[22] INCREASING IN VITRO RESISTANCE TO FLUCONAZOLE IN CRYPTOCOCCUS NEOFORMANS ISOLATED IN CAMBODIA

2nd International AIDS Society Conference on HIV Pathogenesis and Treatment

Paris, France - July 13 - 16, 2003

[TITLE:] INCREASING IN VITRO RESISTANCE TO FLUCONAZOLE IN CRYPTOCOCCUS NEOFORMANS ISOLATED IN CAMBODIA

[AUTHOR(S):] B Sar¹, D Monchy¹, N Prak², C Keo¹ and JL Sarthou¹
¹ Laboratory Microbiology, Institut Pasteur du Cambodge; and ² Department of Infectious Diseases, Prash Bat Norodom Sihanouk Hospital, Phnom Penh, Cambodia

IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 22
Antiviral Therapy 2003; 8(Suppl. 1):S190

[ABSTRACT:] Cryptococcal meningitis is the third most common opportunistic infection in HIV patients in Cambodia. Hospitalized patients are given AmphotericinB (AMB) for initial therapy followed by Fluconazole (FLC) for maintenance therapy. The antifungal drug susceptibilities of two-batch collections of C. neoformans isolated from CSF were determined. The isolates were obtained during active laboratory based surveillance; first batch of isolates was collected from Apr. 2000 to Mar. 2001 (134 new cases isolated) and the second batch from Apr. 2001 to Mar. 2002 (268 new cases isolated). E-test strips (AB BIODISK) were used to detect the MIC of AMB and FLC. The antigenic agglutination slide test Cryptocheck (IATRON) was used to determine the serotype of the isolates. The MICs 50 and MICs 90 changed between the years 2000 to 2002. The MICs 50 for AMB were increased from 0.38 to 0.5 μg/ml, for the first and second batches respectively. The MICs 90 for AMB was also increased from 0.5 to 0.75 μg/ml, for first and second batches respectively. The MICs 90 for FLC was significantly increased from 24 to 192 μg/ml for the first batch and second batches respectively. In addition, in the second batch of isolates the MICs for AMB were elevated (≥4 μg/ml) for 2 isolates and the MICs for FLC were elevated (≥64 μg/ml) for 72 isolates. Analysis of 104 serial isolates from 52 patients showed little change in the AMB MIC. By contrast, FLC showed a big MIC change over time. In addition for 402 isolates the serotypes of C. neoformans were determined. 98.5% of isolate were serotype A and 1.5% were serotype B. Correlation between in vitro resistance to antifungal agents and clinical efficacy of treatment are not significantly established. Our study indicates that the resistance in vitro of C. neoformans to FLC appears to be linked to extended maintenance treatments under strictly controlled clinical prescription. C. neoformans var. neoformans is the isolate predominance of opportunistic infection in Cambodia.

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