TY - JOUR
T1 - A systematic review of the antifungal effectiveness and tolerability of amphotericin B formulations
AU - Barrett, Jane P.
AU - Vardulaki, Katerina A.
AU - Conlon, Christopher
AU - Cooke, Jonathan
AU - Daza-Ramirez, Pascual
AU - Evans, E. Glyn V.
AU - Hawkey, Peter M.
AU - Herbrecht, Raoul
AU - Marks, David I.
AU - Moraleda, Jose M.
AU - Park, Gilbert R.
AU - Senn, Stephen J.
AU - Viscoli, Claudio
N1 - Funding Information:
‘Jane Bawett Teaching and Consultancy, Cambridge, *The Audit Commission, London, 3Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, 4Department of Pharmacy, Withington Hospital, South Manchester University Hospitals National Health Service Trust, Manchester, 5EIan Pharma Ltd., Stevenage, Herts, 6Welsh Mycology Reference Unit, Department of Medical Microbiology and Public Health Laboratory, University Hospital of Wales, Cardif, 7Public Health Laboratory Birmingham Heartlands Hospital, Birmingham, United Kingdom, ‘Department of Hematology and Oncology, Hapita de Hautepierre, Strasbourg, France, gBristol Royal Hospital for Children, Bristol, United Kingdom, ‘OJefeC linico, Unidad de Trasplante de Medula Osea, Hospital Morales Meseguel; Murcia, Spain, “Addenbrooke’s Hospital, Cambridge, 12Department of Statistical Science and Department of Epidemiology and Public Health, University College London, London, United Kingdom, and ‘“University of Genova and National Institutefor Cancer Research, Genova, Italy
PY - 2003/5/1
Y1 - 2003/5/1
N2 - Objective: A systematic review was performed to compare the effectiveness and tolerability of lipid-based amphotericin B (AmB) formulations and conventional AmB in the treatment of systemic fungal infections. Methods: The literature and unpublished studies were searched using MEDLINE, EMBASE, Biological Abstracts, AIDSLINE, CANCERLIT, CRD database, Cochrane Controlled Trials Register, and other databases. Search terms included: amphotericin, liposom*, lipid*, colloid*, antifungal agents, and mycoses. Studies were selected according to predetermined criteria. The outcome measures reviewed were efficacy, mortality, renal toxicity, and infusion-related reactions. Meta-analyses and number-needed-to-treat (NNT) analyses were performed. Results: Seven studies (8 publications) met the entry criteria. Meta-analysis showed that lipid-based formulations significantly reduced all-cause mortality risk by an estimated 28% compared with conventional AmB (odds ratio [OR], 0.72; 95% CI, 0.54 to 0.97). There was no significant difference in efficacy between the lipid-based formulations and conventional AmB (OR, 1.21; 95% CI, 0.98 to 1.49). AmB lipid complex (ABLC) and liposomal AmB (L-AmB) significantly reduced the risk of doubling serum creatinine by an estimated 58% (OR, 0.42; 95% CI, 0.33 to 0.54). There was no significant reduction in risk of infusion-related reactions with lipid-based formulations, although this was difficult to interpret given the lack of consistent control of confounding factors. Comparing the lipid-based formulations with conventional AmB, the overall NNT to prevent 1 death was 31. The NNT to prevent a doubling of serum creatinine for both ABLC and L-AmB compared with conventional AmB was 6. Conclusions: This study demonstrates advantages with lipid-based formulations over conventional AmB in terms of reduced risk of mortality and renal toxicity. Future trials in patients with proven fungal infection should control for factors such as premedication, infusion rates, fluid preloading, sodium/potassium supplementation, and concomitant medication.
AB - Objective: A systematic review was performed to compare the effectiveness and tolerability of lipid-based amphotericin B (AmB) formulations and conventional AmB in the treatment of systemic fungal infections. Methods: The literature and unpublished studies were searched using MEDLINE, EMBASE, Biological Abstracts, AIDSLINE, CANCERLIT, CRD database, Cochrane Controlled Trials Register, and other databases. Search terms included: amphotericin, liposom*, lipid*, colloid*, antifungal agents, and mycoses. Studies were selected according to predetermined criteria. The outcome measures reviewed were efficacy, mortality, renal toxicity, and infusion-related reactions. Meta-analyses and number-needed-to-treat (NNT) analyses were performed. Results: Seven studies (8 publications) met the entry criteria. Meta-analysis showed that lipid-based formulations significantly reduced all-cause mortality risk by an estimated 28% compared with conventional AmB (odds ratio [OR], 0.72; 95% CI, 0.54 to 0.97). There was no significant difference in efficacy between the lipid-based formulations and conventional AmB (OR, 1.21; 95% CI, 0.98 to 1.49). AmB lipid complex (ABLC) and liposomal AmB (L-AmB) significantly reduced the risk of doubling serum creatinine by an estimated 58% (OR, 0.42; 95% CI, 0.33 to 0.54). There was no significant reduction in risk of infusion-related reactions with lipid-based formulations, although this was difficult to interpret given the lack of consistent control of confounding factors. Comparing the lipid-based formulations with conventional AmB, the overall NNT to prevent 1 death was 31. The NNT to prevent a doubling of serum creatinine for both ABLC and L-AmB compared with conventional AmB was 6. Conclusions: This study demonstrates advantages with lipid-based formulations over conventional AmB in terms of reduced risk of mortality and renal toxicity. Future trials in patients with proven fungal infection should control for factors such as premedication, infusion rates, fluid preloading, sodium/potassium supplementation, and concomitant medication.
KW - Lipid-based amphotericin B
KW - Meta-analysis
KW - Mortality
KW - Systematic review
UR - http://www.scopus.com/inward/record.url?scp=0038282815&partnerID=8YFLogxK
U2 - 10.1016/S0149-2918(03)80125-X
DO - 10.1016/S0149-2918(03)80125-X
M3 - Review article
AN - SCOPUS:0038282815
SN - 0149-2918
VL - 25
SP - 1295
EP - 1320
JO - Clinical Therapeutics
JF - Clinical Therapeutics
IS - 5
ER -