Colistin versus meropenem in the empirical treatment of ventilator-associated pneumonia (Magic Bullet study): An investigator-driven, open-label, randomized, noninferiority controlled trial

Autor: Cisneros, José M, Rosso-Fernández, Clara María, Roca-Oporto, Cristina, De Pascale, Gennaro, Jiménez-Jorge, Silvia, Fernández-Hinojosa, Esteban, Matthaiou, Dimitrios K, Ramírez, Paula, Díaz-Miguel, Ramón Ortiz, Estella, Angel, Antonelli, Massimo, Dimopoulos, George, Garnacho-Montero, José, Magic Bullet Working Group WP1
Přispěvatelé: European Commission
Rok vydání: 2019
Předmět:
Male
medicine.medical_specialty
Multidrug-resistant bacteria
Population
Equivalence Trials as Topic
Critical Care and Intensive Care Medicine
Meropenem
Loading dose
law.invention
03 medical and health sciences
0302 clinical medicine
Randomized controlled trial
law
Internal medicine
polycyclic compounds
Medicine
Humans
Ventilator-associated pneumonia
Prospective Studies
education
Aged
0303 health sciences
education.field_of_study
030306 microbiology
business.industry
Colistin
Research
lcsh:Medical emergencies. Critical care. Intensive care. First aid
Pneumonia
Ventilator-Associated
030208 emergency & critical care medicine
lcsh:RC86-88.9
Middle Aged
biochemical phenomena
metabolism
and nutrition
medicine.disease
Interim analysis
bacterial infections and mycoses
3. Good health
Anti-Bacterial Agents
Treatment Outcome
bacteria
Female
Carbapenem-resistant gram-negative bacilli
business
Magic bullet
medicine.drug
Zdroj: Digital.CSIC. Repositorio Institucional del CSIC
instname
Critical Care
Critical Care, Vol 23, Iss 1, Pp 1-13 (2019)
Popis: © The Author(s).
[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. Trial registration: ClinicalTrials.gov, NCT01292031. Registered 9 February 2011.
Funded by the Seventh Framework Program of the European Commission. Magic Bullet grant agreement number 278232.
Databáze: OpenAIRE
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