Meropenem versus piperacillin-tazobactam for definitive treatment of bloodstream infections due to ceftriaxone non-susceptible Escherichia coli and Klebsiella spp (the MERINO trial): study protocol for a randomised controlled trial

Harris, Patrick N.A., Peleg, Anton Y., Iredell, Jon, Ingram, Paul R., Miyakis, Spiros, Stewardson, Andrew J., Rogers, Benjamin A., McBryde, Emma S., Roberts, Jason A., Lipman, Jeff, Athan, Eugene, Paul, Sanjoy K., Baker, Peter, Harris-Brown, Tiffany, and Paterson, David L. (2015) Meropenem versus piperacillin-tazobactam for definitive treatment of bloodstream infections due to ceftriaxone non-susceptible Escherichia coli and Klebsiella spp (the MERINO trial): study protocol for a randomised controlled trial. Trials, 16 (24). pp. 1-8.

[img]
Preview
PDF (Published Version) - Published Version
Available under License Creative Commons Attribution.

Download (614kB) | Preview
View at Publisher Website: http://dx.doi.org/10.1186/s13063-014-054...
 
41
88


Abstract

Background: Gram-negative bacteria such as Escherichia coli or Klebsiella spp. frequently cause bloodstream infections. There has been a worldwide increase in resistance in these species to antibiotics such as third generation cephalosporins, largely driven by the acquisition of extended-spectrum beta-lactamase or plasmid-mediated AmpC enzymes. Carbapenems have been considered the most effective therapy for serious infections caused by such resistant bacteria; however, increased use creates selection pressure for carbapenem resistance, an emerging threat arising predominantly from the dissemination of genes encoding carbapenemases. Recent retrospective data suggest that beta-lactam/beta-lactamase inhibitor combinations, such as piperacillin-tazobactam, may be non-inferior to carbapenems for the treatment of bloodstream infection caused by extended-spectrum beta-lactamase-producers, if susceptible in vitro. This study aims to test this hypothesis in an effort to define carbapenem-sparing alternatives for these infections.

Methods/Design: The study will use a multicentre randomised controlled open-label non-inferiority trial design comparing two treatments, meropenem (standard arm) and piperacillin-tazobactam (carbapenem-sparing arm) in adult patients with bacteraemia caused by E. coli or Klebsiella spp. demonstrating non-susceptibility to third generation cephalosporins. Recruitment is planned to occur in sites across three countries (Australia, New Zealand and Singapore). A total sample size of 454 patients will be required to achieve 80% power to determine non-inferiority with a margin of 5%. Once randomised, definitive treatment will be for a minimum of 4 days, but up to 14 days with total duration determined by treating clinicians. Data describing demographic information, antibiotic use, co-morbid conditions, illness severity, source of infection and other risk factors will be collected. Vital signs, white cell count, use of vasopressors and days to bacteraemia clearance will be recorded up to day 7. The primary outcome measure will be mortality at 30 days, with secondary outcomes including days to clinical and microbiological resolution, microbiological failure or relapse, isolation of a multi-resistant organism or Clostridium difficile infection.

Item ID: 39731
Item Type: Article (Research - C1)
ISSN: 1745-6215
Keywords: Extended-spectrum beta-lactamase, ESBL, Plasmid-AmpC, Therapy, Resistance, Beta-lactam/beta-lactamase inhibitor, Carbapenem, Clinical trial
Additional Information:

© 2015 Harris et al.; licensee BioMed Central.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Funders: Australasian Society for Antimicrobials (ASA), International Society for Chemotherapy (ISC)
Date Deposited: 06 Aug 2015 01:54
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1103 Clinical Sciences > 110309 Infectious Diseases @ 40%
11 MEDICAL AND HEALTH SCIENCES > 1117 Public Health and Health Services > 111706 Epidemiology @ 40%
16 STUDIES IN HUMAN SOCIETY > 1605 Policy and Administration > 160508 Health Policy @ 20%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 60%
92 HEALTH > 9203 Indigenous Health > 920309 Pacific Peoples Health - Health System Performance (incl. Effectiveness of Interventions) @ 20%
92 HEALTH > 9202 Health and Support Services > 920207 Health Policy Evaluation @ 20%
Downloads: Total: 88
Last 12 Months: 21
More Statistics

Actions (Repository Staff Only)

Item Control Page Item Control Page