Ceftazidime-avibactam activity when tested against ceftazidime-nonsusceptible Citrobacter spp., Enterobacter spp., Serratia marcescens, and Pseudomonas aeruginosa from Unites States medical centers (2011–2014)

• Bacteria expressing derepressed AmpC β-lactamases are often resistant to multiple agents.
• Avibactam effectively inactivates class C β-lactamases, protecting companion β-lactams from hydrolysis by AmpC hyperproducing strains.
• Ceftazidime-avibactam retained potent in vitro activity against ceftazidime-nonsusceptible Enterobacteriaceae.
• Overall, 99.3% (1015 of 1022) of ceftazidime-nonsusceptible Enterobacteriaceae were susceptible to ceftazidime-avibactam.
• Ceftazidime-avibactam showed greater in vitro activity than ceftazidime tested alone against P. aeruginosa.

A total of 6910 Enterobacteriaceae with inducible AmpC β-lactamases and 5328 Pseudomonas aeruginosa were collected from 71 US hospitals in 2011–2014 and were susceptibility tested using the reference broth microdilution method. Ceftazidime-avibactam demonstrated potent in vitro activity against all 3 Enterobacteriaceae genus groups evaluated, with MIC50/MIC90 values of 0.12/0.5 μg/mL for Enterobacter spp. and Serratia marcescens and 0.12/0.25 μg/mL for Citrobacter spp. (99.8–99.9% susceptibility rates at ≤8 μg/mL). Furthermore, 99.3% of ceftazidime-nonsusceptible Enterobacteriaceae isolates (1015 of 1022) were susceptible to ceftazidime-avibactam (MIC50/MIC90 of 0.25–0.5/1–2 μg/mL), whereas susceptibility rates for cefepime ranged from 45.9% (Citrobacter spp.) to 80.0% (S. marcescens). Ceftazidime-avibactam was also very active against P. aeruginosa (MIC50/MIC90, 2/4 μg/mL; 96.8% inhibited at ≤8 μg/mL). P. aeruginosa susceptibility rates to other antipseudomonal β-lactams ranged from 79.6% for piperacillin-tazobactam to 84.5% for cefepime. Ceftazidime-avibactam inhibited 67.4% of isolates at ≤8 μg/mL (MIC50/MIC90, 8/32 μg/mL) that were nonsusceptible to ceftazidime, cefepime, piperacillin-tazobactam, and meropenem.