Prevalence and Hospital Management of Amphotericin B Deoxycholate-Related Toxicities during Treatment of HIV-Associated Cryptococcal Meningitis in South Africa.

Susan Meiring,Nelesh P Govender,Ranmini Kularatne,Halima Dawood,Melony Fortuin-De Smidt,Germs-Sa

doi:10.1371/journal.pntd.0004865

Abstract

BackgroundWe aimed to establish the prevalence of amphotericin B deoxycholate (AmBd)-related toxicities among South African patients with cryptococcosis and determine adherence to international recommendations to prevent, monitor and manage AmBd-related toxicities.MethodsClinical data were collected from cases of laboratory-confirmed cryptococcosis at 25 hospitals, October 2012 –February 2013. Anemia was defined as hemoglobin (Hb) concentration <10 g/dl, hypokalemia as serum potassium (K) <3.4 mEq/L and nephrotoxicity as an increase in serum creatinine (Cr) to >1.1 times the upper limit of normal. To determine adherence to toxicity prevention recommendations, we documented whether baseline Hb, K and Cr tests were performed, whether pre-emptive hydration and IV potassium chloride (KCl) was administered prior to 80% and 60% of AmBd doses and whether daily oral KCl supplementation was given ≥60% of the time. To determine adherence to monitoring recommendations, we ascertained whether a daily fluid chart was completed, Hb was monitored weekly and K or Cr were monitored bi-weekly.ResultsOf 846 patients, clinical data were available for 76% (642/846), 82% (524/642) of whom received AmBd. Sixty-four per cent (n = 333) had documented baseline laboratory tests, 40% (n = 211) were given pre-emptive hydration and 14% (n = 72) and 19% (n = 101) received intravenous and oral KCl. While on AmBd, 88% (n = 452) had fluid monitoring; 27% (n = 142), 45% (n = 235) and 44% (n = 232) had Hb, K and Cr levels monitored. Toxicities developed frequently during treatment: anemia, 16% (86/524); hypokalemia, 43% (226/524) and nephrotoxicity, 32% (169/524).ConclusionAmBd-related toxicities occurred frequently but were potentially preventable with adequate monitoring, supplemental fluid and electrolyte therapies.

Highlights

Cryptococcus neoformans is a leading cause of meningitis among severely immunocompromised HIV-infected adults and even with amphotericin B-based therapy, the mortality is high [1,2,3]
Of 846 patients, clinical data were available for 76% (642/846), 82% (524/642) of whom received amphotericin B deoxycholate (AmBd)
The President’s Emergency Plan for AIDS Relief (PEPFAR) funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Summary

Introduction

Cryptococcus neoformans is a leading cause of meningitis among severely immunocompromised HIV-infected adults and even with amphotericin B-based therapy, the mortality is high [1,2,3]. Since publication of recommendations by the South African HIV Clinicians’ Society (SAHIVCS) in 2007, the proportion of patients treated with AmBd-based therapy for CM has increased from 30% to 80% [7,8,9,10]. Despite this increase, there has been no associated decrease in the in-hospital CFR which has remained between 31% and 34% since 2007[11, 12]. We aimed to establish the prevalence of amphotericin B deoxycholate (AmBd)-related toxicities among South African patients with cryptococcosis and determine adherence to international recommendations to prevent, monitor and manage AmBd-related toxicities.

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