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Determinants of amikacin first peak concentration in critically ill patients
Author(s) -
Boidin Clément,
Jenck Sophie,
Bourguig Laurent,
Torkmani Sejad,
RousseyJean Aurore,
Ledochowski Stanislas,
Marry Lucie,
Ammenouche Nacim,
Dupont Hervé,
Marçon Frédéric,
Allaouchiche Bernard,
Bohé Julien,
Lepape Alain,
Goutelle Sylvain,
Friggeri Arnaud
Publication year - 2018
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/fcp.12374
Subject(s) - cmax , amikacin , medicine , renal function , pharmacokinetics , logistic regression , chemistry , biochemistry , antibiotics
Amikacin antimicrobial effect has been correlated with the ratio of the peak concentration ( C max ) to the minimum inhibitory concentration. A target C max ≥ 60–80 mg/L has been suggested. It has been shown that such target is not achieved in a large proportion of critically ill patients in intensive care units. A retrospective analysis was performed to examine the determinants of C max ≥ 80 mg/L on the first peak in 339 critically ill patients treated by amikacin. The influence of available variables on C max target attainment was analyzed using a classification and regression tree ( CART ) and logistic regression. Mean C max in the 339 patients was 73.0 ± 23.9 mg/L, with a target attainment rate ( TAR , C max ≥ 80 mg/L) of 37.5%. In CART analysis, the strongest predictor of amikacin target peak attainment was dose per kilogram of lean body weight (dose/ LBW ). TAR was 60.1% in patients with dose/ LBW ≥ 37.8 vs. 19.9% in patients with lower dose/ LBW ( OR = 6.0 (95% CI: 3.6–10.2)). Renal function was a secondary predictor of C max . Logistic regression analysis identified dose per kilogram of ideal body weight ( OR = 1.13 (95% CI: 1.09–1.17)) and creatinine clearance ( OR = 0.993 (95% CI: 0.988–0.998)) as predictors of target peak achievement. Based on our results, an amikacin dose ≥ 37.8 mg/kg of LBW should be used to optimize the attainment of C max ≥ 80 mg/L after the first dose in critically ill patients. An even higher dose may be necessary in patients with normal renal function.