786. Ceftaroline and Avibactam? Is This a Potential Combination for Mycobacterium abscessus Infection?

Abstract

Background Mycobacterium abscessus harbors a β-lactamase enzyme, BlaMab, able to hydrolyze penicillins, most cephalosporins and carbapenems. As of today, management of M. abscessus with β-lactams does not include combination of β-lactamase inhibitors. The potential benefit of combinations of several β-lactams with new diazabicyclooctane (DBO) inhibitors, such as relebactam and avibactam, has not been well studied. Based upon the ability to inhibit BlaMab by highly potent DBO inhibitors, our goal herein was to investigate the efficacy of a novel combination, ceftaroline (CEF) and avibactam (AVI), to restore susceptibility to β-lactam antibiotics and inhibit growth.MethodsMinimum inhibitory concentrations (MICs) of CEF with or without AVI were examined using the microdilution method.ResultsMIC50 and MIC90 of CEF is 8 mg/L; in the presence of 4 μg/mL of AVI, the MICs of CEF decreased to ≤4 mg/L in 31 of 35 cases (table).ConclusionOur results add to the growing evidence of using β-lactams as agents effective against Mycobacterial infections. Inhibition of the hydrolytic activity of (BlaMab) using DBOs such as AVI suggest that this combination should be evaluated in animal and clinical models.Table 1: MICs of M. abscessus Strains (mg/L).Avibactam (AV), Ceftaroline (CEF)CEFCEF+AVICEFCEF+AVI M. ab 15-10380.25 M. ab (ATCC)160.25 M. ab 15-44281 M. ab IDR1400012185320.25 M. ab 137-1056180.5 M. ab IDR14000111918<0.25 M. ab 15-305162 M. ab IDR130008519162 M. ab (bolletti) 15-148161 M. ab 138-479620.25 M. ab 16-492116-49161 M. ab (ATCC)32<215-228161 M. ab 16-2180.515-23580.5 M. ab 15-22880.5137-1061>1288 M. ab 15-2061281 M. ab 15-20632<0.25 M. ab 15-23580.5 M. ab 15-86640.5 M. ab 138-479632<215-305161 M. ab IDR1300085191616 M. ab 16-2120.5 M. ab IDR1400012185164 M. ab 15-10340.5 M. ab 15-86162 M. ab 15-14881 M. ab 132-105614115-442321 M. ab #341 M. ab 132-1056140.5 M. ab N140.5 M. ab #140.5 M. ab 60-20163232 M. ab #282 M. ab IDR14000111911616 M. ab #340.5 M. ab #14161 M. ab #4162 M. ab W281 M. ab #5>1284 M. ab #120.5<0.125 M. ab #6644 M. ab #13322 M. ab #740.5 M. ab #11160.5 M. ab #881 M. ab #10322 M. ab #9648 M. ab #741 M. ab #10648 M. ab #1160.5 M. ab #1140.5 M. ab #8180.25 M. ab #1240.5 M. ab #9324 M. ab #1340.5 M. ab #6321 M. ab #1481 M. ab #480.5 M. ab 60-20163232 M. ab #240.5 M. ab W280.5 M. ab #5>644 M. ab N140.5Disclosures All authors: No reported disclosures.