title: Otoacoustic emission screen results in critically ill neonates who received gentamicin in the first week of life.
abstract: OBJECTIVE
  To characterize the extent that serum gentamicin concentrations are associated with hearing loss indicated by otoacoustic emission (OAE) screen failure in critically ill neonates receiving gentamicin in accordance with a high-dose, extended-interval dosing protocol.
  
  
  METHODS
  Retrospective medical record review.
  
  
  METHODS
  Two neonatal intensive care units in a pediatric tertiary care system.
  
  
  METHODS
  Sequential sample of 528 critically ill neonates who were admitted between February 2003 and January 2008 and who received a gentamicin pharmacokinetic consultation during the first week of life and an OAE hearing screen before hospital discharge. Neonates were stratified into two groups: very low birth weight (VLBW [≤ 1500 g]) and non-VLBW (> 1500 g).
  
  
  RESULTS
  Gentamicin was dosed intravenously to achieve a target calculated gentamicin peak serum concentration (C(max)) of 7-10 μg/ml and a target trough serum concentration (C(min)) of less than 2 μg/ml. The dosage administered was 4 mg/kg/dose every 48 hours if the neonate's birth weight was less than 1250 g or if the neonate was receiving indomethacin. Otherwise, the dosing interval was every 24 hours. Initial OAE screen results were obtained from the medical records, and follow-up results were collected for neonates who failed the initial OAE screen. The overall rate of OAE screen failure was 13.1% (69/528 patients). The rate of OAE screen failure was 34.1% (29/85 patients) in the VLBW neonates, which was significantly higher than the failure rate in non-VLBW neonates (9.0% [40/443 patients], p=0.001). Multivariate analysis of non-VLBW neonates determined that each 1-μg/ml increase in gentamicin C(max) was associated with an increased risk of OAE screen failure (odds ratio [OR] 1.4, 95% confidence interval (CI) 1.1-1.7, p=0.003). Further, the non-VLBW neonate subpopulation had an increased rate of OAE screen failure if the gentamicin C(max) exceeded 10 μg/ml (OR 2.2, 95% CI 1.1-4.2, p=0.022) compared with neonates whose C(max) was 10 μg/ml or lower. No association between serum gentamicin concentration and OAE screen failure could be determined among the VLBW neonates.
  
  
  CONCLUSIONS
  Neonates weighing more than 1500 g at birth and whose gentamicin C(max) exceeded 10 μg/ml were at an increased risk for OAE screen failure. Monitoring and maintaining gentamicin C(max) at or below 10 μg/ml may minimize hearing impairment; however, further studies are necessary.
authors.affiliation: Department of Pharmacy, Children's Hospitals and Clinics of Minnesota, Minneapolis, Minnesota 55404, USA. aaron.cooper@childrensmn.org
authors.forename: Aaron C
authors.initials: AC
authors.lastname: Cooper
authors.forename: Amy R
authors.initials: AR
authors.lastname: Commers
authors.forename: Marsha
authors.initials: M
authors.lastname: Finkelstein
authors.forename: Polina G
authors.initials: PG
authors.lastname: Lipnik
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Tollefson
authors.forename: Roger A
authors.initials: RA
authors.lastname: Wilcox
authors.forename: David S
authors.initials: DS
authors.lastname: Hoff
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D001724:Birth Weight; D016638:Critical Illness; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D005260:Female; D005839:Gentamicins / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D034381:Hearing Loss / Q000139:chemically induced* / Q000175:diagnosis; D006801:Humans; D007231:Infant, Newborn; D019102:Infant, Very Low Birth Weight; D008297:Male; D015997:Neonatal Screening; D017084:Otoacoustic Emissions, Spontaneous; D012189:Retrospective Studies
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins