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Application of Bayes Theorem to Aminoglycoside-Associated Nephrotoxicity: Comparison of Extended-Interval Dosing, Individualized Pharmacokinetic Monitoring, and Multiple-Daily Dosing

From the Clinical Pharmacology Research Center (Dr. Kim, Dr. Bertino, Dr. Nafziger), Department of Medicine (Dr. Bertino, Dr. Nafziger), Department of Pharmacy Services (Dr. Bertino), and the Research Institute (Dr. Kim, Dr. Bertino, Ms. Erb, Dr. Jenkins, Dr. Nafziger), Bassett Healthcare, Cooperstown, New York.

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 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.

Key Words: Bayes theorem • Bayes factors • aminoglycoside-associated nephrotoxicity • extended-interval dosing • multiple-daily dosing

Address for reprints: Anne N. Nafziger, MD, MHS, Clinical Pharmacology Research Center, Bassett Healthcare, One Atwell Road, Cooperstown, NY 13326-1394.