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

• DOI: 10.1016/j.cct.2021.106346
• Publication Date: 2021-03-07T09:20:19Z
• Authors: Giacomo Monti; Carola Galbiati; Fabio Toffoletto; Maria Grazia Calabrò; Sergio Colombo; Barbara Ferrara; Giuseppe Giardina; Rosalba Lembo; Matteo Marzaroli; Elena Moizo; Milena Mucci; Nicola Pasculli; Valentina Paola P...; Anna Mara Scandro...; Margherita Tozzi; Elena Momesso; Nicoletta Boffa; Rosetta Lobreglio; Giorgia Montrucchio; Fabio Guarracino; Umberto Benedetto; Giuseppe Biondi-Z...; Fabrizio D'Ascenzo; Natascia D'Andrea; Gianluca Paternoster; Sofia Ananiadou; Mariano Ballestra; Antonio De Sio; Vincenzo Pota; Antonella Cotoia; Andrea Della Selva; Andrea Bruni; Giacomo Iapichino; Nikola Bradić; Francesco Corradi; Marco Gemma; Pavel Nogtev; Marina Petrova; Felice Eugenio Agrò; Luca Cabrini; Francesco Forfori; Valery Likhvantsev; Tiziana Bove; Gabriele Finco; Giovanni Landoni; Alberto Zangrillo; Silvia Ajello; Alberto Maria Cap...; Evgeny Fominskiy; Francesco Giusepp...; Vittorio Pazzanese; Marina Pieri; Federico Canavosio; Filippo Palmesino; Mara Bernasconi; Giorgio Gallioli; Giovanni Marino; Luigi Vetrugno; Chiara Millin; Daniela Missio; Francesca Gallicchio; Barbara Azzali; Mattia Bozzetti; Daniele Cristadoro; Romina Perone; Leonarda Pia Cant...; Gianna Curci; Ingrid Marcela Pabon; Eugenio Garofalo; Manuela Mainetti; Italo Calamai; Davide Maraggia; Alessia Mattei; Andrey Yavorovskiy
• Keywords: 0301 basic medicine; Critical Care; Critical patient; Antibiotic resistance; Critical patients; Critical Illness; meropenem ; intermitent or continuous infusion ; critically ill; 610; Meropenem; Antibiotic resistance; Critical patients; Intensive care unit; Meropenem; Mortality; Multi-drug resistant pathogens; Anti-Bacterial Agents; 3. Good health; 03 medical and health sciences; Sepsis; 616; Antibiotic resistance; Critical patients; Intensive care unit; Meropenem; Mortality; Multi-drug resistant pathogens; Anti-Bacterial Agents; Critical Care; Humans; Meropenem; Critical Illness; Sepsis; Humans; Intensive care unit; Mortality; antibiotic resistance; critical patients; intensive care unit; meropenem; mortality; multi-drug resistant pathogens; Multi-drug resistant pathogens

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.Double blind, double dummy, multicenter randomized controlled trial (1:1 allocation ratio).Tertiary and University hospitals.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).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.The trial will provide evidence for choosing intermittent or continuous infusion of meropenem for critically ill patients with multi-drug resistant gram-negative infections.