Real-world experience with ceftolozane-tazobactam for multidrug-resistant gram-negative bacterial infections
Jorgensen SCJ, Trinh TD, Zasowski EJ, Lagnf AM, Simon SP, Bhatia S, Melvin SM, Steed ME, Finch NA, Morrisette T, Estrada SJ, Rosenberg JR, Davis SL, and Rybak MJ. Real-world experience with ceftolozane-tazobactam for multidrug-resistant gram-negative bacterial infections. Antimicrob Agents Chemother 2020.
Antimicrobial agents and chemotherapy
Objective: To describe the prescribing practices, clinical characteristics, and outcomes of patients treated with ceftolozane-tazobactam (C/T) for multidrug-resistant (MDR) gram-negative infections.Methods: Multicenter, retrospective, cohort study at eight U.S. medical centers (2015-2019). Inclusion criteria were age >/=18 years and receipt of C/T (>/=72 hours) for suspected or confirmed MDR gram-negative infection. The primary efficacy outcome, evaluated amongst patients with MDR Pseudomonas aeruginosa infections, was composite clinical failure: 30-day all-cause mortality, 30-day recurrence and/or failure to resolve or improve infection signs or symptoms on C/T.Results: In total, 259 patients were included. P. aeruginosa was isolated in 236(91.1%). The MDR and extremely drug-resistant phenotypes were detected in 95.8% and 37.7% of P. aeruginosa isolates, respectively. The most common infection source was the respiratory tract (RTI, 62.9%). High dose C/T was used in 71.2% of patients with a RTI overall, but in only 39.6% of patients with a RTI who required C/T renal dose adjustment. In the primary efficacy population (n=226), clinical failure and 30-day mortality occurred in 85(37.6) and 39(17.3%) patients, respectively. New C/T MDR P. aeruginosa resistance was detected in three of 31 patients (9.7%) with follow-up cultures. Hospital-acquired infection and APACHE II score were independently associated with clinical failure (aOR 2.472, 95% CI 1.322-4.625 and aOR 1.068, 95% CI 1.031-1.106, respectively). Twenty-five (9.7%) patients experienced >/= one adverse effect (nine acute kidney injury, 13 Clostridioides difficile infection, one hepatotoxicity, two encephalopathy and two gastrointestinal intolerance)Conclusions: C/T addresses an unmet medical need in patients with MDR gram-negative infections.
ePub ahead of print