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

Abstract

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 48-96h 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.

Keywords: Amikacin; Critical care; Nosocomial infection; Pharmacokinetics; Sepsis.