2248. Clinical and Microbiological Outcomes Associated with Real-World Use of Ceftolozane/Tazobactam

BACKGROUND: Ceftolozane/tazobactam (C/T) is a novel cephalosporin/β-lactamase inhibitor combination for treating Gram-negative infections, particularly Pseudomonas aeruginosa (PA). C/T has been FDA-approved for complicated intra-abdominal and urinary tract infections and has just completed a trial in ventilator nosocomial pneumonia, but real-world outcome data are still emerging. METHODS: Demographic, microbiologic, treatment and outcome data of patients who received C/T for ≥48 hours from January 2016 to August 2018 at multiple centers within a single hospital system were retrospectively collected. Available isolates were analyzed for C/T susceptibility (by Etest) and whole-genome sequencing (WGS). Spades v.3.11.1 was used for assembly, multi-locus sequence typing v2.10 performed for in silico MLST with the PubMLST database and Abricate v0.7 was used for resistance gene screening with the CARD database. RESULTS: Among 45 patients, 58% were non-white, 53% were female and 13% were immunocompromised. The median age was 64 years (IQR, 50 to 69). At the time of the index event, a high proportion of patients required ICU care (42%) and pressor support (13%) as well as had invasive devices in place (64%). A minority (2.4%) had prior exposure to C/T. Respiratory infections were most common (38%) followed by urinary tract (20%). Concomitant Gram-negative agents were used in 18%. 69% achieved clinical success (i.e., recovery from infection-related signs and symptoms). The in-hospital mortality rate was 16% of which 5 out of 7 were attributed to infection. Microbiology was available for 91% of patients; 84% had PA isolates resistant to at least 3 antipseudomonal classes (Figures 1 and 2). Ten PA isolates were analyzed with WGS (Table 1). C/T resistance arose during therapy in one patient (MIC increase from 1 to 128 µg/mL). WGS showed a substitution in AmpC β-lactamase (A46D) and presence of bla(CARB-2). CONCLUSION: Although C/T was used in a critically ill population with highly resistant organisms, cure rates were high and mortality was low. Acquired β-lactamases were not frequently seen among the PA isolates. C/T is a vital therapeutic option, particularly on MDR isolates for which options are limited. [Image: see text] [Image: see text] [Image: see text] DISCLOSURES: Samuel L. Aitken, PharmD, Melinta Therapeutoics: Grant/Research Support, Research Grant; Merck, Sharpe, and Dohme: Advisory Board; Shionogi: Advisory Board.