title: Comparing 3 methods of monitoring gentamicin concentrations in patients with febrile neutropenia.
abstract: Several nomograms and algorithms have been developed to individualize pharmacokinetic monitoring with their own advantages and disadvantages. This study compared 3 pharmacokinetic methods for predicting doses and monitoring of gentamicin in adult patients with febrile neutropenia. A retrospective study of 75 patients with febrile neutropenia was conducted at the Royal Adelaide Hospital, South Australia. Each patient received a course of once-daily gentamicin and had 2 sets of paired gentamicin serum concentrations. Pharmacokinetic parameters and ensuing doses were compared using 3 pharmacokinetic methods: (1) sequential Bayesian algorithm for gentamicin (SeBA-GEN), (2) Sawchuk-Zaske, and (3) Therapeutic Guidelines: Antibiotic Dose Adjustment Nomogram. The initial median (range) dose of gentamicin administered was 400 (240-640) mg. SeBA-GEN and Sawchuk-Zaske methods recommended similar subsequent gentamicin dose adjustments of 400 (280-640) mg and 400 (280-640) mg, respectively, whereas the Therapeutic Guidelines recommended an increase to 1390 (210-6240) mg. For the Therapeutic Guidelines, 64% of the patients had measured serum gentamicin concentrations that were below the minimum line of the nomogram for the first set of concentrations with only 32% of these patients having an area under the curve value of <70 mg h/L as calculated by SeBA-GEN. The SeBA-GEN method showed a statistically significant increase (68%-77%) in patients attaining the target concentrations of maximum concentration (Cmax) 15-25 mg/L compared with the Sawchuk-Zaske method (72%-65%, P > 0.05). SeBA-GEN also demonstrated greater precision in predicting the area under the curve, Cmax, and minimum concentration (Cmin) compared with the Sawchuk-Zaske method. In conclusion, as the Bayesian approach, that is, SeBA-GEN demonstrated greater precision and more patients were attaining the target concentrations, it is therefore the preferred method for gentamicin monitoring in patients with febrile neutropenia.
authors.affiliation: School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia. m.avent@uq.edu.au
authors.forename: Minyon L
authors.initials: ML
authors.lastname: Avent
authors.forename: Junlu
authors.initials: J
authors.lastname: Teoh
authors.forename: Judith
authors.initials: J
authors.lastname: Lees
authors.forename: Kerena A
authors.initials: KA
authors.lastname: Eckert
authors.forename: Carl M
authors.initials: CM
authors.lastname: Kirkpatrick
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000097:blood*; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D005839:Gentamicins / Q000097:blood*; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000097:blood* / Q000188:drug therapy; D015203:Reproducibility of Results; D012189:Retrospective Studies; D013997:Time Factors; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins