Publication: Toxicity of amphotericin B deoxycholate-based induction therapy in patients with HIV-associated cryptococcal meningitis
Issued Date
2015-12-01
Resource Type
ISSN
10986596
00664804
00664804
Other identifier(s)
2-s2.0-84954556704
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Mahidol University
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SCOPUS
Bibliographic Citation
Antimicrobial Agents and Chemotherapy. Vol.59, No.12 (2015), 7224-7231
Suggested Citation
Tihana Bicanic, Christian Bottomley, Angela Loyse, Annemarie E. Brouwer, Conrad Muzoora, Kabanda Taseera, Arthur Jackson, Jacob Phulusa, Mina C. Hosseinipour, Charles Van Der Horst, Direk Limmathurotsakul, Nicholas J. White, Douglas Wilson, Robin Wood, Graeme Meintjes, Thomas S. Harrison, Joseph N. Jarvis Toxicity of amphotericin B deoxycholate-based induction therapy in patients with HIV-associated cryptococcal meningitis. Antimicrobial Agents and Chemotherapy. Vol.59, No.12 (2015), 7224-7231. doi:10.1128/AAC.01698-15 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/36247
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Title
Toxicity of amphotericin B deoxycholate-based induction therapy in patients with HIV-associated cryptococcal meningitis
Author(s)
Other Contributor(s)
St George's University of London
London School of Hygiene & Tropical Medicine
St. Elisabeth Ziekenhuis
Mbarara University of Science and Technology
University of North Carolina Project
Mahidol University
Nuffield Department of Clinical Medicine
Edendale Hospital
University of Cape Town
Botswana-UPenn Partnership
University of Pennsylvania
London School of Hygiene & Tropical Medicine
St. Elisabeth Ziekenhuis
Mbarara University of Science and Technology
University of North Carolina Project
Mahidol University
Nuffield Department of Clinical Medicine
Edendale Hospital
University of Cape Town
Botswana-UPenn Partnership
University of Pennsylvania
Abstract
Copyright © 2015 Bicanic et al. Amphotericin B deoxycholate (AmBd) is the recommended induction treatment for HIV-associated cryptococcal meningitis (CM). Its use is hampered by toxicities that include electrolyte abnormalities, nephrotoxicity, and anemia. Protocols to minimize toxicity are applied inconsistently. In a clinical trial cohort of AmBd-based CM induction treatment, a standardized protocol of preemptive hydration and electrolyte supplementation was applied. Changes in blood counts, electrolyte levels, and creatinine levels over 14 days were analyzed in relation to the AmBd dose, treatment duration (short course of 5 to 7 days or standard course of 14 days), addition of flucytosine (5FC), and outcome. In the 368 patients studied, the hemoglobin levels dropped by a mean of 1.5 g/dl (95% confidence interval [CI], 1.0 to 1.9 g/dl) following 7 days of AmBd and by a mean of 2.3 g/dl (95% CI, 1.1 to 3.6 g/dl) after 14 days. Serum creatinine levels increased by 37 μmol/liter (95% CI, 30 to 45 μmol/liter) by day 7 and by 49 μmol/liter (95% CI, 35 to 64μmol/liter) by day 14 of AmBd treatment. Overall, 33% of patients developed grade III/IV anemia, 5.6% developed grade III hypokalemia, 9.5% had creatinine levels that exceeded 220 μmol, and 6% discontinued AmBd prematurely. The addition of 5FC was associated with a slight increase in anemia but not neutropenia. Laboratory abnormalities stabilized or reversed during the second week in patients on short-course induction. Grade III/IV anemia (adjusted odds ratio [aOR], 2.2; 95% CI, 1.1 to 4.3; = 0.028) and nephrotoxicity (aOR, 4.5; 95% CI, 1.8 to 11; = 0.001) were risk factors for 10-week mortality. In summary, routine intravenous saline hydration and preemptive electrolyte replacement during AmBd-based induction regimens for HIV-associated CM minimized the incidence of hypokalemia and nephrotoxicity. Anemia remained a concerning adverse effect. The addition of flucytosine was not associated with increased neutropenia. Shorter AmBd courses were less toxic, with rapid reversibility.