Clinical implications of azole resistance in Aspergillus fumigatus, The Netherlands, 2007-2009

Jan W M van der Linden, Eveline Snelders, Greetje A Kampinga, Bart J A Rijnders, Eva Mattsson, Yvette J Debets-Ossenkopp, Ed J Kuijper, Frank H Van Tiel, Willem J G Melchers, Paul E Verweij, Jan W M van der Linden, Eveline Snelders, Greetje A Kampinga, Bart J A Rijnders, Eva Mattsson, Yvette J Debets-Ossenkopp, Ed J Kuijper, Frank H Van Tiel, Willem J G Melchers, Paul E Verweij

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.

Figures

Figure 1
Figure 1
Number of screened Aspergillus spp. isolates per month (bars) and prevalence (%) of azole resistance (line), the Netherlands, 2007–2009. ITZ, itraconazole.
Figure 2
Figure 2
Prevalence (%) of azole-resistant Aspergillus fumigatus infections in university medical centers, the Netherlands, 2007–2009.

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