JAC Advance Access originally published online on July 14, 2004
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Journal of Antimicrobial Chemotherapy 2004 54(2):563-565; doi:10.1093/jac/dkh361
JAC vol.54 no.2 © The British Society for Antimicrobial Chemotherapy 2004; all rights reserved.
Increasing in vitro resistance to fluconazole in Cryptococcus neoformans Cambodian isolates: April 2000 to March 2002
1 Laboratory of Medical Microbiology, Unit of Clinical Testing, Institut Pasteur du Cambodge, 5 Boulevard Monivong, BP 983, Phnom Penh; 2 Department of Infectious Diseases, Preah Bat Norodom Sihanouk Hospital, Phnom Penh, Cambodia; 3 Instruction des Armées Val-de-Grâce Hospital, 74 Boulevard de Port-Royal, Paris Cedex 05, France
* Corresponding author. Tel: +855-23-368-036; Fax: +855-23-426-013; Email: sborann{at}pasteur-kh.org
Objectives: Cryptococcal meningitis is the third-most-common opportunistic infection in HIV patients in Cambodia. Hospitalized patients were given amphotericin B for initial therapy followed by fluconazole for maintenance therapy. The antifungal drug susceptibility of Cryptococcus neoformans isolated from cerebrospinal fluid (CSF) was determined.
Methods: Isolates of C. neoformans were collected during active laboratory-based surveillance, the first batch from April 2000 to March 2001 (134 new cases), the second batch from April 2001 to March 2002 (268 new cases). Etest strips were used to determine the MICs of amphotericin B and fluconazole. The antigenic agglutination slide test was used for serotyping.
Results: The MIC50s and MIC90s of fluconazole changed significantly from year 2000 to 2002; the MIC50s increased from 4 to 12 mg/L, and the MIC90s from 12 to 96 mg/L. For amphotericin B, the MIC50s and MIC90s remained stable. Moreover, in the second batch, fluconazole MICs were 
256 mg/L for 20 isolates. By serotyping, it was found that 98.5% of the isolates were serotype A.
Conclusions: C. neoformans strains isolated from CSF of AIDS patients in Cambodia remain susceptible in vitro to amphotericin B. These strains are less susceptible in vitro to fluconazole, 2.5% being resistant in the first year and 14% in the second year of study. Nevertheless, in vitro resistance of C. neoformans to fluconazole appeared to be linked to extended maintenance treatments.
Keywords: cryptococcal meningitis , antifungals , Etest
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