title: Predictive performance of gentamicin dosing nomograms.
abstract: BACKGROUND
  Several nomograms have been proposed to facilitate the determination of initial gentamicin dosing regimens in clinical settings. This study aimed to assess the predictive performance of these nomograms in Korean patients.
  
  
  METHODS
  Gentamicin concentrations were determined in 84 patients with infective endocarditis (IE) and in 95 patients with other infections. All patients underwent therapeutic drug monitoring in Seoul National University Hospital from 2006 to 2012. Individual pharmacokinetic parameters were estimated using a Bayesian method, which predicted steady state peak and trough serum concentrations. Six nomograms were evaluated in patients with "other" infections: the Thomson guidelines, Hull-Sarubbi table, and Rule of Eights, for multiple daily dosing; and the Hartford nomogram, Barnes-Jewish Hospital nomogram, and Sanford Guide, for extended-interval dosing. In IE patients, synergistic combination dosing nomograms, based on the American Heart Association dosing interval guidelines, were evaluated.
  
  
  RESULTS
  Gentamicin dosing nomograms performed poorly in attaining the target peak serum concentrations. Multiple-daily dosing nomograms predicted peak serum gentamicin concentrations better than did the extended-interval dosing nomograms (31.9%-72.3% vs 4.3%-45.7%, respectively). Similarly, in patients with IE, the once-daily dosing nomogram resulted in a significantly lower percentage of patients achieving target peak gentamicin concentrations than that associated with the thrice-daily dosing nomogram (P=0.0015). All of the multiple-daily dosing, extended-interval dosing, and synergistic combination dosing nomograms predicted the nontoxic target trough concentrations in >80% of patients.
  
  
  CONCLUSIONS
  Gentamicin dosing nomograms performed poorly in achieving the target peak serum concentrations. New gentamicin nomograms may be required in patients with IE, particularly for once-daily dosing. Therapeutic drug monitoring is highly recommended for gentamicin to ensure that the target concentrations are achieved.
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea.
authors.forename: Jieon
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea.
authors.forename: Seonghae
authors.initials: S
authors.lastname: Yoon
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea.
authors.forename: Donghoon
authors.initials: D
authors.lastname: Shin
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea.
authors.forename: HyeKyung
authors.initials: H
authors.lastname: Han
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea ; Department of Statistics, College of Natural Sciences, Seoul National University, Seoul, Korea.
authors.forename: Hyungmi
authors.initials: H
authors.lastname: An
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea.
authors.forename: Jongtae
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, CHA University School of Medicine and CHA Bundang Medical Center, Seongnam, Korea.
authors.forename: Kyoung Soo
authors.initials: KS
authors.lastname: Lim
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea.
authors.forename: Kyung-Sang
authors.initials: KS
authors.lastname: Yu
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea.
authors.forename: Howard
authors.initials: H
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001424:Bacterial Infections / Q000188:drug therapy; D001499:Bayes Theorem; D016903:Drug Monitoring / Q000379:methods; D004697:Endocarditis, Bacterial / Q000188:drug therapy*; D005260:Female; D005839:Gentamicins / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006785:Hospitals, University; D006801:Humans; D008297:Male; D008875:Middle Aged; D049451:Nomograms; D017410:Practice Guidelines as Topic; D056910:Republic of Korea; D012189:Retrospective Studies
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins
keywords: Bayesian method; antibiotics; infectious endocarditis; therapeutic drug monitoring