624. Probability of Target Attainment of Ceftolozane/Tazobactam Among Adult Patients with Hospital-Acquired Pneumonia/Ventilator-Associated Pneumonia Secondary to Pseudomonas aeruginosa in Latin America

Abstract

Abstract Background Pseudomonas aeruginosa (Pa) is a common cause of nosocomial pneumonia; resistance among traditionally used empiric agents is observed frequently. To improve patient outcomes, a heightened focus has been placed on evaluating the adequacy of recommended dosing regimens, particularly of beta-lactams. The Phase 3 study ASPECT-NP demonstrated the efficacy and safety of 3 g of ceftolozane/tazobactam (C/T) infused every 8 h for 8 to 14 days for treatment of adults with Hospital-Acquired Pneumonia/Ventilator-Associated Pneumonia (HAP/VAP). We assessed the Probability of Target Attainment (PTA) of the C/T 3g dosage regimen in patients with HAP/VAP due to Pa, with an additional focus on carbapenem-resistant Pa, from Latin America. Methods Non duplicate Pa isolates from a respiratory source were collected as part of the SMART surveillance program from 36 sites in 10 Latin American countries during 2017-2020. MICs were determined by broth microdilution and interpreted by CLSI criteria. C and T concentration-time profiles were simulated in plasma and ELF following administration of the approved 3g (2g/1g) C/T dose (or equivalent dose adjusted based on renal function) administered by 1-hour infusion every 8 hours. PTA in plasma and ELF was calculated using the PK/PD target of 30% fT > MIC for C. T does not contribute to the antipseudomonal activity of C and therefore was not considered. Results A total of 2,757 P. aeruginosa were collected, of which 1208 (43.8%) were carbapenem nonsusceptible. C/T susceptiblity was 87.7% against all Pa and 73.4% among carbapenem nonsusceptible strains. At C/T doses of 2g/1g (CrCL > 50mL/min); 1g/0.5g (30mL/min≤ CrCL≤ 50mL/min), and 500mg/250mg (15mL/min≤ CrCL≤29mL/min), steady-state ceftolozane plasma and ELF PTA was 100% and > 99%, respectively, for isolates with an MIC at the Pa susceptiblity breakpoint of 4 µg/mL. Ceftolozane plasma and ELF PTA remained above 90% up to an MIC of 16 µg/mL and 8 µg/mL, respectively. Conclusion The regulatory approved pneumonia dosage regimen of C/T 3g (administered over 1 hour) every 8 hours (or equivalent dose adjusted based on renal function) resulted in high plasma and ELF PTAs sufficient to cover the vast majority of circulating P. aeruginosa present in Latin America, including carbapenem resistant strains. Disclosures Aline Okuma, PharmD, MSD Brazil: Employee Thales Polis, MD, MSD Brazil: Employee Jacqueline Pavia, MD, MSD COLOMBIA: EMPLOYEE Gustavo Mizuno, PharmD, MSD Brazil: Employee Jacqueline Ferrari, MD, MSD Brazil: Employee Charles A. DeRyke, PharmD, Merck & Co., Inc. Merck Research Laboratories: Stocks/Bonds.