Please use this identifier to cite or link to this item: http://hdl.handle.net/10668/3157
Title: Colistin versus meropenem in the empirical treatment of ventilator-associated pneumonia (Magic Bullet study): an investigator-driven, open-label, randomized, noninferiority controlled trial. Critical Care. 2019 Nov 23:383
Authors: Cisneros, José M.
Rosso-Fernández, Clara María
Roca-Oporto, Cristina
De Pascale, Gennaro
Jiménez-Jorge, Silvia
Fernández-Hinojosa, Esteban
Matthaiou, Dimitrios K.
Ramírez, Paula
Ortiz Díaz-Miguel, Ramón
Estella, Angel
Antonelli, Massimo
Dimopoulos, George
Garnacho-Montero, José
metadata.dc.contributor.authoraffiliation: [Cisneros,JM; Roca-Oporto,C] Department of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville (IBIS), University Hospital Virgen del Rocio CSIC, University of Seville, Seville, Spain. [Rosso-Fernández,CM; Jiménez-Jorge,S] Clinical Trial Unit, Hospital Universitario Virgen del Rocío, Seville, Spain. [De Pascale,G; Antonelli,M] Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. [Fernández-Hinojosa,E] Intensive Care Clinical Unit, Hospital Universitario Virgen del Rocío, Seville, Spain. [Matthaiou,DK; Dimopoulos,G] Department of Critical Care, University Hospital ATTIKON, National and Kapodistrian University of Athens, Athens, Greece. [Ramírez,P] Intensive Medicine Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain. [Ortiz Díaz-Miguel,R] Intensive Medicine Unit, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain. [Estella,A] Intensive Care Unit, Hospital Universitario de Jerez, Jerez de la Frontera, Cádiz, Spain. [Antonelli,M] Università Cattolica del Sacro Cuore, Rome, Italy. [Garnacho-Montero,J] Intensive Care Clinical Unit, Hospital Universitario Virgen Macarena, Seville, Spain.
metadata.dc.contributor.group: Magic Bullet Working Group WP1
Keywords: Colistin;Ventilator-associated pneumonia;Multidrug-resistant bacteria;Carbapenem-resistant gram-negative bacilli;Colistina;Neumonía asociada al ventilador;Drug resistance, bacterial;Farmacorresistencia Bacteriana;Gram-negative bacteria;Bacterias gramnegativas;Carbapenem-resistant enterobacteriaceae;Enterobacteriaceae resistentes a los carbapenémicos
metadata.dc.subject.mesh: Medical Subject Headings::Persons::Persons::Age Groups::Adult::Aged
Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Anti-Bacterial Agents
Medical Subject Headings::Chemicals and Drugs::Polycyclic Compounds::Macrocyclic Compounds::Peptides, Cyclic::Polymyxins::Colistin
Medical Subject Headings::Check Tags::Female
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Check Tags::Male
Medical Subject Headings::Persons::Persons::Age Groups::Adult::Middle Aged
Medical Subject Headings::Diseases::Bacterial Infections and Mycoses::Infection::Cross Infection::Pneumonia, Ventilator-Associated
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Treatment Outcome
Issue Date: 28-Nov-2019
Citation: Cisneros JM, Rosso-Fernández CM, Roca-Oporto C, De Pascale G, Jiménez-Jorge S, Fernández-Hinojosa E, et al. Colistin versus meropenem in the empirical treatment of ventilator-associated pneumonia (Magic Bullet study): an investigator-driven, open-label, randomized, noninferiority controlled trial. Critical Care. 2019 23:383
Abstract: Background: Colistin is recommended in the empirical treatment of ventilator-associated pneumonia (VAP) with a high prevalence of carbapenem-resistant gram-negative bacilli (CR-GNB). However, the efficacy and safety of colistin are not well defined. Methods: A multicenter prospective randomized trial conducted in 32 European centers compared the efficacy and safety of colistin (4.5 million unit loading dose followed by a maintenance dose of 3 million units every 8 h) versus meropenem (2 g every 8 h), both in combination with levofloxacin (500 mg every 12 h) for 7-14 days in patients with late VAP. Between May 2012 and October 2015, 232 patients were randomly assigned to the 2 treatment groups. The primary endpoint was mortality at 28 days after randomization in the microbiologically modified intention-to-treat (mMITT) population. Secondary outcomes included clinical and microbiological cure, renal function at the end of the treatment, and serious adverse events. The study was interrupted after the interim analysis due to excessive nephrotoxicity in the colistin group; therefore, the sample size was not achieved. Results: A total of 157 (67.7%) patients were included in the mMITT population, 36 of whom (22.9%) had VAP caused by CR-GNB. In the mMITT population, no significant difference in mortality between the colistin group (19/82, 23.2%) and the meropenem group (19/75, 25.3%) was observed, with a risk difference of - 2.16 (- 15.59 to 11.26, p = 0.377); the noninferiority of colistin was not demonstrated due to early termination and limited number of patients infected by carbapenem-resistant pathogens. Colistin plus levofloxacin increased the incidence of renal failure (40/120, 33.3%, versus 21/112, 18.8%; p = 0.012) and renal replacement therapy (11/120, 9.1%, versus 2/112, 1.8%; p = 0.015). Conclusions: This study did not demonstrate the noninferiority of colistin compared with meropenem, both combined with levofloxacin, in terms of efficacy in the empirical treatment of late VAP but demonstrated the greater nephrotoxicity of colistin. These findings do not support the empirical use of colistin for the treatment of late VAP due to early termination.
URI: http://hdl.handle.net/10668/3157
metadata.dc.identifier.doi: 10.1186/s13054-019-2627-y
ISSN: 1364-8535 (Print)
1466-609X (Online)
Appears in Collections:01- Artículos - Hospital de Jerez
01- Artículos - Hospital Virgen del Rocío
01- Artículos - Hospital Virgen Macarena
01- Artículos - IBIS. Instituto de Biomedicina de Sevilla

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