title: Prevalence and Hospital Management of Amphotericin B Deoxycholate-Related Toxicities during Treatment of HIV-Associated Cryptococcal Meningitis in South Africa.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  AmBd-related toxicities occurred frequently but were potentially preventable with adequate monitoring, supplemental fluid and electrolyte therapies.
authors.affiliation: National Institute for Communicable Diseases (NICD), a Division of the National Health Laboratory Service (NHLS), Johannesburg, South Africa.
authors.forename: Susan
authors.identifier: 0000-0003-4508-5469
authors.initials: S
authors.lastname: Meiring
authors.affiliation: National Institute for Communicable Diseases (NICD), a Division of the National Health Laboratory Service (NHLS), Johannesburg, South Africa.|Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Melony
authors.initials: M
authors.lastname: Fortuin-de Smidt
authors.affiliation: Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.|National Health Laboratory Service, Johannesburg, South Africa.
authors.forename: Ranmini
authors.initials: R
authors.lastname: Kularatne
authors.affiliation: Pietermaritzburg Hospital Complex, Pietermaritzburg and University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Halima
authors.initials: H
authors.lastname: Dawood
authors.affiliation: National Institute for Communicable Diseases (NICD), a Division of the National Health Laboratory Service (NHLS), Johannesburg, South Africa.|Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.|Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
authors.forename: Nelesh P
authors.initials: NP
authors.lastname: Govender
mesh_terms: D000666:Amphotericin B / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D003840:Deoxycholic Acid / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D004338:Drug Combinations; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000453:epidemiology*; D006760:Hospitalization; D006801:Humans; D008297:Male; D016919:Meningitis, Cryptococcal / Q000188:drug therapy* / Q000209:etiology*; D015995:Prevalence; D012189:Retrospective Studies; D013019:South Africa / Q000453:epidemiology
chemical_list: D000935:Antifungal Agents; D004338:Drug Combinations; D003840:Deoxycholic Acid; D000666:Amphotericin B; C059765:amphotericin B, deoxycholate drug combination