Methods: In the current study, we tested the in vitro activity of ceftaroline (CPT, a broad-spectrum cephalosporin), ceftazidime (CAZ, a third-generation cephalosporin), and aztreonam (ATM, a monobactam) with and without AVI, against 12 recent clinical isolates including Mycobacterium abscessus (4), Mycobacterium fortuitum (4), Mycobacterium marinum (2), Mycobacterium avium (1) and Mycobacterium smegmatis (1). Using a micro-dilution assay with 7H10 media, a range of drug concentrations from 2–512 µg/mL, was evaluated with and without AVI at a constant concentration of 4 µg/mL.
Results:ATM and CAZ, alone or in combination with AVI were ineffective against the different NTM species with most MICs >32 µg/mL. In contrast, CPT activity ranged from 8–16 µg/mL for most of the isolates and in combination with AVI, the MIC was generally lowered, including to MICs <4 µg/mL against 5 isolates.
Conclusion: These findings provide evidence that with a suitable β-lactam, AVI can reduce MICs against the majority of the NTM species and they justify the inclusion of these emerging pathogens in screens that assess novel β-lactamase inhibitors.
W. W. Nichols, AstraZeneca: Employee and Shareholder , Salary
B. N. Kreiswirth, None