LAUSR

Abstract Background The dissemination of multi-drug-resistant Enterobacteriaceae (MDR Eba) threatens the treatment of Gram-negative infections. Ceftazidime–avibactam (CAZ-AVI) is a novel antimicrobial with activity against Eba producing Class A, C and some Class D β-lactamases. This study evaluates the in vitro activity of CAZ-AVI against Eba isolates from urinary tract infections (UTI), intra-abdominal infections (IAI) and lower respiratory tract infections (LRTI) gathered in Latin America (LA) from 2012 to 2016. Methods A total of 7,037 non-duplicate Eba were collected from UTI, IAI, or LRTI in 26 sites in 6 countries in LA, as a part of the INFORM surveillance study from 2012 to 2016. Susceptibility testing was by broth microdilution using CLSI 2018 breakpoints. CAZ-AVI was tested with a fixed concentration of 4 µg/mL avibactam. Meropenem nonsusceptibility prompted β-lactamase screening by PCR and sequencing. Results CAZ-AVI demonstrated potent in vitro activity against Eba from UTIs, IAIs and LRTIs (99.6%, 99.8%, and 99.5% susceptible, respectively). CAZ-AVI was active against colistin-resistant and MDR Eba as well as meropenem-non-susceptible Eba not encoding metallo-β-lactamases (96.5%, 98.4% and 99.4% susceptible, respectively) (table). Phenotype CAZ-AVI (%Susceptible, n) All (n) UTI (n) IAI (n) LRTI (n) Eba, All 99.6% (7,037) 99.6% (2,918) 99.8% (2,401) 99.5% (1,718) CAZ-NS 98.7% (2,110) 98.4% (797) 99.2% (709) 98.5% (604) MEM-NS 93.8% (372) 93.2% (147) 95.7% (116) 92.7% (109) MEM-NS, MBL-negative 99.4% (351) 99.3% (138) 99.1% (112) 100% (101) CST-Ra 96.5% (144) 98.4% (63) 97.3% (37) 93.2% (44) MDRb 98.4% (1,456) 98.1% (591) 98.8% (480) 98.2% (385) Infection source: UTI, urinary tract; IAI, intra-abdominal tract; LRTI, lower respiratory tract. CAZ-AVI, ceftazidime–avibactam; CAZ, ceftazidime; MEM, meropenem; CST, colistin; MDR, multidrug-resistant; MBL, metallo-β-lactamase; NS, non-susceptible; R, resistant. aExcludes Proteeae and Serratia spp; CST breakpoints are by EUCAST 2018. bMDR, resistant to agents from ≥3 classes. Conclusion CAZ-AVI exhibited potent in vitro activity against Eba from UTIs, IAIs and LRTIs isolated in Latin America from 2012 to 2016 and provides a vital alternative to colistin and meropenem when MBLs are not present. Disclosures M. Estabrook, Pfizer, Inc.: Consultant, Consulting fee. IHMA, Inc.: Employee, Salary. K. Kazmierczak, Pfizer Inc.: Consultant, Consulting fee. IHMA, Inc.: Employee, Salary. G. G. Stone, Pfizer Inc.: Employee, Salary. AstraZeneca: Former Employee and Shareholder, Salary. D. Sahm, Pfizer Inc.: Consultant, Consulting fee. IHMA, Inc.: Employee, Salary.