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 1: 24.1-24.8. doi:10.1186/s13063-014-0541-9

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Author 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
Paterson, David L.
Title 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
Formatted title
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
Journal name Trials   Check publisher's open access policy
ISSN 1745-6215
Publication date 2015-01-27
Sub-type Article (original research)
DOI 10.1186/s13063-014-0541-9
Open Access Status DOI
Volume 16
Issue 1
Start page 24.1
End page 24.8
Total pages 8
Place of publication London, United Kingdom
Publisher BioMed Central
Collection year 2016
Language eng
Formatted 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.
Trial registration: The MERINO trial is registered under the Australian New Zealand Clinical Trials Register (ANZCTR),
reference number: ACTRN12613000532707 (registered 13 May 2013) and the US National Institute of Health
ClinicalTrials.gov register, reference number: NCT02176122 (registered 24 June 2014).
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2016 Collection
School of Medicine Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 7 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 8 times in Scopus Article | Citations
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