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Objectives   Evaluating the activity of nineteen  β -lactams in combination with different  β -lactamase inhibitors to determine the most potent combination against  Mycobacterium tuberculosis  (MTB)  in vitro .Methods   Drug activity was examined by drug susceptibility test with 122 clinical isolates from China. Mutations of  blaC  and drug targets  ldt   Mt1  ,  ldt   Mt2  ,  dacB2,  and  crfA  were analyzed by nucleotide sequencing.Results   Tebipenem (TBM) in combination with clavulanate (CLA) exhibited the highest anti-TB activity. The MIC of  β -lactam antibiotics was reduced most evidently in the presence of CLA, compared to avibactam (AVI) and sulbactam (SUB). Eight polymorphism sites were identified in  blaC , which were not associated with  β -lactams resistance. Interestingly, one strain carrying G514A mutation in  blaC  was highly susceptible to  β -lactams regardless of the presence of inhibitors. The transpeptidase encoding genes,  ldt   Mt1  ,  ldt   Mt2  , and  dacB2 , harboured three mutations, two mutations, and one mutation, respectively, but no correlation was found between these mutations and drug resistance.Conclusion   The activity of  β -lactams against MTB and different synergetic effect of  β -lactamase inhibitors were indicated. TBM/CLA exhibited the most activity and has a great prospect in developing novel anti-TB regimen; however, further clinical research is warranted. Moreover, the resistance to the  β -lactam antibiotics might not be conferred by single target mutation in MTB and requires further studies.

biomed research international

In Vitro Activity of β-Lactams in Combination with β-Lactamase Inhibitors against Mycobacterium tuberculosis Clinical Isolates