Liposomal amphotericin B as initial therapy for invasive mold infection: a randomized trial comparing a high-loading
Oliver A Cornely1, Johan Maertens, Mark Bresnik
11st Dept. of Internal Medicine, University of Cologne, Germany. oliver.cornely@uni-koeln.de
Background:
Treatment of invasive mold infection in immunocompromised patients remains challenging. Voriconazole has been shown to have efficacy and survival benefits over amphotericin B deoxycholate, but its utility is limited by drug interactions. Liposomal amphotericin B achieves maximum plasma levels at a dosage of 10 mg/kg per day, but clinical efficacy data for higher doses are lacking.
Methods:
In a double-blind trial, patients with proven or probable invasive mold infection were randomized to receive liposomal amphotericin B at either 3 or 10 mg/kg per day for 14 days, followed by 3 mg/kg per day. The primary end point was favorable (i.e., complete or partial) response at the end of study drug treatment. Survival and safety outcomes were also evaluated.
Results:
Of 201 patients with confirmed invasive mold infection, 107 received the 3-mg/kg daily dose, and 94 received the 10-mg/kg daily dose. Invasive aspergillosis accounted for 97% of cases. Hematological malignancies were present in 93% of patients, and 73% of patients were neutropenic at baseline. A favorable response was achieved in 50% and 46% of patients in the 3- and 10-mg/kg groups, respectively (difference, 4%; 95% confidence interval, -10% to 18%; P>.05); the respective survival rates at 12 weeks were 72% and 59% (difference, 13%; 95% confidence interval, -0.2% to 26%; P>.05). Significantly higher rates of nephrotoxicity and hypokalemia were seen in the high-dose group.
Conclusions:
In highly immunocompromised patients, the effectiveness of 3 mg/kg of liposomal amphotericin B per day as first-line therapy for invasive aspergillosis is demonstrated, with a response rate of 50% and a 12-week survival rate of 72%. The regimen of 10 mg/kg per day demonstrated no additional benefit and higher rates of nephrotoxicity.
Insights
For invasive mold infections in immunocompromised patients, 3 mg/kg of liposomal amphotericin B daily showed effectiveness. Higher doses did not improve outcomes and increased toxicity, indicating the lower dose is preferable.
Area of Science:
- Mycology
- Infectious Diseases
- Pharmacology
Background:
- Invasive mold infections pose significant challenges for immunocompromised patients.
- Voriconazole offers benefits but has drug interaction limitations.
- Liposomal amphotericin B's efficacy at doses exceeding 10 mg/kg/day requires further investigation.
Purpose of the Study:
- To evaluate the efficacy and safety of different doses of liposomal amphotericin B for invasive mold infections.
- To compare a 3 mg/kg/day dose with a 10 mg/kg/day dose of liposomal amphotericin B.
- To assess response rates, survival, and toxicity in a randomized trial.
Main Methods:
- A double-blind trial randomized 201 patients with invasive mold infection to receive liposomal amphotericin B at 3 or 10 mg/kg/day.
- Treatment involved 14 days of the assigned dose, followed by 3 mg/kg/day.
- Primary endpoint was favorable response; survival and safety outcomes were also monitored.
Main Results:
- A favorable response was observed in 50% of the 3 mg/kg group and 46% of the 10 mg/kg group (P>.05).
- Twelve-week survival rates were 72% for the 3 mg/kg group and 59% for the 10 mg/kg group (P>.05).
- The 10 mg/kg/day dose group experienced significantly higher rates of nephrotoxicity and hypokalemia.
Conclusions:
- Liposomal amphotericin B at 3 mg/kg/day is effective as first-line therapy for invasive aspergillosis in highly immunocompromised patients.
- This lower dose achieved a 50% response rate and 72% 12-week survival.
- The 10 mg/kg/day regimen offered no additional benefit and was associated with increased nephrotoxicity.
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