Background Isavuconazole is a triazole antifungal drug, approved for the treatment of invasive aspergillosis and mucormycosis. Isavuconazole is metabolised by CYP3A4 and CYP3A5, and it has been... Show moreBackground Isavuconazole is a triazole antifungal drug, approved for the treatment of invasive aspergillosis and mucormycosis. Isavuconazole is metabolised by CYP3A4 and CYP3A5, and it has been shown that the CYP3A inducer rifampin reduces isavuconazole exposure. By extrapolation, the concomitant use of isavuconazole with moderate and strong CYP450 inducers is contraindicated, although it is known that some CYP450 inducers are less potent in comparison with rifampin.Objectives We aim to document exposure to isavuconazole in patients concomitantly treated with a CYP450 inducer that is less potent compared to rifampin. Moreover, although it is well known that CYP3A enzymes are important for the metabolism of isavuconazole, this induction effect has never been studied in combination with the patient's CYP3A genotype.Patients We report three patients treated with both isavuconazole and a CYP3A inducer that is less potent compared to rifampin (rifabutin or phenobarbital), in whom we determined isavuconazole concentrations.Results These cases suggest that the CYP3A4/5 genotype is an important determinant for isavuconazole exposure and that it might also influence the CYP450 induction interaction.Conclusions CYP3A inducers that are less potent compared to rifampin, may be combined with isavuconazole in patients with loss of CYP3A5 activity (CYP3A5*3/*3). Therapeutic drug monitoring is recommended during this combination. However, low-isavuconazole exposure was observed in the extensive metaboliser with CYP3A4*1/*1 and CYP3A5*1/*3 alleles. Show less
Grootveld, R. van; Paassen, J. van; Boer, M.G.J. de; Claas, E.C.J.; Kuijper, E.J.; Beek, M.T. van der; LUMC-COVID-19 Research Grp 2021
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
Schauwvlieghe, A.F.A.D.; Jonge, N. de; Dijk, K. van; Verweij, P.E.; Bruggemann, R.J.; Biemond, B.J.; ... ; Rijnders, B.J.A. 2018
A survey of diagnosis and treatment of invasive aspergillosis was conducted in eight University Medical Centers (UMCs) and eight non-academic teaching hospitals in the Netherlands. Against a... Show moreA survey of diagnosis and treatment of invasive aspergillosis was conducted in eight University Medical Centers (UMCs) and eight non-academic teaching hospitals in the Netherlands. Against a background of emerging azole resistance in Aspergillus fumigatus routine resistance screening of clinical isolates was performed primarily in the UMCs. Azole resistance rates at the hospital level varied between 5% and 10%, although rates up to 30% were reported in high-risk wards. Voriconazole remained first choice for invasive aspergillosis in 13 out of 16 hospitals. In documented azole resistance 14 out of 16 centres treated patients with liposomal amphotericin B. Show less
Peppel, R.J. van de; Borne, P.A.V.; Cessie, S. le; Boer, M.G.J. de 2015
Tinea capitis is endemic among schoolchildren in tropical Africa. The objective was to determine the prevalence of symptomatic tinea capitis in schoolchildren in Gabon. A cross-sectional study was... Show moreTinea capitis is endemic among schoolchildren in tropical Africa. The objective was to determine the prevalence of symptomatic tinea capitis in schoolchildren in Gabon. A cross-sectional study was conducted with 454 children aged 4-17 years, attending a rural school and an urban school. The diagnosis of tinea capitis was based on clinically manifest infection, direct microscopic examination using 20% potassium hydroxide (KOH) solution and fungal culture. Based on clinical examination, 105 (23.1%) of 454 children had tinea capitis. Seventy-four (16.3%) children were positive by direct examination (KOH) and/or fungal culture. The prevalence of tinea capitis depended on the school studied and ranged from 20.4% in the urban school with a higher socioeconomic status to 26.3% in the rural school with a lower socioeconomic status. Similarly, the spectrum of causative species varied between the different schools. Taken the schools together, Trichophyton soudanense (29.4%) was the most prominent species, followed by Trichophyton tonsurans (27.9%) and Microsporum audouinii (25.0%). Clinically manifest tinea capitis is endemic among schoolchildren in the Lambarene region in Gabon. The prevalence of tinea capitis and the causative species depended on the type of school that was investigated. Show less
