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

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.

Ceftolozane/Tazobactam and Ceftazidime/Avibactam for Multidrug-Resistant Gram-Negative Infections in Immunocompetent Patients: A Single-Center Retrospective Study

“…The study highlighted the use of ceftolozane/tazobactam also in patients with ESBL-non-producing GNB infections. A careful analysis of the data has shown that this use coincided temporally with the lack of availability of piperacillin/tazobactam in Italy due to the high demand due to the increase in the incidence of ESBL-producing Enterobacterales [ 18 ].…”

Molecular Mechanisms, Epidemiology, and Clinical Importance of β-Lactam Resistance in Enterobacteriaceae

“…On the other hand, a recent meta-analysis showed no significant differences in the prognosis for BSIs caused by ESBL-E and treated with carbapenems or BL/BLIs, indicating the usefulness of BL/BLIs for empirical and definitive therapies [ 175 ]. A multicenter retrospective study performed in Italy between 2016 and 2019 revealed a high clinical success rate in patients who received ceftolozane-tazobactam in empiric and/or targeted therapy for severe infections [ 176 ]. Concerning new drugs for a carbapenem-sparing approach, a recent real-life study assessed the role of ceftazidime-avibactam for the targeted treatment of patients with ESBL-E infections in selected cases, but the small study sample limited the drawing of definitive conclusions [ 177 ].…”

Treatment of Bloodstream Infections Due to Gram-Negative Bacteria with Difficult-to-Treat Resistance

“…A recent Italian multicenter retrospective study reported the largest clinical experience regarding the use of C/T therapy for the treatment of serious ESBL-producing Enterobacteriales infections in daily clinical practice (NP 31.7%, acute bacterial skin and skin-structure infection [SSTI] 20.8%, cUTI 13.9%, cIAI 12.9%, bone infection 8.9% and primary bacteremia 5.9%), and showed C/T to be a valid option in empiric and/or targeted therapy, with favorable clinical outcomes in 128/153 (83.7%). Interestingly, the risk of clinical failure was associated with standard-dose C/T therapy in septic patients receiving continuous renal replacement therapy (CRRT) [ 26 ].…”