2125. Activity of Novel β-Lactam/β-Lactamase Inhibitor Combinations against Serine-Carbapenemase producing Carbapenem-Resistant Pseudomonas aeruginosa

BACKGROUND: Antimicrobial resistance in Pseudomonas aeruginosa is complex and multifaceted. While the novel β-lactamase inhibitors (BLI), avibactam, relebactam, and vaborbactam inhibit serine-based β-lactamases, the comparative potency of the novel β-lactam (BL) /BLI combinations against serine-carbapenemase producing P. aeruginosa is unknown. The present study sought to compare the in vitro activity of ceftazidime/avibactam, ceftazidime, imipenem/relebactam, imipenem, meropenem/vaborbactam, and meropenem against serine-β-lactamase producing P. aeruginosa. METHODS: Carbapenem-resistant P. aeruginosa were collated through the Enhancing Rational Antimicrobials against Carbapenem-resistant P. aeruginosa (ERACE-PA) Global Surveillance. Isolates positive for serine-based carbapenemases were assessed. Minimum inhibitory concentrations (MICs) were determined by broth microdilution to each novel-BL/BLI and BL alone. In vitro potency was assessed by MIC(50/90) and percent of isolates susceptible per CLSI guidance. RESULTS: GES was the most common carbapenemase identified (n=59) followed by KPC (n=8). Ceftazidime/avibactam had MIC(50)/MIC(90) values of 4/8 mg/L and 91% of isolates were susceptible. Conversely, ceftazidime alone was active against only 3% of isolates. The MIC(50)/MIC(90) of imipenem/relebactam were 16/ >16 mg/L and 13% of all isolates were defined as susceptibility. Against the KPC-producing isolates, 38% were susceptible to imipenem/relebactam compared with 0% for imipenem. The meropenem/vaborbactam MIC(50)/MIC(90) were >16/ >16 mg/L, and 6% of isolates were susceptible which was similar to meropenem alone (MIC(50)/(90), >8/ >8 mg/L; 3% susceptible) suggesting the addition of vaborbactam cannot overcome co-expressed, non-enzymatic resistance mechanisms. CONCLUSION: Among the novel BL/BLIs, ceftazidime/avibactam displayed better in vitro activity and thus is a rational treatment option for serine-carbapenemase harboring P. aeruginosa. While imipenem/relebactam displayed some activity particularly against isolates with bla(KPC), meropenem/vaborbactam exhibited poor activity with MICs similar to meropenem alone. These data can be integrated with rapid molecular diagnostics to guide empiric therapy. DISCLOSURES: Christian M. Gill, PharmD, Cepheid: Grant/Research Support|Entasis therapeutics: Grant/Research Support|Everest Medicines: Grant/Research Support|Shionogi: Grant/Research Support David P. Nicolau, PharmD, Allergan: Advisor/Consultant|Allergan: Grant/Research Support|Cepheid: Advisor/Consultant|Cepheid: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Tetraphase: Advisor/Consultant|Tetraphase: Grant/Research Support|Venatorx: Advisor/Consultant|Venatorx: Grant/Research Support|Wockhardt: Advisor/Consultant|Wockhardt: Grant/Research Support