The treatment of community-acquired pneumonia (CAP) is based on early diagnosis and swift initiation of appropriate antibiotic treatment. Despite effective treatment, CAP is still one of the... Show moreThe treatment of community-acquired pneumonia (CAP) is based on early diagnosis and swift initiation of appropriate antibiotic treatment. Despite effective treatment, CAP is still one of the leading causes of morbidity and mortality due to infectious diseases worldwide. This thesis aimed to identify strategies to optimise the treatment of hospitalised CAP patients outside an intensive care unit (ICU) setting with a focus on corticosteroid treatment. First, this thesis focused on the question whether oral adjunctive corticosteroid treatment improves outcomes in hospitalised CAP patients and tries to identify a subgroup of CAP patients, based on inflammatory status at admission, in whom the beneficial effects of adjunctive corticosteroid treatment outweigh the disadvantages associated with corticosteroid use. Next, this thesis investigated whether obesity and overweight are associated with worse clinical outcomes in a population of hospitalised COVID-19 patients who were all treated with the recommended 6 mg dexamethasone dose. Last, this thesis focused on optimising antibiotic treatment by exploring whether extensive microbiological testing facilitates early antibiotic alterations in CAP patients. Show less
The human body is colonized by microorganisms, collectively referred to as the human microbiota. Microbiota disturbance has been associated with a wide range of diseases and is the focus of many... Show moreThe human body is colonized by microorganisms, collectively referred to as the human microbiota. Microbiota disturbance has been associated with a wide range of diseases and is the focus of many research initiatives. The most widely used approach is based on sequencing of the 16S rRNA gene. This method can also be very valuable for clinical microbiology as it enables identification of a theoretically unlimited number of bacteria present in a specimen and permits (semi)quantitative information about the composition of a microbial community. In this thesis we investigated whether 16S rRNA gene profiling would have added value for direct diagnostics and/or as an indirect tool for evaluating cheaper diagnostic tests or evaluating treatments. The studies in this thesis were focused on respiratory tract infections, bacterial vaginosis, atopic dermatitis or male genital lichen sclerosus. The main challenge of 16S rRNA gene profiling is the clinical interpretation of relative abundance of the identified bacteria in clinical specimens. More clinical studies with appropriate control groups are needed to define and validate clinically relevant cut-off values, to measure microbiota variability over time and to determine microbial phenotypes. The clinical value of 16S rRNA gene profiling will probably become clear in the forthcoming years. Show less
Munckhof, E.H.A. van den; Hafkamp, H.C.; Kluijver, J. de; Kuijper, E.J.; Koning, M.N.C. de; Quint, W.G.V.; Knetsch, C.W. 2020
BackgroundThe elderly (>= 65years) are one of the populations most at risk for respiratory tract infections (RTIs). The aim of this study was to determine whether nasal and/or oropharyngeal... Show moreBackgroundThe elderly (>= 65years) are one of the populations most at risk for respiratory tract infections (RTIs). The aim of this study was to determine whether nasal and/or oropharyngeal microbiota profiles are associated with age and RTIs.MethodsNasal and oropharyngeal swabs of 152 controls and 152 patients with an RTI were included. The latter group consisted of 72 patients with an upper respiratory tract infection (URTI) and 80 with a lower respiratory tract infection (LRTI). Both nasal and oropharyngeal swabs were subjected to microbiota profiling using amplicon sequencing of the 16S rRNA gene. Moraxella species were determined using quantitative real-time PCR and culture.ResultsBased on the microbiota profiles of the controls and the patients with an RTI, eight nasal and nine oropharyngeal microbiota clusters were defined. Nasal microbiota dominated by either Moraxella catarrhalis or Moraxella nonliquefaciens was significantly more prevalent in elderly compared to mid-aged adults in the control group (p=0.002). Dominance by M. catarrhalis/nonliquefaciens was significantly less prevalent in elderly with an LRTI (p=0.001) compared to controls with similar age.ConclusionsNasal microbiota dominated by M. catarrhalis/nonliquefaciens is associated with respiratory health in the elderly population. Show less
Different aspects of respiratory tract infection have been studied. Automatic syndromic surveillance for early detection of infections is feasible. Peak in ILI in hospitals is most flu seasons... Show moreDifferent aspects of respiratory tract infection have been studied. Automatic syndromic surveillance for early detection of infections is feasible. Peak in ILI in hospitals is most flu seasons before rise in cases in primary care. Influenza vaccination can safely be given to oncology patients who use checkpoint inhibitors. we were unable to demonstrate an attenuation of immune response in patients treated with non-lytic rifampicin for pneumococcal pneumonia. Cardiac surgery during influenza season is a risk factor for postoperative ARDS. Show less
Background: Diagnosing pneumonia can be challenging in general practice but is essential to distinguish from other respiratory tract infections because of treatment choice and outcome prediction.... Show moreBackground: Diagnosing pneumonia can be challenging in general practice but is essential to distinguish from other respiratory tract infections because of treatment choice and outcome prediction. We determined predictive signs, symptoms and biomarkers for the presence of pneumonia in patients with acute respiratory tract infection in primary care.Methods: From March 2012 until May 2016 we did a prospective observational cohort study in three radiology departments in the Leiden-The Hague area, The Netherlands. From adult patients we collected clinical characteristics and biomarkers, chest X ray results and outcome. To assess the predictive value of C-reactive protein (CRP), procalcitonin and midregional pro-adrenomedullin for pneumonia, univariate and multivariate binary logistic regression were used to determine risk factors and to develop a prediction model.Results: Two hundred forty-nine patients were included of whom 30 (12%) displayed a consolidation on chest X ray. Absence of runny nose and whether or not a patient felt ill were independent predictors for pneumonia. CRP predicts pneumonia better than the other biomarkers but adding CRP to the clinical model did not improve classification (- 4%); however, CRP helped guidance of the decision which patients should be given antibiotics.Conclusions: Adding CRP measurements to a clinical model in selected patients with an acute respiratory infection does not improve prediction of pneumonia, but does help in giving guidance on which patients to treat with antibiotics. Our findings put the use of biomarkers and chest X ray in diagnosing pneumonia and for treatment decisions into some perspective for general practitioners. Show less
