Comparison of posaconazole versus weekly amphotericin B lipid complex for the prevention of invasive fungal infections in hematopoietic stem-cell transplantation

Background: Antifungal prophylaxis is shown to decrease the risk of invasive fungal infection (IFI) after hematopoietic stem-cell transplantation (HSCT). Posaconazole has been approved for prophylaxis in HSCT. However, it is only available orally given three times per day. We evaluated once weekly intravenous amphotericin B lipid complex (ABLC), given its broad-spectrum antifungal activity and prolonged half-life (172 hr), as an alternative prophylaxis in HSCT. Methods: We prospectively randomized allogeneic HSCT patients to receive 7.5 mg/kg of intravenous ABLC weekly or 200 mg of posaconazole orally three times per day as prophylaxis for up to 6 weeks. Endpoints were the incidence of IFI and drug-related toxicities. ABLC was discontinued if creatinine level increased to two times the baseline or greater. Results: A total of 46 patients were randomized; 40 received at least one dose of the drug and were included in the analysis: 19 received ABLC and 21 received posaconazole. All patients received tacrolimus. Apache II score, neutropenia, and creatinine, bilirubin, and alanine aminotransferase levels were similar in both groups at baseline. One patient in the ABLC arm and none in posaconazole arm developed IFI (5% vs. 0%, P=0.48). More patients in the ABLC arm doubled their serum creatinine (53% vs. 5%, P=0.001) necessitating discontinuation of the study drug. CONCLUSION: High-dose prophylactic ABLC in HSCT was associated with nephrotoxicity that could be aggravated by the concomitant use of other nephrotoxic agents. Further studies are needed to evaluate the role of weekly high-dose ABLC as antifungal prophylaxis in patients at lower risk for nephrotoxicity.