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


Por: Cisneros, J, Rosso-Fernandez, C, Roca-Oporto, C, De Pascale, G, Jimenez-Jorge, S, Fernandez-Hinojosa, E, Matthaiou, D, Ramirez, P, Diaz-Miguel, R, Estella, A, Antonelli, M, Dimopoulos, G, Garnacho-Montero, J, Di Gravio, V, Bello, G, Gonzalez, V, Leal, R, Puppo, A, Lepe, J, Gutierrez-Pizarraya, A, Villarreal, E, Espinosa, M, Polanco, M, Lopez, M, Herrera-Gutierrez, M, Seller, G, Zakinthinos, S, Malachias, S, Komnos, A, Zafeiridis, T, Sierra, R, Gonzalez, A, Zakynthinos, E, Alvarez-Rocha, L, de la Torre, M, Dominguez, P, Bitsan, M, Koutsoukou, A, Zaragoza, R, De Roberts, E, Allegue, J, Pozo, J, Nakos, G, Ferrer, R, Pneumatikos, I, Vidal, P and Magic Bullet Working Grp WP1

Publicada: 28 nov 2019
Categoría: Critical care and intensive care medicine

Resumen:
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.

Filiaciones:
Cisneros, J:
 Univ Seville, Univ Hosp Virgen del Rocio, Inst Biomed Seville IBIS, CSIC,Dept Infect Dis Microbiol & Prevent Med, Ave Manuel Siurot S-N, Seville 41013, Spain

Rosso-Fernandez, C:
 Univ Hosp Virgen del Rocio, Clin Trial Unit, Ave Manuel Siurot S-N, Seville 41013, Spain

Roca-Oporto, C:
 Univ Seville, Univ Hosp Virgen del Rocio, Inst Biomed Seville IBIS, CSIC,Dept Infect Dis Microbiol & Prevent Med, Ave Manuel Siurot S-N, Seville 41013, Spain

De Pascale, G:
 Fdn Policlin Univ A Gemelli IRCCS, Rome, Italy

Jimenez-Jorge, S:
 Univ Hosp Virgen del Rocio, Clin Trial Unit, Ave Manuel Siurot S-N, Seville 41013, Spain

Fernandez-Hinojosa, E:
 Hosp Univ Virgen del Rocio, Intens Care Clin Unit, Ave Manuel Siurot S-N, Seville 41013, Spain

Matthaiou, D:
 Univ Athens, Univ Hosp ATTIKON, Dept Crit Care, Athens, Greece

Ramirez, P:
 Hosp Univ & Politecn La Fe, Intens Med Unit, Avinguda Fernando Abril Martorell 106, Valencia 46026, Spain

Diaz-Miguel, R:
 Hosp Gen Univ Ciudad Real, Intens Med Unit, Calle Obispo Rafael Torija S-N, Ciudad Real 13005, Spain

Estella, A:
 Hosp Univ Jerez, Intens Care Unit, Carretera Nacl 4 S-N, Cadiz 11407, Spain

Antonelli, M:
 Fdn Policlin Univ A Gemelli IRCCS, Rome, Italy

 Univ Cattolica Sacro Cuore, Rome, Italy

Dimopoulos, G:
 Univ Athens, Univ Hosp ATTIKON, Dept Crit Care, Athens, Greece

Garnacho-Montero, J:
 Hosp Univ Virgen Macarena, Intens Care Clin Unit, Calle Dr Fedriani 3, Seville 41009, Spain

Di Gravio, V:
 Gemelli Hosp, Rome, Italy

Bello, G:
 Gemelli Hosp, Rome, Italy

Gonzalez, V:
 Virgen del Rocio Hosp, Seville, Spain

Leal, R:
 Virgen del Rocio Hosp, Seville, Spain

Puppo, A:
 Virgen del Rocio Hosp, Seville, Spain

Lepe, J:
 Virgen del Rocio Hosp, Seville, Spain

Gutierrez-Pizarraya, A:
 Virgen del Rocio Hosp, Seville, Spain

Villarreal, E:
 La Fe Hosp, Valencia, Spain

Espinosa, M:
 Ciudad Real Hosp, Ciudad Real, Spain

Polanco, M:
 Ciudad Real Hosp, Ciudad Real, Spain

Lopez, M:
 Jerez de la Frontera Hosp, Jerez de la Frontera, Spain

Herrera-Gutierrez, M:
 Carlos Haya Hosp, Malaga, Spain

Seller, G:
 Carlos Haya Hosp, Malaga, Spain

Zakinthinos, S:
 Evagelismos Hosp, Paphos, Cyprus

Malachias, S:
 Evagelismos Hosp, Paphos, Cyprus

Komnos, A:
 Gen Larissa Hosp, Larisa, Greece

Zafeiridis, T:
 Gen Larissa Hosp, Larisa, Greece

Sierra, R:
 Puerta del Mar Hosp, Cadiz, Spain

Gonzalez, A:
 Marques Vaidecilla Hosp, Santander, Spain

Zakynthinos, E:
 MSU Thessalia, UH Larissa, Volos, Greece

Alvarez-Rocha, L:
 A Coruna Hosp, La Coruna, Spain

de la Torre, M:
 Virgen de la Victoria Hosp, Malaga, Spain

Dominguez, P:
 Juan Ramon Jimenez Hosp, Huelva, Spain

Bitsan, M:
 Papanikolau Hosp, Pilea Chortiatis, Greece

Koutsoukou, A:
 SOTIRIA Hosp, Athens, Greece

:
 UCI, Dr Peset Hosp, Valencia, Spain

De Roberts, E:
 Napoli Federico II Hosp, Naples, Italy

Allegue, J:
 Santa Lucia Hosp, San Borja, Peru

Pozo, J:
 Reina Sofia Hosp, Seville, Spain

Nakos, G:
 UH Ioannina MSU Ipirus, Ioannina, Greece

Ferrer, R:
 Mutua Tarrassa Hosp, Terrassa, Spain

Pneumatikos, I:
 Alexandroupoli Hosp, Alexandroupolis, Greece

Vidal, P:
 Orense Hosp, Orense, Spain
ISSN: 13648535





CRITICAL CARE
Editorial
BIOMED CENTRAL LTD, 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND, Reino Unido
Tipo de documento: Article
Volumen: 23 Número: 1
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WOS Id: 000499951600001
ID de PubMed: 31779711
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