1438. Routine Electrolyte Supplementation Improves Survival During Amphotericin Therapy for Cryptococcal Meningitis in Resource-Limited Settings
Session: Poster Abstract Session: Fungal Infections
Saturday, October 5, 2013
Room: The Moscone Center: Poster Hall C
  • IDSA 2013 Poster final.pdf (1.3 MB)
  • Background: Amphotericin B is the preferred treatment for cryptococcal meningitis (CM); however, amphotericin has cumulative severe side effects, including nephrotoxicity that may manifest as hypokalemia, hypomagnesemia, and anemia.  In resource-limited settings, amphotericin-induced severe hypokalemia may predispose to cardiac arrhythmias and death.  We hypothesized that intravenous (IV) fluid and electrolyte management during amphotericin therapy is an essential component of care to minimize toxicity and optimize survival.

    Methods: HIV-infected, antiretroviral therapy (ART)-naïve adults with CM were prospectively enrolled at Mulago Hospital in Kampala, Uganda in three sequential cohorts with amphotericin-based induction treatment.  IV fluids use was intermittent in 2001-02 (n=92), and universal in 2006-10 (n=182) and 2011-12 (n=50).  In 2001-2010 electrolytes were monitored at day 1,7,14 of amphotericin with replacement (K+, Mg2+) per clinician discretion. In 2011-2012, electrolytes were monitored beginning on day 1 of amphotericin and approximately every 48 hours thereafter with universal supplementation and standardized replacement. Mortality outcomes were compared between time periods.

    Results: When limited IV fluids were available and intermittent shortages occurred, the 14-day survival was 55% (50/91) in 2001-02.  With universal provision of IV fluids, the 28-day survival was 63% (115/182). In 2011-12, with universal supplementation of fluids and electrolytes the 28-day survival improved to 82% (41/50) (log-rank from Kaplan-Meier Curve P=0.016). Routine electrolyte and fluid supplementation had overwhelming cost-benefit at $224.84 (95% CI: $134.03 to 697.38) per life saved, number needed to treat 5.32 (95% CI 3.17-16.49) when comparing the 2011 cohort with the 2006 cohort.

    Conclusion: Fluid and electrolyte management is an important aspect of cryptococcal meningitis therapy to reduce amphotericin-related toxicity. While unmeasured differences between the three cohort time periods may exist, we believe management of amphotericin toxicity is a vital aspect of care to improve cryptococcal survival in resource limited settings.

    Nathan Bahr, MD1, Melissa Rolfes, MPH1, Abdu Musubire, MMed2, Henry Nabeta, MBChB2, Darlisha Williams, MPH1, David Meya, MMed2 and David Boulware, MD, MPH1, (1)University of Minnesota, Minneapolis, MN, (2)Infectious Diseases Institute, Makerere University, Kampala, Uganda


    N. Bahr, None

    M. Rolfes, None

    A. Musubire, None

    H. Nabeta, None

    D. Williams, None

    D. Meya, None

    D. Boulware, None

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