Ceftolozane/Tazobactam for Treatment of Severe ESBL-Producing Enterobacterales Infections: A Multicenter Nationwide Clinical Experience (CEFTABUSE II Study)
Matteo Bassetti, Antonio Vena, Daniele Roberto Giacobbe, Marco Falcone, Giusy Tiseo, Maddalena Giannella, Renato Pascale, Marianna Meschiari, Margherita Digaetano, Alessandra Oliva, Cristina Rovelli, Novella Carannante, Angela Raffaella Losito, Sergio Carbonara, Michele Fabiano Mariani, Antonio Mastroianni, Gioacchino Angarano, Mario Tumbarello, Carlo Tascini, Paolo Grossi, Claudio Maria Mastroianni, Cristina Mussini, Pierluigi Viale, Francesco Menichetti, Claudio Viscoli, Alessandro Russo, for the CEFTABUSE Study Group, Matteo Bassetti, Antonio Vena, Daniele Roberto Giacobbe, Claudio Viscoli, Alessandro Russo, Marco Falcone, Giusy Tiseo, Francesco Menichetti, Stefano Verdenelli, Silvia Fabiani, Nadia Castaldo, Davide Pecori, Alessia Carnellutti, Filippo Givone, Elena Graziano, Maria Merelli, Barbara Cadeo, Maddalena Peghin, Maddalena Giannella, Renato Pascale, Pierlugi Viale, Anna Maria Cattelan, Ludovica Cipriani, Davide Coletto, Cristina Mussini, Margherita Digaetano, Carlo Tascini, Novella Carannante, Claudio Maria Mastroianni, Gianluca Russo, Alessandra Oliva, Maria Rosa Ciardi, Camilla Ajassa, Tiziana Tieghi, Mario Tumbarello, Angela Raffaella Losito, Francesca Raffaelli, Paolo Grossi, Cristina Rovelli, Stefania Artioli, Giorgia Caruana, Roberto Luzzati, Giulia Bontempo, Nicola Petrosillo, Alessandro Capone, Giuliano Rizzardini, Massimo Coen, Matteo Passerini, Antonio Mastroianni, Giuliana Guadagnino, Filippo Urso, Guglielmo Borgia, Ivan Gentile, Alberto Enrico Maraolo, Massimo Crapis, Sergio Venturini, Giustino Parruti, Francesca Trave, Gioacchino Angarano, Sergio Carbonara, Michele Fabiano Mariani, Massimo Girardis, Antonio Cascio, Claudia Gioè, Marco Anselmo, Emanuele Malfatto
Abstract
Abstract Background Few data are reported in the literature about the outcome of patients with severe extended-spectrum β-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.