Comparison of four β-lactamase inhibitors in combination with ampicillin against Mycobacterium tuberculosis

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Abstract
The in-vitro activity of a β-lactamase inhibitor (clavulanic acid, sulbactam, BL-P2013 or BL-P2090) in combination with ampicillin against 13 isolates of Mycobacterium tuberculosis was determined by broth dilution. The agents were tested in 1:1 molar ratio of ampicillin to β-lactamase inhibitor. The β-lactamase inhibitors alone did not inhibit growth at the highest concentration tested. The MIC90 for ampicillin alone was > 32 mg/l. Clavulanic acid plus ampicillin was the most active combination with an MIC90 of 11 μM (4 mg/l of ampicillin). The MIC90 of ampicillin in combination with sulbactam, BL-P2013 or BL-P2090 was 23 μM (8 mg/l of ampicillin). A 1:1 ratio of ampicillin to inhibitor was more active than was a 2:1 ratio. The addition of a β-lactamase inhibitor to ampicillin greatly improves its in-vitro activity against M. tuberculosis.