Real-world experience with ceftolozane-tazobactam for multidrug-resistant gram-negative bacterial infections

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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.

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ePub ahead of print