Ceftolozane/Tazobactam for Treatment of Severe ESBL-Producing Enterobacterales Infections: A Multicenter Nationwide Clinical Experience (CEFTABUSE II Study)
Authors: 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 ,   for the CEFTABUSE Study Group, Bassetti Matteo , Vena Antonio , Giacobbe Daniele Roberto , Viscoli Claudio , Russo Alessandro , Falcone Marco , Tiseo Giusy , Menichetti Francesco , Verdenelli Stefano , Fabiani Silvia , Castaldo Nadia , Pecori Davide , Carnellutti Alessia , Givone Filippo , Graziano Elena , Merelli Maria , Cadeo Barbara , Peghin Maddalena , Giannella Maddalena , Pascale Renato , Viale Pierlugi , Cattelan Annamaria , Cipriani Ludovica , Coletto Davide , Mussini Cristina , Digaetano Margherita , Tascini Carlo , Carannante Novella , Mastroianni Claudio Maria , Gianluca Russo , Oliva Alessandra , Ciardi Maria Rosa , Ajassa Camilla , Tieghi Tiziana , Tumbarello Mario , Losito Angela Raffaella , Raffaelli Francesca , Grossi Paolo , Rovelli Cristina , Artioli Stefania , Caruana Giorgia , Luzzati Roberto , Bontempo Giulia , Petrosillo Nicola , Capone Alessandro , Rizzardini Giuliano , Coen Massimo , Passerini Matteo , Mastroianni Antonio , Guadagnino Giuliana , Urso Filippo , Borgia Guglielmo , Gentile Ivan , Maraolo Alberto Enrico , Crapis Massimo , Venturini Sergio , Parruti Giustino , Trave Francesca , Angarano Gioacchino , Carbonara Sergio , Mariani Michele Fabiano , Girardis Massimo , Cascio Antonio , Gioe Claudia , Anselmo Marco , Malfatto Emanuele 
Published: April 2020

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 &gt;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 &lt; .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 &lt; .001) and adequate source control of infection (OR, 0.42; 95% CI, 0.14–0.55; P &lt; .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.