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. 2023 Jun 15;67(6):e0157922.
doi: 10.1128/aac.01579-22. Epub 2023 May 8.

In Vitro Synergistic Effects of Omadacycline with Other Antimicrobial Agents against Mycobacterium abscessus

Keiji Fujiwara  1   2   3 , Akio Aono  1 , Takahiro Asami  1 , Kozo Morimoto  2   4   5 , Keisuke Kamada  1 , Yuta Morishige  1 , Yuriko Igarashi  1 , Kinuyo Chikamatsu  1 , Yoshiro Murase  1 , Hiroyuki Yamada  1 , Akiko Takaki  1 , Satoshi Mitarai  1   3
Affiliations

In Vitro Synergistic Effects of Omadacycline with Other Antimicrobial Agents against Mycobacterium abscessus

Keiji Fujiwara et al. Antimicrob Agents Chemother. .

Abstract

The clinical importance of Mycobacterium abscessus species (MABS) infections has been increasing. However, the standard treatment regimens recommended in the current guidelines often result in unfavorable outcomes. Therefore, we investigated the in vitro activity of omadacycline (OMC), a novel tetracycline, against MABS to explore its potential as a novel therapeutic option. The drug susceptibilities of 40 Mycobacterium abscessus subsp. abscessus (Mab) clinical strains obtained from the sputum of 40 patients from January 2005 to May 2014 were investigated. The MIC results for OMC, amikacin (AMK), clarithromycin (CLR), clofazimine (CLO), imipenem (IPM), rifabutin (RFB), and tedizolid (TZD) alone and their combined effects (with OMC) were examined using the checkerboard method. Additionally, we studied the differences in the effectiveness of the antibiotic combinations based on the colony morphotype of Mab. The MIC50 and MIC90 of OMC alone were 2 and 4 μg/mL, respectively. The combinations of OMC with AMK, CLR, CLO, IPM, RFB, and TZD showed synergy against 17.5%, 75.8%, 25.0%, 21.1%, 76.9%, and 34.4% of the strains, respectively. Additionally, OMC combined with CLO (47.1% versus 9.5%, P = 0.023) or TZD (60.0% versus 12.5%, P = 0.009) showed significantly higher synergy against strains with rough morphotypes than those with smooth morphotypes. In conclusion, the checkerboard analyses revealed that the synergistic effects of OMC were observed most frequently with RFB, followed by CLR, TZD, CLO, IPM, and AMK. Furthermore, OMC tended to be more effective against rough-morphotype Mab strains.

Keywords: Mycobacterium abscessus; checkerboard method; nontuberculous mycobacteria; omadacycline; synergy.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

FIG 1
FIG 1
The MIC values and cumulative percentages of inhibited strains for seven antimicrobial agents and six combinations (omadacycline-based) tested in this study against 40 M. abscessus subsp. abscessus clinical strains.
FIG 2
FIG 2
The MIC values for the seven antimicrobial agents tested in this study and the cumulative percentages of inhibited strains among 38 M. abscessus subsp. abscessus clinical strains divided according to whether the colony morphotype was smooth or rough (smooth; n = 21, rough; n = 17).
See this image and copyright information in PMC

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