Ertapenem for the treatment of bloodstream infections due to ESBL-producing Enterobacteriaceae: a multinational pre-registered cohort study
Belén Gutiérrez-Gutiérrez, Robert A Bonomo, Yehuda Carmeli, David L Paterson, Benito Almirante, Luis Martínez-Martínez, Antonio Oliver, Esther Calbo, Carmen Peña, Murat Akova, Johann Pitout, Julia Origüen, Vicente Pintado, Elisa García-Vázquez, Oriol Gasch, Axel Hamprecht, Nuria Prim, Mario Tumbarello, German Bou, Pierluigi Viale, Evelina Tacconelli, Manel Almela, Federico Pérez, Helen Giamarellou, José Miguel Cisneros, Mitchell J Schwaber, Mario Venditti, Warren Lowman, Joaquín Bermejo, Po-Ren Hsueh, Marta Mora-Rillo, Irene Gracia-Ahulfinger, Alvaro Pascual, Jesús Rodríguez-Baño, REIPI/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, Belén Gutiérrez-Gutiérrez, Robert A Bonomo, Yehuda Carmeli, David L Paterson, Benito Almirante, Luis Martínez-Martínez, Antonio Oliver, Esther Calbo, Carmen Peña, Murat Akova, Johann Pitout, Julia Origüen, Vicente Pintado, Elisa García-Vázquez, Oriol Gasch, Axel Hamprecht, Nuria Prim, Mario Tumbarello, German Bou, Pierluigi Viale, Evelina Tacconelli, Manel Almela, Federico Pérez, Helen Giamarellou, José Miguel Cisneros, Mitchell J Schwaber, Mario Venditti, Warren Lowman, Joaquín Bermejo, Po-Ren Hsueh, Marta Mora-Rillo, Irene Gracia-Ahulfinger, Alvaro Pascual, Jesús Rodríguez-Baño, REIPI/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
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.
© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
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Source: PubMed