Herpesvirus infections in immunocompromised patients : treatment, treatment failure and antiviral resistance

The research described in this thesis aims to study determinants of the course and outcome of treatment of herpesvirus infections in immunocompromised patients. Both viral factors, such as antiviral resistance, and patient factors, including immunological parameters, were investigated. Techniques to study antiviral resistance were optimized for use in a clinical diagnostic setting. The aim of this research is to improve and facilitate management of herpesvirus infections in immunocompromised patients.Research: none. Printing thesis: Netherlands Society of Medical Microbiology (NVMM) and the Royal Netherlands Society for Microbiology (KNVM), GlaxoSmithKline and Novartis.UBL - phd migration 201

Predicting neonatal early onset sepsis a 14-year cohort study

Background: In many infants, treatment is started for suspicion of early onset sepsis (EOS), of whom the majority do not have an infection. Early prediction of the absence of a culture-proven sepsis (CPS) would significantly reduce the time of antibiotic treatment and hospitalization. Our objective was to analyze 3 criteria in infants with CPS: positive blood culture (BC) at 24 hours after the onset of suspicion of EOS (OSEOS), C-reactive protein (CRP) >= 10 mg/L and clinical signs of infection, so we can consequently consider to stop antibiotic treatment in infants without these criteria.Methods: We included all infants with suspicion of EOS from 2007 until 2020. The proportion was calculated of (1) infants with CPS with, at 24 hours, a positive BC and/or CRP >= 10 mg/L and/or clinical signs of infection and (2) infants without CPS with CRP = 24 hours in 8 (16%) infants, of whom 7 infants had a raised CRP and/or clinical symptoms of infection within 24 hours. In 1095 (74%) of infants without CPS in whom CRP was measured between 12 and 24 hours after OSEOS, CRP was <10 mg/L.Conclusion: A combination of BC, CRP, and clinical signs of infection can diagnose 98% (49/50) of infants with CPS 24 hours after OSEOS. Based on normal CRP and the absence of a positive BC, the decision to stop antibiotics could have been brought forward to 24 hours in 74% of infants.Developmen

The road to zero nosocomial infections in neonates: a narrative review

Aim Nosocomial infections (NI) in neonates are associated with prolonged hospitalisation, adverse neurodevelopmental outcome and high mortality. Over the past decade, numerous prevention strategies have resulted in significant reductions in NI rates. In this review, we aim to provide an overview of current NI rates from large, geographically defined cohorts.Methods PubMed, Web of Science, EMBASE and Cochrane Library were searched for evidence regarding epidemiology and prevention of NI in neonates. Extracted studies were synthesised in a narrative form with experiential reflection.Results Despite the abundance of geographically defined incidence proportions, an epidemiological overview of NI is difficult to provide, given the lack of consensus definition for neonatal NI and different baseline populations being compared. Successful prevention efforts have focused on implementing evidence-based practices while eliminating outdated strategies. The most promising model for reduction in infection rates is based on quality improvement (QI) collaboratives and benchmarking, involving identification and implementation of best practices, selection of measurable outcomes and fostering a sense of community and transparency.Conclusion The preventative rather than curative approach forms the new paradigm for reducing the burden of neonatal infections. Despite progress achieved, continued work towards improved prevention practices is required in the strive towards zero NIs.Developmen

Improved diagnostics in bacterial neonatal meningitis using a next-generation sequencing platform

IntroductionBacterial meningitis in infants is an infrequent but life-threatening condition. Empiric therapy should begin as soon as meningitis is thought likely. Consequently, the causative microorganisms may not always be detected using culturing techniques, as cerebrospinal fluid (CSF) cultures are influenced by antibiotics. Nucleic acid amplification tests, such as polymerase chain reaction (PCR) (multiplex panels), may overcome this limitation but require a priori knowledge of the likely pathogen present within the sample. With this in mind, we investigated to what extent a culture-free, broad-range 16S rRNA gene next-generation sequencing (NGS) platform (MYcrobiota) could add to the microbiological diagnosis of meningitis.MethodsRetrospective cohort study at level III neonatal intensive care unit. Included were all infants with suspected meningitis admitted between 10 November 2017 and 31 December 2020. A comparison was made of the bacterial pathogen detection rate between MYcrobiota and conventional bacterial culture.ResultsIn a 3-year period, 37 CSF samples (diagnostic and follow-up) from 35 infants with proven or possible meningitis were available for MYcrobiota testing. MYcrobiota detected the presence of bacterial pathogens in 11 samples (30%), in contrast with the conventional CSF culture, which detected bacteria in 2 of 36 samples (5.6%).ConclusionAddition of 16S rRNA sequencing to conventional culturing greatly improved the identification of the aetiology of bacterial meningitis compared to culturing of CSF samples alone.Molecular basis of bacterial pathogenesis, virulence factors and antibiotic resistanc

Use of Automated Urine Microscopy Analysis in Clinical Diagnosis of Urinary Tract Infection: Defining an Optimal Diagnostic Score in an Academic Medical Center Population

Molecular basis of bacterial pathogenesis, virulence factors and antibiotic resistanc

Systematic screening for COVID-19 associated invasive aspergillosis in ICU patients by culture and PCR on tracheal aspirate

Background A high prevalence of COVID-19 associated pulmonary aspergillosis (CAPA) has been reported, though histopathological evidence is frequently lacking. To assess the clinical significance of Aspergillus species in respiratory samples of mechanically ventilated COVID-19 patients, we implemented routine screening for Aspergillus in tracheal aspirate (TA).Patients/methods From all adult COVID-19 patients admitted to the intensive care unit (ICU), TA samples were collected twice a week for Aspergillus screening by PCR and or culture. Bronchoalveolar lavage (BAL) sampling was performed in patients with a positive screening result if possible. Clinical information was obtained from the electronic patient record and patients were categorised according to the recently published consensus case definition for CAPA.Results Our study population consisted of 63 predominantly (73%) male patients, with a median age of 62 years and total median ICU stay of 18 days. Aspergillus species were present in TA screening samples from 15 patients (24%), and probable CAPA was diagnosed in 11 (17%) patients. Triazole resistance was detected in one patient (14%). Concordance between TA and BAL was 86%, and all TA culture positives were confirmed in BAL. We were able to withhold treatment in three of fifteen patients with positive screening (20%) but negative BAL results.Conclusions Positive culture, molecular detection and or antigen detection of Aspergillus species do not equal infection. Until we understand the clinical relevance of Aspergillus species detected in respiratory samples of COVID-19 patients, minimal-invasive screening by TA is a feasible method to monitor patients. Positive screening results should be an indication to perform a BAL to rule out upper airway colonisation.Perioperative Medicine: Efficacy, Safety and Outcome (Anesthesiology/Intensive Care

Use of monomeric and oligomeric flavanols in the dietary management of patients with type 2 diabetes mellitus and microalb

__Background:__ Patients with type 2 diabetes mellitus (T2D) are prone to micro- and macro-vascular complications. Monomeric and oligomeric flavanols (MOF) isolated from grape seeds (Vitis vinifera) have been linked to improved endothelial function and vascular health. The aim of this study is to determine the effect of a daily supplementation of 200 mg MOF on renal endothelial function of patients with T2D and microalbuminuria. __Methods/design:__ For this double-blind, placebo-controlled, randomized, multicenter trial 96 individuals (ages 40-85 years) with T2D and microalbuminuria will be recruited. Participants will be randomly assigned to the intervention group, receiving 200 mg of MOF daily for 3 months, or to the control group, receiving a placebo. The primary endpoint is the evolution over time in albumin excretion rate (AER) until 3 months of intervention as compared with placebo. Secondary endpoints are the evolution over time in established plasma markers of renal endothelial function-asymmetric dimethylarginine (ADMA), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular cell adhesion molecule-1 (sICAM-1), interleukin-6 (IL-6), and von Willebrand Factor (vWF)-until 3 months of intervention as compared with placebo. Mixed modeling will be applied for the statistical analysis of the data. __Discussion:__ We hypothesize that T2D patients with microalbuminuria have a medically determined requirement for MOF and that fulfilling this requirement will result in a decrease in AER and related endothelial biomarkers. If confirmed, this may lead to new insights in the dietary management of patients with T2D

Comparison of norovirus genogroup I, II and IV seroprevalence among children in the Netherlands, 1963, 1983 and 2006

Noroviruses are a major cause of acute gastroenteritis worldwide and are a genetically diverse group of viruses. Since 2002, an increasing number of norovirus outbreaks have been reported globally, but it is not clear whether this increase has been caused by a higher awareness or reflects the emergence of new genogroup II genotype 4 (GII.4) variants. The hypothesis that norovirus prevalence has increased post-2002 and is related to the emergence of GII.4 is tested in this study. Sera collected from children aged <5 years of three Dutch cross-sectional population based cohorts in 1963, 1983 and 2006/2007 (n=143, n=130 and n=376, respectively) were tested for specific serum IgG by protein array using antigens to GII.4 and a range of other antigens representing norovirus GI, GII and GIV genotypes. The protein array was validated by paired sera of norovirus infected patients and supernatants of B-cell cultures with single epitope specificity. Evidence for norovirus infection was found to be common among Dutch children in each cohort, but the prevalence towards different genotypes changed over time. At the genogroup level, GI seroprevalence decreased significantly between 1963 and 2006/2007, while a significant increase of GII and, in particular, specific antibodies of the genotype GII.4 was detected in the 2006/2007 cohort. There were no children with only GII.4 antibodies in the 1963 cohort. This study shows that the high GII.4 norovirus incidence in very young children is a recent phenomenon. These findings are of importance for vaccine development and trials that are currently focusing mostly on GII.4 viruses