16. The efficacy of of colistin Combined with Amikacin on Carbapenem resistant Klebsiella pneumoniae isolates

Ngo Van Quynh, Pham Hong Nhung

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Abstract

In this study, we evaluate the efficacy of the combination of colistin and amikacin in vitro using the checkerboard technique on 57 carbapenem resistant K. pneumoniae isolates. Combination of colistin with amikacin were synergic in 11/57 (19%) of the strains. At MIC of amikacin being 1, 2, 4, 8, 16, 32, the synergy activities were observed in 2/7, 4/14, 1/5, 2/6, 1/17 and 1/8, respectively. At MIC of colistin being 0.125, 0.25, 0.5, 1, 4, 8, 16, 32, the synergy activities were observed in 0/2, 0/11, 5/24, 3/5, 0/1, 1/4, 1/7 and 1/3, respectively. The combination of colistin with amikacin showed good synergism. The synergistic combinations reduced the MICs of amikacin and colistin to the threshold for achieving pharmacokinetic/pharmacodynamic (PK/PD) goals. The synergistic interaction tends to increase as the colistin MIC increases respectively.

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References

1. Peleg AY, Hooper DC. Hospital-Acquired Infections Due to Gram-Negative Bacteria. N Engl J Med. 2010; 362(19): 1804-1813. doi: 10.1056/NEJMra0904124.
2. Magill SS, Edwards JR, Bamberg W, et al. Multistate Point-Prevalence Survey of Health Care–Associated Infections. N Engl J Med. 2014; 370(13): 1198-1208. doi: 10.1056/NEJMoa1306801.
3. Karaiskos I, Lagou S, Pontikis K, Rapti V, Poulakou G. The “Old” and the “New” Antibiotics for MDR Gram-Negative Pathogens: For Whom, When, and How. Front Public Health. 2019; 7. doi: 10.3389/fpubh.2019.00151.
4. Candan ED, Aksöz N. Klebsiella pneumoniae: characteristics of carbapenem resistance and virulence factors. Acta Biochim Pol. 2015; 62(4): 867-874. doi: 10.18388/abp.2015_1148.
5. Sheu CC, Chang YT, Lin SY, Chen YH, Hsueh PR. Infections Caused by Carbapenem-Resistant Enteroba cteriaceae: An Update on Therapeutic Options. Front Microbiol. 2019; 10. doi: 10.3389/fmicb.2019.00080.
6. Yu L, Zhang J, Fu Y, et al. Synergetic Effects of Combined Treatment of Colistin With Meropenem or Amikacin on Carbapenem-Resistant Klebsiella pneumoniae in vitro. Front Cell Infect Microbiol. 2019; 9. doi: 10.3389/fcimb.2019.00422.
7. Sato T, Wada T, Nishijima S, et al. Emergence of the Novel Aminoglycoside Acetyltransferase Variant aac(6′)-Ib-D179Y and Acquisition of Colistin Heteroresistance in Carbapenem-Resistant Klebsiella pneumoniae Due to a Disrupting Mutation in the DNA Repair Enzyme MutS. mBio. 2020; 11(6). doi: 10.1128/mBio.01954-20.
8. Ontong JC, Ozioma NF, Voravuthikunchai SP, Chusri S. Synergistic antibacterial effects of colistin in combination with aminoglycoside, carbapenems, cephalosporins, fluoroquinolones, tetracyclines, fosfomycin, and piperacillin on multidrug resistant Klebsiella pneumoniae isolates. PLOS ONE. 2021; 16(1) :e0244673. doi: 10.1371/journal.pone.0244673.
9. Amy L. Leber. Clinical Microbiology Procedures Handbook, Fourth Edition. American Society of Microbiology; 2016. doi: 10.1128/9781555818814.
10. Tsala M, Vourli S, Georgiou PC, et al. Exploring colistin pharmacodynamics against Klebsiella pneumoniae: a need to revise current susceptibility breakpoints. J Antimicrob Chemother. 2018; 73(4): 953-961. doi: 10.1093/jac/dkx522.
11. Cheah SE, Wang J, Nguyen VTT, Turnidge JD, Li J, Nation RL. New pharmacokinetic/pharmacodynamic studies of systemically administered colistin against Pseudomonas aeruginosa and Acinetobacter baumannii in mouse thigh and lung infection models: smaller response in lung infection. J Antimicrob Chemother. 2015; 70(12): 3291-3297. doi: 10.1093/jac/dkv267.
12. Tsuji BT, Pogue JM, Zavascki AP, et al. International Consensus Guidelines for the Optimal Use of the Polymyxins: Endorsed by the American College of Clinical Pharmacy (ACCP), European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Infectious Diseases Society of America (IDSA), International Society for Anti-infective Pharmacology (ISAP), Society of Critical Care Medicine (SCCM), and Society of Infectious Diseases Pharmacists (SIDP). Pharmacotherapy. 2019; 39(1): 10-39. doi: 10.1002/phar.2209.
13. Nation RL, Garonzik SM, Thamlikitkul V, et al. Dosing Guidance for Intravenous Colistin in Critically Ill Patients. Clin Infect Dis Off Publ Infect Dis Soc Am. 2017; 64(5): 565-571. doi: 10.1093/cid/ciw839.
14. Kuti JL, Wang Q, Chen H, Li H, Wang H, Nicolau DP. Defining the potency of amikacin against Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii derived from Chinese hospitals using CLSI and inhalation-based breakpoints. Infect Drug Resist. 2018; 11: 783-790. doi: 10.2147/IDR.S161636.
15. Taccone FS, Laterre PF, Spapen H, et al. Revisiting the loading dose of amikacin for patients with severe sepsis and septic shock. Crit Care. 2010; 14(2): R53. doi: 10.1186/cc8945.
16. Sadeghi K, Hamishehkar H, Najmeddin F, et al. High-dose amikacin for achieving serum target levels in critically ill elderly patients. Infect Drug Resist. 2018; 11: 223-228. doi: 10.2147/IDR.S150839.
17. Logre E, Enser M, Tanaka S, et al. Amikacin pharmacokinetic/pharmacodynamic in intensive care unit: a prospective database. Ann Intensive Care. 2020; 10:75. doi: 10.1186/s13613-020-00685-5.