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Increasing in vitro resistance to fluconazole in Cryptococcus neoformans Cambodian isolates: April 2000 to March 2002
Borann Sar1, Didier Monchy, Mich Vann
1Laboratory of Medical Microbiology, Unit of Clinical Testing, Institut Pasteur du Cambodge, 5 Boulevard Monivong, BP 983, Phnom Penh, Cambodia. sborann@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 MIC(50)s and MIC(90)s of fluconazole changed significantly from year 2000 to 2002; the MIC(50)s increased from 4 to 12 mg/L, and the MIC(90)s from 12 to 96 mg/L. For amphotericin B, the MIC(50)s and MIC(90)s 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.
Insights
Cryptococcus neoformans causing meningitis in HIV patients in Cambodia remains susceptible to amphotericin B. However, resistance to fluconazole is increasing, potentially linked to extended treatment durations.
Area of Science:
- Mycology
- Infectious Diseases
- HIV/AIDS Research
Background:
- Cryptococcal meningitis is a significant opportunistic infection in HIV patients in Cambodia.
- Standard treatment involves amphotericin B followed by fluconazole maintenance therapy.
Purpose of the Study:
- To determine the in vitro antifungal drug susceptibility of Cryptococcus neoformans isolates from cerebrospinal fluid (CSF) in Cambodian HIV patients.
- To assess changes in susceptibility to amphotericin B and fluconazole over time.
Main Methods:
- Collection of C. neoformans isolates from CSF during two surveillance periods (2000-2001 and 2001-2002).
- Determination of Minimum Inhibitory Concentrations (MICs) for amphotericin B and fluconazole using Etest strips.
- Serotyping of isolates using an antigenic agglutination slide test.
Main Results:
- Fluconazole MICs showed a significant increase from 2000 to 2002, with MIC(50) rising from 4 to 12 mg/L and MIC(90) from 12 to 96 mg/L.
- Amphotericin B MICs remained stable.
- In the second year, 20 isolates exhibited fluconazole MICs of ≥256 mg/L, and 98.5% of isolates were serotype A.
Conclusions:
- C. neoformans strains from Cambodian HIV patients remain susceptible to amphotericin B in vitro.
- In vitro resistance to fluconazole is increasing, with 14% of isolates showing resistance in the second study year.
- Emerging fluconazole resistance appears associated with prolonged maintenance therapy.
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