title: Hearing loss and vestibular dysfunction among children with cancer after receiving aminoglycosides.
abstract: BACKGROUND
  Children undergoing cancer therapy often receive aminoglycosides to treat febrile neutropenia or gram-negative infections. The magnitude of the risk of developing aminoglycoside-induced ototoxicity and the dose threshold at which that risk significantly increases are unknown.
  
  
  METHODS
  Eligible cancer patients received the aminoglycoside amikacin at Children's Medical Center between 2004 and 2007. They were aged 3-8 years; were without prior hearing loss; had no platinum-based chemotherapy, cranial radiation, nor bone marrow transplant; and received no loop diuretics within 6 weeks of testing. Consenting patients underwent complete hearing and vestibular testing.
  
  
  RESULTS
  We tested 23 patients who had significant amikacin exposure. Three (13%) had abnormal hearing tests, and four (17%) had subclinical vestibular dysfunction; none had both. Of those with hearing loss, two were known to have developed hearing loss after aminoglycoside exposure, but the third had moderate to severe high-frequency sensorineural hearing loss bilaterally that had been undiagnosed. We observed clear dose-dependent ototoxicity; of the eight patients who received amikacin for a cumulative total of more than 50 days, five (68%) developed toxicity. Similarly, of the seven who received a cumulative total of more than 1,200 mg/kg, five developed toxicity.
  
  
  CONCLUSIONS
  These data highlight the risks of prolonged aminoglycoside administration and warrant further validation in a larger group of patients. Patients to be treated with prolonged aminoglycoside therapy may benefit from prospective hearing screening.
authors.affiliation: Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas; Children's Medical Center, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Chen
authors.forename: Alicia
authors.initials: A
authors.lastname: Bach
authors.forename: Angela
authors.initials: A
authors.lastname: Shoup
authors.forename: Naomi J
authors.initials: NJ
authors.lastname: Winick
mesh_terms: D000583:Amikacin / Q000009:adverse effects*; D000617:Aminoglycosides / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D005260:Female; D034381:Hearing Loss / Q000139:chemically induced*; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000188:drug therapy*; D015837:Vestibular Diseases / Q000139:chemically induced*; D058585:Vestibular Evoked Myogenic Potentials / Q000187:drug effects
chemical_list: D000617:Aminoglycosides; D000970:Antineoplastic Agents; D000583:Amikacin
keywords: aminoglycoside; late effects; ototoxicity