Impact of Specific Antimicrobials and MIC Values on the Outcome of Bloodstream Infections Due to Extended-spectrum Beta-lactamase (ESBL) or Carbapenemase-producing Enterobacteriaceae: an Observational Multinational Study

NCT01764490 | Completed DMC

• 2 other identifiers: REIPI-1WP701JRB-ANT-2012-01
• Study Type: observational
• Target: 1,344
• Locations: 1 country
• Sites: 1

Brief Summary

Main objective: to observationally assess the efficacy of different antimicrobials in Bloodstream Infection (BSI) due to Enterobacteriaceae producing ESBLs or carbapenemases. Specific objectives: Bacteraemic infections due to ESBL-producing Enterobacteriaceae:

• To demonstrate that β-lactam/β-lactam inhibitors are not associated with worse cure rate and mortality than carbapenems after controlling for confounders, both as empirical and definitive therapy.
• To demonstrate that fluoroquinolones as definitive therapy are not associated with worse cure rate and mortality than carbapenems after controlling for confounders.
• To demonstrate that empirical cephalosporins in monotherapy are associated with worse cure rate and mortality than carbapenems after controlling for confounders in infections others than urinary tract infections.
• To demonstrate that the association of active aminoglycosides with cephalosporins or fluoroquinolines is not associated with worse cure rate and mortality than carbapenems after controlling for confounders.
• To demonstrate that combination empirical and definitive therapy is not associated with better cure rate than monotherapy after controlling for confounders.
• For tigecycline, colistin, and fosfomycin, no hypothesis. The objective is to provide adjusted estimations of their association with outcome variables in comparison with carbapenem monotherapy according to clinical situation and infection. Bacteraemic infections due to carbapenemase-producing Enterobacteriaceae:
• To demonstrate that combination therapy is associated with worse cure rate and mortality than monotherapy after controlling for confounders.
• To show that carbapenems are associated with worse cure rate and mortality when used in infections other than urinary tract caused by isolates showing MIC \<2 µg/mL for imipenem or meropenem in comparison to those caused by isolates with higher MIC, after controlling for confounders.
• To show that colistin used at a dose \>6 million IU per day is associated with improved outcomes in comparison with lower dose, after controlling for confounders.

Conditions

Clinically Significant Bacteremia

Keywords

Bloodstream infections caused by multidrug-resistant Enterobacteriaceae, extended-spectrum β-lactamase-producers, carbapenemase-producing organisms

Outcome Measures

Primary Outcomes (1)

• Cure rate at day 14

  o Cure: resolution of all signs and symptoms related to the infection, and antibiotic therapy is no longer necessary

  within the first 14 days after treatment started

Secondary Outcomes (6)

• Mortality at 72 hours

  within the first 72 hours

• Mortality at 7 days

  within 7 days after treatment started

• Mortality at 14 days

  within 14 days after treatment started

• Mortality at 30 days

  within 30 days after treatment started

• Clinical Improvement at 72 hours

  within the first 72 hours after treatment started

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

\- Episode of clinically-significant monomicrobial BSI due to ESBL or carbapenemase-producing Enterobacteriaceae, including community and nosocomial ones

You may qualify if:

• Episode of clinically-significant monomicrobial BSI due to ESBL or carbapenemase-producing Enterobacteriaceae, including community and nosocomial ones.
• For ESBL-producers, detection by standard phenotypic method as recommended by CLSI is enough (although PCR-based characterisation is preferred, see below).
• For carbapenemase-producers, characterisation by at least PCR is necessary (isolates in which carbapenemase production is suspected based on antimicrobial susceptibility profile plus phenotypic tests alone is not acceptable, see below).
• Subsequent episodes in a patient caused by the same microorganism may be included if the interval between them is \>3 months.
• No age limits.

You may not qualify if:

• Polymicrobial or non-clinically significant episodes. Episodes in which a potential contaminant (e.g., coagulase-negative staphylococci) is isolated only in one set of blood cultures and there is not a typical source of infection for that kind of organism (e.g. catheter-related) may be included.
• Unavailability of key data (such cases should be counted to analyse a potential selection bias)
• Episode occurring before January 2004.

Sponsors & Collaborators

• JESUS RODRIGUEZ BAÑO: lead

Study Sites (1)

Virgen Macarena University Hospital

Seville, Andalusia, 41009, Spain

Location

Related Publications (4)

• Scheuerman O, Schechner V, Carmeli Y, Gutierrez-Gutierrez B, Calbo E, Almirante B, Viale PL, Oliver A, Ruiz-Garbajosa P, Gasch O, Gozalo M, Pitout J, Akova M, Pena C, Molina J, Hernandez-Torres A, Venditti M, Prim N, Origuen J, Bou G, Tacconelli E, Tumbarello M, Hamprecht A, Karaiskos I, de la Calle C, Perez F, Schwaber MJ, Bermejo J, Lowman W, Hsueh PR, Navarro-San Francisco C, Bonomo RA, Paterson DL, Pascual A, Rodriguez-Bano J; REIPI/ESGBIS/INCREMENT investigators. Comparison of Predictors and Mortality Between Bloodstream Infections Caused by ESBL-Producing Escherichia coli and ESBL-Producing Klebsiella pneumoniae. Infect Control Hosp Epidemiol. 2018 Jun;39(6):660-667. doi: 10.1017/ice.2018.63. Epub 2018 Apr 5.

  PMID: 29618394 DERIVED

• Gutierrez-Gutierrez B, Salamanca E, de Cueto M, Hsueh PR, Viale P, Pano-Pardo JR, Venditti M, Tumbarello M, Daikos G, Canton R, Doi Y, Tuon FF, Karaiskos I, Perez-Nadales E, Schwaber MJ, Azap OK, Souli M, Roilides E, Pournaras S, Akova M, Perez F, Bermejo J, Oliver A, Almela M, Lowman W, Almirante B, Bonomo RA, Carmeli Y, Paterson DL, Pascual A, Rodriguez-Bano J; REIPI/ESGBIS/INCREMENT Investigators. Effect of appropriate combination therapy on mortality of patients with bloodstream infections due to carbapenemase-producing Enterobacteriaceae (INCREMENT): a retrospective cohort study. Lancet Infect Dis. 2017 Jul;17(7):726-734. doi: 10.1016/S1473-3099(17)30228-1. Epub 2017 Apr 22.

  PMID: 28442293 DERIVED

• Gutierrez-Gutierrez B, Perez-Galera S, Salamanca E, de Cueto M, Calbo E, Almirante B, Viale P, Oliver A, Pintado V, Gasch O, Martinez-Martinez L, Pitout J, Akova M, Pena C, Molina J, Hernandez A, Venditti M, Prim N, Origuen J, Bou G, Tacconelli E, Tumbarello M, Hamprecht A, Giamarellou H, Almela M, Perez F, Schwaber MJ, Bermejo J, Lowman W, Hsueh PR, Mora-Rillo M, Natera C, Souli M, Bonomo RA, Carmeli Y, Paterson DL, Pascual A, Rodriguez-Bano J. A Multinational, Preregistered Cohort Study of beta-Lactam/beta-Lactamase Inhibitor Combinations for Treatment of Bloodstream Infections Due to Extended-Spectrum-beta-Lactamase-Producing Enterobacteriaceae. Antimicrob Agents Chemother. 2016 Jun 20;60(7):4159-69. doi: 10.1128/AAC.00365-16. Print 2016 Jul.

  PMID: 27139473 DERIVED

• Gutierrez-Gutierrez B, Bonomo RA, Carmeli Y, Paterson DL, Almirante B, Martinez-Martinez L, Oliver A, Calbo E, Pena C, Akova M, Pitout J, Origuen J, Pintado V, Garcia-Vazquez E, Gasch O, Hamprecht A, Prim N, Tumbarello M, Bou G, Viale P, Tacconelli E, Almela M, Perez F, Giamarellou H, Cisneros JM, Schwaber MJ, Venditti M, Lowman W, Bermejo J, Hsueh PR, Mora-Rillo M, Gracia-Ahulfinger I, Pascual A, Rodriguez-Bano J; REIPI/ESGBIS/INCREMENT Group. Ertapenem for the treatment of bloodstream infections due to ESBL-producing Enterobacteriaceae: a multinational pre-registered cohort study. J Antimicrob Chemother. 2016 Jun;71(6):1672-80. doi: 10.1093/jac/dkv502. Epub 2016 Feb 22.

  PMID: 26907184 DERIVED

Study Officials

• JESUS RODRIGUEZ BAÑO, MD, PhD

  Spanish Network for Research in Infectious Diseases

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: GENERAL COORDINATOR

Study Record Dates

• First Submitted: December 26, 2012
• First Posted: January 9, 2013
• Study Start: January 1, 2013
• Primary Completion: December 1, 2013
• Study Completion: May 1, 2014
• Last Updated: June 27, 2014

Record last verified: 2014-06

Locations

ES (1)