title: Risk factors of amphotericin B toxicty in the nonneonatal pediatric population.
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.
authors.affiliation: From the Section of Infectious Diseases, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, TX 77030, USA. ankhidutta@gmail.com
authors.forename: Ankhi
authors.initials: A
authors.lastname: Dutta
authors.forename: Debra L
authors.initials: DL
authors.lastname: Palazzi
mesh_terms: D000293:Adolescent; D000666:Amphotericin B / Q000008:administration & dosage / Q000009:adverse effects*; D000704:Analysis of Variance; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects*; D058387:Candidemia / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007008:Hypokalemia / Q000139:chemically induced; D007223:Infant; D007674:Kidney Diseases / Q000139:chemically induced; D008297:Male; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D000935:Antifungal Agents; D000666:Amphotericin B