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

Abstract

OBJECTIVE\nMeropenem 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.\n\n\nDESIGN\nDouble blind, double dummy, multicenter randomized controlled trial (1:1 allocation ratio).\n\n\nSETTING\nTertiary and University hospitals.\n\n\nINTERVENTIONS\n600 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\u202fg/24\u202fh or an equal dose divided into three daily boluses (i.e. 1g q8h).\n\n\nMEASUREMENTS\nThe 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.\n\n\nCONCLUSIONS\nThe trial will provide evidence for choosing intermittent or continuous infusion of meropenem for critically ill patients with multi-drug resistant gram-negative infections.