Continuous infusion of amphotericin B deoxycholate in the treatment of cryptococcal meningoencephalitis: analysis of safety and fungicidal activity

Falci D.R., Lunardi L., Ramos C.G., Aquino V.R., Goldani L.Z.

Author address: 

NULL

Abstract: 

Objective: Cryptococcosis is a deep mycosis commonly seen in immunocompromised hosts. The mainstay of treatment remains amphotericin B deoxycholate, which is associated with nephrotoxicity and other adverse events. New lipid formulations provide a good solution to toxicity concerns. Reduction in nephrotoxicity and side effects can be explained by slower drug distribution in tissues. However, costs of these formulations are prohibitive. In this scenario, continuous infusion of amphotericin B deoxycholate for the treatment of serious fungal infections like cryptococcosis could reveal a promising strategy. Our objective in this study is to evaluate safety, clinical and microbiological efficacy of continuous infusion of amphotericin B deoxycholate in treatment of cryptococcal meningoencephalitis. Methods: Non-comparative clinical trial, including patients with disseminated cryptococcosis. All patients received continuous infusion of amphotericin B deoxycholate (0.7mg/kg daily) and oral flucytosine (25mg/kg four times a day), during induction phase of 14 days. We measured fungicidal activity using serial quantitative cultures of cerebrospinal fluid (CSF) obtained from lumbar punctures in days 0, 3, 7 and 14 of treatment. We monitored patients in hospital for 2 weeks. At this time of study, 6 patients have been included. Results: Analysis of data on 6 patients has shown that all patients presented a progressive reduction in CSF cryptococcal colony-forming units (CFU), and LCR was sterile at 2 weeks of treatment. An exponential reduction of CFU counts was observed (figure 1). Although two patients developed severe hypokalemia, glomerular renal function was well preserved in all patients with creatinine serum levels below 1.5 mg/dl at end of 14 days of antifungal therapy. We observed the occurrence of anaemia (decrease of hemoglobin at least of 3g/dL) in 3 patients. Conclusions: The preliminary data presented here are indicating that continuous infusion of amphotericin B seems to be safe and well tolerated, despite the development of anaemia and hypokalemia in some patients. Mycological efficacy was comparable as standard of treatment, with adequate reduction rate of CFU and sterilization of CSF. These results could suggest that continuous infusion reduces nephrotoxicity while keeping fungicidal activity. Larger and comparative trials, against new lipid formulations and even novel antifungal agents, are necessary to further
2009

abstract No: 

P 1741

Full conference title: 

19th European Congress of Clinical Microbiology and Infectious Diseases
    • ECCMID 19th (2009)