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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
- Source :
- Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid, Consejería de Sanidad de la Comunidad de Madrid, Digital.CSIC. Repositorio Institucional del CSIC, instname, ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau, idUS. Depósito de Investigación de la Universidad de Sevilla
- Publication Year :
- 2016
-
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.)<br />The work was funded by the Ministerio de Economía y Competitividad, Instituto de Salud Carlos III, cofinanced by European Development Regional Fund titled A Way To Achieve Europe ERDF, the Spanish Network for Research in Infectious Diseases (REIPI RD12/0015), and FIS (PI10/02021). Participants in the study received support for research from the Innovative Medicines Initiative Joint Undertaking under the Combatting Bacterial Resistance in Europe—Molecule against Gram Negative Infections (COMBACTE-MAGNET) agreement 115737 resources, which are composed of financial contributions from the European Union's Seventh Framework Programme (FP7/2007-2013) and the European Federation of Pharmaceutical Industries and Associations (EFPIA) companies' in kind contributions (A. Pascua and J. Rodríguez-Baño), the Cleveland Department of Veterans Affairs, the Veterans Affairs Merit Review Program, the Geriatric Research Education and Clinical Center VISN 10 (VISN 10 GRECC), and NIAID, NIH, under award numbers R01AI072219 and R01AI063517 (R. A. Bonomo).
- Subjects :
- 0301 basic medicine
Male
Carbapenem
medicine.medical_specialty
Pediatrics
030106 microbiology
Infectious Disease
Bacteremia
Kaplan-Meier Estimate
Clinical Therapeutics
Settore MED/17 - MALATTIE INFETTIVE
beta-Lactams
Microbiology
beta-Lactamases
03 medical and health sciences
0302 clinical medicine
Aged
Anti-Bacterial Agents
Carbapenems
Enterobacteriaceae
Female
Humans
Middle Aged
Multivariate Analysis
Odds Ratio
Retrospective Studies
beta-Lactamase Inhibitors
Internal medicine
medicine
Pharmacology (medical)
030212 general & internal medicine
Pharmacology & Pharmacy
Beta-Lactamase Inhibitors
Pharmacology
business.industry
Mortality rate
Retrospective cohort study
Odds ratio
bacterial infections and mycoses
Confidence interval
3. Good health
Infectious Diseases
Cohort
business
medicine.drug
Cohort study
Subjects
Details
- Language :
- English
- ISSN :
- 00664804
- Database :
- OpenAIRE
- Journal :
- Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid, Consejería de Sanidad de la Comunidad de Madrid, Digital.CSIC. Repositorio Institucional del CSIC, instname, ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau, idUS. Depósito de Investigación de la Universidad de Sevilla
- Accession number :
- edsair.doi.dedup.....7ea336e012575f1a2cac6eb3bfa2f14e