title: Emerging aspergillosis by azole-resistant Aspergillus fumigatus at an intensive care unit in the Netherlands, 2010 to 2013.
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.
authors.affiliation: Leiden University Medical Centre, intensive care department, Leiden, the Netherlands.
authors.forename: Judith
authors.initials: J
authors.lastname: van Paassen
authors.forename: Anne
authors.initials: A
authors.lastname: Russcher
authors.forename: Astrid Wm
authors.initials: AW
authors.lastname: In 't Veld-van Wingerden
authors.forename: Paul E
authors.initials: PE
authors.lastname: Verweij
authors.forename: Eduard J
authors.initials: EJ
authors.lastname: Kuijper
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D001228:Aspergillosis / Q000188:drug therapy* / Q000401:mortality; D001232:Aspergillus fumigatus / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D003577:Cytochrome P-450 Enzyme System; D025141:Drug Resistance, Fungal / Q000235:genetics; D005656:Fungal Proteins / Q000235:genetics; D005838:Genotype; D006785:Hospitals, University; D006801:Humans; D007362:Intensive Care Units; D008826:Microbial Sensitivity Tests; D009426:Netherlands / Q000453:epidemiology; D011379:Prognosis; D012189:Retrospective Studies; D016896:Treatment Outcome; D065819:Voriconazole / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000935:Antifungal Agents; D005656:Fungal Proteins; D003577:Cytochrome P-450 Enzyme System; C465526:cytochrome P-450 CYP51A, Aspergillus; D065819:Voriconazole
keywords: Fungal infections; Intensive Care Unit; Invasive Asperillosis; antimicrobial resistance