Optimal Amikacin Levels for Patients with Sepsis in Intensive Care Unit of Cipto Mangunkusumo Hospital, Jakarta, Indonesia

Gestina Aliska, Rianto Setiabudi, purwantyastuti purwantyastuti, Anis Karuniawati, Rudyanto Sedono, Trisni U Dewi, Muhammad K Azwar

Abstract


Background: Amikacin is one of the antibiotics of choice for sepsis and septic shock. Pharmacokinetic of amikacin can be influenced by septic condition with subsequent effect on its pharmacodynamic. At Cipto Mangunkusumo Hospital (RSCM), Jakarta, adult patients in the ICU were given standard amikacin dose of 1 g/day, however the achievement of optimal plasma level had never been evaluated. This study aimed to evaluate whether the optimal plasma level of amikacin was achieved with the use of standard dose in septic conditions.
Methods: all septic patients admitted to the intensive care unit of a national tertiary hospital receiving standard dose of 1g/day IV amikacin during May-September 2015 were included in this study. Information of minimum inhibitory concentration MIC was obtained from microbial culture. Cmax of amikacin was measured 30 minutes after administration and optimal level was calculated. Optimal amikacin level was considered achieved when Cmax/MIC ratio >8. Results: average Cmax achieved for all patients was 86.4 (43.5-238) µg/mL with 87% patients had Cmax of >64 µg/mL.MIC data were available for 7 of 23 patients. MICs for identified pathogens were 0.75 - >256 µg/mL (K. pneumonia), 0.75 - >256 µg/mL(A. baumanii), 1.5 - >256 µg/mL (P. aeruginosa)and 0.75 – 16 µg/mL(E. coli). Four out of seven patients achieved optimal amikacin level. Conclusion: despite high Cmax, only half of the patients achieved optimal amikacin level with highly variable Cmax. This study suggests that measurement of Cmax and MIC are important to optimize septic patients management.

Keywords


amikacin; aminoglycoside; sepsis; ICU; MIC

References


Zhou J, Qian C, Zhao M, Yu X, Kang Y, Ma X, et al. Epidemiology and outcome of severe sepsis and septic shock in intensive care units in mainland China. PLoS One 2014;9(9):e107181.

Quenot JP, Binquet C, Kara F, Martinet O, Ganster F, Navellou JC, et al. The epidemiology of septic shock in French intensive care units: the prospective multicenter cohort EPISS study. Crit Care 2013;17(2):R65.

Phua J, Koh Y, Du B, Tang YQ, Divatia JV, Tan CC, et al. Management of severe sepsis in patients admitted to Asian intensive care units: prospective cohort study. Brit Med J 2011;342:d3245.

Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving sepsis campaign: International guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med 2013) 39:165–228.

Vincent JL, Rello J, Marshall J, Silva E, Anzueto A, Martin CD, et al. International study of the prevalence and outcomes of infection in intensive care units. JAMA 2009;302:2323-9.

Deck DH, Winston LG. Aminoglycosides & spectinomycin. In: Katzung BG, Masters SB, Trevor AJ, eds. Basic & Clinical Pharmacology. 12th ed. Singapore: McGraw-Hill; 2012. p.821-7.

Mahmoudi L, Mohammadpour AH, Ahmadi A, Niknam R, Mojtaheddzadeh M. Influence of sepsis on higher daily dose of amikacin pharmacokinetics in critically ill patients. Eur Rev Med Pharmacol Sci 2013;17:285-91.

Gooding PG, Berman E, Lane AZ, Agre K. A review of results of clinical trials with amikacin. J Infect Dis 1976;134 SUPPL:S441-5.

MacDougall C, Chambers HF. Aminoglycosides. In: Hardman JG, Limbird LE, eds. Goodman & Gilman’s the Pharmacological Basis of Therapeutics. 12th ed. New York: McGraw-Hill; 2011. p.1505-18.

Roberts J, Lipman J. Antibacterial dosing in intensive care: pharmacokinetics, degree of disease and pharmacodynamics of sepsis. Clin Pharmacokinet 2006;45:755-73.

Taccone FS, Laterre PF, Spapen H, Dugernier T, Dellatre I, Layeux B, et al. Revisiting the loading dose of amikacin for patients with severe sepsis and septic shock. Crit Care 2010;14:R53.

EUCAST: Aminoglycosides: EUCAST clinical MIC breakpoints. Diakses dari: http://www.srgaorg/eucastwt/MICTAB/MICaminoglycosides.html.

Rea RS, Capitano B, Bies R, Bigos KL, Smith R, Lee H. Suboptimal aminoglycoside dosing in critically ill patients. Ther Drug Monit 2008;30:674-81.

Burdet C, Pajot O, Couffignal C, Armand-Lefèvre L, Foucrier A, Laouénan C, et al. Population pharmacokinetics of single-dose amikacin in critically ill patients with suspected ventilator-associated pneumonia. Eur J Clin Pharmacol 2015;71:75-83.

Clinical and Laboratory Standards Institute. M100-S25 Performance standards for antimicrobial susceptibility testing; twenty-fifth informational supplement. January 2015.

Duszynska W, Taccone FS, Hurkacz M, Kowalska-Krochmal B, Wiela-Hojeńska A, Kübler A. Therapeutic drug monitoring of amikacin in septic patients. Crit Care 2013:17:R165.

Najmeddin F, Ahmadi A, Mahmoudi L, Sadeghi K, Khalili H, Ahmadvand A, et al. Administration of higher doses of amikacin in early stages of sepsis in critically ill patients. Acta Med Iran 2014;52:703-9.

Setiawati A, Suyatna FD, Gan S. Pengantar farmakologi. Dalam: Gunawan S, Setiabudy R, editor. Farmakologi dan Terapi. Edisi ke-5. Jakarta: Badan Penerbit FKUI. 2011. Hal.1-27.

Winter ME. Basic Clinical Pharmacokinetics Fourth Edition. Lippincott Williams & Wilkins. Philadelphia. 2004; 19,131-171, 451-76.

Botha FJ, van der Bijl P, Seifart HI, Parkin DP. Fluctuation of the volume of distribution of amikacin and its effect on once-daily dosage and clearance in a seriously ill patient. Intensive Care Med 1996;22:443-6.

Lugo G, Castañeda-Hernández G. Relationship between hemodynamic and vital support measures and pharmacokinetic variability of amikacin in critically ill patients with sepsis. Crit Care Med 1997;25:806-11.

Panomvana D, Kiatjaroensin SA, Phiboonbanakit D. Correlation of the pharmacokinetic parameters of amikacin and ceftazidime. Clin Pharmacokinet 2007;46:859-66.

Lee HS, Loh YX, Lee JJ, Liu CS, Chu C. Antimicrobial consumption and resistance in five Gram-negative bacterial species in a hospital from 2003 to 2011. J Microbiol Immunol Infect 2014. pii: S1684-1182(14)00074-7.

Vaidya VK. Horizontal transfer of antimicrobial resistance by extended-spectrum β-lactamase-producing Enterobacteriaceae. J Lab Physicians 2011;3:37–42.

Kizirgil A, Demirdag K, Ozden M, Bulut Y, Yakupogullari Y, Toraman ZA. In vitro activity of three different antimicrobial agents against ESBL producing Escherichia coli and Klebsiella pneumoniae blood isolates. Microbiol Res 2005;160:135-40.


Full Text: PDF

Refbacks

  • There are currently no refbacks.


Copyright (c) 2017 Acta Medica Indonesiana