580. Evaluation of Avibactam Combined with β-lactams Against Non-Tuberculous Mycobacteria
Session: Poster Abstract Session: Non-Tuberculosis Mycobacterial
Thursday, October 27, 2016
Room: Poster Hall
Background: Nontuberculous mycobacteria (NTM), defined as any mycobacterial pathogen other than Mycobacterium tuberculosis, are a diverse group of pathogens that collectively cause substantial but often unappreciated illness worldwide. As a result of their intrinsic resistance to M. tuberculosis drugs and general antibiotics, there are limited treatment options against NTM infections. β-lactams have not been routinely used against NTMs due to intrinsic resistance, caused in some by chromosomally-encoded β-lactamases. The recent approval of avibactam (AVI), a non-β-lactam, β-lactamase inhibitor raises the possibility that its use in combination with a β-lactam might have activity against NTMs.

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.

Ruchi Pandey, PhD, Public Health Research Institute, Rutgers University, Newark, NJ, Gregory G. Stone, PhD, AstraZeneca, Waltham, MA, Wright W. Nichols, PhD, Formerly AstraZeneca Pharmaceuticals, Waltham, MA and Barry N. Kreiswirth, PhD, Public Health Research Institute Tuberculosis Center, Rutgers University, Newark, NJ

Disclosures:

R. Pandey, None

G. G. Stone, AstraZeneca: Employee and Shareholder , Salary

W. W. Nichols, AstraZeneca: Employee and Shareholder , Salary

B. N. Kreiswirth, None

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