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In vitro Antimicrobial Activity Comparison of Linezolid, Tedizolid, Sutezolid and Delpazolid Against Slowly Growing Mycobacteria Isolated in Beijing, China

ABSTRACT:

Background

The antimicrobial activities of some new oxazolidinones against slowly growing mycobacteria (SGM) have never been well evaluated.

Methods

We evaluate the in vitro susceptibility of 20 reference strains and 157 clinical isolates, pertaining different SGM species, against four oxazolidinones, ie, delpazolid, sutezolid, tedizolid and linezolid. In addition, the association of linezolid resistance and mutations in 23srRNA, rplC, rplD were also tested.

Results

Sutezolid presented the strongest antimicrobial activity against the clinical isolates of M. intracellulare than the other oxazolidinones, with MIC50 at 2 μg/mL and MIC90 at 4 μg/mL. MICs of sutezolid were usually 4- to 8-fold lower than these of linezolid against M. intracellulare and M. avium. The tested isolates of M. kansasii were susceptible to all of the four oxazolidinones. According to the multiple sequence alignment, novel 23srRNA mutations (A2267C and A2266G) in M. intracellulare and rplD mutations (Thr147Ala) in M. avium were identified in this study which have plausible involvement in rendering resistance against linezolid.

Conclusion

This study showed that sutezolid harbors the strongest inhibitory activity against M. intracellulare, M. avium and M. kansasii in vitro, which provided important insights on the potential clinical application of oxazolidinones for treating SGM infections.

SUBMITTER: Yu X

PROVIDER: S-EPMC8590452 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:OBJECTIVE:The objective of the research was to assess the susceptibility of the slowly growing nontuberculous mycobacteria strains to the antimicrobial drugs used for mycobaterioses treatment using SLOMYCO test system. MATERIALS AND METHODS:We assessed 363 NTM strains: 177 MAC (161 M. avium, 16 M. intracellulare), 112 M. kansasii and 74 M. xenopi collected from the respiratory material of the patients were under the treatment or under diagnostic procedures at our Center, affiliates and the diagnostic department in 2010-2016. Drug sucseptibility for NTM was tested using the Sensititre SLOWMYCO system (TREK DIAGNOSTIC Systems Ltd., UK). MICs were established by microdilutions in Mueller-Hinton broth on polystyrene 96-well plates. The statistical analysis was done using the StatGraphics Plus 5.0 software. The data were compared pairwise using Pearson ?2 test with Yates correction. 95% confidence interval (CI) were calculated. Statistically significant differences were considered for p <0.05. Log-rank test and Kaplan-Meier curves were used to assess the concentration-dependent surveillance probability. RESULTS:The statistically significant differences were revealed in sensitivity/resistance isolates of M. avium and M. intracellulare: M. avium strains were resistant to higher concentrations of amikacin, clarithromycin, linezolid and streptomycin (p <0.01); M. intracellulare strains were resistant to higher concentrations of ethionamide (p <0.05). The isolates of M. avium were significantly more resistant than M. kansasii to amikacin, doxycycline, isoniazid, clarithromycin, linezolid, moxifloxacin, rifabutin, rifampicin, streptomycin, trimethoprim/sulfamethoxazole, ciprofloxacin, ethambutol, ethionamide (visible growth of M. avium were inhibited by higher drug concentrations, p <0.01). The isolates of M. avium showed significantly higher resistance than M. xenopi to amikacin, doxycycline, isoniazid, clarithromycin, linezolid, moxifloxacin, rifampicin, streptomycin, trimethoprim/sulfamethoxazole, ciprofloxacin, ethambutol, and ethionamide (visible growth of M. avium were inhibited by higher drug concentrations, p <0.01). Statistically significant differences in the dynamics of the response to the antibacterial effects of isoniazid, linezolid, moxifloxacin, rifampicin, trimethoprim/sulfamethoxazole, ethambutol, and ethionamide were found for M. intracellulare and M. xenopi (complete inhibition of the visible growth of M. intracellulare required higher drugs concentrations, p <0, 05). Comparison of the Kaplan-Meyer curves revealed statistically significant differences in survialence probability of M. kansasii and M. xenopi for amikacin, doxycycline, rifampicin, trimethoprim/sulfamethoxazole, ciprofloxacin, ethambutol, and ethionamide (a higher number of isolates of M. xenopi were inhibited by low drugs concentrations, p <0.05). CONCLUSIONS:Our data show that M. avium and M. intracellulare were more resistant to the majority of the studied drugs than M. kansasii and M. xenopi.