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; CEFTABUSE Study Group

doi:10.1093/ofid/ofaa139

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

Open Forum Infect Dis. 2020 Apr 21;7(5):ofaa139. doi: 10.1093/ofid/ofaa139. eCollection 2020 May.

Authors

Matteo Bassetti¹, Antonio Vena¹, Daniele Roberto Giacobbe¹, Marco Falcone², Giusy Tiseo², Maddalena Giannella³, Renato Pascale³, Marianna Meschiari⁴, Margherita Digaetano⁴, Alessandra Oliva^{5

6}, Cristina Rovelli⁷, Novella Carannante⁸, Angela Raffaella Losito⁹, Sergio Carbonara¹⁰, Michele Fabiano Mariani¹⁰, Antonio Mastroianni¹¹, Gioacchino Angarano¹⁰, Mario Tumbarello¹², Carlo Tascini⁸, Paolo Grossi⁷, Claudio Maria Mastroianni⁵, Cristina Mussini⁴, Pierluigi Viale³, Francesco Menichetti², Claudio Viscoli¹, Alessandro Russo²; CEFTABUSE Study Group

Collaborators

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, Annamaria Cattelan, Ludovica Cipriani, Davide Coletto, Cristina Mussini, Margherita Digaetano, Carlo Tascini, Novella Carannante, Claudio Maria Mastroianni, Russo Gianluca, 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 Gioe, Marco Anselmo, Emanuele Malfatto

Affiliations

¹ Department of Health Sciences, University of Genoa, Genoa, Italy.
² Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
³ Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
⁴ Infectious Diseases Clinic, University of Modena and Reggio Emilia, Modena, Italy.
⁵ Department of Public Health and Infectious Diseases, 'Sapienza' University of Rome, Rome, Italy.
⁶ IRCCS Neuromed, Pozzilli, Isernia, Italy.
⁷ Department of Infectious and Tropical Diseases, University of Insubria, Ospedale di Circolo-Fondazioni Macchi, Varese, Italy.
⁸ First Division of Infectious Diseases, Cotugno Hospital, AORN dei Colli, Naples, Italy.
⁹ UOC Malattie Infettive, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy.
¹⁰ Clinic of Infectious Diseases, University of Bari, Bari, Italy.
¹¹ Infectious Diseases Unit, 'Annunziata' Hospital, Cosenza, Italy.
¹² UOC Malattie Infettive, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy.

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.

Keywords: CRRT; ESBL; Enterobacterales; ceftolozane/tazobactam; septic shock.