What was the Merino 2 trial?

The MERINO Trial: A Randomized Controlled Trial Comparing Piperacillin-Tazobactam vs. Meropenem for Bloodstream Infections

The MERINO trial was a landmark randomized controlled trial that failed to demonstrate non-inferiority of piperacillin-tazobactam compared to meropenem for the treatment of bloodstream infections caused by third-generation cephalosporin-resistant Enterobacterales. 1

Background and Design

• The MERINO trial was designed as a double-blind, non-inferiority trial comparing piperacillin-tazobactam with meropenem for treating bloodstream infections caused by third-generation cephalosporin-resistant Escherichia coli and Klebsiella species 2, 1
• The trial was conducted in response to conflicting retrospective data about whether beta-lactam/beta-lactamase inhibitor combinations (BLBLIs) were as effective as carbapenems for treating extended-spectrum beta-lactamase (ESBL)-producing organisms 1
• The study enrolled patients with bloodstream infections caused by ceftriaxone-resistant E. coli or Klebsiella pneumoniae 2, 1

Key Findings

• The primary endpoint analysis showed that piperacillin-tazobactam did not meet the non-inferiority criteria compared to meropenem for all-cause mortality at 30 days 1
• A post-hoc win ratio analysis of the MERINO trial data showed a win ratio of 0.40 (95% CI, 0.22-0.71; p=0.002), strongly favoring meropenem over piperacillin-tazobactam when considering a hierarchical composite endpoint of mortality, microbiological relapse, and secondary infection 2
• The trial results challenged previous observational studies that had suggested non-inferiority of BLBLIs compared to carbapenems 1, 3

Clinical Implications

• The MERINO trial results have significant implications for antimicrobial stewardship, as they suggest that carbapenems may be preferred over piperacillin-tazobactam for bloodstream infections caused by ESBL-producing organisms 1, 3
• However, concerns exist about the widespread adoption of carbapenem treatment due to potential detrimental effects on antimicrobial stewardship in areas endemic for ESBL and carbapenem-resistant bacteria 1
• The results have prompted further research, including the PeterPen trial, which aims to re-examine this comparison before changing clinical practice 1

Follow-up Studies

• The MERINO-2 trial was designed as a follow-up study to further investigate optimal treatment strategies for these infections 4
• Additionally, the MERINO-3 trial is comparing ceftolozane-tazobactam versus meropenem for definitive treatment of bloodstream infections due to ESBL and AmpC-producing Enterobacterales 4
• These follow-up studies aim to provide more comprehensive evidence to guide clinical decision-making in the treatment of resistant gram-negative infections 4

Controversies and Limitations

• Some experts have questioned whether using third-generation cephalosporin non-susceptibility as a proxy for ESBL production is accurate, suggesting that molecular testing for specific resistance mechanisms might be more appropriate 3
• The trial has sparked debate about the balance between effective treatment of individual patients and broader antimicrobial stewardship concerns 1, 3
• The implications of the MERINO trial must be considered in the context of increasing carbapenem resistance globally 1

The MERINO trial represents a significant contribution to our understanding of optimal treatment strategies for resistant gram-negative infections, though its findings continue to be debated and further investigated through ongoing research.