title: Once-daily gentamicin in infants and children: a prospective cohort study evaluating safety and the role of therapeutic drug monitoring in minimizing toxicity.
abstract: BACKGROUND
  The clinical evidence base for ototoxicity and nephrotoxicity outcomes with once-daily dosing (ODD) of gentamicin in children is suboptimal. Therapeutic drug monitoring (TDM) in once-daily gentamicin regimens is variable and its role in predicting or preventing clinical toxicity is unclear. We aimed to assess the safety of ODD of gentamicin and the usefulness of TDM in a pediatric cohort.
  
  
  METHODS
  Children with suspected sepsis were prospectively enrolled to receive ODD of gentamicin at 7 mg/kg/day. Hearing and renal function were objectively assessed at baseline, during therapy, and after therapy. TDM was performed using an interval-adjusted graphical method (Hartford nomogram).
  
  
  RESULTS
  A total of 79 children (median age: 5.6 years; range: 1 month-16 years) received 106 episodes of therapy. In all, 61% of these episodes were for febrile neutropenia. Evaluation was complete in 88% for ototoxicity and 92% for nephrotoxicity. Two patients (1.88%, 95% confidence interval: 0.10%-7.13%) experienced permanent hearing loss. One patient (0.94%, 95% confidence interval: <0.10%-5.73%) experienced transient nephrotoxicity. No abnormal serum gentamicin values were detected, even in those experiencing toxicity. Children experiencing toxicity were undergoing treatment for malignancies and had received nephrotoxic or ototoxic medicines before gentamicin.
  
  
  CONCLUSIONS
  In this pediatric cohort receiving ODD of gentamicin, nephrotoxicity was uncommon and reversible, but irreversible ototoxicity occurred more frequently. TDM using a nomogram neither predicted nor prevented toxicity, which was only observed in those with risk factors.
authors.affiliation: Discipline of Paediatrics, School of Women's and Children's Health, University of New South Wales, New South Wales, Australia. ebest@adhb.govt.nz
authors.forename: Emma J
authors.initials: EJ
authors.lastname: Best
authors.forename: Madlen
authors.initials: M
authors.lastname: Gazarian
authors.forename: Richard
authors.initials: R
authors.lastname: Cohn
authors.forename: Monica
authors.initials: M
authors.lastname: Wilkinson
authors.forename: Pamela
authors.initials: P
authors.lastname: Palasanthiran
mesh_terms: D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D005839:Gentamicins / Q000008:administration & dosage* / Q000009:adverse effects*; D006309:Hearing / Q000187:drug effects; D006320:Hearing Tests; D006801:Humans; D007223:Infant; D007668:Kidney / Q000187:drug effects; D007677:Kidney Function Tests; D008297:Male; D011446:Prospective Studies; D018805:Sepsis / Q000188:drug therapy*
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins