Standardized electrolyte supplementation and fluid management improves survival during amphotericin therapy for cryptococcal meningitis in resource-limited settings

Nathan C. Bahr, Melissa A. Rolfes, Abdu Musubire, Henry Nabeta, Darlisha A. Williams, Joshua Rhein, Andrew Kambugu, David B. Meya, David R. Boulware

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21 Scopus citations


Background. Amphotericin B is the preferred treatment for cryptococcal meningitis, but it has cumulative severe side effects, including nephrotoxicity, hypokalemia, and hypomagnesemia. Amphotericin-induced severe hypokalemia may predispose the patient to cardiac arrhythmias and death, and there is very little data available regarding these toxicities in resource-limited settings. We hypothesized that standardized electrolyte management during amphotericin therapy is essential to minimize toxicity and optimize survival in sub-Saharan Africa. Methods. Human immunodeficiency virus-infected, antiretroviral therapy naive adults with cryptococcal meningitis were prospectively enrolled at Mulago Hospital in Kampala, Uganda in 3 sequential cohorts with amphotericin B deoxycholate induction treatment. Intravenous fluid use was intermittent in 2001-2002, and universal in 2006-2012. In 2001-2009, serum potassium (K+) was monitored on days 1, 7, and 14 of treatment with replacement (K+, Mg2+) per clinician discretion. In 2011-2012, K+ was measured on days 1, 5, and approximately every 48 hours thereafter with universal electrolyte (K+, Mg2+) supplementation and standardized replacement. Clinical outcomes were retrospectively compared between fluid and electrolyte management strategies. Results. With limited intravenous fluids, the 14-day survival was 49% in 2001-2002.With universal intravenous fluids, the 30-day survival improved to 62% in 2006-2010 (P = .003). In 2011-2012, with universal supplementation of fluids and electrolytes, 30-day cumulative survival improved to 78% (P = .021 vs 2006-2010 cohort). The cumulative incidence of severe hypokalemia (<2.5 mEq/L) decreased from 38% in 2010 to 8.5% in 2011-2012 with universal supplementation (P < .001). Conclusions. Improved survival was seen in a resource-limited setting with proactive fluid and electrolyte management (K+, Mg2+), as part of comprehensive amphotericin-based cryptococcal therapy.

Original languageEnglish (US)
JournalOpen Forum Infectious Diseases
Issue number2
StatePublished - Sep 1 2014

Bibliographical note

Funding Information:
Acknowledgments We thank support and input from Drs. Thomas Harrison, Tihana Bicanic, Graeme Meintjes, Yukari Manabe, Radha Rajasingham, Paul Bohjanen, and Melanie Lo, as well as Ali El Bireer, and the MU-JHU laboratory staff. We thank Dr. Meagan O''Brien for clinical care in 2001-2002, and Dr. Merle Sande for mentorship. We also thank the Accordia Global Health Foundation for support of the Infectious Disease Institute. Financial support. This work was supported by the National Institute of Allergy and Infectious Diseases and Fogarty International Center at the National Institutes of Health (K23AI073192, U01AI089244, R25TW009345, T32AI055433) and the University of Minnesota Foundation.

Publisher Copyright:
© The Author 2014.


  • Amphotericin
  • Cryptococcal meningitis
  • Potassium
  • Side effect


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