Impact of amikacin pharmacokinetic/pharmacodynamic index on treatment response in critically ill patients. (March 2018)

• Record Type: Journal Article
• Authors: Ruiz, Jesus; Ramirez, Paula; Company, María José; Gordon, Mónica; Villarreal, Esther; Concha, Pablo; Aroca, María; Frasquet, Juan; Remedios-Marqués, María; Castellanos-Ortega, Álvaro
• Is Part Of: Journal of global antimicrobial resistance. Volume 12(2018)
• Page Start: 90
• Page End: 95
• Publication Date: 2018-03
• Subjects: Amikacin -- Critical care -- Sepsis -- Pharmacokinetics -- Nosocomial infection; Drug resistance -- Periodicals; Drug resistance -- Periodicals; Drug resistance; Periodicals; 616.9041
• DOI: 10.1016/j.jgar.2017.09.019
• Languages: English
• ISSNs: 2213-7165

Abstract

Highlights: C max /MIC ratio of amikacin in critically ill patients is associated with clinical response to treatment. Selection of amikacin-resistant strains may be associated with the initial C max /MIC ratio. AUC/MIC ratio is not associated with treatment response but may be used as a predictor of amikacin-induced renal toxicity. Amikacin dose should be individualised based on changes in pathophysiological status, infection focus and amikacin MICs. 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 48–96 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.