In vitro susceptibility of Mycobacterium tuberculosis isolates to tebipenem alone or in combination with -lactamase inhibitors

Objective To investigate the in vitro susceptibility of Mycobacterium tuberculosis isolates to tebipenem(TBM) alone or in combination with -lactamase inhibitors,as well as the correlation between its anti TB drug resistant phenotype and genotype and its susceptibility to tebipenem. Methods A total of 128 clinical isolates of drug sensitive(DS)and multidrug/extensively drug-resistant(M/XDR)M. tuberculosis were collected,of which 96(75.0%)belonged to the Beijing family and 32 (25.0%) belonged to non-Beijing family. The minimum inhibitory concentrations (MICs) were determined by the broth microdilution method based on Microplate Alamar Blue Assay(MABA). The differences in drug resistant rate between single use and combined use of the antibiotic were analyzed with 2 test. Results Tebipenem/clavulanate(TBM/CLA)showed the highest potent activity against M. tuberculosis strains(MIC90,2 g/ml),followed by tebipenem/avibactam(TBM/AVI)(MIC90, 4 g/ml). There were only 2 and 5 strains resistant to TBM/CLA and TBM/AVI,respectively. Among the different anti-TB drug resistance type strains,the resistant rates of DS strains to TBM,TBM/AVI and TBM/CLA were higher than those of M/XDR strains,but there was no significant difference(P0.05). Among the different genotype strains,the resistant rate of Beijing family strains to TBM(60.4%)was obviously higher than that of non-Beijing family strains(37.5%) (2=5.09,P=0.024),the difference was significant(P0.05). While the resistant rates to TBM/AVI of the two genotype strains had no significant difference (P0.05). Conclusion The combined use of TBM and CLA or AVI showed excellent activity against M. tuberculosis clinical isolates in vitro and there was a correlation between the Beijing genotype and TBM resistance phenotype, while it was not possible to determine whether the anti-TB drug resistance phenotype was associated with TBM resistance.