TY - JOUR
TI - A Randomized Trial of the Amikacin Fosfomycin Inhalation System for the Adjunctive Therapy of Gram-Negative Ventilator-Associated Pneumonia: IASIS Trial
AU - Kollef, M.H.
AU - Ricard, J.-D.
AU - Roux, D.
AU - Francois, B.
AU - Ischaki, E.
AU - Rozgonyi, Z.
AU - Boulain, T.
AU - Ivanyi, Z.
AU - János, G.
AU - Garot, D.
AU - Koura, F.
AU - Zakynthinos, E.
AU - Dimopoulos, G.
AU - Torres, A.
AU - Danker, W.
AU - Montgomery, A.B.
JO - Journal of Chest Surgery
PY - 2017
VL - 151
TODO - 6
SP - 1239-1246
PB - HANLEY & BELFUS-ELSEVIER INC
SN - null
TODO - 10.1016/j.chest.2016.11.026
TODO - amikacin plus fosfomycin;  antibiotic agent;  colistin;  placebo;  unclassified drug;  amikacin;  antiinfective agent;  fosfomycin, Acinetobacter baumannii;  acute kidney failure;  adjuvant therapy;  adult;  aerosol;  Article;  bronchospasm;  Clinical Pulmonary Infection Score;  controlled study;  diarrhea;  double blind procedure;  drug blood level;  drug efficacy;  drug safety;  drug tissue level;  drug withdrawal;  Enterobacter aerogenes;  Enterobacter cloacae;  Escherichia coli;  female;  human;  hypokalemia;  Klebsiella oxytoca;  Klebsiella pneumoniae;  major clinical study;  male;  methicillin resistant Staphylococcus aureus;  MIC50;  MIC90;  middle aged;  mortality;  multicenter study;  nausea;  nebulizer;  parallel design;  phase 2 clinical trial;  pleura effusion;  pneumonia;  pneumothorax;  priority journal;  Proteus mirabilis;  Pseudomonas aeruginosa;  randomized controlled trial;  scoring system;  septic shock;  Serratia marcescens;  Stenotrophomonas maltophilia;  unspecified side effect;  ventilator associated pneumonia;  adjuvant chemotherapy;  aged;  APACHE;  clinical trial;  Gram-Negative Bacterial Infections;  inhalational drug administration;  Pneumonia, Ventilator-Associated;  treatment outcome, Administration, Inhalation;  Adult;  Aged;  Amikacin;  Anti-Bacterial Agents;  APACHE;  Chemotherapy, Adjuvant;  Double-Blind Method;  Female;  Fosfomycin;  Gram-Negative Bacterial Infections;  Humans;  Male;  Middle Aged;  Pneumonia, Ventilator-Associated;  Treatment Outcome
TODO - Background Clinical failures in ventilator-associated pneumonia (VAP) caused by gram-negative bacteria are common and associated with substantial morbidity, mortality, and resource utilization. Methods We 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. Results There 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. Conclusions In 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 Registry ClinicalTrials.gov; No.: NCT01969799; URL: www.clinicaltrials.gov © 2016 American College of Chest Physicians
ER -