Background. Ventilator-associated pneumonia (VAP) is one of the most common and severe hospital-adquired infections, and multidrugresistant gram-negative bacilli (MDR-GNB) constitute the main etiology in many countries. Inappropriate empiric antimicrobial treatment is associated with increased mortality. In this context, the empirical treatment of choice for VAP is unknown. Colistin, and “old” drug, is now the antimicrobial with greatest in vitro activity against MDR-GNB. However, no randomized clinical trial with colistin has been carried out. Additional aspects of colistin are also not well known, such as the appearance of resistant strains or alterations in the intestinal microbiome during treatment. Furthermore, conventional microbiological techniques take 48 to 72 hours to identify pathogens and determine their susceptibility. This is too long if empiric treatment is inappropriate.Objetives. The overall goal is the optimisation of the treatment of VAP caused by MDR-GNB, by defining a gold standard empiric therapy and reducing the period of time needed for the determination of the etiology and susceptibility of pathogens.Methods. MagicBullet proposes a randomized, open label, multicenter, clinical trial to compare the safety and efficacy of colistin vs. meropenem, both combined with levofloxacin, for empirical treatment of VAP. The pharmacokinetic and pharmacodynamic characteristics of colistin will be determined. Evaluation of the impact of the both treatments in the intestinal microbiome of patients and in the Ventilator-associated pneumonia (VAP) is one of the most common and severe hospital-adquired infections, and multidrug-resistant gramnegative bacilli (MDR-GNB) constitute the main etiology in many countries. Inappropriate empiric antimicrobial treatment is associated with increased mortality. In this context, the empirical treatment of choice for VAP is unknown. Colistin, and “old” drug, is now the antimicrobial with greatest in vitro activity against MDR-GNB. However, no randomized clinical trial with colistin has been carried out. Additional aspects of colistin are also not well known, such as the appearance of resistant strains or alterations in the intestinal microbiome during treatment. Furthermore, conventional microbiological techniques take 48 to 72 hours to identify pathogens and determine their susceptibility. This is too long if empiric treatment is inappropriate.