Ceftolozane/Tazobactam for Treatment of Severe ESBL-Producing Enterobacterales Infections: A Multicenter Nationwide Clinical Experience (CEFTABUSE II Study)

Bassetti, Matteo; Vena, Antonio; Giacobbe, Daniele Roberto; Falcone, Marco; Tiseo, Giusy; Giannella, Maddalena; Pascale, Renato; Meschiari, Marianna; Digaetano, Margherita; Oliva, Alessandra; Rovelli, Cristina; Carannante, Novella; Losito, Angela Raffaella; Carbonara, Sergio; Mariani, Michele Fabiano; Mastroianni, Antonio; Angarano, Gioacchino; Tumbarello, Mario; Tascini, Carlo; Grossi, Paolo; Mastroianni, Claudio Maria; Mussini, Cristina; Viale, Pierluigi; Menichetti, Francesco; Viscoli, Claudio; Russo, Alessandro &amp;; Luzzati R.

Ceftolozane/Tazobactam for Treatment of Severe ESBL-Producing Enterobacterales Infections: A Multicenter Nationwide Clinical Experience (CEFTABUSE II Study)

Bassetti, Matteo

•

Vena, Antonio

•

Giacobbe, Daniele Roberto

altro

Luzzati R.

2020

journal article

Periodico

OPEN FORUM INFECTIOUS DISEASES

Abstract

Background. Few data are reported in the literature about the outcome of patients with severe extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) infections treated with ceftolozane/tazobactam (C/T), in empiric or definitive 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.