Risk factors of amphotericin B toxicty in the nonneonatal pediatric population

Pediatr Infect Dis J. 2012 Sep;31(9):910-4. doi: 10.1097/INF.0b013e31825d649a.

Abstract

Background: Amphotericin B (AmB) traditionally has been the mainstay of therapy for children with candidemia but is associated with drug-related toxicities (DRT). Studies investigating the risk factors for AmB DRT in children are limited.

Methods: A retrospective review of patients aged 6 months to ≤18 years with candidemia who received ≥1 dose of AmB from 2003 to 2009 was conducted at Texas Children's Hospital, Houston, TX. Patient demographics, risk factors, drug dosages, laboratory adverse effects and infusion-related side effects (INFRT) were recorded.

Results: A total of 223 episodes of candidemia occurred in 179 patients. AmB was administered in 172 (77%) episodes. Amphotericin B deoxycholate, Amphotericin B lipid complex and liposomal Amphotericin B were administered in 65 (38%), 96 (55%) and 11 (6.4%) episodes, respectively. When the first episode of AmB use was analyzed separately (n = 138), DRT occurred in 83% (n = 114); nephrotoxicity occurred in 45% (n = 62), hypokalemia in 47% (n = 62) and INFRT in 31 % (n = 41). The most common INFRT was chills and rigors (80%, n = 33) followed by fever (31.7%, n = 13) and hypotension (9.7%, n = 4). Patients with lower baseline creatinine clearance were at increased risk of having nephrotoxicity than those with higher baseline creatinine clearance (P = 0.004). Nephrotoxicity was less likely in patients who received immunosuppressants (P = 0.02). Neutropenia (P = 0.02) and prior hypokalemia (P = 0.001) were independently associated with hypokalemia. The receipt of premedication was independently associated with a lower likelihood of INFRT (P ≤ 0.0001). It is important to note that most AmB-related DRT was quickly reversible.

Conclusions: AmB-associated DRT was common and reversible in our nonneonatal pediatric population. Prospective studies are required to further evaluate risk factors and determine whether they are modifiable.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Amphotericin B / administration & dosage
  • Amphotericin B / adverse effects*
  • Analysis of Variance
  • Antifungal Agents / administration & dosage
  • Antifungal Agents / adverse effects*
  • Candidemia / drug therapy*
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Hypokalemia / chemically induced
  • Infant
  • Kidney Diseases / chemically induced
  • Male
  • Retrospective Studies
  • Risk Factors

Substances

  • Antifungal Agents
  • Amphotericin B