1450 - Frequency of Carbapenem-resistant Pseudomonas aeruginosa Among Respiratory Pathogens Impacts First-Line Beta-Lactam Susceptibility: Potential Role for Ceftolozane/Tazobactam (C/T) and/or Imipenem/Relebactam (I/R)

Background: Carbapenem-resistant P. aeruginosa (CRPA) are associated with increased mortality and impose significant treatment challenges for clinicians. Among CRPA, co-resistance to 1^st line antipseudomonal agents piperacillin/tazobactam (TZP) and cefepime (FEP) is common and often results in delays to timely effective therapy. A simple strategy for identifying patients at risk for suboptimal therapy is evaluation of institutional or unit specific frequency of CRPA. The purpose of this analysis is to identify beta-lactam (BL) susceptibility trends based on CRPA frequency observed in intensive care units (ICU).

Methods: In 2016-2019, ~20 US institutions per year submitted up to 250 consecutive, aerobic or facultatively anaerobic, gram-negative pathogens from blood, intra-abdominal, urinary, and lower respiratory tract infections as part of the Study for Monitoring Antimicrobial Resistance Trends. A total of 871 P. aeruginosa (PA) isolates were collected from lower respiratory tract specimens obtained from ICU patients.  MICs were determined using CLSI broth microdilution method and interpreted with CLSI 2020 or FDA breakpoints.  Institutions were then stratified into one of three categories based on CRPA frequency: CRPA rates ≤20% (CR1), 21 – 40% (CR2), and ≥41% (CR3).  BL susceptibility was then evaluated relative to CRPA frequency.

Results: Thirty-seven (46%), 25 (31%), and 18 (23%) institutions were stratified into CR1, CR2, and CR3, respectively. Overall, CRPA was identified in 28.4% of all ICU lower respiratory isolates. Significant declines in FEP and TZP susceptibility were observed in institutions that demonstrated higher CRPA frequency (p< 0.00001) (Table 1) with >25% of isolates showing resistance in CR2 and CR3. In contrast, C/T susceptibility remained above 90% for all categories. I/R susceptibility remained above 90% for CR1 and CR2.Table 1. P. aeruginosa susceptibility among ICU lower respiratory tract isolates stratified by unit specific frequency of carbapenem resistance


Conclusion: C/T and I/R provide robust activity against PA isolates obtained from the lower respiratory tract of critically ill patients, regardless of CR frequency. Assessing CRPA frequency may be useful for identifying inflection points in which novel agents could be considered. In settings where CRPA frequency exceeded 20%, additional testing or early switch to C/T or I/R may be warranted.