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Title

Ertapenem for the treatment of bloodstream infections due to ESBL-producing Enterobacteriaceae: a multinational pre-registered cohort study

AuthorsGutiérrez-Gutiérrez, Belén; Bonomo, Robert A.; Carmeli, Yehuda; Paterson, David L.; Almirante, Benito; Martínez-Martínez, Luis; Oliver, Antonio; Calbo, Esther; Peña, Carmen; Akova, Murat; Pitout, Johann; Origüen, Julia; Pintado, Vicente; García-Vázquez, Elisa; Gasch, Oriol; Hamprecht, Axel; Prim, Nuria; Tumbarello, Mario; Bou, Germán; Viale, Pierluigi; Tacconelli, Evelina; Almela, Manel; Pérez, Federico; Giamarellou, Helen; Cisneros, José Miguel; Schwaber, Mitchell J.; Venditti, Mario; Lowman, Warren; Bermejo, Joaquín; Hsueh, Po-Ren; Mora-Rillo, Marta; Gracia-Ahufinger, Irene; Pascual, Álvaro; Rodríguez-Baño, Jesús
KeywordsSeptic shock
Carbapenem
Enterobacteriaceae
Mortality
Ertapenem
Sepsis
Severe extended-spectrum beta lactamases
Bloodstream infections
Sensitivity analysis
Molecular targeted therapy
Issue DateJun-2016
PublisherOxford University Press
CitationJournal of Antimicrobial Chemotherapy 71(6): 1672-1680 (2016)
Abstract[Objectives] Data about the efficacy of ertapenem for the treatment of bloodstream infections (BSI) due to ESBL-producing Enterobacteriaceae (ESBL-E) are limited. We compared the clinical efficacy of ertapenem and other carbapenems in monomicrobial BSI due to ESBL-E.
[Methods] A multinational retrospective cohort study (INCREMENT project) was performed (ClinicalTrials.gov identifier: NCT01764490). Patients given monotherapy with ertapenem or other carbapenems were compared. Empirical and targeted therapies were analysed. Propensity scores were used to control for confounding; sensitivity analyses were performed in subgroups. The outcome variables were cure/improvement rate at day 14 and all-cause 30 day mortality.
[Results] The empirical therapy cohort (ETC) and the targeted therapy cohort (TTC) included 195 and 509 patients, respectively. Cure/improvement rates were 90.6% with ertapenem and 75.5% with other carbapenems (P = 0.06) in the ETC and 89.8% and 82.6% (P = 0.02) in the TTC, respectively; 30 day mortality rates were 3.1% and 23.3% (P = 0.01) in the ETC and 9.3% and 17.1% (P = 0.01) in the TTC, respectively. Adjusted ORs (95% CI) for cure/improvement with empirical and targeted ertapenem were 1.87 (0.24–20.08; P = 0.58) and 1.04 (0.44–2.50; P = 0.92), respectively. For the propensity-matched cohorts it was 1.18 (0.43–3.29; P = 0.74). Regarding 30 day mortality, the adjusted HR (95% CI) for targeted ertapenem was 0.93 (0.43–2.03; P = 0.86) and for the propensity-matched cohorts it was 1.05 (0.46–2.44; P = 0.90). Sensitivity analyses were consistent except for patients with severe sepsis/septic shock, which showed a non-significant trend favouring other carbapenems.
[Conclusions] Ertapenem appears as effective as other carbapenems for empirical and targeted therapy of BSI due to ESBL-E, but further studies are needed for patients with severe sepsis/septic shock.
DescriptionREIPI/ESGBIS/INCREMENT Group: J. Gálvez, M. de Cueto, E. Salamanca, M. Falcone, A. Russo, G. Daikos, I. Karaiskos, E. M. Trecarichi, A. R. Losito, D. L. Paterson, A. Hernández, 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. Molina, V. González, V. 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, Ö. K. Azap, M. Souli, A. Antoniadou, G. Poulakou, D. Virmani, I. Machuca, E. Pérez-Nadales, J. Torre-Cisneros, Ö. Helvaci, A. O. Sahin, R. Cantón, P. Ruiz, M. Bartoletti, M. Giannella, F. Riemenschneider, C. Badia, M. Xercavins, D. Fontanals, E. Jové.
Publisher version (URL)https://doi.org/10.1093/jac/dkv502
URIhttp://hdl.handle.net/10261/196739
DOI10.1093/jac/dkv502
ISSN0305-7453
E-ISSN1460-2091
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