1603 - Comparison of Ceftolozane/Tazobactam, Ceftazidime/Avibactam, and Meropenem/Vaborbactam Activity Against P. aeruginosa: A Multicenter Evaluation

Background: Recent data have shown high rates of resistance and co-resistance of P. aeruginosa (PsA) to traditional first-line β-lactam antibiotics (piperacillin/tazobactam, ceftazidime, cefepime, and meropenem), with < 45% susceptibility to the others when resistance to one agent is present, driving a large medical need for newer agents. We compared the in vitro activity of newer Gram-negative antibiotics ceftolozane/tazobactam (CT), ceftazidime/avibactam (CA), and meropenem/vaborbactam (MV) against a global collection of PsA isolates.

Methods: Data were collected from multiple US hospitals as part of the SMART Surveillance Program (2019). Susceptibility testing (MIC, mg/L) was performed by broth microdilution, with susceptibility determined by CLSI breakpoints except for MV where EUCAST breakpoints were applied due to CLSI offering no susceptibility breakpoint criteria.

Results: 865 clinical P. aeruginosa isolates (one unique initial isolate per patient) were submitted from 21 US medical centers in 2019. 32% were from ICU patients; 71% were from lower respiratory tract infections. The phenotypic β-lactam susceptibility profile in this population was piperacillin/tazobactam (79%), ceftazidime (82%), cefepime (83%), and meropenem (78%). The table provides the comparative susceptibility rates. Co-resistance between commonly prescribed first line β-lactam antibiotics was common. CT, CA and MV were more active than traditional β-lactams, with CT having higher in vitro activity regardless of phenotype, followed by CA and then MV.Table. Probability of Coverage for P. aeruginosa when Non-Susceptibility or Resistance to a Given First Line β-lactam Antibiotic


Conclusion: To our knowledge, this is the largest multicenter head to head comparison of the activities of ceftolozane/tazobactam, ceftazidime/avibactam and meropenem/vaborbactam among P. aeruginosa with varying resistant phenotypes. Among the newer agents, ceftolozane/tazobactam demonstrated the most reliable in vitro activity against P. aeruginosa with resistance to traditional first-line β-lactams. Further studies are needed to translate the potential clinical relevance of these findings in different practice settings with varying rates of antimicrobial resistance among P. aeruginosa.