Ertapenem for the treatment of bloodstream infections due to ESBL-producing Enterobacteriaceae: a multinational pre-registered cohort study. (22nd February 2016)

• Record Type: Journal Article
• Authors: Gutiérrez-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, German; 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-Ahulfinger, Irene; Pascual, Alvaro; Rodríguez-Baño, Jesús; Gálvez, J.; de Cueto, M.; Salamanca, E.; Falcone, M.; Russo, A.; Daikos, G.; Karaiskos, I.; Trecarichi, E. M.; Losito, A. R.; Paterson, D. L.; Hernández, A.; Gómez, J.; Roilides, E.; Iosifidis, E.; Doi, Y.; Tuon, F. F.; Navarro, F.; Mirelis, B.; Juan, R. San; Fernández-Ruiz, M.; Larrosa, N.; Puig, M.; Molina, J.; González, V.; Rucci, V.; de Gopegui, E. Ruiz; Marinescu, C. I.; Fariñas, M. C.; Cano, M. E.; Gozalo, M.; Paño-Pardo, J. R.; Francisco, C. Navarro-San; Gómez-Zorrilla, S.; Tubau, F.; Pournaras, S.; Tsakris, A.; Zarkotou, O.; Azap, Ö. K.; Souli, M.; Antoniadou, A.; Poulakou, G.; Virmani, D.; Machuca, I.; Pérez-Nadales, E.; Torre-Cisneros, J.; Helvaci, Ö.; Sahin, A. O.; Cantón, R.; Ruiz, P.; Bartoletti, M.; Giannella, M.; Riemenschneider, F.; Badia, C.; Xercavins, M.; Fontanals, D.; Jové, E.;
• Is Part Of: Journal of antimicrobial chemotherapy. Volume 71:Number 6(2016:Jun.)
• Page Start: 1672
• Page End: 1680
• Publication Date: 2016-02-22
• Subjects: Anti-infective agents -- Periodicals; Chemotherapy -- Periodicals; 615.58
• DOI: 10.1093/jac/dkv502
• Languages: English
• ISSNs: 0305-7453

Abstract

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.