Amphotericin B for cryptococcal meningitis in HIV positive patients: Low dose versus high dose

Aim: To compare the safety and efficacy of low dose vs high dose of amphotericin B in cryptococcal meningitis associated with HIV infection.
Materials and Methods: Retrospective data of patients admitted with clinical diagnosis with or without microbiological evidence of cryptococcal meningitis was collected from Jan 2000-Mar 2006. Patients′ details were collected in a proforma which included patient′s age, weight, signs and symptoms of disease and microbiological report (blood and CSF analysis). Data also included coexisting disease; concomitant medications taken along with amphotericin B. Adverse drug reactions which occurred during the period of treatment were recorded. Patients were grouped as low dose group and high dose group depending on the dose of amphotericin B given for the treatment of cryptococcal meningitis. Patients who received amphotericin B at doses of 0.33 to 0.64 mg/kg body weight per day were categorized under low dose group and patients who received amphotericin B at doses of 0.7 to 1.1 mg/kg/day were categorized under high dose group. All data were pooled and analyzed between the groups using chi square test.
Result: Total number of patients included in the study were 38, 26 in the low dose group and 12 in the high dose group. In the low dose group, 20 were males and six were females, in the high dose group eight were males and four were females. The commonest underlying diseases were tuberculosis (17 in low dose group, nine in high dose group), Pneumocystis carinii (jeroveci) pneumonia (16 in low dose group, seven in high dose group) and oral candidiasis (eight in low dose group, seven in high dose group), Toxoplasmosis (three in low dose group, one in high dose group), hypertension (1 in group A) and diabetes mellitus (1 in group B). Concomitant medication received along with amphotericin B for coexisting diseases in both the groups were antitubercular therapy, cotrimoxazole, antiviral therapy and premedications such as Ondansetran, Domperidone, Diclofenac, Mannitol, Dexamethazone and Pheniramine. Comparison between the groups showed that the cure rate is similar in both the groups ( P =0.440, where as over all mortality was higher in low dose group than in high dose group which was statistically significant ( P =0.03). Adverse effects were higher in high dose group than in low dose group such as hypokalemia ( P =0.04), facial puffiness ( P =0.01). Other adverse effects were comparable in both the groups.
Conclusion: High dose of amphotericin B therapy is more efficacious. However hypokalemia and clinical features of nephrotoxicity was higher with patients on high dose therapy, which can be managed by proper monitoring.

Keywords
Amphotericin B, cryptococal meningitis, human immunodeficiency virus, hypokalemia