NEW YORK (Reuters Health) – For the initial treatment of HIV-associated cryptococcal meningitis, amphotericin B plus fluconazole is a good alternative to amphotericin B plus flucytosine (5-FC), the current standard initial therapy, a study suggests.

The study found no statistically significant difference in early fungicidal activity between amphotericin B plus fluconazole and amphotericin B plus 5-FC.

This finding is highly relevant to patients in Asia and Africa, where 5-FC remains largely unavailable, Dr. Thomas Harrison, of St. George's University of London, United Kingdom and colleagues point out in a report online November 3 in Clinical Infectious Diseases.

In a linked commentary, Dr. John Bennett, of the National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, praises Dr. Harrison and colleagues for continuing to “lead the way in efforts to improve care of South African AIDS patients with cryptococcal meningitis.”

The randomized unblinded four-armed study included 80 HIV-seropositive, antiretroviral naïve patients with a first episode of cryptococcal meningitis.

All patients received amphotericin B 0.7 to 1.0 mg/kg once daily for two weeks, along with either flucytosine 25mg/kg four times per day (21 patients), fluconazole 800 milligrams once daily (22 patients), fluconazole 600 milligrams twice daily (23 patients), or voriconazole 300 milligrams twice daily (13 patients).

According to the investigators, there were no statistically significant differences in the rate of clearance of infection from the cerebrospinal fluid (CSF), the primary outcome. Overall mortality was 12% at two weeks and 29% at 10 weeks, with no statistically significant differences among groups.

Dr. Harrison and colleagues say the second-line drugs were well tolerated overall. They found “few laboratory abnormalities” related to the second agents given; in particular, there were no statistically significant increases in alanine transaminase level or decreases in neutrophil count, they say.

This study, writes Dr. Bennett, “argues convincingly” that 2 weeks of amphotericin B (0.7 to 1.0 mg/kg once daily) can provide the same benefit whether flucytosine or fluconazole is the companion drug. “This conclusion provides an important option for initial therapy of cryptococcal meningitis in South African retroviral-naive AIDS patients,” he concludes.

Dr. Harrison and colleagues say their findings support the use of amphotericin B plus fluconazole at a dosage of at least 800 mg daily in Africa and elsewhere where 5-FC is not currently available.”

They note that amphotericin B plus voriconazole is also “an effective alternative combination in patients not receiving interacting medications.”

Reference:

Comparison of the Early Fungicidal Activity of High-Dose Fluconazole, Voriconazole, and Flucytosine as Second-Line Drugs Given in Combination With Amphotericin B for the Treatment of HIV-Associated Cryptococcal Meningitis

Clin Infec Dis 2011.