Antifungal Susceptibilities of Cryptococcus Neoformans Cerebrospinal Fluid Isolates and Clinical Outcomes of Cryptococcal Meningitis in HIV-Infected Patients with/without Fluconazole Prophylaxis
Weerawat Manosuthi MD*, Somnuek Sungkanuparph MD**, Supeda Thongyen BEd*, Nopphanath Chumpathat MEd*, Boonchuay Eampokalap MSc*, Unchana Thawornwan BSc*, Suporn Foongladda PhD***
Affiliation : * Bamrasnaradura Institute, Ministry of Public Health, Nonthaburi ** Faculty of Medicine Ramathibodi Hospital, Mahidol University *** Faculty of Medicine Siriraj Hospital, Mahidol University
Objectives : To compare the MICs of FLUconazole (FLU) and amphotericin B against isolates of Cryptococcus
neoformans (C. neoformans) obtained from the CerebroSpinal Fluid (CSF); and clinical outcomes of HIV-
infected patients diagnosed with cryptococcal meningitis.
Materials and Methods : There were two groups including those who did not receive FLU (group A) and those
who did receive either FLU 400 mg/week for primary prophylaxis cryptococosis or 200 mg/day for secondary
prophylaxis cryptococosis (group B). CSF isolates of C. neoformans from group A and group B between
January 2003 and October 2004 were retrospectively studied. The MICs were determined by using the stan-
dard NCCLS broth microdilution methods (M27-A). The MICs of FLU and amphotericin B, and clinical
outcomes after 10 weeks of cryptococcal meningitis treatment were determined.
Results : There were 98 isolates; 80 in group A and 18 in group B. The patients in group B had a higher
proportion of previous opportunistic infections (p = 0.008). The other baseline characteristics between the
two groups were not different. The median (range) MIC of FLU was 8.0 (0.5-32) µg/ml in group A, and 6.0 (0.5-
32) µg/ml in group B (p = 0.926). The median (range) MIC of amphotericin B was 0.25 (0.03-1.0) µg/ml in
group A, and 0.25 (0.12-1.0) µg/ml in group B (p = 0.384). Sixty patients from group A and 14 from group B
received standard treatment and continued to follow-up. After the 10-week treatment, 39/60 (65%) patients in
group A and 7/14 (50%) in group B had complete recovery (p = 0.364; RR = 0.538, 95%CI = 0.166-1.742).
The overall mortality rate was 14/60 (23.3%) in group A and 7/14 (50.0%) in group B (p = 0.096; RR = 3.286,
95%CI = 0.983-10.979).
Conclusion : The MICs of FLU and amphotericin B against CSF isolates of C. neoformans and clinical out-
comes between HIV-infected patients who receive or did not receive FLU prophylaxis are not different.
Keywords : Fluconazole, Amphotericin B, Susceptibility, C. neoformans, HIV
