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The synergetic effect of sitafloxacin-arbekacin combination in the Mycobacterium abscessus species.

ABSTRACT: Mycobacterium abscessus species (MABS) is the most commonly isolated rapidly growing mycobacteria (RGM) and is one of the most antibiotic-resistant RGM with rapid progression, therefore, treatment of MABS is still challenging. We here presented a new combination treatment with sitafloxacin that targeted rough morphotypes of MABS, causing aggressive infections. Thirty-four clinical strains of MABS were isolated from various clinical samples at the Juntendo university hospital from 2011 to 2020. The susceptibility to a combination of sitafloxacin and antimicrobial agents was compared to that of the antimicrobial agents alone. Out of 34 MABS, 8 strains treated with sitafloxacin-amikacin combination, 9 of sitafloxacin-imipenem combination, 19 of sitafloxacin-arbekacin combination, and 9 of sitafloxacin-clarithromycin combination showed synergistic effects, respectively. Sitafloxacin-arbekacin combination also exhibited the synergistic effects against 10 of 22 Mycobacterium abscessus subspecies massiliense (Mma) strains and 8 of 11 Mycobacterium abscessus subspecies abscessus (Mab) strains, a highly resistant subspecies of MABS. The sitafloxacin-arbekacin combination revealed more synergistic effects in rough morphotypes of MABS (p = 0.008). We demonstrated the synergistic effect of the sitafloxacin-arbekacin combination against MABS. Further, this combination regimen might be more effective against Mab or rough morphotypes of MABS.

SUBMITTER: Watanabe J

PROVIDER: S-EPMC9899205 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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The synergetic effect of sitafloxacin-arbekacin combination in the Mycobacterium abscessus species.

Watanabe Junko J Ihara Hiroaki H Takei Satomi S Nakamura Ayako A Fujimoto Yuichi Y Handoh Tetsuya T Kurokawa Kana K Arai Yuta Y Shibayama Kohei K Sumiyoshi Issei I Ochi Yusuke Y Okabe Takahiro T Misawa Shigeki S Togo Shinsaku S Naito Toshio T Tabe Yoko Y Miida Takashi T Takahashi Kazuhisa K

Scientific reports 20230204 1

Mycobacterium abscessus species (MABS) is the most commonly isolated rapidly growing mycobacteria (RGM) and is one of the most antibiotic-resistant RGM with rapid progression, therefore, treatment of MABS is still challenging. We here presented a new combination treatment with sitafloxacin that targeted rough morphotypes of MABS, causing aggressive infections. Thirty-four clinical strains of MABS were isolated from various clinical samples at the Juntendo university hospital from 2011 to 2020. T ...[more]

PMID: 36739345

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Project description:Our previous study identified that the Mycobacterium abscessus subsp. abscessus T28 sequevar does not fully represent inducible macrolide resistance. Thus, we initiated a correlation study between genotypes and phenotypes. In total, 75 isolates from patients with skin and soft tissue infections were enrolled in the study. These strains were tested against 11 antimycobacterial agents using Sensitire RAPMYCO plates and the CLSI-recommended broth microdilution method. In order to analyze erm(41) and partial hsp65, rpoB, secA1, and rrl genes, bacterial genomic DNA was extracted from bacteria. The MEGA X software was used for phylogenetic analyses. The most active agents against most M. abscessus species were amikacin and tigecycline. Clarithromycin was effective toward M. abscessus subsp. massiliense and nearly all M. abscessus subsp. abscessus C28 sequevars. Two varieties of M. abscessus subsp. abscessus T28 sequevars did not represent inducible macrolide resistance. Most M. abscessus species showed intermediate susceptibility to cefoxitin and imipenem. Six additional agents were less effective against M. abscessus species. Following phylogenetic analyses, two outliers of M. abscessus subsp. abscessus T28 sequevars seem to represent no inducible macrolide resistance. In addition, we discovered genetic mosaicism of hsp65, rpoB, and secA1 in M. abscessus species was common. T28 sequevars of M. abscessus subsp. abscessus do not fully represent inducible macrolide resistance. The outlier of erm(41) phylogeny of the M. abscessus subsp. abscessus T28 sequevar is possibly due to macrolide susceptibility. Evaluation of the antimicrobial susceptibility of M. abscessus species is a reliable tool for assisting physicians in selecting the most effective antimycobacterial agent(s). IMPORTANCE Macrolides are the mainstays of the antimycobacterial regimens against Mycobacterium abscessus species (formerly Mycobacterium abscessus complex). erm(41) confers inducible macrolide resistance for M. abscessus subsp. bolletii strains, and the majority of M. abscessus subsp. abscessus T28 sequevars. Furthermore, the acquired macrolide resistance of M. abscessus species is due to a point mutation in rrl. However, not all M. abscessus subsp. abscessus T28 sequevars have inducible macrolide resistance. Exploration of the mechanism of macrolide resistance requires an understanding of genetic diversity. The genetic mosaicism of the erm(41), rpoB, hsp65, and secA1 genes within three subspecies of M. abscessus species is not uncommon. The T28 sequevar of erm(41) confers inducible macrolide resistance to the genetic mosaic strain. The development of new anti-M. abscessus species infection overcoming inducible macrolide resistance and/or acquired macrolide resistance is a crucial issue.

Dataset Information

The synergetic effect of sitafloxacin-arbekacin combination in the Mycobacterium abscessus species.

Publications

The synergetic effect of sitafloxacin-arbekacin combination in the Mycobacterium abscessus species.

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