Ventilator-associated infection: the role for inhaled antibioticsLucy B. Palmer Current opinion in pulmonary medicine 2015, 21:239249 Introduction Pathophysiology and rationale Clinical trials Drug resistance Conclusionoutline Ventilator-associated pneumonia (VAP)Ventilator-associated tracheobronchitis (VAT) multidrug resistant (MDR) extensively drug-resistant (XDR) inhaled antibiotics nebulizersIntroduction Subglottic secretions， disturbed mucociliary clearance, damaged mucosa, bacterial biofilm. Pathophysiology and rationalePathophysiology and rationale 2007，Ioannidou et al，meta-analysis，higher rates of resolution of signs and symptoms of VAP，OR 3.14 recent studies （listed below）Clinical trialsClinical trials1.2.3.4.5.6.Clinical trials7.8.9.10.Clinical trials11.12. 多研究VAP，1提及VAT，2、12VAT，同一作者。细菌鲍曼不动、铜绿假单胞、 肺炎克雷伯多见。抗生素粘菌素多见，万古、庆大、阿米卡星+头孢他啶、妥 布等。雾化器多样，部分未描述雾化器。雾化吸入多联合静脉用药。 多未见副作用，6提及低氧血症、滤器堵塞、心脏骤停？ 结论：雾化吸入无耐药、缩短全身抗生素使用时间、减少抗生素使用量。细菌 根除率高？临床治愈率高？存活率高？ Peak antibiotic concentrations 200-fold (AA+i.v.) Vs (placebo+i.v.):signs of respiratory infectionextubated more oftenneed of additional antibioticsbacterial resistance VAT VAPVAT Clinical trialsXVAT Clinical trials Clinical Pulmonary Infection Score volume of secretions（ml/4h） AA：eradicationdrug-resistance Colistin neurological and renal toxicity stop for 40 years drug-resistance AAColistin Clinical trialsColistin Clinical trials7.AA+i.v.: more MDROs (52.6 vs. 14.9%) , higher APACHE II scores (21.45.7 vs. 17.55.3), But Survive more. 8.Lu et al.，AA/(AA+i.v. 3 days) to resistant vs. i.v. to susceptible organisms: cure rate/mortality no difference.AA+i.v. better？ 11. Tumbarello et al.，AA+i.v. vs. i.v. to COS:cure rate (69.2 vs. 54.8%) ,mechanical ventilation (8 vs. 12 days),Eradication (63.4 vs. 50%, p=0.08),mortality, ICU stay, AKI: No differences. Colistin Clinical trials 10.Doshi et al.，AA+i.v. vs. i.v. to MDROs: Cure rate(54.5 vs. 39.2%;p=0.135) , Eradication(44.4 vs. 40.7%;p=0.805), Motality(40 vs. 70%;p=0.055), High quality culture subgroup cure rate (57.1 vs. 31.3%;p=0.033).Colistin Clinical trials 3. AA+i.v.: no new resistance, 1. AA/AA+i.v.: no new resistance, 2.AA/AA+i.v. vs. placebo+i.v.: 0 vs.33%, 6. AA vs. i.v.: 0 vs. 45%, 12. AA+i.v. vs. placebo+i.v.: 0 vs. 56%, 8.AA/AA+i.v. to resistant vs. i.v. to susceptible organisms :25% susceptible vs.75% resistant. Hypothesis：AA very high antibiotic concentration eradicate the highly resistant organismsdrug-resistanceDrug resistance The concentrations of antibiotics needed? The best delivery devices ? Systemic antibiotic use ? Drug resistance consistently?Conclusion/QuestionThanks