Clinical Implications of Azole Resistance inAspergillus fumigatus, the Netherlands, 2007–2009

Abstract

The prevalence and spread of azole resistance in clinical Aspergillus fumigatus isolates in the Netherlands are currently unknown. Therefore, we performed a prospective nationwide multicenter surveillance study to determine the effects of resistance on patient management strategies and public health. From June 2007 through January 2009, all clinical Aspergillus spp. isolates were screened for itraconazole resistance. In total, 2,062 isolates from 1,385 patients were screened; the prevalence of itraconazole resistance in A. fumigatus in our patient cohort was 5.3% (range 0.8%–9.5%). Patients with a hematologic or oncologic disease were more likely to harbor an azole-resistant isolate than were other patient groups (p<0.05). Most patients (64.0%) from whom a resistant isolate was identified were azole naive, and the case-fatality rate of patients with azole-resistant invasive aspergillosis was 88.0%. Our study found that multiazole resistance in A. fumigatus is widespread in the Netherlands and is associated with a high death rate for patients with invasive aspergillosis.

High prevalence of clinical and environmental triazole-resistant Aspergillus fumigatus in Iran: is it a challenging issue?

“…Over 90 % of azole-resistant A. fumigatus isolates harbour a leucine-to-histidine substitution at codon 98, along with a 34 bp tandem repeat in the CYP51A promoter region. This issue, which is associated with high rates of treatment failure, has become a major medical concern (Howard et al, 2009;Snelders et al, 2009;van der Linden et al, 2011;Verweij et al, 2007). However, a novel CYP51A-promoter duplication mutation, known as TR 46 /Y121F/T289A, has recently been introduced, which is considered responsible for the elevated MIC of voriconazole (Chowdhary et al, 2013;van der Linden et al, 2013).…”

“…Austria, Belgium, Denmark, France, Germany, the Netherlands, Norway, Spain and Turkey), the USA, South America and Asian countries (e.g. China, India, Iran, Japan and Kuwait), with an incidence rate of 3.3-38 % (Badali et al, 2013;Bader et al, 2013;Bueid et al, 2010;Burgel et al, 2012;Chowdhary et al, 2011;Chryssanthou, 1997;Howard et al, 2009;Lockhart et al, 2011;Mortensen et al, 2010;Pham et al, 2014;Seyedmousavi et al, 2013;Snelders et al, 2008;van der Linden et al, 2011;van Ingen et al, 2014). According to a recent international surveillance study on the clinical isolates of azole-resistant A. fumigatus, an incidence rate of 3.2 % was reported, which introduced a novel phase in the management of invasive aspergillosis (van der Linden et al, 2015).…”

Novel Antifungal Drugs Against Fungal Pathogens: Do They Provide Promising Results for Treatment?

“…The blood concentration of those drugs could not be monitored in our study, but monitorization of drug concentration increases efficacy and decreases the risk for toxicity since blood concentrations of drugs could not reach to therapeutic levels in some patients [22,23]. Main problem observed with orally administered drugs is the emergence of azole resistance in Aspergillus and Candida species and related infections among patients who received those drugs as mentioned earlier [24]. Either L-AmB or CAS should be evaluated for treatment if an IFI develops during or after treatment [25,26].…”

Latest Trends in Fungal Epidemiology Inform Treatment Choices and Stewardship Initiatives

“…Guinea Ortega cited data from a recent study of over 2000 isolates tested in 1385 patients in The Netherlands, which showed a prevalence of itraconazole resistance in A. fumigatus of 5.3%, with levels ranging from 0.8 to 9.5% depending on which part of the country the isolates came from [11]. Patients with a hematologic or oncologic disease were at greatest risk of itraconazole-resistant infection, and 64% of patients with resistant isolates were azole naive.…”