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Kim, Ko, Choi, Kang, Park, and Jang: Assessment of the synergistic effect of seven antimicrobial combinations on extensively drugresistant Acinetobacter baumannii strains
Original article

Ann Clin Microbiol 2022;25(4):125-136.

Published online: 20 December 2022

DOI: https://doi.org/10.5145/ACM.2022.25.4.3

Assessment of the synergistic effect of seven antimicrobial combinations on extensively drugresistant Acinetobacter baumannii strains

Choon-Mee Kim1, Young-Jin Ko2, Ji Ae Choi3, Seong-Ho Kang2, Geon Park2, Sook-Jin Jang2

1Premedical Science

2Department of Laboratory Medicine, Chosun University College of Medicine, Gwangju

3Division of Infectious Disease Investigation 2, Jeollanam-do Institute of Health and Environment, Suncheon, Korea

Corresponding author: Sook-Jin Jang E-mail: sjbjang@chosun.ac.kr

Received 2 September 2022       Revised 1 December 2022       Accepted 8 December 2022

© Korean Society of Clinical Microbiology. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background: To solve the difficulty in determining the appropriate treatment regimen for patients infected with extensively drug-resistant Acinetobacter baumannii (XDRAB), it is necessary to develop various strategies to increase the therapeutic effect of antimicrobial agents. The purpose of this study was to select the treatment combination showing the greatest antimicrobial effect among seven candidate antimicrobial substances. Methods: Seven strains of XDRAB were used in this study. The composition of the treatment consisted of colistin as the base and one of the seven antimicrobial substances, doripenem, minocycline, tigecycline, linezolid, fusidic acid, vancomycin, or alyteserin E4K peptide. The interaction between the drugs in each combination was evaluated by measuring the synergy rates using time-kill analysis. Results: The synergy rates of the seven combinations tested in the time-kill assay in this study were as follows, in descending order from the combination with the highest synergy rate: colistin + minocycline (57.1%), colistin + alyteserin E4K (50.0%), colistin + tigecycline (42.9%), colistin + vancomycin (28.6%), colistin + doripenem (14.3%), colistin + fusidic acid (14.3%), and colistin + linzolid (0%). None of the combinations showed antagonism. The three combinations showing bactericidal activity and the rates of their bactericidal activity were colistin + alyteserin E4K combination (33.3%), colistin + minocycline (14.3%), and colistin + vancomycin (14.3%). Conclusion: The colistin + minocycline and colistin + alyteserin E4K treatment combinations, which showed high synergy rates, can be considered as promising candidates for future in vivo experiments evaluating combination therapies.

Keywords: Drug Combinations, Synergy, Colistin, Minocycline, Antimicrobial cationic peptides

[in Korean]

Supplementary materials

The Data Supplement is available with this article at https://doi.org/10.5145/ACM.2022.25.4.3.

Ethics statement

It is not a human population study; therefore, approval by the institutional review board or the obtainment of informed consent is not required.

Conflicts of interest

No potential conflicts of interest relevant to this article were reported.

Funding

이 연구는 2021년도 조선대학교병원 의료질 향상 학술 연구비(Grant No. 2021-18)의 지원을 받아 수행되었음.

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Table 1
Results of time-kill assay against two-drug combinations of colistin and various antibiotics or a peptide for seven extensively drugresistant A. baumannii clinical isolates
ACM-2504-03-t1-1.png
Table 1
Results of time-kill assay against two-drug combinations of colistin and various antibiotics or a peptide for seven extensively drugresistant A. baumannii clinical isolates (continued)
ACM-2504-03-t1-2.png

*≥3 log10 CFU/mL reduction compared with the initial inoculums; † <2 log10 change in CFU/mL at 24 hr with the combination compared with the most active single agent; ‡≥2 log10 CFU/mL reduction with the combination compared with the most active single agent of 24hr.

Abbreviation: VC, viable colony count; I, Indifference; NB, non-bactericidal; B, bactericidal; ND, not done; MASA, most active single agent.

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