A multinational, preregistered cohort study of β-lactam/β-lactamase inhibitor combinations for treatment of bloodstream infections due to extended-spectrum-β-lactamase-producing enterobacteriaceae

REIPI/ESGBIS/INCREMENT Group

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Abstract

The spread of extended-spectrum-β-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-E) is leading to increased carbapenem consumption. Alternatives to carbapenems need to be investigated. We investigated whether β-lactam/β-lactamase inhibitor (BLBLI) combinations are as effective as carbapenems in the treatment of bloodstream infections (BSI) due to ESBL-E. A multinational, retrospective cohort study was performed. Patients with monomicrobial BSI due to ESBL-E were studied; specific criteria were applied for inclusion of patients in the empirical-therapy (ET) cohort (ETC; 365 patients), targeted-therapy (TT) cohort (TTC; 601 patients), and global cohort (GC; 627 patients). The main outcome variables were cure/improvement rate at day 14 and all-cause 30-day mortality. Multivariate analysis, propensity scores (PS), and sensitivity analyses were used to control for confounding. The cure/improvement rates with BLBLIs and carbapenems were 80.0% and 78.9% in the ETC and 90.2% and 85.5% in the TTC, respectively. The 30-day mortality rates were 17.6% and 20% in the ETC and 9.8% and 13.9% in the TTC, respectively. The adjusted odds ratio (OR) (95% confidence interval [CI]) values for cure/improvement rate with ET with BLBLIs were 1.37 (0.69 to 2.76); for TT, they were 1.61 (0.58 to 4.86). Regarding 30-day mortality, the adjusted OR (95% CI) values were 0.55 (0.25 to 1.18) for ET and 0.59 (0.19 to 1.71) for TT. The results were consistent in all subgroups studied, in a stratified analysis according to quartiles of PS, in PS-matched cases, and in the GC. BLBLIs, if active in vitro, appear to be as effective as carbapenems for ET and TT of BSI due to ESLB-E regardless of the source and specific species. These data may help to avoid the overuse of carbapenems. (This study has been registered at ClinicalTrials.gov under registration no. NCT01764490.)

Original languageEnglish
Pages (from-to)4159-4169
Number of pages11
JournalAntimicrobial agents and chemotherapy
Volume60
Issue number7
DOIs
Publication statusPublished - 01-07-2016

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Lactams
Enterobacteriaceae
Carbapenems
Cohort Studies
Infection
Propensity Score
Therapeutics
Mortality
Odds Ratio
Confidence Intervals
Multivariate Analysis
Retrospective Studies

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

@article{f77b480f4c674e8c916a73f7e91da049,
title = "A multinational, preregistered cohort study of β-lactam/β-lactamase inhibitor combinations for treatment of bloodstream infections due to extended-spectrum-β-lactamase-producing enterobacteriaceae",
abstract = "The spread of extended-spectrum-β-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-E) is leading to increased carbapenem consumption. Alternatives to carbapenems need to be investigated. We investigated whether β-lactam/β-lactamase inhibitor (BLBLI) combinations are as effective as carbapenems in the treatment of bloodstream infections (BSI) due to ESBL-E. A multinational, retrospective cohort study was performed. Patients with monomicrobial BSI due to ESBL-E were studied; specific criteria were applied for inclusion of patients in the empirical-therapy (ET) cohort (ETC; 365 patients), targeted-therapy (TT) cohort (TTC; 601 patients), and global cohort (GC; 627 patients). The main outcome variables were cure/improvement rate at day 14 and all-cause 30-day mortality. Multivariate analysis, propensity scores (PS), and sensitivity analyses were used to control for confounding. The cure/improvement rates with BLBLIs and carbapenems were 80.0{\%} and 78.9{\%} in the ETC and 90.2{\%} and 85.5{\%} in the TTC, respectively. The 30-day mortality rates were 17.6{\%} and 20{\%} in the ETC and 9.8{\%} and 13.9{\%} in the TTC, respectively. The adjusted odds ratio (OR) (95{\%} confidence interval [CI]) values for cure/improvement rate with ET with BLBLIs were 1.37 (0.69 to 2.76); for TT, they were 1.61 (0.58 to 4.86). Regarding 30-day mortality, the adjusted OR (95{\%} CI) values were 0.55 (0.25 to 1.18) for ET and 0.59 (0.19 to 1.71) for TT. The results were consistent in all subgroups studied, in a stratified analysis according to quartiles of PS, in PS-matched cases, and in the GC. BLBLIs, if active in vitro, appear to be as effective as carbapenems for ET and TT of BSI due to ESLB-E regardless of the source and specific species. These data may help to avoid the overuse of carbapenems. (This study has been registered at ClinicalTrials.gov under registration no. NCT01764490.)",
author = "{REIPI/ESGBIS/INCREMENT Group} and Bel{\'e}n Guti{\'e}rrez-Guti{\'e}rrez and Salvador P{\'e}rez-Galera and Elena Salamanca and {De Cueto}, Marina and Esther Calbo and Benito Almirante and Pierluigi Viale and Antonio Oliver and Vicente Pintado and Oriol Gasch and Luis Mart{\'i}nez-Mart{\'i}nez and Johann Pitout and Murat Akova and Carmen Pe{\~n}a and Jos{\'e} Molina and Alicia Hern{\'a}ndez and Mario Venditti and Nuria Prim and Julia Orig{\"u}en and German Bou and Evelina Tacconelli and Mario Tumbarello and Axel Hamprecht and Helen Giamarellou and Manel Almela and Federico P{\'e}rez and Schwaber, {Mitchell J.} and Joaqu{\'i}n Bermejo and Warren Lowman and Hsueh, {Po Ren} and Marta Mora-Rillo and Clara Natera and Maria Souli and Bonomo, {Robert A.} and Yehuda Carmeli and Paterson, {David L.} and Alvaro Pascual and Jes{\'u}s Rodr{\'i}guez-Ba{\~n}o and J. G{\'a}lvez and {Del Toro}, {M. D.} and P. Retamar and M. Falcone and A. Russo and G. Daikos and I. Karaiskos and Trecarichi, {E. M.} and Losito, {A. R.} and E. Garc{\'i}a-V{\'a}zquez and J. G{\'o}mez and Yohei Doi",
year = "2016",
month = "7",
day = "1",
doi = "10.1128/AAC.00365-16",
language = "English",
volume = "60",
pages = "4159--4169",
journal = "Antimicrobial Agents and Chemotherapy",
issn = "0066-4804",
publisher = "American Society for Microbiology",
number = "7",

}

TY - JOUR

T1 - A multinational, preregistered cohort study of β-lactam/β-lactamase inhibitor combinations for treatment of bloodstream infections due to extended-spectrum-β-lactamase-producing enterobacteriaceae

AU - REIPI/ESGBIS/INCREMENT Group

AU - Gutiérrez-Gutiérrez, Belén

AU - Pérez-Galera, Salvador

AU - Salamanca, Elena

AU - De Cueto, Marina

AU - Calbo, Esther

AU - Almirante, Benito

AU - Viale, Pierluigi

AU - Oliver, Antonio

AU - Pintado, Vicente

AU - Gasch, Oriol

AU - Martínez-Martínez, Luis

AU - Pitout, Johann

AU - Akova, Murat

AU - Peña, Carmen

AU - Molina, José

AU - Hernández, Alicia

AU - Venditti, Mario

AU - Prim, Nuria

AU - Origüen, Julia

AU - Bou, German

AU - Tacconelli, Evelina

AU - Tumbarello, Mario

AU - Hamprecht, Axel

AU - Giamarellou, Helen

AU - Almela, Manel

AU - Pérez, Federico

AU - Schwaber, Mitchell J.

AU - Bermejo, Joaquín

AU - Lowman, Warren

AU - Hsueh, Po Ren

AU - Mora-Rillo, Marta

AU - Natera, Clara

AU - Souli, Maria

AU - Bonomo, Robert A.

AU - Carmeli, Yehuda

AU - Paterson, David L.

AU - Pascual, Alvaro

AU - Rodríguez-Baño, Jesús

AU - Gálvez, J.

AU - Del Toro, M. D.

AU - Retamar, P.

AU - Falcone, M.

AU - Russo, A.

AU - Daikos, G.

AU - Karaiskos, I.

AU - Trecarichi, E. M.

AU - Losito, A. R.

AU - García-Vázquez, E.

AU - Gómez, J.

AU - Doi, Yohei

PY - 2016/7/1

Y1 - 2016/7/1

N2 - The spread of extended-spectrum-β-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-E) is leading to increased carbapenem consumption. Alternatives to carbapenems need to be investigated. We investigated whether β-lactam/β-lactamase inhibitor (BLBLI) combinations are as effective as carbapenems in the treatment of bloodstream infections (BSI) due to ESBL-E. A multinational, retrospective cohort study was performed. Patients with monomicrobial BSI due to ESBL-E were studied; specific criteria were applied for inclusion of patients in the empirical-therapy (ET) cohort (ETC; 365 patients), targeted-therapy (TT) cohort (TTC; 601 patients), and global cohort (GC; 627 patients). The main outcome variables were cure/improvement rate at day 14 and all-cause 30-day mortality. Multivariate analysis, propensity scores (PS), and sensitivity analyses were used to control for confounding. The cure/improvement rates with BLBLIs and carbapenems were 80.0% and 78.9% in the ETC and 90.2% and 85.5% in the TTC, respectively. The 30-day mortality rates were 17.6% and 20% in the ETC and 9.8% and 13.9% in the TTC, respectively. The adjusted odds ratio (OR) (95% confidence interval [CI]) values for cure/improvement rate with ET with BLBLIs were 1.37 (0.69 to 2.76); for TT, they were 1.61 (0.58 to 4.86). Regarding 30-day mortality, the adjusted OR (95% CI) values were 0.55 (0.25 to 1.18) for ET and 0.59 (0.19 to 1.71) for TT. The results were consistent in all subgroups studied, in a stratified analysis according to quartiles of PS, in PS-matched cases, and in the GC. BLBLIs, if active in vitro, appear to be as effective as carbapenems for ET and TT of BSI due to ESLB-E regardless of the source and specific species. These data may help to avoid the overuse of carbapenems. (This study has been registered at ClinicalTrials.gov under registration no. NCT01764490.)

AB - The spread of extended-spectrum-β-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-E) is leading to increased carbapenem consumption. Alternatives to carbapenems need to be investigated. We investigated whether β-lactam/β-lactamase inhibitor (BLBLI) combinations are as effective as carbapenems in the treatment of bloodstream infections (BSI) due to ESBL-E. A multinational, retrospective cohort study was performed. Patients with monomicrobial BSI due to ESBL-E were studied; specific criteria were applied for inclusion of patients in the empirical-therapy (ET) cohort (ETC; 365 patients), targeted-therapy (TT) cohort (TTC; 601 patients), and global cohort (GC; 627 patients). The main outcome variables were cure/improvement rate at day 14 and all-cause 30-day mortality. Multivariate analysis, propensity scores (PS), and sensitivity analyses were used to control for confounding. The cure/improvement rates with BLBLIs and carbapenems were 80.0% and 78.9% in the ETC and 90.2% and 85.5% in the TTC, respectively. The 30-day mortality rates were 17.6% and 20% in the ETC and 9.8% and 13.9% in the TTC, respectively. The adjusted odds ratio (OR) (95% confidence interval [CI]) values for cure/improvement rate with ET with BLBLIs were 1.37 (0.69 to 2.76); for TT, they were 1.61 (0.58 to 4.86). Regarding 30-day mortality, the adjusted OR (95% CI) values were 0.55 (0.25 to 1.18) for ET and 0.59 (0.19 to 1.71) for TT. The results were consistent in all subgroups studied, in a stratified analysis according to quartiles of PS, in PS-matched cases, and in the GC. BLBLIs, if active in vitro, appear to be as effective as carbapenems for ET and TT of BSI due to ESLB-E regardless of the source and specific species. These data may help to avoid the overuse of carbapenems. (This study has been registered at ClinicalTrials.gov under registration no. NCT01764490.)

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U2 - 10.1128/AAC.00365-16

DO - 10.1128/AAC.00365-16

M3 - Article

VL - 60

SP - 4159

EP - 4169

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

SN - 0066-4804

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ER -