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OBJECTIVES: To determine in vitro antimicrobial susceptibility and synergistic activity of colistin in combination with tigecycline against clinical strains of carbapenem- resistant Acinetobacter baumannii (CRAB).
MATERIAL AND METHODS: Colistin and tigecycline minimum inhibitory concentrations (MICs) of 12-clinical CRAB isolates were determined by broth microdilution. Checkerboard testing was performed to assess the interaction of the colistin-tigecycline combination. Fractional inhibitory concentration indexes (ΣFIC) in the range of 0.5 to 1.0, > 1.0 to < 4.0 and ≥ 4.0 are considered as additive, indifferent, and antagonistic effects, respectively.
RESULTS: All CRAB isolates were susceptible to colistin. Three out of 12 CRABs were susceptible to tigecycline based on a pharmacokinetic-pharmacodynamics (PK-PD) breakpoint (MICs ≤ 0.25 μg/mL). The MIC of both antimicrobials was decreased in most of the CRAB isolates in the checkerboard synergy testing. The interaction of colistin and tigecycline combination revealed both additive and indifferent effects in five and seven of the 12-CRAB isolates, respectively. Neither synergism nor antagonism of colistin and tigecycline combination was demonstrated.
CONCLUSION: No synergistic effect between colistin and tigecycline against CRAB isolates was detected. However, the combination of these two drugs is likely to result in a decrease in the MIC of both drugs. Further studies with a larger sample to determine the in vitro synergistic activity of colistin and tigecycline combination are required.
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1. Chaisathaphol T, Chayakulkeeree M. Epidemiology of infections caused by multidrug-resistant gram-negative bacteria in adult hospitalized patients at Siriraj Hospital. J Med Assoc Thai 2014;97(Suppl 3):S35-45.
2. Inchai J, Pothirat C, Liwsrisakun C, et al. Ventilator-associated pneumonia: epidemiology and prognostic indicators of 30-day mortality. Jpn J Infect Dis 2015;68(3):181-6.
3. Werarak P, Waiwarawut J, Tharavichitkul P, et al. Acinetobacter baumannii nosocomial pneumonia in tertiary care hospitals in Thailand. J Med Assoc Thai 2012;95(Suppl 2):S23-33.
4. Santimaleeworagun W, Wongpoowarak P, Chayakul P, et al. Clinical outcomes of patients infected with carbapenem- resistant Acinetobacter baumannii treated with single or combination antibiotic therapy. J Med Assoc Thai 2011;94(7):863-70.
5. National antimicrobial resistant service center, Thailand (NARST). Percentage of susceptible organisms isolated from all specimen, 74 hospitals, Jan - Dec 2017. (Accessed June 3, 2018, at http://narst.dmsc.moph.go.th/antibiograms/2017/12/ Jan-Dec2017-All.pdf).
6. Lemos EV, de la Hoz FP, Einarson TR, et al. Carbapenem resistance and mortality in patients with Acinetobacter baumannii infection: systematic review and meta-analysis. Clin Microbiol Infect 2014;20(5):416-23.
7. Aydemir H, Akduman D, Piskin N, et al. Colistin vs. the combination of colistin and rifampicin for the treatment of carbapenem-resistant Acinetobacter baumannii ventilator- associated pneumonia. Epidemiol Infect 2013;141(6):1214-22.
8. Li J, Yang X, Chen L, et al. In Vitro activity of various antibiotics in combination with tigecycline against Acinetobacter baumannii: A systematic review and meta-analysis. Microb Drug Resist 2017;23(8):982-93.
9. Ni W, Shao X, Di X, et al. In vitro synergy of polymyxins with other antibiotics for Acinetobacter baumannii: a systematic review and meta-analysis. Int J Antimicrob Agents 2015;45(1):8-18.
10. Tigecycline. In: In Depth Answers [database on the Internet]. Greenwood Village (CO): Truven Health Analytics; 2018. (Accessed June 20, 2018, at www.micromedexsolutions.com. Subscription required to view.).
11. Slover CM, Rodvold KA, Danziger LH. Tigecycline: a novel broad-spectrum antimicrobial. Ann Pharmacother 2007;41(6):965-72.
12. Gotfried MH, Horn K, Garrity-Ryan L, et al. Comparison of Omadacycline and Tigecycline Pharmacokinetics in the Plasma, Epithelial Lining Fluid, and Alveolar Cells of Healthy Adult Subjects. Antimicrob Agents Chemother 2017;61(9): e01135-17.
13. Khawcharoenporn T, Pruetpongpun N, Tiamsak P, et al. Colistin-based treatment for extensively drug-resistant Acinetobacter baumannii pneumonia. Int J Antimicrob Agents 2014;43(4):378-82.
14. Papst L, Beovic B, Pulcini C, et al. Antibiotic treatment of infections caused by carbapenem-resistant Gram-negative bacilli: an international ESCMID cross-sectional survey among infectious diseases specialists practicing in large hospitals. Clin Microbiol Infect 2018;pii:S1198- 743X(18)30069-7.
15. Karaoglan I, Zer Y, Bosnak VK, et al. In vitro synergistic activity of colistin with tigecycline or beta-lactam antibiotic/beta-lactamase inhibitor combinations against carbapenem-resistant Acinetobacter baumannii. J Int Med Res 2013;41(6):1830-7.
16. Kaya IA, Guner MD, Akca G, et al. Evaluation of the synergistic effect of a combination of colistin and tigecycline against multidrug-resistant Acinetobacter baumannii. Pak J Med Sci 2017;33(2):393-7.
17. Cikman A, Gulhan B, Aydin M, et al. In vitro Activity of Colistin in Combination with Tigecycline against Carbapenem- Resistant Acinetobacter baumannii Strains Isolated from Patients with Ventilator-Associated Pneumonia. Int J Med Sci 2015;12(9):695-700.
18. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing. 28th ed. Wayne: Clinical and Laboratory Standards Institute; 2018.
19. The European Committee on Antimicrobial Susceptibility Testing. Breakpoint tables for interpretation of MICs and zone diameters Version 8.1 [online]. 2018. (Accessed April 10, 2018, at http://www.eucast.org/clinical_breakpoints/.)
20. Conte JE Jr, Golden JA, Kelly MG, et al. Steady-state serum and intrapulmonary pharmacokinetics and pharmacodynamics of tigecycline. Int J Antimicrob Agents 2005;25(6):523-9.
21. Arthur LE, Kizor RS, Selim AG, et al. Antibiotics for ventilator-associated pneumonia. Cochrane Database Syst Rev 2016;10:CD004267.
22. Chuang YC, Cheng CY, Sheng WH, et al. Effectiveness of tigecycline-based versus colistin- based therapy for treatment of pneumonia caused by multidrug-resistant Acinetobacter baumannii in a critical setting: a matched cohort analysis. BMC Infect Dis 2014;14:102.
23. Cheng A, Chuang YC, Sun HY, et al. Excess mortality associated with colistin-tigecycline compared with colistin-carbapenem combination therapy for extensively drug-resistant Acinetobacter baumannii Bacteremia: A multicenter prospective observational study. Crit Care Med 2015;43(6):1194-204.