Predictors of outcome in patients with severe sepsis or septic shock due to extended-spectrum β-lactamase-producing Enterobacteriaceae

A. Russo, M. Falcone, B. Gutiérrez-Gutiérrez, E. Calbo, B. Almirante, P.L. Viale, A. Oliver, P. Ruiz-Garbajosa, O. Gasch, M. Gozalo, J. Pitout, M. Akova, C. Peña, J.M. Cisneros, A. Hernández-Torres, A. Farcomeni, N. Prim, J. Origüen, G. Bou, E. Tacconelli, M. Tumbarello, A. Hamprecht, I. Karaiskos, C. de la Calle, F. Pérez, M.J. Schwaber, J. Bermejo, W. Lowman, P.-R. Hsueh, M. Mora-Rillo, J. Rodriguez-Gomez, M. Souli, R.A. Bonomo, D.L. Paterson, Y. Carmeli, A. Pascual, J. Rodríguez-Baño, M. Venditti, REIPI/ESGBIS/INCREMENT investigators

Few data are reported in literature regarding severe sepsis or septic shock due to extended-spectrum β-lactamases (ESBL)-producing Enterobacteriaceae (E). The aim of this study was to assess predictors of outcome in septic patients with bloodstream infection (BSI) caused by ESBL-E. Patients with severe sepsis or septic shock and BSI due to ESBL-E were selected from the INCREMENT database. The primary endpoint of the study was the evaluation of predictors of outcome after 30 days from development of severe sepsis or septic shock due to ESBL-E infection. To perform analysis were created three cohorts: global, empirical-therapy and targeted-therapy cohorts. 367 septic patients were analyzed. Overall mortality was 43.9% at 30 days; Escherichia coli (62.4%) and Klebsiella pneumoniae (27.2%) were the most frequent isolates. β-lactam/β-lactamase inhibitor (BLBLI) combinations was the most empirically used drug (43.6%), followed by carbapenems (29.4%); empirical therapy resulted active in vitro in 249 (67.8%) patients, but an escalation of antibiotic therapy was reported in 287 (78.2%) patients. Cox regression analysis showed that age, Charlson Comorbidity Index, McCabe classification, Pitt bacteremia score, abdominal source of infection and escalation of antibiotic therapy were independently associated with 30-day mortality. No differences were reported about survival in patients treated with BLBLI combinations or carbapenems in empirical or definitive therapy. BSI due to ESBL-E in patients who developed severe sepsis or septic shock was associated with high 30-day mortality; comorbidities, severity scores, source of infection and need of antibiotic therapy escalation were important determinants of unfavorable outcome.