This site needs JavaScript to work properly. Please enable it to take advantage of the complete set of features!
Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

NIH NLM Logo
Log in
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2015 Dec;59(12):7224-31.
doi: 10.1128/AAC.01698-15. Epub 2015 Sep 8.

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

Affiliations
Clinical Trial

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

Tihana Bicanic et al. Antimicrob Agents Chemother. 2015 Dec.

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.

PubMed Disclaimer

Figures

FIG 1
FIG 1
Individual data points and fitted LOESS curves for hemoglobin values over the first 14 days of antifungal therapy. (a) All patients receiving 14 days of AmB-based induction therapy. (b) Plot by AmB duration (short-course versus standard treatment). (c) Plot by sex. The broken line indicates a DAIDS grade IV adverse-event threshold of 6.5 g/dl.
FIG 2
FIG 2
Individual data points and fitted LOESS curves for creatinine values over the first 14 days of antifungal therapy. (a) All patients receiving 14 days of AmB-based induction therapy. (b) Plot by AmB dose (0.7 versus 1 mg/kg/day). (c) Plot by AmB duration (short-course versus standard treatment). The broken line indicates a threshold of 220 μmol/liter (protocol definition of nephrotoxicity).

References

    1. Gallis HA, Drew RH, Pickard WW. 1990. Amphotericin B: 30 years of clinical experience. Rev Infect Dis 12:308–329. doi:10.1093/clinids/12.2.308. - DOI - PubMed
    1. Dismukes WE, Cloud G, Gallis HA, Kerkering TM, Medoff G, Craven PC, Kaplowitz LG, Fisher JF, Gregg CR, Bowles CA. 1987. Treatment of cryptococcal meningitis with combination amphotericin B and flucytosine for four as compared with six weeks. N Engl J Med 317:334–341. doi:10.1056/NEJM198708063170602. - DOI - PubMed
    1. Bennett JE, Dismukes WE, Duma RJ, Medoff G, Sande MA, Gallis H, Leonard J, Fields BT, Bradshaw M, Haywood H. 1979. A comparison of amphotericin B alone and combined with flucytosine in the treatment of cryptoccal [sic] meningitis. N Engl J Med 301:126–131. doi:10.1056/NEJM197907193010303. - DOI - PubMed
    1. Atkinson AJ, Bennett JE. 1978. Amphotericin B pharmacokinetics in humans. Antimicrob Agents Chemother 13:271–276. doi:10.1128/AAC.13.2.271. - DOI - PMC - PubMed
    1. Larsen RA, Leal MAE, Chan LS. 1990. Fluconazole compared with amphotericin B plus flucytosine for cryptococcal meningitis in AIDS. A randomized trial. Ann Intern Med 113:183–187. doi:10.7326/0003-4819-113-3-183. - DOI - PubMed

Publication types

MeSH terms

Full text links
Atypon full text link Atypon Free PMC article
Cite

AltStyle によって変換されたページ (->オリジナル) /