• Marin H Kollef, Jean-Damien Ricard, Damien Roux, Bruno Francois, Eleni Ischaki, Zsolt Rozgonyi, Thierry Boulain, Zsolt Ivanyi, Gál János, Denis Garot, Firas Koura, Epaminondas Zakynthinos, George Dimopoulos, Antonio Torres, Wayne Danker, and A Bruce Montgomery.
• Washington University School of Medicine, Saint Louis, MO. Electronic address: kollefm@wustl.edu.
• Chest. 2017 Jun 1; 151 (6): 1239-1246.

BackgroundClinical failures in ventilator-associated pneumonia (VAP) caused by gram-negative bacteria are common and associated with substantial morbidity, mortality, and resource utilization.MethodsWe assessed the safety and efficacy of the amikacin fosfomycin inhalation system (AFIS) for the treatment of gram-negative bacterial VAP in a randomized double-blind, placebo-controlled, parallel group, phase 2 study between May 2013 and March 2016. We compared standard of care in each arm plus 300 mg amikacin/120 mg fosfomycin or placebo (saline), delivered by aerosol twice daily for 10 days (or to extubation if < 10 days) via the investigational eFlow Inline System (PARI GmbH). The primary efficacy end point was change from baseline in the Clinical Pulmonary Infection Score (CPIS) during the randomized course of AFIS/placebo, using the subset of patients with microbiologically proven baseline infections with gram-negative bacteria.ResultsThere were 143 patients randomized: 71 to the AFIS group, and 72 to the placebo group. Comparison of CPIS change from baseline between treatment groups was not different (P = .70). The secondary hierarchical end point of no mortality and clinical cure at day 14 or earlier was also not significant (P = .68) nor was the hierarchical end point of no mortality and ventilator-free days (P = .06). The number of deaths in the AFIS group was 17 (24%) and 12 (17%) in the placebo group (P = .32). The AFIS group had significantly fewer positive tracheal cultures on days 3 and 7 than placebo.ConclusionsIn this trial of adjunctive aerosol therapy compared with standard of care IV antibiotics in patients with gram-negative VAP, the AFIS was ineffective in improving clinical outcomes despite reducing bacterial burden.Trial RegistryClinicalTrials.gov; No.: NCT01969799; URL: www.clinicaltrials.gov.Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

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