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Safety and Effectiveness of High-dose Liposomal Amphotericin B: A Systematic Review and Meta-analysis
Background:
Although the level of medical care has been improved in recent years, the probability of patients contracting pathogens has increased greatly, with a rising incidence of invasive fungal infections. Deep-seated fungi have become common pathogens of nosocomial infections.
Objective:
This study aims to systematically assess the effectiveness, mortality, survival rate, and adverse reactions (ARs) of high-dose (HD) liposomal amphotericin B (L-AMB) for human diseases.
Methods:
Ten articles (1661 patients) of randomized controlled trials (RCTs; whether randomized, single-blind, or double-blind) from January 1, 1960, to December 31, 2020, of HD-L-AMB treatment of diseases were retrieved from the PubMed, Embase, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials databases. The primary outcome measure was the overall therapeutic effect, and the secondary outcome measures were mortality, ≥10-week survival, and ARs. Data were meta-analyzed using RevMan 5.3.
Results:
Ten RCTs involving 1661 patients were included. HD-L-AMB did not show a significant therapeutic advantage in anti-infection treatment. In addition, HD-L-AMB treatment of invasive Aspergillus infection led to high mortality and low survival (≥10 weeks, OR = 0.57, 95%CI 0.34-0.94, P = .03). According to subgroup analysis, the incidence of ARs and the incidence of renal dysfunction associated with invasive fungal infection treatment were higher with HD-L-AMB than with regular-dose L-AMB.
Conclusion:
HD-L-AMB had no obvious advantage for the treatment of diseases and was accompanied by increased mortality, reduced long-term survival, and increased ARs (including renal insufficiency). Therefore, the use of HD-L-AMB to control infections is recommended with caution only when the preferred treatment is contraindicated.
Insights
High-dose liposomal amphotericin B (HD-L-AMB) shows no significant benefit for treating invasive fungal infections. This high-dose formulation is linked to increased mortality, lower survival rates, and more adverse reactions, including kidney dysfunction.
Area of Science:
- Infectious Diseases
- Pharmacology
- Critical Care Medicine
Background:
- Rising incidence of nosocomial infections and invasive fungal infections.
- Deep-seated fungi are increasingly common causes of hospital-acquired infections.
Purpose of the Study:
- To systematically evaluate the effectiveness, mortality, survival rates, and adverse reactions of high-dose liposomal amphotericin B (HD-L-AMB).
Main Methods:
- Meta-analysis of 10 randomized controlled trials (RCTs) including 1661 patients.
- Studies were retrieved from major databases (PubMed, Embase, Scopus, Web of Science, Cochrane).
- Primary outcome: overall therapeutic effect; Secondary outcomes: mortality, survival, adverse reactions.
Main Results:
- HD-L-AMB did not demonstrate a significant therapeutic advantage in anti-infection treatment.
- Treatment with HD-L-AMB for invasive Aspergillus infection was associated with high mortality and low survival (OR = 0.57).
- Higher incidence of adverse reactions, including renal dysfunction, was observed with HD-L-AMB compared to regular-dose L-AMB.
Conclusions:
- High-dose liposomal amphotericin B offers no clear advantage for treating invasive fungal infections.
- HD-L-AMB is associated with increased mortality, reduced long-term survival, and a higher risk of adverse events, notably renal insufficiency.
- Caution is advised when using HD-L-AMB, particularly when standard treatments are contraindicated.
