Abstract
The prevalence of invasive aspergillosis (IA) at the intensive care unit (ICU) is unknown and difficult to assess since IA also develops in patients lacking specific host factors. In the Netherlands, increasing azole-resistance in Aspergillus fumigatus complicates treatment of patients with IA. The aim of this study was to determine the prevalence of IA by azole-resistant A. fumigatus at the ICU among patients receiving antifungal treatment and to follow their clinical outcome and prognosis. A retrospective cohort study was conducted in a university hospital ICU from January 2010 to December 2013. From all patients who received antifungal treatment for suspected IA, relevant clinical and microbiological data were collected using a standardised questionnaire. Of 9,121 admitted ICU-patients, 136 had received antifungal treatment for suspected IA, of which 38 had a positive A. fumigatus culture. Ten of the 38 patients harboured at least one azole-resistant isolate. Resistance mechanisms consisted of alterations in the cyp51A gene, more specific TR34/L98H and TR46/T289A/Y121F. Microsatellite typing did not show clonal relatedness, though isolates from two patients were genetically related. The overall 90-day mortality of patients with IA by azole-resistant A. fumigatus and patients with suspicion of IA by azole-susceptible isolates in the ICU was 100% (10/10) vs 82% (23/28) respectively. We conclude that the changing pattern of IA in ICU patients requires appropriate criteria for recognition, diagnosis and rapid resistance tests. The increase in azole resistance rates also challenges a reconsideration of empirical antifungal therapy.
Highlights
Azole resistance is an emerging problem in Aspergillus infections caused by Aspergillus fumigatus, with increasing reports of azole treatment failure [1,2,3,4,5,6]
Surveillance studies from the Netherlands revealed azole resistance to be endemic, with dominance of the TR34/L98H and TR46/Y121F/T289A cyp51A-gene mediated resistance mechanisms [3]. These studies were based on routinely screening for the presence of azole resistance in all Aspergillus spp. isolates cultured from clinical samples in five university hospitals, irrespective of the clinical relevance of the culture result [3]
The study population consisted of intensive care unit (ICU) patients who were treated for suspected invasive aspergillosis (IA) and in whom A. fumigatus was cultured, since resistance testing can only be done on cultured isolates
Summary
Azole resistance is an emerging problem in Aspergillus infections caused by Aspergillus fumigatus, with increasing reports of azole treatment failure [1,2,3,4,5,6]. Surveillance studies from the Netherlands revealed azole resistance to be endemic, with dominance of the TR34/L98H and TR46/Y121F/T289A cyp51A-gene mediated resistance mechanisms [3] These studies were based on routinely screening for the presence of azole resistance in all Aspergillus spp. isolates cultured from clinical samples in five university hospitals, irrespective of the clinical relevance of the culture result [3]. These surveys provide insight in the overall prevalence of azole resistance in culture-positive patients, the implications of azole resistance for specific patient groups remain unknown. As information on IA by azole-resistant A. fumigatus in the ICU is scarce, we performed a retrospective cohort study in order to investigate the prevalence of azole resistance and its implications for patient treatment
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