title: Application of Bayes theorem to aminoglycoside-associated nephrotoxicity: comparison of extended-interval dosing, individualized pharmacokinetic monitoring, and multiple-daily dosing.
abstract: The objective of this study was to examine the incidence of aminoglycoside-associated nephrotoxicity related to extended-interval dosing, individualized pharmacokinetic monitoring, and multiple-daily dosing by applying Bayes theorem. An electronic literature search of MEDLINE (1966-2003) and a manual search of references from published meta-analyses and review articles were performed. Studies using extended-interval dosing, individualized pharmacokinetic monitoring, or multiple-daily dosing and reported aminoglycoside-associated nephrotoxicity for patients > or = 16 years of age were included. Quality scores were assigned based on the rigor of definition of aminoglycoside-associated nephrotoxicity, duration of therapy, and length of follow-up of renal function after completion of therapy. Inclusion criteria were then based on these quality scores. Quantitative data on the incidence of aminoglycoside-associated nephrotoxicity were abstracted. Twelve extended-interval dosing studies (n = 916), 10 individualized pharmacokinetic monitoring studies (n = 2066), and 27 multiple-daily dosing studies (n = 4251) met the inclusion criteria. Prior probabilities of aminoglycoside-associated nephrotoxicity were derived from a combination of a review of published studies and expert judgment. The maximum densities for the final posterior probabilities of aminoglycoside-associated nephrotoxicity for extended-interval dosing, individualized pharmacokinetic monitoring, and multiple-daily dosing were located at 12% to 13%, 10% to 11%, and 13% to 14%, respectively. Application of Bayes theorem demonstrates that aminoglycoside dosing by individualized pharmacokinetic monitoring results in less aminoglycoside-associated nephrotoxicity than extended-interval dosing or multiple-daily dosing.
authors.affiliation: Clinical Pharmacology Research Center, Bassett Healthcare, One Atwell Road, Cooperstown, NY 13326-1394, USA.
authors.forename: Myong-Jin
authors.initials: MJ
authors.lastname: Kim
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Bertino
authors.forename: Tara A
authors.initials: TA
authors.lastname: Erb
authors.forename: Paul L
authors.initials: PL
authors.lastname: Jenkins
authors.forename: Anne N
authors.initials: AN
authors.lastname: Nafziger
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000617:Aminoglycosides / Q000008:administration & dosage* / Q000009:adverse effects*; D001499:Bayes Theorem; D002986:Clinical Trials as Topic; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged
chemical_list: D000617:Aminoglycosides