1. Continuous infusion versus intermittent administration of meropenem in critically ill patients (MERCY): A multicenter randomized double-blind trial. Rationale and design
- Author
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Ingrid Marcela Pabon, Barbara Azzali, Mattia Bozzetti, Vincenzo Pota, Antonio De Sio, Andrey Yavorovskiy, Natascia D'Andrea, Rosetta Lobreglio, Andrea Della Selva, Evgeny Fominskiy, Federico Canavosio, Barbara Ferrara, Vittorio Pazzanese, Francesca Gallicchio, Nicola Pasculli, Valery Likhvantsev, Eugenio Garofalo, Sergio Colombo, Anna Mara Scandroglio, Felice Eugenio Agrò, Margherita Tozzi, Gianluca Paternoster, Francesco Corradi, Tiziana Bove, Filippo Palmesino, Elena Momesso, Luigi Vetrugno, Francesco Giuseppe Nisi, Giorgia Montrucchio, Daniela Missio, Mara Bernasconi, Giacomo Monti, Mariano Ballestra, Marco Gemma, Giovanni Marino, Silvia Ajello, Alberto Zangrillo, Rosalba Lembo, Maria Grazia Calabrò, Romina Perone, Andrea Bruni, Pavel Nogtev, Alberto Cappelletti, Gabriele Finco, Daniele Cristadoro, Leonarda Pia Cantatore, Marina Pieri, Sofia Ananiadou, Italo Calamai, Chiara Millin, A. Mattei, Luca Cabrini, Marina Petrova, Valentina Paola Plumari, Nicoletta Boffa, Davide Maraggia, Elena Moizo, Gianna Curci, Giovanni Landoni, Giuseppe Biondi-Zoccai, Giuseppe Giardina, Giacomo Iapichino, Carola Galbiati, Fabio Guarracino, Antonella Cotoia, Matteo Marzaroli, Nikola Bradic, Umberto Benedetto, Giorgio Gallioli, Fabrizio D'Ascenzo, Francesco Forfori, Fabio Toffoletto, Milena Mucci, Manuela Mainetti, Monti, G., Galbiati, C., Toffoletto, F., Calabro, M. G., Colombo, S., Ferrara, B., Giardina, G., Lembo, R., Marzaroli, M., Moizo, E., Mucci, M., Pasculli, N., Plumari, V. P., Scandroglio, A. M., Tozzi, M., Momesso, E., Boffa, N., Lobreglio, R., Montrucchio, G., Guarracino, F., Benedetto, U., Biondi-Zoccai, G., D'Ascenzo, F., D'Andrea, N., Paternoster, G., Ananiadou, S., Ballestra, M., De Sio, A., Pota, V., Cotoia, A., Della Selva, A., Bruni, A., Iapichino, G., Bradic, N., Corradi, F., Gemma, M., Nogtev, P., Petrova, M., Agro, F. E., Cabrini, L., Forfori, F., Likhvantsev, V., Bove, T., Finco, G., Landoni, G., Zangrillo, A., Ajello, S., Cappelletti, A. M., Fominskiy, E., Nisi, F. G., Pazzanese, V., Pieri, M., Canavosio, F., Palmesino, F., Bernasconi, M., Gallioli, G., Marino, G., Vetrugno, L., Millin, C., Missio, D., Gallicchio, F., Azzali, B., Bozzetti, M., Cristadoro, D., Perone, R., Cantatore, L. P., Curci, G., Pabon, I. M., Garofalo, E., Mainetti, M., Calamai, I., Maraggia, D., Mattei, A., Yavorovskiy, A., Monti, Giacomo, Galbiati, Carola, Toffoletto, Fabio, Calabrò, Maria Grazia, Colombo, Sergio, Ferrara, Barbara, Giardina, Giuseppe, Lembo, Rosalba, Marzaroli, Matteo, Moizo, Elena, Mucci, Milena, Pasculli, Nicola, Plumari, Valentina, Scandroglio, Anna Mara, Tozzi, Margherita, Momesso, Elena, Boffa, Nicoletta, Lobreglio, Rosetta, Montrucchio, Giorgia, Guarracino, Fabio, Benedetto, Umberto, Biondi-Zoccai, Giuseppe, D'Ascenzo, Fabrizio, D'Andrea, Natascia, Paternoster, Gianluca, Ananiadou, Sofia, Ballestra, Mariano, De Sio, Antonio, Pota, Vincenzo, Cotoia, Antonella, Selva, Andrea Della, Bruni, Andrea, Iapichino, Giacomo, Bradić, Nikola, Corradi, Francesco, Gemma, Marco, Nogtev, Pavel, Petrova, Marina, Agrò, Felice Eugenio, Cabrini, Luca, Forfori, Francesco, Likhvantsev, Valery, Bove, Tiziana, Finco, Gabriele, Landoni, Giovanni, and Zangrillo, Alberto
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medicine.medical_specialty ,Randomization ,Critical Care ,Antibiotic resistance ,Critical patients ,Critical Illness ,Population ,meropenem ,intermitent or continuous infusion ,critically ill ,Intensive care unit ,Meropenem ,Mortality ,Multi-drug resistant pathogens ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Sepsis ,medicine ,Clinical endpoint ,polycyclic compounds ,Humans ,Pharmacology (medical) ,030212 general & internal medicine ,education ,Antibacterial agent ,education.field_of_study ,030505 public health ,Septic shock ,business.industry ,Critical patient ,General Medicine ,medicine.disease ,Anti-Bacterial Agents ,Emergency medicine ,0305 other medical science ,business ,medicine.drug - Abstract
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.
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- 2021