Continuous infusion versus intermittent administration of meropenem in critically ill patients (MERCY): A multicenter randomized double-blind trial. Rationale and design

Contemp Clin Trials. 2021 May:104:106346. doi: 10.1016/j.cct.2021.106346. Epub 2021 Mar 6.


Objective: Meropenem is a β-lactam, carbapenem antibacterial agent with antimicrobial activity against gram-negative, gram-positive and anaerobic micro-organisms and is important in the empirical treatment of serious infections in Intensive Care Unit (ICU) patients. Multi-drug resistant gram-negative organisms, coupled with scarcity of new antibiotic classes, forced healthcare community to optimize the therapeutic potential of available antibiotics. Our aim is to investigate the effect of continuous infusion of meropenem against bolus administration, as indicated by a composite outcome of reducing death and emergence of extensive or pan drug-resistant pathogens in a population of ICU patients.

Design: Double blind, double dummy, multicenter randomized controlled trial (1:1 allocation ratio).

Setting: Tertiary and University hospitals.

Interventions: 600 ICU patients with sepsis or septic shock, needing by clinical judgment antibiotic therapy with meropenem, will be randomized to receive a continuous infusion of meropenem 3 g/24 h or an equal dose divided into three daily boluses (i.e. 1g q8h).

Measurements: The primary endpoint will be a composite outcome of reducing death and emergence of extensive or pan drug-resistant pathogens. Secondary endpoints will be death from any cause at day 90, antibiotic-free days at day 28, ICU-free days at day 28, cumulative SOFA-free (Sequential Organ Failure Assessment) score from randomization to day 28 and the two, separate, components of the primary endpoint. We expect a primary outcome reduction from 52 to 40% in the continuous infusion group.

Conclusions: The trial will provide evidence for choosing intermittent or continuous infusion of meropenem for critically ill patients with multi-drug resistant gram-negative infections.

Keywords: Antibiotic resistance; Critical patients; Intensive care unit; Meropenem; Mortality; Multi-drug resistant pathogens.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / therapeutic use
  • Critical Care
  • Critical Illness*
  • Humans
  • Meropenem
  • Sepsis* / drug therapy


  • Anti-Bacterial Agents
  • Meropenem