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
Open Access
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