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Toxicity of Amphotericin B Deoxycholate-Based Induction Therapy in Patients with HIV-Associated Cryptococcal Meningitis.

Bicanic, T; Bottomley, C; Loyse, A; Brouwer, AE; Muzoora, C; Taseera, K; Jackson, A; Phulusa, J; Hosseinipour, MC; van der Horst, C; et al. Bicanic, T; Bottomley, C; Loyse, A; Brouwer, AE; Muzoora, C; Taseera, K; Jackson, A; Phulusa, J; Hosseinipour, MC; van der Horst, C; Limmathurotsakul, D; White, NJ; Wilson, D; Wood, R; Meintjes, G; Harrison, TS; Jarvis, JN (2015) Toxicity of Amphotericin B Deoxycholate-Based Induction Therapy in Patients with HIV-Associated Cryptococcal Meningitis. Antimicrobial Agents and Chemotherapy, 59 (12). pp. 7224-7231. https://doi.org/10.1128/AAC.01698-15
SGUL Authors: Harrison, Thomas Stephen Jarvis, Joseph Nicholas Bicanic, Tihana Loyse, Angela

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Abstract

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; P = 0.028) and nephrotoxicity (aOR, 4.5; 95% CI, 1.8 to 11; P = 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.

Item Type: Article
Additional Information: Copyright © 2015 Bicanic et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 3.0 Unported license.
Keywords: Microbiology, 0605 Microbiology, 1108 Medical Microbiology, 1115 Pharmacology And Pharmaceutical Sciences
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: Antimicrobial Agents and Chemotherapy
Language: eng
Dates:
DateEvent
8 September 2015Published
Publisher License: Creative Commons: Attribution 3.0
Projects:
Project IDFunderFunder ID
093956Wellcome Trusthttp://dx.doi.org/10.13039/100004440
098316Wellcome Trusthttp://dx.doi.org/10.13039/100004440
2-D43 TW01039Fogarty International Centerhttp://dx.doi.org/10.13039/100000061
G0501476Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
P30-AI50410National Institute of Allergy and Infectious Diseaseshttp://dx.doi.org/10.13039/100000060
WT 081794Wellcome Trusthttp://dx.doi.org/10.13039/100004440
WT 089966Wellcome Trusthttp://dx.doi.org/10.13039/100004440
PubMed ID: 26349818
Web of Science ID: WOS:000368337300008
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/107664
Publisher's version: https://doi.org/10.1128/AAC.01698-15

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