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... Show moreBackground 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. Show less
Outline of the Thesis Part I Pneumocystis in kidney transplant recipients: transmission, risk factors , new diagnostic and chemo-prophylactic strategies. Chapter 2 describes the characteristics of... Show moreOutline of the Thesis Part I Pneumocystis in kidney transplant recipients: transmission, risk factors , new diagnostic and chemo-prophylactic strategies. Chapter 2 describes the characteristics of a large outbreak of Pneumocystis pneumonia among kidney transplant recipients. By performing a classical outbreak investigation and by application of new molecular genotyping techniques, the potential of the __interhuman transmission hypothesis__ is addressed and discussed. In Chapter 3 all currently available data on reported outbreaks of Pneumocystis pneumonia is systematically reviewed with the emphasis on mortality data, clinical risk factors and transmission analyses. In the case-control study described in Chapter 4, we performed a detailed risk factor analysis for development of PCP in kidney transplant recipients and used the multivariate output data to estimate the effects of several chemoprophylactic strategies by modeling the expected incidence and number-needed-to-treat to provide efficient PCP chemoprophylaxis over a 2-year period post transplantation. Chapter 5 reports the data of a prospective study on the serum markers S-adenosylmethionine and (1-->3)-_-D-glucan serum levels and correlation with clinical parameters in HIVnegative immunocompromised patients __ the majority kidney transplant recipients - with Pneumocystis pneumonia. Potential applicability for treatment monitoring and assessment of P. jirovecii pulmonary load is also discussed. Part II Genetic predisposition for development of invasive aspergillosis in stem cell transplant recipients Chapter 6 describes a multicenter study on the impact of the Y238X stop mutation in the human Dectin-1 receptor (which senses and attaches to glucan moieties of the fungal cell wall) on the risk of development of invasive aspergillosis in stem cell transplant recipients. In Chapter 7 a retrospective study of the influence of genetic variation in the macrophage activation route with respect to the relative additional risk for development of invasive aspergillosis is presented. Part III Experimental markers for detection of fungal infection: scintigraphic imaging. In Chapter 8 the clinical applicability of radiolabeled antimicrobial peptides and antifungal drugs for the diagnosis of invasive fungal infections is reviewed, together with a concise discussion about how promising agents should be further developed. The results of the thesis are summarized and discussed in Chapter 9. Show less
