A multinational, preregistered cohort study of β-lactam/β-lactamase inhibitor combinations for treatment of bloodstream infections due to extended-spectrum-β-lactamase-producing enterobacteriaceae

Mario Tumbarello, Evelina Tacconelli, Enrico Maria Trecarichi, Angela Raffaella Losito, Belén Gutiérrez-Gutiérrez, Salvador Pérez-Galera, Elena Salamanca, Marina De Cueto, Esther Calbo, Benito Almirante, Pierluigi Viale, Antonio Oliver, Vicente Pintado, Oriol Gasch, Luis Martínez-Martínez, Johann Pitout, Murat Akova, Carmen Peña, José Molina, Alicia HernándezMario Venditti, Nuria Prim, Julia Origüen, German Bou, Axel Hamprecht, Helen Giamarellou, Manel Almela, Federico Pérez, Mitchell J. Schwaber, Joaquín Bermejo, Warren Lowman, Po-Ren Hsueh, Marta Mora-Rillo, Clara Natera, Maria Souli, Robert A. Bonomo, Yehuda Carmeli, David L. Paterson, Alvaro Pascual, Jesús Rodríguez-Baño, J. Gálvez, M. D. Del Toro, P. Retamar, M. Falcone, A. Russo, G. Daikos, I. Karaiskos, E. García-Vázquez, J. Gómez, E. Roilides, E. Iosifidis, Y. Doi, F. F. Tuon, F. Navarro, B. Mirelis, R. San Juan, M. Fernández-Ruiz, N. Larrosa, M. Puig, J. M. Cisneros, V. González, Victoria Rucci, E. Ruiz De Gopegui, C. I. Marinescu, M. C. Fariñas, M. E. Cano, M. Gozalo, J. R. Paño-Pardo, C. Navarro-San Francisco, S. Gómez-Zorrilla, F. Tubau, S. Pournaras, A. Tsakris, O. Zarkotou, K. Azap, A. Antoniadou, G. Poulakou, D. Virmani, J. Torre-Cisneros, E. Pérez-Nadales, I. Gracia-Ahulfinger, Helvaci, A. O. Sahin, R. Cantón, P. Ruiz, M. Bartoletti, M. Giannella, F. Riemenschneider, C. Badia, Mariona Xercavins, D. Fontanals, E. Jové

Risultato della ricerca: Contributo in rivistaArticolo in rivista

90 Citazioni (Scopus)

Abstract

The spread of extended-spectrum-β-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-E) is leading to increased carbapenem consumption. Alternatives to carbapenems need to be investigated. We investigated whether β-lactam/β-lactamase inhibitor (BLBLI) combinations are as effective as carbapenems in the treatment of bloodstream infections (BSI) due to ESBL-E. A multinational, retrospective cohort study was performed. Patients with monomicrobial BSI due to ESBL-E were studied; specific criteria were applied for inclusion of patients in the empirical-therapy (ET) cohort (ETC; 365 patients), targeted-therapy (TT) cohort (TTC; 601 patients), and global cohort (GC; 627 patients). The main outcome variables were cure/improvement rate at day 14 and all-cause 30-day mortality. Multivariate analysis, propensity scores (PS), and sensitivity analyses were used to control for confounding. The cure/improvement rates with BLBLIs and carbapenems were 80.0% and 78.9% in the ETC and 90.2% and 85.5% in the TTC, respectively. The 30-day mortality rates were 17.6% and 20% in the ETC and 9.8% and 13.9% in the TTC, respectively. The adjusted odds ratio (OR) (95% confidence interval [CI]) values for cure/improvement rate with ET with BLBLIs were 1.37 (0.69 to 2.76); for TT, they were 1.61 (0.58 to 4.86). Regarding 30-day mortality, the adjusted OR (95% CI) values were 0.55 (0.25 to 1.18) for ET and 0.59 (0.19 to 1.71) for TT. The results were consistent in all subgroups studied, in a stratified analysis according to quartiles of PS, in PS-matched cases, and in the GC. BLBLIs, if active in vitro, appear to be as effective as carbapenems for ET and TT of BSI due to ESLB-E regardless of the source and specific species. These data may help to avoid the overuse of carbapenems. (This study has been registered at ClinicalTrials.gov under registration no. NCT01764490.)
Lingua originaleEnglish
pagine (da-a)4159-4169
Numero di pagine11
RivistaAntimicrobial Agents and Chemotherapy
Volume60
DOI
Stato di pubblicazionePubblicato - 2016

Keywords

  • Infectious Diseases
  • Pharmacology
  • Pharmacology (medical)

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