The 2017 Update of the German Clinical Guideline on Epidemiology, Diagnostics, Therapy, Prevention, and Management of Uncomplicated Urinary Tract Infections in Adult Patients. Part II: Therapy and Prevention

Background: We aimed to update the 2010 evidence- and consensus-based national clinical guideline on the diagnosis and management of uncomplicated urinary tract infections (UTIs) in adult patients. Results are published in 2 parts. Part 1 covers methods, the definition of patient groups, and diagnostics. This second publication focuses on treatment of acute episodes of cystitis and pyelonephritis as well as on prophylaxis of recurrent UTIs. Materials and Methods: An interdisciplinary group consisting of 17 representatives of 12 medical societies and a patient representative was formed. Systematic literature searches were conducted in MEDLINE, EMBASE, and the Cochrane Library to identify literature published in 2010–2015. Results: For the treatment of acute uncomplicated cystitis (AUC), fosfomycin-trometamol, nitrofurantoin, nitroxoline, pivmecillinam, and trimethoprim (depending on the local rate of resistance) are all equally recommended. Cotrimoxazole, fluoroquinolones, and cephalosporins are not recommended as antibiotics of first choice, for concern of an unfavorable impact on the microbiome. Mild to moderate uncomplicated pyelonephritis should be treated with oral cefpodoxime, ceftibuten, ciprofloxacin, or levofloxacin. For AUC with mild to moderate symptoms, instead of antibiotics symptomatic treatment alone may be considered depending on patient preference after discussing adverse events and outcomes. Primarily non-antibiotic options are recommended for prophylaxis of recurrent urinary tract infection. Conclusion: In accordance with the global antibiotic stewardship initiative and considering new insights in scientific research, we updated our German clinical UTI guideline to promote a responsible antibiotic use and to give clear hands-on recommendations for the diagnosis and management of UTIs in adults in Germany for healthcare providers and patients

The 2017 Update of the German Clinical Guideline on Epidemiology, Diagnostics, Therapy, Prevention, and Management of Uncomplicated Urinary Tract Infections in Adult Patients: Part 1

Objectives: We aimed to update the 2010 evidence- and consensus-based national clinical guideline on the diagnosis and management of uncomplicated urinary tract infections (UTIs) in adult patients. Materials and Methods: An interdisciplinary group consisting of 17 representatives of 12 medical societies and a patient representative was formed. Systematic literature searches were conducted in MEDLINE, ­EMBASE, and the Cochrane Library to identify literature published in 2010–2015. Results: We provide 75 recommendations and 68 statements in the updated evidence- and consensus-based national clinical guideline. The diagnostics part covers practical recommendations on cystitis and pyelonephritis for each defined patient group. Clinical examinations, as well as laboratory testing and microbiological pathogen assessment, are addressed. Conclusion: In accordance with the global antibiotic stewardship initiative and considering new insights in scientific research, we updated our German clinical UTI guideline to promote a responsible antibiotic use and to give clear hands-on recommendations for the diagnosis and management of UTIs in adults in Germany for healthcare providers and patients

High-Temperature Short-Time Treatment of Human Milk for Bacterial Count Reduction

Background: Human milk (HM) for preterm infants will often be pasteurized for cytomegalovirus (CMV) inactivation and reduction of its bacterial count. High-temperature short-time (HTST) treatment compared to standard Holder pasteurization (HoP) reduces the impact of heat treatment on bioactive HM proteins while effectively inactivating CMV. No data are available for the efficacy of bacterial count reduction using HTST treatments that are available for clinical use.Objective: To test the antiviral and antibacterial efficacy of HTST treatment protocols in HM using a modified HTST treatment device compared to standard HoP.Methods: Holder pasteurized 95 mL HM samples were inoculated with Staphylococcus aureus (ATCC 6538), Enterococcus faecalis (ATCC 29212), Pseudomonas aeruginosa (ATCC 27853), Serratia marcescens (Smarc 00697), two different strains of Klebsiella pneumoniae (ATCC 700603 and Kpn 01605) or spiked with 2 × 105 50% tissue culture infective dose of CMV (AD169) and subsequently subjected to HoP (62.5°C/30 min) or HTST treatment (62°C/5 s, 62°C/15 s, 72°C/5 s, 72°C/15 s, 87°C/2 s, and 87°C/5 s). Bacterial count was determined after treated HM was cultured for 24 h. CMV infectivity was determined by the number of specific CMV immediate early antigen stained nuclei after inoculating human fibroblasts with appropriately prepared HM samples.Results: Holder pasteurized samples revealed no growth after 24 h incubation. Viable bacterial cultures were retrieved from all tested strains after HTST treatment with the default HTST protocol (62°C/5 s) that is available for clinical use. Using other time-temperature combinations, growth rates of S. aureus, E. faecalis, P. aeruginosa, K. pneumoniae, K. pneumonia, and S. marcescens were depending on treatment time, treatment temperature, bacterial genera and strain. Only after treatment temperatures above 72°C no bacterial growth was observed. CMV was inactivated by any tested time-temperature combination.Conclusions: HTST treatment inactivates CMV in 95 mL HM samples but is less effective than HoP in bacterial count reduction at a time-temperature combination of 62°C/5 s. For a reliable bacterial count reduction HTST treatment at 87°C was required in this study

Sensitivity, specificity, and diagnostic accuracy of WHO 2013 criteria for diagnosis of gestational diabetes mellitus in low risk early pregnancies: international, prospective, multicentre cohort study

Objective: To evaluate the predictability of gestational diabetes mellitus wth a 75 g oral glucose tolerance test (OGTT) in early pregnancy, based on the 2013 criteria of the World Health Organization, and to test newly proposed cut-off values. Design: International, prospective, multicentre cohort study.SettingSix university or cantonal departments in Austria, Germany, and Switzerland, from 1 May 2016 to 31 January 2019.ParticipantsLow risk cohort of 829 participants aged 18-45 years with singleton pregnancies attending first trimester screening and consenting to have an early 75 g OGTT at 12-15 weeks of gestation. Participants and healthcare providers were blinded to the results. Main outcome measures: Fasting, one hour, and two hour plasma glucose concentrations after an early 75 g OGTT (12-15 weeks of gestation) and a late 75 g OGTT (24-28 weeks of gestation). Results: Of 636 participants, 74 (12%) developed gestational diabetes mellitus, according to World Health Organization 2013 criteria, at 24-28 weeks of gestation. Applying WHO 2013 criteria to the early OGTT with at least one abnormal value gave a low sensitivity of 0.35 (95% confidence interval 0.24 to 0.47), high specificity of 0.96 (0.95 to 0.98), positive predictive value of 0.57 (0.41 to 0.71), negative predictive value of 0.92 (0.89 to 0.94), positive likelihood ratio of 10.46 (6.21 to 17.63), negative likelihood ratio of 0.65 (0.55 to 0.78), and diagnostic odds ratio of 15.98 (8.38 to 30.47). Lowering the postload glucose values (75 g OGTT cut-off values of 5.1, 8.9, and 7.8 mmol/L) improved the detection rate (53%, 95% confidence interval 41% to 64%) and negative predictive value (0.94, 0.91 to 0.95), but decreased the specificity (0.91, 0.88 to 0.93) and positive predictive value (0.42, 0.32 to 0.53) at a false positive rate of 9% (positive likelihood ratio 5.59, 4.0 to 7.81; negative likelihood ratio 0.64, 0.52 to 0.77; and diagnostic odds ratio 10.07, 6.26 to 18.31). Conclusions: The results of this prospective low risk cohort study indicated that the 75 g OGTT as a screening tool in early pregnancy is not sensitive enough when applying WHO 2013 criteria. Postload glucose values were higher in early pregnancy complicated by diabetes in pregnancy. Lowering the postload cut-off values identified a high risk group for later development of gestational diabetes mellitus or those who might benefit from earlier treatment. Results from randomised controlled trials showing a beneficial effect of early intervention are unclear. Trial registrationClinicalTrials.govNCT02035059

Multiomic spatial landscape of innate immune cells at human central nervous system borders

The innate immune compartment of the human central nervous system (CNS) is highly diverse and includes several immune-cell populations such as macrophages that are frequent in the brain parenchyma (microglia) and less numerous at the brain interfaces as CNS-associated macrophages (CAMs). Due to their scantiness and particular location, little is known about the presence of temporally and spatially restricted CAM subclasses during development, health and perturbation. Here we combined single-cell RNA sequencing, time-of-flight mass cytometry and single-cell spatial transcriptomics with fate mapping and advanced immunohistochemistry to comprehensively characterize the immune system at human CNS interfaces with over 356,000 analyzed transcriptomes from 102 individuals. We also provide a comprehensive analysis of resident and engrafted myeloid cells in the brains of 15 individuals with peripheral blood stem cell transplantation, revealing compartment-specific engraftment rates across different CNS interfaces. Integrated multiomic and high-resolution spatial transcriptome analysis of anatomically dissected glioblastoma samples shows regionally distinct myeloid cell-type distributions driven by hypoxia. Notably, the glioblastoma-associated hypoxia response was distinct from the physiological hypoxia response in fetal microglia and CAMs. Our results highlight myeloid diversity at the interfaces of the human CNS with the periphery and provide insights into the complexities of the human brain's immune system.</p

Enterococcal colonization of infants in a neonatal intensive care unit: associated predictors, risk factors and seasonal patterns

<p>Abstract</p> <p>Background</p> <p>During and shortly after birth, newborn infants are colonized with enterococci. This study analyzes predictors for early enterococcal colonization of infants in a neonatal intensive care unit and describes risk factors associated with multidrugresistant enterococci colonization and its seasonal patterns.</p> <p>Methods</p> <p>Over a 12-month period, we performed a prospective epidemiological study in 274 infants admitted to a neonatal intensive care unit. On the first day of life, we compared infants with enterococcal isolates detected in meconium or body cultures to those without. We then tested the association of enterococcal colonization with peripartal predictors/risk factors by using bivariate and multivariate statistical methods.</p> <p>Results</p> <p>Twenty-three percent of the infants were colonized with enterococci. The three most common enterococcal species were <it>E. faecium </it>(48% of isolates), <it>E. casseliflavus </it>(25%) and <it>E. faecalis </it>(13%). Fifty-seven percent of the enterococci found were resistant to three of five antibiotic classes, but no vancomycin-resistant isolates were observed. During winter/spring months, the number of enterococci and multidrug-resistant enterococci were higher than in summer/fall months (p = 0.002 and p < 0.0001, respectively). With respect to enterococcal colonization on the first day of life, predictors were prematurity (p = 0.043) and low birth weight (p = 0.011). With respect to colonization with multidrug-resistant enterococci, risk factors were prematurity (p = 0.0006), low birth weight (p < 0.0001) and prepartal antibiotic treatment (p = 0.019). Using logistic regression, we determined that gestational age was the only parameter significantly correlated with multidrug-resistant enterococci colonization. No infection with enterococci or multidrugresistant enterococci in the infants was detected. The outcome of infants with and without enterococcal colonization was the same with respect to death, necrotizing enterocolitis, intracerebral hemorrhage and bronchopulmonary dysplasia.</p> <p>Conclusion</p> <p>In neonatal intensive care units, an infant's susceptibility to early colonization with enterococci in general, and his or her risk for colonization with multidrug-resistant enterococci in particular, is increased in preterm newborns, especially during the winter/spring months. The prepartal use of antibiotics with no known activity against enterococci appears to increase the risk for colonization with multidrug-resistant enterococci.</p

Streptococcus agalactiae clones infecting humans were selected and fixed through the extensive use of tetracycline

Streptococcus agalactiae (Group B Streptococcus, GBS) is a commensal of the digestive and genitourinary tracts of humans that emerged as the leading cause of bacterial neonatal infections in Europe and North America during the 1960s. Due to the lack of epidemiological and genomic data, the reasons for this emergence are unknown. Here we show by comparative genome analysis and phylogenetic reconstruction of 229 isolates that the rise of human GBS infections corresponds to the selection and worldwide dissemination of only a few clones. The parallel expansion of the clones is preceded by the insertion of integrative and conjugative elements conferring tetracycline resistance (TcR). Thus, we propose that the use of tetracycline from 1948 onwards led in humans to the complete replacement of a diverse GBS population by only few TcR clones particularly well adapted to their host, causing the observed emergence of GBS diseases in neonates. \ua9 2014 Macmillan Publishers Limited. All rights reserved

The German National Pandemic Cohort Network (NAPKON): rationale, study design and baseline characteristics

Schons M, Pilgram L, Reese J-P, et al. The German National Pandemic Cohort Network (NAPKON): rationale, study design and baseline characteristics. European Journal of Epidemiology . 2022.The German government initiated the Network University Medicine (NUM) in early 2020 to improve national research activities on the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic. To this end, 36 German Academic Medical Centers started to collaborate on 13 projects, with the largest being the National Pandemic Cohort Network (NAPKON). The NAPKON's goal is creating the most comprehensive Coronavirus Disease 2019 (COVID-19) cohort in Germany. Within NAPKON, adult and pediatric patients are observed in three complementary cohort platforms (Cross-Sectoral, High-Resolution and Population-Based) from the initial infection until up to three years of follow-up. Study procedures comprise comprehensive clinical and imaging diagnostics, quality-of-life assessment, patient-reported outcomes and biosampling. The three cohort platforms build on four infrastructure core units (Interaction, Biosampling, Epidemiology, and Integration) and collaborations with NUM projects. Key components of the data capture, regulatory, and data privacy are based on the German Centre for Cardiovascular Research. By April 01, 2022, 34 university and 40 non-university hospitals have enrolled 5298 patients with local data quality reviews performed on 4727 (89%). 47% were female, the median age was 52 (IQR 36-62-) and 50 pediatric cases were included. 44% of patients were hospitalized, 15% admitted to an intensive care unit, and 12% of patients deceased while enrolled. 8845 visits with biosampling in 4349 patients were conducted by April 03, 2022. In this overview article, we summarize NAPKON's design, relevant milestones including first study population characteristics, and outline the potential of NAPKON for German and international research activities.Trial registration https://clinicaltrials.gov/ct2/show/NCT04768998 . https://clinicaltrials.gov/ct2/show/NCT04747366 . https://clinicaltrials.gov/ct2/show/NCT04679584. © 2022. The Author(s)

Obesity in pregnant women: a 20-year analysis of the German experience

Background/objective!#!To investigate the longitudinal development of maternal body weight and analyze the influence of obesity on obstetrics during more than two decades in Germany.!##!Subjects/methods!#!Data collected from the Federal state of Schleswig-Holstein (German Perinatal Survey) were analyzed with regard to the dynamics of maternal anthropometric variables (body weight, BMI) between 1995-7 and 2004-17. In total 335,511 mothers substantiated the presented study-collective. The statistical analysis was performed using IBM SPSS Statistics for Windows, Version 26.0. Armonk, NY.!##!Results!#!Maternal BMI advanced significantly over the study period. Among a rise in mean periconceptional body weight (67.6-72.0 kg), the segment of obese women increased disproportionately (in average 9.4-19.2%). Despite the observed trend to late giving birth (mean maternal age 1995: 29.3 vs. 30.7 years in 2017), it was not advanced maternal age but parity that influenced the continuous increase in maternal weight (mean maternal body weight 1995-7: primi- bi-, multiparae 67.4, 68.3 and 69.0 kg vs. 2004-17: primi- bi-, multiparae 70.0, 71.5 and 73.2 kg respectively).!##!Conclusion!#!Obesity is a major problem on health issues in obstetrics. Advancing maternal BMI, increasing mother's age and derived prenatal risks considerably complicate pregnancy and delivery. It has to be emphasized that its consequences do not end with delivery or childbed, but represent a livelong burden to the mother and their offspring. Hence, multimodal strategies to reduce/control periconceptional body weight are mandatory