Ceftolozane/tazobactam for treatment of severe ESBL-producing enterobacterales infections: A multicenter nationwide clinical experience (CEFTABUSE II Study)

Background: Few data are reported in the literature about the outcome of patients with severe extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-E) infections treated with cefolozane/tazobactam (C/T), in empiric or defnitive therapy. Methods: A multicenter retrospective study was performed in Italy (June 2016-June 2019). Successful clinical outcome was defined as complete resolution of clinical signs/symptoms related to ESBL-E infection and lack of microbiological evidence of infection. The primary end point was to identify predictors of clinical failure of C/T therapy. Results: C/T treatment was documented in 153 patients: pneumonia was the most common diagnosis (n = 46, 30%), followed by 34 cases of complicated urinary tract infections (22.2%). Septic shock was observed in 42 (27.5%) patients. C/T was used as empiric therapy in 46 (30%) patients and as monotherapy in 127 (83%) patients. Favorable clinical outcome was observed in 128 (83.7%) patients; 25 patients were considered to have failed C/T therapy. Overall, 30-day mortality was reported for 15 (9.8%) patients. At multivariate analysis, Charlson comorbidity index >4 (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.9-3.5; P =.02), septic shock (OR, 6.2; 95% CI, 3.8-7.9; P <.001), and continuous renal replacement therapy (OR, 3.1; 95% CI, 1.9-5.3; P =.001) were independently associated with clinical failure, whereas empiric therapy displaying in vitro activity (OR, 0.12; 95% CI, 0.01-0.34; P <.001) and adequate source control of infection (OR, 0.42; 95% CI, 0.14-0.55; P <.001) were associated with clinical success. Conclusions: Data show that C/T could be a valid option in empiric and/or targeted therapy in patients with severe infections caused by ESBL-producing Enterobacterales. Clinicians should be aware of the risk of clinical failure with standard-dose C/T therapy in septic patients receiving CRRT.