Impact of amikacin pharmacokinetic/pharmacodynamic index on treatment response in critically ill patients

Objectives: This study evaluated the association between the pharmacokinetic/pharmacodynamic index and treatment response to amikacin in critically ill patients. Methods: An observational prospective study was designed. Critically ill adult patients with infection due to amikacin-sensitive Gram-negative bacteria treated with amikacin were included. Amikacin maximum (C-max) and minimum (C-min) plasma concentration samples were taken during the first 48-96 h after the beginning of treatment. The impact of C-max/MIC ratio and area under the concentration-time curve (AUC)/MIC ratio on early and final clinical response, microbiological eradication, development of resistant strains and renal toxicity was analysed using a multivariate model. Results: A total of 85 patients received amikacin treatment, of whom 71 (83.5%) achieved a C-max/MIC > 6, 66 (77.6%) a C-max/MIC > 8, 64 (75.3%) a C-max/MIC > 10 and 72 (84.7%) an AUC/MIC > 65. Clinical response at the end of treatment was significantly greater in patients with C-max/MIC > 6 [OR = 5.48 (95% CI 1.28-11.40)], C-max/MIC > 8 [OR = 6.01 (2.41-12.2)] and C-max/MIC > 10 [OR = 8.02 (2.21-14.2)]. C-max/MIC > 10 was associated with a non-significant increase in microbiological eradication [OR = 2.84 (0.76-10.61)]. Achieving C-max/MIC > 6 was associated with a lower proportion of patients with selection of resistant strains or with an increase in amikacin MIC (27.8% vs. 10.2%). Amikacin AUC was associated with development of nephrotoxicity [ROC curve 0.77 (0.66-0.87)]. Conclusions: The C-max/MIC ratio of amikacin in critically ill patients is directly related to the response to treatment and the selection of resistant strains. (C) 2017 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.