Emergence of azole cross-resistance in Candida glabrata following exposure to azole antifungals in a surgical intensive care unit

Abstract number: O369

Grenouillet F., Millon L., Fournel X., Blasco G., Roussel S., Pili-Floury S., Samain E., Piarroux R.

Objectives: Fluconazole (FLC) is widely used for prophylactic, preemptive and curative treatments of invasive candidiasis in surgical intensive care unit (SICU) patients. Acquired resistance to azoles in Candida glabrata (Cg) strains after exposure were not rare but data on its incidence were lacking.

The aim of this study was to assess the incidence of acquired FLC resistance and azole cross-resistance in Cg following azoles exposure in SICU.

Methods: Three-year prospective survey (02/2003–01/2006) with systematic mycological screening performed on all patients admitted to the SICU, immediately at admittance, then weekly until discharge. Patients with more than 2 weeks of Cg colonisation were retrospectively included in this study. For each patient, each isolate was genotyped using microsatellite-based MLVA method. Susceptibilities of Cg isolates to azoles were determined with NCCLS reference method (first and last isolate per strain per patient, susceptibilities to FLC, itraconazole, voriconazole VRC and posaconazole). Patient data (including azoles exposure during SICU stay) were retrospectively collected. Acquired FLC resistance was defined by MIC of the last isolate for FLC > 8 mg/mL and a 4x-fold increase of this MIC during SICU stay.

Results: Thirty nine patients out of 1218 admitted in SICU were included. Characteristics of patients included were: mean age 65 years (±15), median SICU stay 30 days [range: 18–160], mean SAPS II score 44 (±14). Main underlying disorders were abdominal surgery and polytrauma.

All patients harbored only one Cg strain, except one patient colonised with two different strains. Acquired azole resistance was not observed in six patients without azole exposure. Thirty three patients were given azole antifungals during SICU stay, all with high daily dose (DD) of FLC or VRC (mean DD: 470 mg/day). Nine out of 33 (27%) presented SICU-acquired resistance of their own Cg strain. Cg strains with FLC acquired resistance all showed cross-resistance to other azoles.

No significant risk factor of acquisition was identified among patient data, characteristics of azole regimens used (duration, total dose) and Cg genotypes.

Conclusion: Acquisition of cross-azole resistance following azoles exposure occurs frequently in SICU patients. Antifungal agents others than azoles (i.e. candins, polyenes) should be considered as initial therapy in SICU patients with suspected invasive candidiasis in the setting of prior azole exposure.

Session Details

Date: 19/04/2008
Time: 00:00-00:00
Session name: 18th European Congress of Clinical Microbiology and Infectious Diseases
Location: Barcelona, Spain
Presentation type:
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