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. 2016 Jul 28;10(7):e0004865.
doi: 10.1371/journal.pntd.0004865. eCollection 2016 Jul.

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

Susan Meiring  1 , Melony Fortuin-de Smidt  1   2 , Ranmini Kularatne  2   3 , Halima Dawood  4 , Nelesh P Govender  1   2   5 ; GERMS-SA
Affiliations

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

Susan Meiring et al. PLoS Negl Trop Dis. .

Abstract

Background: 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.

Methods: Clinical 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.

Results: Of 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).

Conclusion: AmBd-related toxicities occurred frequently but were potentially preventable with adequate monitoring, supplemental fluid and electrolyte therapies.

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Conflict of interest statement

I have read the journal's policy and the authors of this manuscript have the following competing interests: NPG has received speaker honoraria/ travel grants from Pfizer, Astellas and MSD (Pty) Ltd; has been the recipient of an investigator-initiated research grant from Pfizer for unrelated work; has provided educational materials for TerraNova; and has acted a temporary consultant for Fujifilm Pharmaceuticals. HD has received honoraria from Pfizer-South Africa, Novartis-South Africa and MSD-South Africa for speaking engagements; and travel grants from Novartis-South Africa and Myalan-South Africa. The remaining authors have no conflicts of interest to declare.

Figures

Fig 1
Fig 1. Enrolment of patients with cryptococcosis from 25 enhanced surveillance sites into the nested cross-sectional study, October 2012 through February 2013.
Footnote: AmBd: amphotericin B deoxycholate. *Other reason: 10 (8%) no antifungal therapy was given; 3 (3%) AmBd was out of stock
See this image and copyright information in PMC

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