Correlation of anti-fungal susceptibility with clinical outcomes in patients with cryptococcal meningitis

BACKGROUND This study aimed to investigate the correlation of minimum inhibiting concentrations (MICs), obtained by broth micro-dilution, and clinical response in patients with cryptococcal meningitis. METHODS Using retrospective analyses covering the period 2001-2010, factors affecting clinical therapeutic cure in patients with cryptococcal meningitis 10 weeks after the start of anti-fungal therapy were identified. Specific emphasis was placed on the role of anti-fungal susceptibility. RESULTS Of 46 patients with cryptococcal meningitis identified, 21 were cured after 10 weeks of treatment. Overall, 12 strains (26.1%) were resistant to fluconazole (>8 μg/ml) and 8 (17.4%) had an MIC >1 μg/ml for amphotericin B. Twenty-three patients received combination amphotericin B and fluconazole as their initial antifungal therapy, 17 were given amphotericin B only, five received fluconazole only, and one received a combination of amphotericin B and flucytosine. After 2 weeks, all patients received fluconazole (400-600 mg daily for 8 weeks at least, then 200 mg daily thereafter). The presence of isolates resistant to fluconazole (MIC >8 μg/ml; 4.8% vs. 44%, p < 0.01) were statistically significant among patients who were cured. Anti-fungal susceptibility, reflected by fluconazole MIC >8 μg/ml, was an independent predictor of therapeutic cure at 10-week evaluation (OR = 15.7; 95% CI: 1.8-135.9; p = 0.01), but higher MIC of amphotericin B (>1 μg/ml) was not. CONCLUSIONS The MICs of fluconazole, determined by the CLSI method, may be a potential predictor of therapeutic cure in patients with cryptococcal meningitis.