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

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

Matteo Bassetti  1 , Antonio Vena  1 , Daniele Roberto Giacobbe  1 , Marco Falcone  2 , Giusy Tiseo  2 , Maddalena Giannella  3 , Renato Pascale  3 , Marianna Meschiari  4 , Margherita Digaetano  4 , Alessandra Oliva  5   6 , Cristina Rovelli  7 , Novella Carannante  8 , Angela Raffaella Losito  9 , Sergio Carbonara  10 , Michele Fabiano Mariani  10 , Antonio Mastroianni  11 , Gioacchino Angarano  10 , Mario Tumbarello  12 , Carlo Tascini  8 , Paolo Grossi  7 , Claudio Maria Mastroianni  5 , Cristina Mussini  4 , Pierluigi Viale  3 , Francesco Menichetti  2 , Claudio Viscoli  1 , Alessandro Russo  2 ; CEFTABUSE Study Group
Collaborators, Affiliations

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

Matteo Bassetti et al. Open Forum Infect Dis. .

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.

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Figures

Figure 1.
Figure 1.
Comparison of successful clinical outcome in patients receiving ceftolozane/tazobactam in different sites of infection. Abbreviations: ABSSSI, acute bacterial skin and skin-structure infection; cIAI, complicated intra-abdominal infection; cUTI, complicated urinary tract infection.
Figure 2.
Figure 2.
Comparison of successful clinical outcome in patients receiving ceftolozane/tazobactam (C/T) as empiric therapy in comparison with those who received C/T as targeted or rescue therapy.
See this image and copyright information in PMC

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