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.
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; Null, Null; 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. - In: OPEN FORUM INFECTIOUS DISEASES. - ISSN 2328-8957. - 7:5(2020). [10.1093/ofid/ofaa139]
Ceftolozane/Tazobactam for Treatment of Severe ESBL-Producing Enterobacterales Infections: A Multicenter Nationwide Clinical Experience (CEFTABUSE II Study)
Falcone, Marco;Graziano, Elena;Borgia, Guglielmo;Gentile, Ivan;Maraolo, Alberto Enrico;
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 >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.| File | Dimensione | Formato | |
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