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 rateswere 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.

Ertapenem for the treatment of bloodstream infections due to ESBL-producing Enterobacteriaceae: A multinational pre-registered cohort study / 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; Karaiskos, I.; Trecarichi, E. M.; Losito, A. R.; Hernández, A.; Gómez, J.; Navarro, F.; Mirelis, B.; Larrosa, N.; Puig, M.; Rucci, V.; Bartoletti, M.; Giannella, M.; Riemenschneider, F.; Badia, C.; Xercavins, M.; Gálvez, J.; de Cueto, M.; Salamanca, E.; Falcone, Marco; Russo, Alessandro; Daikos, G.; Paterson, D. L.; Roilides, E.; Iosifidis, E.; Doi, Y.; Tuon, F. F.; San Juan, R.; Fernández Ruiz, M.; Molina, J.; González, V.; Ruiz de Gopegui, E.; Marinescu, C. I.; Fariñas, M. C.; Cano, M. E.; Gozalo, M.; Paño Pardo, J. R.; Navarro San Francisco, C.; 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.; Fontanals, D.; Jové, E.. - In: JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY. - ISSN 0305-7453. - 71:6(2016), pp. 1672-1680. [10.1093/jac/dkv502]

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

VENDITTI, Mario;FALCONE, MARCO;RUSSO, ALESSANDRO;
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 rateswere 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.
2016
Pharmacology; Pharmacology (medical); Infectious Diseases
01 Pubblicazione su rivista::01a Articolo in rivista
Ertapenem for the treatment of bloodstream infections due to ESBL-producing Enterobacteriaceae: A multinational pre-registered cohort study / 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; Karaiskos, I.; Trecarichi, E. M.; Losito, A. R.; Hernández, A.; Gómez, J.; Navarro, F.; Mirelis, B.; Larrosa, N.; Puig, M.; Rucci, V.; Bartoletti, M.; Giannella, M.; Riemenschneider, F.; Badia, C.; Xercavins, M.; Gálvez, J.; de Cueto, M.; Salamanca, E.; Falcone, Marco; Russo, Alessandro; Daikos, G.; Paterson, D. L.; Roilides, E.; Iosifidis, E.; Doi, Y.; Tuon, F. F.; San Juan, R.; Fernández Ruiz, M.; Molina, J.; González, V.; Ruiz de Gopegui, E.; Marinescu, C. I.; Fariñas, M. C.; Cano, M. E.; Gozalo, M.; Paño Pardo, J. R.; Navarro San Francisco, C.; 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.; Fontanals, D.; Jové, E.. - In: JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY. - ISSN 0305-7453. - 71:6(2016), pp. 1672-1680. [10.1093/jac/dkv502]
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