P31

Mycobacterium tuberculosis (Mtb) are intrinsically resistant to β-lactam antibiotics due to a β-lactamase, BlaC, but resistance may be overcome by a β-lactamase inhibitor (BLI). Thus, the repurposing of carbapenems, in combination with BLIs, may provide new treatment options. Therefore, we determined minimum inhibitory concentrations (MICs) for Mtb of meropenem-vaborbactam/clavulanic acid and tebipenem-clavulanic acid. Mtb isolates (n=102) were selected to include both wild-type (n=62) and drug-resistant strains assigned to lineage 1–5 and 7. Broth microdilution (BMD) MICs were determined according to the EUCAST reference method, with Middlebrook 7H9 (10% OADC) media in 96-well microtiter plates. Test concentrations of meropenem 0.5–32 mg/L and tebipenem 0.25–16 mg/L were used, combined with vaborbactam 8 mg/L and clavulanic-acid 4 mg/L (2 mg/L when combined with meropenem) respectively. H37Rv ATCC27294 was used as quality control for all batches. The addition of clavulanic-acid to tebipenem resulted in a 4-fold reduction of modal Mtb MIC, with similar results for 2 and 4 mg of clavulanic acid. The addition of a BLI also reduced the Mtb MICs of meropenem, more prominent for clavulanic-acid than vaborbactam. No significant difference in MIC levels was seen for different Mtb lineages or drug susceptibility pattern for other TB drugs. Mutations in the crfA and blaC regions, two potential resistance genes, did not affect the MIC either. The presence of a BLI significantly reduced the Mtb MICs of meropenem and tebipenem. In particular, the reduction in MICs of the orally available drugs tebipenem-clavulanic acid was most notable.