Background: Carbapenem-nonsusceptible Enterobacteriaceae (CRE) are often multidrug-resistant and infections caused by these organisms are associated with increased morbidity and mortality. The combination of avibactam (AVI), a non-β-lactam/β-lactamase inhibitor of Class A, C, and some D serine β-lactamases, with ceftazidime (CAZ) and aztreonam (ATM) is being developed to treat infections caused by CRE. CAZ-AVI reveals potent in vitro activity against CRE, except those producing metallo-β-lactamases (MBLs), whereas ATM-AVI inhibits growth of both MBL-positive and MBL-negative CRE. We evaluated the in vitro activity of CAZ-AVI and ATM-AVI against Enterobacteriaceae (Eba) isolates non-susceptible to meropenem (MEM-NS) collected in 2014-2017 in Latin America through the INFORM global surveillance program.
Methods: Non-duplicate clinically significant isolates were collected from 29 hospital laboratories located in Argentina, Brazil, Chile, Colombia, Mexico, and Venezuela. Susceptibility testing was performed by CLSI broth microdilution. AVI was tested at a fixed concentration of 4 µg/mL in combination with CAZ and ATM. MEM-NS Eba (MIC >1 µg/mL) were screened for the presence of β-lactamase genes by PCR and sequencing.
Results: 557 MEM-NS isolates were identified (440 Klebsiella pneumoniae and 117 isolates of 13 other species). Of these, 441 (79.2%) carried carbapenemases (Cpase) (KPC only, n=383; MBL only, n=48; OXA-48-like only, n=5; KPC and OXA-48-like, n=2; MBL and GES, n=2; MBL and KPC, n=1). CAZ-AVI showed potent in vitro activity against Cpase-positive MBL-negative and Cpase-negative Eba and against all MEM-NS Eba, but was not active against MBL-positive Eba. 100% of MEM-NS Eba were inhibited by ≤8 µg/mL of ATM-AVI.
Conclusion: CAZ-AVI and ATM-AVI displayed potent in vitro activity against MEM-NS Eba collected in LA. These agents could serve as promising options for treatment of infections caused by CRE.
G. G. Stone, Pfizer Inc.: Employee , Salary . AstraZeneca: Former Employee and Shareholder , Salary .
D. Sahm, Pfizer Inc.: Consultant , Consulting fee . IHMA, Inc.: Employee , Salary .