Abstract
Therapeutic options for treating Mycobacterium abscessus infections are extremely limited; quinolones are important. The in vitro anti-M. abscessus activities of nine quinolones, emphasizing sitafloxacin, were investigated. Antimicrobial susceptibility testing was performed on 10 non-tuberculous mycobacterium reference strains and 194 clinical, M. abscessus isolates. The activity of sitafloxacin against intracellular M. abscessus residing within macrophages was also evaluated. A checkerboard assay was conducted to determine synergy between sitafloxacin and 10 clinically important antibiotics. Among the nine quinolones tested, sitafloxacin exhibited the greatest anti-M. abscessus activity with MIC50 and MIC90 of 1 and 2 mg/L, respectively. Sitafloxacin exerted a bacteriostatic effect on M. abscessus and inhibited the intracellular growth of M. abscessus at concentrations equivalent to clarithromycin. No antagonism between sitafloxacin and 10 clinically important anti-M. abscessus antibiotics was evident. In summary, sitafloxacin exhibited a significant advantage relative to other quinolones in inhibiting the growth of M. abscessus in vitro, suggesting the potential inclusion of sitafloxacin in new strategies to treat M. abscessus infections.
Highlights
The number of infections caused by non-tuberculous mycobacteria (NTM) is increasing globally (Cowman et al, 2019; Johansen et al, 2020; Mourad et al, 2021)
Subspecies analysis found that M. abscessus subsp. abscessus isolates were significantly more sensitive to sitafloxacin than M. abscessus subsp. massiliense isolates (Table 2)
The minimum bactericidal concentration (MBC)/MIC ratio evidenced the bacteriostatic activity expressed by sitafloxacin toward M. abscessus, which is the same as that exhibited by other quinolones
Summary
The number of infections caused by non-tuberculous mycobacteria (NTM) is increasing globally (Cowman et al, 2019; Johansen et al, 2020; Mourad et al, 2021). M. abscessus infections are the most challenging to treat due to an intrinsic resistance to many common antibiotics (Fletcher et al, 2016; Degiacomi et al, 2019). Sitafloxacin is an oral quinolone, which exhibits excellent antibacterial activity by simultaneously inhibiting DNA gyrase and topoisomerase IV in a broad range of bacteria including mycobacteria (Tomioka et al, 1999; Sato et al, 2003; Amano et al, 2016; Nakajima et al, 2016; Asakura et al., 2019; Kamada et al, 2021). Reports of the successful treatment of cases of M. abscessus-associated pneumonia with drug combinations that included sitafloxacin have provoked a recent interest
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