1603. Comparison of Ceftolozane/Tazobactam, Ceftazidime/Avibactam, and Meropenem/Vaborbactam Activity Against P. aeruginosa: A Multicenter Evaluation
Authors: Moise Pamela , DeRyke C Andrew , Gonzalez Marcela , Alekseeva Irina , Lopez Diego , Akrich Brune , Sahm Daniel F , Hackel Meredith , Young Katherine , Motyl Mary 
Published: January 2021

Abstract

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 &lt; 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.

Disclosures
Pamela Moise, PharmD, Merck & Co., Inc. (Employee, Shareholder) C. Andrew DeRyke, PharmD, Merck & Co., Inc. (Employee, Shareholder) Marcela Gonzalez, MD, MSD (Employee, Shareholder) Irina Alekseeva, MD, PhD, MSD (Employee, Shareholder) Diego Lopez, MD, MSD (Employee, Shareholder) Brune Akrich, MD, MSD (Employee, Shareholder) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor) Katherine Young, MS, Merck & Co., Inc. (Employee, Shareholder)Merck & Co., Inc. (Employee, Shareholder) Mary Motyl, PhD, Merck & Co, Inc (Employee, Shareholder)