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. 2022 May 9;12(1):7541.
doi: 10.1038/s41598-022-11464-6.

In vitro synergistic antimicrobial activity of a combination of meropenem, colistin, tigecycline, rifampin, and ceftolozane/tazobactam against carbapenem-resistant Acinetobacter baumannii

Yong Guk Ju  1 , Hak Joon Lee  1 , Hong Soon Yim  2 , Min-Goo Lee  2 , Jang Wook Sohn  1   3 , Young Kyung Yoon  4   5
Affiliations

In vitro synergistic antimicrobial activity of a combination of meropenem, colistin, tigecycline, rifampin, and ceftolozane/tazobactam against carbapenem-resistant Acinetobacter baumannii

Yong Guk Ju et al. Sci Rep. .

Abstract

We investigated the in vitro activity of various antimicrobial combinations against carbapenem-resistant Acinetobacter baumannii (CRAB) isolates. The in vitro activity of six two-drug combinations against CRAB isolates collected from the blood samples of patients with bloodstream infection was evaluated using the checkerboard method and time-kill assay [0.5 ×, 1 ×, and 2 × minimum inhibitory concentration (MIC)] to identify potential synergistic and bactericidal two-drug combinations against CRAB isolates. The effects of meropenem, colistin, tigecycline, rifampin, and ceftolozane/tazobactam combinations were investigated. All 10 CRAB isolates in our study produced the OXA-58-type and OXA-23-type carbapenem-hydrolyzing oxacillinases. The colistin-ceftolozane/tazobactam combination showed synergistic effects in both the time-kill assay (using an antibiotic concentration of 1 × MIC) and the checkerboard method. It also showed bactericidal effects in the time-kill assay. For all 10 CRAB isolates, time-kill curves showed synergistic bactericidal activity of the colistin-ceftolozane/tazobactam combination at 0.5 × MIC. Overall, there was substantial discordance of synergistic activity between the checkerboard microdilution and time-kill assays (with a concordance of 31.7%). Our study demonstrated that two-drug combinations of colistin and ceftolozane/tazobactam could be useful treatment alternatives for CRAB infections. The effects of these antibiotic combinations should be evaluated using in vivo experimental models.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Time-kill curves of Acinetobacter baumannii isolates (CRAB 34) at 1 × minimum inhibitory concentration (MIC) for six combinations of antibiotics.
Figure 2
Figure 2
Time-kill curves of the 10 Acinetobacter baumannii isolates for six combinations of antibiotics with the different concentrations. C, colistin; C/T, ceftolozane/tazobactam; Me meropenem, R rifampin, T tigecycline.
See this image and copyright information in PMC

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