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

REIPI/ESGBIS/INCREMENT Group

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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.

Original languageEnglish
Pages (from-to)1672-1680
Number of pages9
JournalJournal of Antimicrobial Chemotherapy
Volume71
Issue number6
DOIs
Publication statusPublished - 13-06-2016

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Enterobacteriaceae
Cohort Studies
Carbapenems
Infection
Therapeutics
Septic Shock
Mortality
Sepsis
Propensity Score
ertapenem
Retrospective Studies

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

Cite this

@article{b30ed9e8dc694042a1c324af9bf7fe4a,
title = "Ertapenem for the treatment of bloodstream infections due to ESBL-producing Enterobacteriaceae: A multinational pre-registered cohort study",
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.",
author = "{REIPI/ESGBIS/INCREMENT Group} and Bel{\'e}n Guti{\'e}rrez-Guti{\'e}rrez and Bonomo, {Robert A.} and Yehuda Carmeli and Paterson, {David L.} and Benito Almirante and Luis Mart{\'i}nez-Mart{\'i}nez and Antonio Oliver and Esther Calbo and Carmen Pe{\~n}a and Murat Akova and Johann Pitout and Julia Orig{\"u}en and Vicente Pintado and Elisa Garc{\'i}a-V{\'a}zquez and Oriol Gasch and Axel Hamprecht and Nuria Prim and Mario Tumbarello and German Bou and Pierluigi Viale and Evelina Tacconelli and Manel Almela and Federico P{\'e}rez and Helen Giamarellou and Cisneros, {Jos{\'e} Miguel} and Schwaber, {Mitchell J.} and Mario Venditti and Warren Lowman and Joaqu{\'i}n Bermejo and Hsueh, {Po Ren} and Marta Mora-Rillo and Irene Gracia-Ahulfinger and Alvaro Pascual and Jes{\'u}s Rodr{\'i}guez-Ba{\~n}o and I. Karaiskos and Trecarichi, {E. M.} and Losito, {A. R.} and A. Hern{\'a}ndez and J. G{\'o}mez and F. Navarro and B. Mirelis and N. Larrosa and M. Puig and V. Rucci and M. Bartoletti and M. Giannella and F. Riemenschneider and C. Badia and M. Xercavins and Yohei Doi",
year = "2016",
month = "6",
day = "13",
doi = "10.1093/jac/dkv502",
language = "English",
volume = "71",
pages = "1672--1680",
journal = "Journal of Antimicrobial Chemotherapy",
issn = "0305-7453",
publisher = "Oxford University Press",
number = "6",

}

Ertapenem for the treatment of bloodstream infections due to ESBL-producing Enterobacteriaceae : A multinational pre-registered cohort study. / REIPI/ESGBIS/INCREMENT Group.

In: Journal of Antimicrobial Chemotherapy, Vol. 71, No. 6, 13.06.2016, p. 1672-1680.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Ertapenem for the treatment of bloodstream infections due to ESBL-producing Enterobacteriaceae

T2 - A multinational pre-registered cohort study

AU - REIPI/ESGBIS/INCREMENT Group

AU - Gutiérrez-Gutiérrez, Belén

AU - Bonomo, Robert A.

AU - Carmeli, Yehuda

AU - Paterson, David L.

AU - Almirante, Benito

AU - Martínez-Martínez, Luis

AU - Oliver, Antonio

AU - Calbo, Esther

AU - Peña, Carmen

AU - Akova, Murat

AU - Pitout, Johann

AU - Origüen, Julia

AU - Pintado, Vicente

AU - García-Vázquez, Elisa

AU - Gasch, Oriol

AU - Hamprecht, Axel

AU - Prim, Nuria

AU - Tumbarello, Mario

AU - Bou, German

AU - Viale, Pierluigi

AU - Tacconelli, Evelina

AU - Almela, Manel

AU - Pérez, Federico

AU - Giamarellou, Helen

AU - Cisneros, José Miguel

AU - Schwaber, Mitchell J.

AU - Venditti, Mario

AU - Lowman, Warren

AU - Bermejo, Joaquín

AU - Hsueh, Po Ren

AU - Mora-Rillo, Marta

AU - Gracia-Ahulfinger, Irene

AU - Pascual, Alvaro

AU - Rodríguez-Baño, Jesús

AU - Karaiskos, I.

AU - Trecarichi, E. M.

AU - Losito, A. R.

AU - Hernández, A.

AU - Gómez, J.

AU - Navarro, F.

AU - Mirelis, B.

AU - Larrosa, N.

AU - Puig, M.

AU - Rucci, V.

AU - Bartoletti, M.

AU - Giannella, M.

AU - Riemenschneider, F.

AU - Badia, C.

AU - Xercavins, M.

AU - Doi, Yohei

PY - 2016/6/13

Y1 - 2016/6/13

N2 - 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.

AB - 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.

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DO - 10.1093/jac/dkv502

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JO - Journal of Antimicrobial Chemotherapy

JF - Journal of Antimicrobial Chemotherapy

SN - 0305-7453

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