The Journal of antimicrobial chemotherapy · 2025
Liposomal amphotericin B prophylaxis in paediatrics: a systematic review.
СтатьяСистематический обзорНазвание и аннотация: Перевод в очереди
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Thorley Emma V, Hatch Jennifer, Li Monica, Mashida Sharlene N, Castagnola Elio, Mesini Alessio, Lehrnbecher Thomas, Groll Andreas H, Warris Adilia, Ferreras-Antolin Laura
Аннотация
BACKGROUND: Liposomal amphotericin B (LAmB) is widely used for prophylaxis in paediatric patients at high risk of invasive fungal diseases (IFD) but its use is off-label and there is significant variability in dosage and frequency. This systematic review was conducted to evaluate the published data on prophylactic LAmB use in the paediatric population and to present the reported proportions of breakthrough IFD and the associated toxicity profile.
METHODS: EMBASE, Medline, Web of Science and the Cochrane Database were systematically searched for primary research reporting on the use of LAmB as prophylaxis for IFD in the paediatric population up to 7 December 2023, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
RESULTS: Twenty studies, comprising three clinical trials, 12 cohort studies, two point-prevalence surveys and three pharmacokinetic (PK) studies, with 2015 patients were included. A total of 717 cases presented individual patient data. Breakthrough IFD occurred in 7.2% (49/676). The most recognized side effects were hypokalaemia in 23.2% (125/538) and derangement of liver function tests in 15.0% (49/327). Discontinuation due to toxicity occurred in 6.0% (30/503) of patients. Of the four studies reporting PK data, two examined serum levels of LAmB, one analysed CSF levels and the remaining study peritoneal levels.
CONCLUSIONS: Despite widespread use of prophylactic LAmB, this systematic review highlights the paucity of paediatric data supporting its use. The heterogeneity observed in populations, dosing regimens and study design prevents conclusions being reached on its efficacy or the superiority of one dosing regimen. Overall, there is a clear need for further high-quality robust clinical data and targeted PK studies.
METHODS: EMBASE, Medline, Web of Science and the Cochrane Database were systematically searched for primary research reporting on the use of LAmB as prophylaxis for IFD in the paediatric population up to 7 December 2023, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
RESULTS: Twenty studies, comprising three clinical trials, 12 cohort studies, two point-prevalence surveys and three pharmacokinetic (PK) studies, with 2015 patients were included. A total of 717 cases presented individual patient data. Breakthrough IFD occurred in 7.2% (49/676). The most recognized side effects were hypokalaemia in 23.2% (125/538) and derangement of liver function tests in 15.0% (49/327). Discontinuation due to toxicity occurred in 6.0% (30/503) of patients. Of the four studies reporting PK data, two examined serum levels of LAmB, one analysed CSF levels and the remaining study peritoneal levels.
CONCLUSIONS: Despite widespread use of prophylactic LAmB, this systematic review highlights the paucity of paediatric data supporting its use. The heterogeneity observed in populations, dosing regimens and study design prevents conclusions being reached on its efficacy or the superiority of one dosing regimen. Overall, there is a clear need for further high-quality robust clinical data and targeted PK studies.