Document Detail

The epidemiology of nephrotoxicity associated with conventional amphotericin B therapy.
MedLine Citation:
PMID:  11705428     Owner:  NLM     Status:  MEDLINE    
PURPOSE: We sought to quantify the incidence of, define risk factors for, and examine the relation between renal functional impairment and treatment with conventional amphotericin B. SUBJECTS AND METHODS: We performed a 9-year retrospective analysis of amphotericin B-associated nephrotoxicity in 494 adult inpatients who received > or = 2 doses of amphotericin B. Nephrotoxicity was classified according to two nonmutually exclusive severity categories (50% increase or doubling in the baseline creatinine level). RESULTS: The median cumulative dosage of amphotericin B was 240 mg (interquartile range, 113 to 500 mg), with the majority of patients (n = 361) receiving it for empiric treatment. Overall, 139 (28%) patients experienced renal toxicity, including 58 (12%) with moderate-to-severe nephrotoxicity. The rate of nephrotoxicity was relatively constant during amphotericin B treatment. For each 10-mg increase in the mean daily amphotericin B dose, the adjusted rate of renal toxicity increased by a factor of 1.13 (95% confidence interval: 1.02 to 1.25). We defined 5 categorical risk factors: mean daily amphotericin B dose > or = 35 mg, male sex, weight > or = 90 kg, chronic renal disease, and use of amikacin or cyclosporine. The incidence of moderate-to-severe nephrotoxicity was 4% (6 of 137) in patients with none of these risk factors, 8% (14 of 181) in those with 1 risk factor, 18% (21 of 117) in those with 2 risk factors, and 29% (17 of 59) in patients with > or = 3 risk factors. Nephrotoxicity rarely led to hemodialysis (n = 3); however, at the time of discharge or death, 70% of patients with moderate-to-severe nephrotoxicity had a serum creatinine level that was > or = 0.5 mg/dL above baseline. CONCLUSION: Amphotericin B-related nephrotoxicity is an important dose-dependent and duration-dependent toxicity that is accentuated by certain nephrotoxic drugs and patient characteristics. Patients with more than two risk factors for nephrotoxicity are potential candidates for alternative antifungal therapy.
S Harbarth; S L Pestotnik; J F Lloyd; J P Burke; M H Samore
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The American journal of medicine     Volume:  111     ISSN:  0002-9343     ISO Abbreviation:  Am. J. Med.     Publication Date:  2001 Nov 
Date Detail:
Created Date:  2001-11-13     Completed Date:  2001-12-07     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0267200     Medline TA:  Am J Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  528-34     Citation Subset:  AIM; IM    
Division of Infectious Diseases, Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
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MeSH Terms
Amphotericin B / adverse effects*,  therapeutic use
Dose-Response Relationship, Drug
Kidney / drug effects*
Proportional Hazards Models
Retrospective Studies
Risk Factors
Reg. No./Substance:
1397-89-3/Amphotericin B
Comment In:
Am J Med. 2002 Sep;113(4):351   [PMID:  12361831 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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