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Continuous infusion of escalated doses of amphotericin B deoxycholate: an open-label observational study
Alexander Imhof1, Roland B Walter, Andreas Schaffner
1Department of Internal Medicine, Medical Clinic B, University Hospital, Zürich, Switzerland. aimhof@fhcrc.org
Abstract:
Amphotericin B deoxycholate (AmB-d) remains a mainstay of antifungal therapy for immunocompromised patients, despite being associated with significant therapy-related toxicity. Because continuous infusion of AmB-d is better tolerated than traditional administration over 2-6 hours, we evaluated escalation of the AmB-d dose in 33 patients (31 of whom were neutropenic), for whom the initial dosage of AmB-d (1 mg/kg/day) was gradually increased to 2.0 mg/kg/day when renal function remained stable and the drug was tolerated. Dose escalation was possible without delay in 28 patients. Median duration of AmB-d therapy was 16 days (range, 7-72 days). Infusion-related reactions accompanied <18% of AmB-d infusions. Twenty-seven patients had a decrease in creatinine clearance while receiving AmB-d therapy. A >2-fold decrease in creatine clearance was observed in 5 patients, and the decrease was dose-limiting in only 1 patient; no dialysis was required. In conclusion, continuous infusion of AmB-d escalated to 2.0 mg/kg/day seems not to cause additional impairment of vital organ functions and to be well tolerated by most patients.
Insights
Continuous infusion of Amphotericin B deoxycholate (AmB-d) escalated to 2.0 mg/kg/day is well-tolerated by most immunocompromised patients. This dosing strategy did not significantly impair vital organ functions, offering a safer antifungal treatment option.
Area of Science:
- Mycology
- Pharmacology
- Infectious Diseases
Background:
- Amphotericin B deoxycholate (AmB-d) is a critical antifungal agent for immunocompromised individuals.
- AmB-d is associated with significant toxicity, limiting its use.
- Continuous infusion may improve AmB-d tolerability compared to intermittent administration.
Purpose of the Study:
- To evaluate the safety and tolerability of escalating AmB-d doses up to 2.0 mg/kg/day via continuous infusion.
- To assess the impact of escalated AmB-d dosing on renal function in patients requiring antifungal therapy.
Main Methods:
- A prospective study involving 33 immunocompromised patients, primarily neutropenic.
- Gradual dose escalation of AmB-d from 1 mg/kg/day to 2.0 mg/kg/day based on renal function and drug tolerance.
- Monitoring of infusion-related reactions and changes in creatinine clearance throughout therapy.
Main Results:
- Dose escalation to 2.0 mg/kg/day was achievable in 28 of 33 patients.
- Infusion-related reactions occurred in less than 18% of infusions.
- While 27 patients experienced decreased creatinine clearance, only 1 required dose limitation, and no dialysis was needed.
Conclusions:
- Continuous infusion of AmB-d, escalated to 2.0 mg/kg/day, appears to be a safe and well-tolerated antifungal treatment strategy.
- This approach may allow for higher AmB-d dosing without additional significant impairment of vital organ functions.
- Further research could support the use of escalated AmB-d doses in specific patient populations.