant follow-up was maternal depression (OR, 3.52; 95% CI, 1.18-10.52; p = 0.024). Interpretation: Although the results are reassuring, several modifiable risk factors for adverse postpartum outcome, such as late treatment initiation and depression, were identified. These factors should be addressed in HIV care of all WLWH, especially those opting to breastfeed in resource-rich countries. Funding: This study has been financed within the framework of the Swiss HIV Cohort Study, supported by the Swiss National Science Foundation (grant #201369), by SHCS project 850 and by the SHCS research foundation.

Nucleoside/nucleotide reverse transcriptase inhibitor sparing regimen with once daily integrase inhibitor plus boosted darunavir is non-inferior to standard of care in virologically-suppressed children and adolescents living with HIV - Week 48 results of the randomised SMILE Penta-17-ANRS 152 clinical trial.

Background: Integrase inhibitor (INSTI) with boosted darunavir (DRV/r), a regimen with a high-resistance barrier, avoiding NRTI toxicities, might be a switching option in children living with HIV (CLWHIV). Methods: SMILE is a randomised non-inferiority trial evaluating safety and antiviral efficacy of once-daily INSTI + DRV/r vs. continuing on current standard-of-care (SOC) triple ART (2NRTI + boosted PI/NNRTI) in virologically-suppressed CLWHIV aged 6-18 years. The primary outcome is the proportion with confirmed HIV-RNA ≥50 copies/mL by week 48, estimated by Kaplan-Meier method. Non-inferiority margin was 10%. Registration number for SMILE are: ISRCTN11193709, NCT #: NCT02383108. Findings: Between 10th June 2016 and 30th August 2019, 318 participants were enrolled from Africa 53%, Europe 24%, Thailand 15% and Latin America 8%, 158 INSTI + DRV/r [153 Dolutegravir (DTG); 5 Elvitegravir (EVG)], 160 SOC. Median (range) age was 14.7 years (7.6-18.0); CD4 count 782 cells/mm3 (227-1647); 61% female. Median follow-up was 64.3 weeks with no loss to follow-up. By 48 weeks, 8 INSTI + DRV/r vs. 12 SOC had confirmed HIV-RNA ≥50 copies/mL; difference (INSTI + DRV/r-SOC) -2.5% (95% CI: -7.6, 2.5%), showing non-inferiority. No major PI or INSTI resistance mutations were observed. There were no differences in safety between arms. By week 48, difference (INSTI + DRV/r-SOC) in mean CD4 count change from baseline was -48.3 cells/mm3 (95% CI: -93.4, -3.2; p = 0.036). Difference (INSTI + DRV/r-SOC) in mean HDL change from baseline was -4.1 mg/dL (95% CI: -6.7, -1.4; p = 0.003). Weight and Body Mass Index (BMI) increased more in INSTI + DRV/r than SOC [difference: 1.97 kg (95% CI: 1.1, 2.9; p < 0.001), 0.66 kg/m2 (95% CI: 0.3, 1.0; p < 0.001)]. Interpretation: In virologically-suppressed children, switching to INSTI + DRV/r was non-inferior virologically, with similar safety profile, to continuing SOC. Small but significant differences in CD4, HDL-cholesterol, weight and BMI were observed between INSTI + DRV/r vs. SOC although clinical relevance needs further investigation. SMILE data corroborate adult findings and provide evidence for this NRTI-sparing regimen for children and adolescents. Funding: Fondazione Penta Onlus, Gilead, Janssen, INSERM/ANRS and UK MRC. ViiV-Healthcare provided Dolutegravir.

Migrating a Well-Established Longitudinal Cohort Database From Oracle SQL to Research Electronic Data Entry (REDCap): Data Management Research and Design Study.

BACKGROUND: Providing user-friendly electronic data collection tools for large multicenter studies is key for obtaining high-quality research data. Research Electronic Data Capture (REDCap) is a software solution developed for setting up research databases with integrated graphical user interfaces for electronic data entry. The Swiss Mother and Child HIV Cohort Study (MoCHiV) is a longitudinal cohort study with around 2 million data entries dating back to the early 1980s. Until 2022, data collection in MoCHiV was paper-based. OBJECTIVE: The objective of this study was to provide a user-friendly graphical interface for electronic data entry for physicians and study nurses reporting MoCHiV data. METHODS: MoCHiV collects information on obstetric events among women living with HIV and children born to mothers living with HIV. Until 2022, MoCHiV data were stored in an Oracle SQL relational database. In this project, R and REDCap were used to develop an electronic data entry platform for MoCHiV with migration of already collected data. RESULTS: The key steps for providing an electronic data entry option for MoCHiV were (1) design, (2) data cleaning and formatting, (3) migration and compliance, and (4) add-on features. In the first step, the database structure was defined in REDCap, including the specification of primary and foreign keys, definition of study variables, and the hierarchy of questions (termed "branching logic"). In the second step, data stored in Oracle were cleaned and formatted to adhere to the defined database structure. Systematic data checks ensured compliance to all branching logic and levels of categorical variables. REDCap-specific variables and numbering of repeated events for enabling a relational data structure in REDCap were generated using R. In the third step, data were imported to REDCap and then systematically compared to the original data. In the last step, add-on features, such as data access groups, redirections, and summary reports, were integrated to facilitate data entry in the multicenter MoCHiV study. CONCLUSIONS: By combining different software tools-Oracle SQL, R, and REDCap-and building a systematic pipeline for data cleaning, formatting, and comparing, we were able to migrate a multicenter longitudinal cohort study from Oracle SQL to REDCap. REDCap offers a flexible way for developing customized study designs, even in the case of longitudinal studies with different study arms (ie, obstetric events, women, and mother-child pairs). However, REDCap does not offer built-in tools for preprocessing large data sets before data import. Additional software is needed (eg, R) for data formatting and cleaning to achieve the predefined REDCap data structure.

Successful implementation of new Swiss recommendations on breastfeeding of infants born to women living with HIV.

INTRODUCTION: Swiss national recommendations advise, since end of 2018, supporting women with HIV who wish to breastfeed. Our objective is to describe the motivational factors and the outcome of these women and of their infants. METHODS: mothers included in MoCHiV with a delivery between January 2019 and February 2021 who fulfilled the criteria of the "optimal scenario" (adherence to cART, regular clinical care, and suppressed HIV plasma viral load (pVL) of <50 RNA copies/ml) and who decided to breastfeed after a shared decision-making process, were approached to participate in this nested study and asked to fill-in a questionnaire exploring the main motivating factors for breastfeeding. RESULTS: Between January 9, 2019 and February 7, 2021, 41 women gave birth, and 25 decided to breastfeed of which 20 accepted to participate in the nested study. The three main motivational factors of these women were bonding, neonatal and maternal health benefits. They breastfed for a median duration of 6.3 months (range 0.7-25.7, IQR 2.5-11.1). None of the breastfed neonates received HIV post-exposure prophylaxis. There was no HIV transmission: 24 infants tested negative for HIV at least 3 months after weaning; one mother was still breastfeeding when we analyzed the data. CONCLUSIONS: As a result of a shared decision-making process, a high proportion of mothers expressed a desire to breastfeed. No breastfed infant acquired HIV. The surveillance of breastfeeding mother-infant pairs in high resource settings should be continued to help update guidelines and recommendations.

Swiss Evaluation Registry for Pediatric Infective Endocarditis (SERPIE) - Risk factors for complications in children and adolescents with infective endocarditis.

BACKGROUND: Infective endocarditis (IE) in pediatric patients is a severe cardiac disease and its actual epidemiology and clinical outcome in Switzerland is scarcely studied. METHODS: Retrospective nationwide multicenter data analysis of pediatric IE in children (<18 years) between 2011 and 2020. RESULTS: 69 patients were treated for definite (40/69;58%) or possible IE (29/69;42%). 61% (42/69) were male. Diagnosis was made at median 6.4 years (IQR 0.8-12.6) of age with 19 patients (28%) during the first year of life. 84% (58/69) had congenital heart defects. IE was located on pulmonary (25/69;35%), mitral (10/69;14%), tricuspid (8/69;12%) and aortic valve (6/69;9%), and rarely on ventricular septal defect (VSD;4/69;6%) and atrial septal defect (ASD;1/69;1%). In 22% (16/69) localization was unknown. 70% (48/69) had postoperative IE, with prosthetic material involved in 60% (29/48; right ventricular to pulmonary artery conduit (24), VSD (4), ASD (1)). Causative organisms were mostly Staphylococci spp. (25;36%) including Staphylococcus aureus (19;28%), and Streptococci spp. (13;19%). 51% (35/69) suffered from severe complications including congestive heart failure (16;23%), sepsis (17;25%) and embolism (19;28%). Staphylococcus aureus was found as a predictor of severe complications in univariate and multivariate analysis (p = 0.02 and p = 0.033). In 46% (32/69) cardiac surgery was performed. 7% (5/69) died. CONCLUSIONS: IE in childhood remains a severe cardiac disease with relevant mortality. The high morbidity and high rate of complications is associated with Staphylococcus aureus infections. Congenital heart defects act as a risk factor for IE, in particular the high number of cases associated with prosthetic pulmonary valve needs further evaluation and therapeutic alternatives.

Swiss recommendations on perioperative antimicrobial prophylaxis in children.

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.

Pharmacogenetic Analysis of Voriconazole Treatment in Children.

Voriconazole is among the first-line antifungal drugs to treat invasive fungal infections in children and known for its pronounced inter- and intraindividual pharmacokinetic variability. Polymorphisms in genes involved in the metabolism and transport of voriconazole are thought to influence serum concentrations and eventually the therapeutic outcome. To investigate the impact of these genetic variants and other covariates on voriconazole trough concentrations, we performed a retrospective data analysis, where we used medication data from 36 children suffering from invasive fungal infections treated with voriconazole. Data were extracted from clinical information systems with the new infrastructure SwissPKcdw, and linear mixed effects modelling was performed using R. Samples from 23 children were available for DNA extraction, from which 12 selected polymorphism were genotyped by real-time PCR. 192 (49.1%) of 391 trough serum concentrations measured were outside the recommended range. Voriconazole trough concentrations were influenced by polymorphisms within the metabolizing enzymes CYP2C19 and CYP3A4, and within the drug transporters ABCC2 and ABCG2, as well as by the co-medications ciprofloxacin, levetiracetam, and propranolol. In order to prescribe an optimal drug dosage, pre-emptive pharmacogenetic testing and careful consideration of co-medications in addition to therapeutic drug monitoring might improve voriconazole treatment outcome of children with invasive fungal infections.

Decrease of condom use in heterosexual couples and its impact on pregnancy rates: the Swiss HIV Cohort Study (SHCS).

INTRODUCTION: Following the 'Swiss statement' in 2008 it became an option to omit the use of condoms in serodiscordant couples and to conceive naturally. We analysed its impact on condom use and pregnancy events. METHODS: In all, 3023 women (aged 18-49 years) participating in the Swiss HIV Cohort Study were included. Observation time was divided into pre- and post-Swiss statement phases (July 2005-December 2008 and January 2009-December 2019). We used descriptive statistics, Poisson interrupted time series analysis for pregnancy incidence, and logistic regression to identify predictors of live births, spontaneous and induced abortions. RESULTS: Condomless sex in sexually active women increased from 25% in 2005 to 75% in 2019, while pregnancy incidence did not. Women after 2008 experienced higher spontaneous abortion rates (12.1% vs. 17.2%, p = 0.02) while induced abortion and live birth rates did not change significantly. Spontaneous abortions were more common in older women [adjusted odds ratio (aOR) = 1.4, 95% CI: 1.2-1.7, p < 0.001], in women consuming alcohol (aOR = 2.8, 95% CI: 1.9-4.1, p < 0.001) and in those with non-suppressed viral load (aOR = 0.2, 95% CI: 0.1-0.4, p ≤ 0.001). Induced abortions were more likely in women with depression (aOR = 3.4, 95% CI: 1.8-6.3, p < 0.001) and non-suppressed viral load (aOR = 0.3, 95% CI: 0.2-0.7, p = 0.003). CONCLUSIONS: The publication of the Swiss statement resulted in more condomless sex in heterosexual women, but this did not result in a higher incidence of pregnancy. Maternal age and spontaneous abortion rates increased over time, while induced abortion rates were not significantly affected. Women living with HIV in Switzerland have an unmet need regarding family planning counselling.

SwissPedData: Standardising hospital records for the benefit of paediatric research.

BACKGROUND: Improvement of paediatric healthcare is hampered by inefficient processes for generating new evidence. Clinical research often requires extra encounters with patients, is costly, takes place in an artificial situation with a biased selection of patients, and entails long delays until new evidence is implemented into health care. Electronic health records (EHR) contain detailed information on real patients and cover the entirety of patients. However, the use of EHR for research is limited because they are not standardised between hospitals. This leads to disproportionate amounts of work for extracting data of interest and frequently data are incomplete and of poor quality. AIMS: SwissPedData aims to lay the foundation for a paediatric learning health system in Switzerland by facilitating EHR-based research. In this project, we aimed to assess the way routine clinical data are currently recorded in large paediatric clinics in Switzerland and to develop a national EHR-based set of common data elements (CDEs) that covers all processes of routine paediatric care in hospitals. METHODS: A taskforce of paediatricians from large Swiss children's hospitals reviewed the current status of routine data documentation in paediatric clinical care and the extent of digitalisation. We then used a modified Delphi method to reach a broad consensus on a national EHR-based set of CDEs. RESULTS: All Swiss children's hospitals use EHR to document some or all aspects of care. One hundred and nineteen paediatricians, representing eight hospitals and all paediatric subspecialties, participated in an extended Delphi process to create SwissPedData. The group agreed on a national set of CDEs that comprises a main module with general paediatric data and sub-modules relevant to paediatric subspecialties. The data dictionary includes 336 CDEs: 76 in the main module on general paediatrics and between 11 and 59 CDEs per subspecialty module. Among these, 266 were classified as mandatory, 52 as recommended and 18 as optional. CONCLUSION: SwissPedData is a set of CDEs for information to be collected in EHR of Swiss children's hospitals. It covers all care processes including clinical and paraclinical assessment, diagnosis, treatment, disposition and care site. All participating hospitals agreed to implement SwissPedData in their clinical routine and clinic information systems. This will pave the way for a national paediatric learning health system in Switzerland that enables fast and efficient answers to urgent clinical questions by facilitating high-quality nationwide retrospective and prospective observational studies and recruitment of patients for nested prospective studies and clinical trials.

SwissPKcdw - A clinical data warehouse for the optimization of pediatric dosing regimens.

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 (SwissPKcdw ) 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 SwissPKcdw .

Gentamicin Population Pharmacokinetics in Pediatric Patients-A Prospective Study with Data Analysis Using the saemix Package in R.

The aminoglycoside gentamicin is used for the empirical treatment of pediatric infections. It has a narrow therapeutic window. In this prospective study at University Children's Hospital Zurich, Switzerland, we aimed to characterize the pharmacokinetics of gentamicin in pediatric patients and predict plasma concentrations at typical recommended doses. We recruited 109 patients aged from 1 day to 14 years, receiving gentamicin (7.5 mg/kg at age ≥ 7 d or 5 mg/kg). Plasma levels were determined 30 min, 4 h and 24 h after the infusion was stopped and then transferred, together with patient data, to the secure BioMedIT node Leonhard Med. Population pharmacokinetic modeling was performed with the open-source R package saemix on the SwissPKcdw platform in Leonhard Med. Data followed a two-compartment model. Bodyweight, plasma creatinine and urea were identified as covariates for clearance, with bodyweight as a covariate for central and peripheral volumes of distribution. Simulations with 7.5 mg/kg revealed a 95% CI of 13.0-21.2 mg/L plasma concentration at 30 min after the stopping of a 30-min infusion. At 24 h, 95% of simulated plasma levels were <1.8 mg/L. Our study revealed that the recommended dosing is appropriate. It showed that population pharmacokinetic modeling using R provides high flexibility in a secure environment.

Clinical data for paediatric research: the Swiss approach : Proceedings of the National Symposium in Bern, Switzerland, Dec 5-6, 2019.

BACKGROUND AND PURPOSE: Continuous improvement of health and healthcare system is hampered by inefficient processes of generating new evidence, particularly in the case of rare diseases and paediatrics. Currently, most evidence is generated through specific research projects, which typically require extra encounters with patients, are costly and entail long delays between the recognition of specific needs in healthcare and the generation of necessary evidence to address those needs. The Swiss Personalised Health Network (SPHN) aims to improve the use of data obtained during routine healthcare encounters by harmonizing data across Switzerland and facilitating accessibility for research. The project "Harmonising the collection of health-related data and biospecimens in paediatric hospitals throughout Switzerland (SwissPedData)" was an infrastructure development project funded by the SPHN, which aimed to identify and describe available data on child health in Switzerland and to agree on a standardised core dataset for electronic health records across all paediatric teaching hospitals. Here, we describe the results of a two-day symposium that aimed to summarise what had been achieved in the SwissPedData project, to put it in an international context, and to discuss the next steps for a sustainable future. The target audience included clinicians and researchers who produce and use health-related data on children in Switzerland. KEY HIGHLIGHTS: The symposium consisted of state-of-the-art lectures from national and international keynote speakers, workshops and plenary discussions. This manuscript summarises the talks and discussions in four sections: (I) a description of the Swiss Personalized Health Network and the results of the SwissPedData project; (II) examples of similar initiatives from other countries; (III) an overview of existing health-related datasets and projects in Switzerland; and (IV) a summary of the lessons learned and future prospective from workshops and plenary discussions. IMPLICATIONS: Streamlined processes linking initial collection of information during routine healthcare encounters, standardised recording of this information in electronic health records and fast accessibility for research are essential to accelerate research in child health and make it affordable. Ongoing projects prove that this is feasible in Switzerland and elsewhere. International collaboration is vital to success. The next steps include the implementation of the SwissPedData core dataset in the clinical information systems of Swiss hospitals, the use of this data to address priority research questions, and the acquisition of sustainable funding to support a slim central infrastructure and local support in each hospital. This will lay the foundation for a national paediatric learning health system in Switzerland.

Swiss consensus recommendations on urinary tract infections in children.

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.

Lymphocyte Subsets in HIV-Exposed Uninfected Infants: The Impact of Neonatal Postexposure Prophylaxis With Zidovudine.

HIV-exposed, uninfected (HEU) infants receiving neonatal postexposure prophylaxis with zidovudine showed nonsignificant trends of lower CD4 and CD8 T cells as well as CD19 B cells than those who did not, suggesting toxicity that might impact the overall health of HEU children.

Impact of rapid enterovirus polymerase chain reaction testing on management of febrile young infants < 90 days of age with aseptic meningitis.

BACKGROUND: Diagnostic evaluation of febrile young infants is challenging. Empirical antimicrobial treatment is therefore common practice in this setting despite high percentage of causative viral infections. The objective of this study was to investigate the impact of rapid enterovirus cerebrospinal fluid polymerase chain reaction (CSF EV PCR) test on hospital length of stay (LOS) and antimicrobial treatment duration in young febrile infants. METHODS: Retrospective observational study comparing duration of antimicrobial treatment and hospital LOS before (May 1, 2014 - May 30, 2015, untested group) and after (June 1, 2015 - June 30, 2017, tested group) the introduction of rapid CSF EV PCR testing in infants < 90 days of age presenting with fever and CSF pleocytosis at the University Children's Hospital Zurich. Additionally, the same variables were compared after test introduction between CSF EV PCR positive and negative children. RESULTS: One hundred twenty-eight children were enrolled in the study, 58 before and 70 after the introduction of rapid CSF EV PCR testing. Duration of antimicrobial treatment was significantly shortened in EV positive (n = 42) compared to both EV negative (n = 28) (median 18 h and 48 h, respectively, p < 0.001) and untested patients (n = 58) (median 18 h and 48 h, respectively, p < 0.001), and also in tested compared to untested group patients (median 36 vs 48 h, p < 0.001). Hospital LOS was significantly shortened in EV positive compared to EV negative patients (median 3 days and 4 days respectively, p = 0.013), while an overall reduction was not observed between tested and untested group patients. CONCLUSIONS: In this study we demonstrate that antimicrobial treatment duration could be significantly shortened in neonates and young infants < 90 days of age with aseptic meningitis after the introduction of a rapid CSF EV PCR test compared to untested patients before test introduction.

Risk factors for central line-associated bloodstream infections in children with tunneled central venous catheters.

BACKGROUND: Central line-associated bloodstream infections (CLABSIs) are among the most common complications of central venous catheters (CVCs). The aim of this study was to examine the epidemiology of CLABSIs in tunneled CVCs and analyze their risk factors in a general pediatric population. METHODS: Children with a tunneled CVC inserted at the University Children's Hospital Zürich between January 2009 and December 2015 were eligible for the study. The influence of CVC dwell time on the risk of CLABSI was examined using life tables. Hazard ratios (HRs) for CLABSIs were analyzed using Cox regression for age and diagnosis with cluster robust standard errors. RESULTS: Fifty-five CLABSIs were observed in 193 patients with 284 tunneled CVCs. Overall, CVCs in children with gastrointestinal disorders and in children 2 to 5 years of age showed the highest incidence rates of 6.06 and 5.85 CLABSIs per 1,000 catheter days, respectively, during the first 90 days after placement. Gastrointestinal disease (HR, 3.89; 95% CI, 2.19-6.90; P < .001) and age 2 to 5 years (HR, 2.48; 95% CI, 1.45-4.22; P = .001) were identified as independent risk factors for CLABSI. In children without gastrointestinal disease, tunneled CVCs showed an increasing risk of CLABSI after a dwell time of 90 days. CONCLUSIONS: The need for tunneled CVCs requires the evaluation of targeted CLABSI prevention measures, especially in young children with underlying gastrointestinal disease.

Improved Diagnostics Help to Identify Clinical Features and Biomarkers That Predict Mycoplasma pneumoniae Community-acquired Pneumonia in Children.

BACKGROUND: There are no reliable signs or symptoms that differentiate Mycoplasma pneumoniae (Mp) infection in community-acquired pneumonia (CAP) from other etiologies. Additionally, current diagnostic tests do not reliably distinguish between Mp infection and carriage. We previously determined that the measurement of Mp-specific immunoglobulin M antibody-secreting cells (ASCs) by enzyme-linked immunospot assay allowed for differentiation between infection and carriage. Using this new diagnostic test, we aimed to identify clinical and laboratory features associated with Mp infection. METHODS: This is a prospective cohort study of children, 3-18 years of age, with CAP from 2016 to 2017. Clinical features and biomarkers were compared between Mp-positive and -negative groups by Mann-Whitney U test or Fisher exact test, as appropriate. Area under the receiver operating characteristic curve (AUC) differences and optimal thresholds were determined by using the DeLong test and Youden J statistic, respectively. RESULTS: Of 63 CAP patients, 29 were Mp-positive (46%). Mp positivity was statistically associated with older age (median, 8.6 vs 4.7 years), no underlying disease, family with respiratory symptoms, prior antibiotic treatment, prolonged prodromal respiratory symptoms and fever, and extrapulmonary (skin) manifestations. Lower levels of C-reactive protein, white blood cell count, absolute neutrophil count, and procalcitonin (PCT), specifically PCT <0.25 µg/L, were statistically associated with Mp infection. A combination of age >5 years (AUC = 0.77), prodromal fever and respiratory symptoms >6 days (AUC = 0.79), and PCT <0.25 µg/L (AUC = 0.81) improved diagnostic performance (AUC = 0.90) (P = .05). CONCLUSIONS: A combination of clinical features and biomarkers may aid physicians in identifying patients at high risk for Mp CAP.