Ammar Mona Ahmed, Abdalla Waleed
Department of Anesthesiology and Intensive Care, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Saudi J Anaesth. 2018 Jan-Mar;12(1):89-94. doi: 10.4103/sja.SJA_148_17.
Ventilator-associated pneumonia (VAP) due to multidrug-resistant organisms (MDROs) is associated with a significant mortality in the Intensive Care Unit (ICU). The aim of this study was to compare the efficacy and safety of extended infusion of meropenem and nebulized amikacin on VAP caused by Gram-negative MDRO versus intravenous (IV) meropenem and amikacin alone.
A randomized nonblinded controlled trial was performed on ninety patients with VAP. Patients were randomized into three equal groups: Group I received IV amikacin 20 mg/kg/24 h and meropenem 2 g over 30 min/8 h. Group II received the same as Group I in addition to nebulized amikacin 25 mg/kg/day every 8 h. Group III received IV amikacin 20 mg/kg/24 h, nebulized amikacin 25 mg/kg/day every 8 h, and meropenem 2 g diluted in 240 ml normal saline over 3 h/8 h. The primary outcome was the clinical outcome of VAP. Secondary outcomes were microbiological outcome, VAP-related mortality, duration of MV, ICU stay, and nephrotoxicity.
Group II and Group III compared to Group I showed higher incidence of clinical cure (53.33% in Group II and 66.67% in Group III vs. 26.67% in Group I, = 0.007). Group II compared to Group I showed significant reduction in ventilator days (5.32 ± 1.86 vs. 7.3 ± 2.1 days, respectively, < 0.001) and reduction in ICU days (11.87 ± 2.6 vs. 15.3 ± 3.1 days, respectively, < 0.001). Group III compared to Group II showed significant reduction in ventilator days (4.22 ± 1.32 vs. 5.32 ± 1.86, respectively, = 0.011) and highly significant reduction in ICU days (9.21 ± 1.17 vs. 11.87 ± 2.6, respectively, < 0.001). All groups were comparable as regards nephrotoxicity or mortality.
Adding nebulized amikacin to systemic antibiotics in patients with VAP caused by Gram-negative MDRO may offer efficacy benefits, and the use of extended infusions of meropenem could improve the clinical outcomes in critically ill populations.
多重耐药菌（MDRO）引起的呼吸机相关性肺炎（VAP）与重症监护病房（ICU）的显著死亡率相关。本研究的目的是比较美罗培南延长输注联合雾化阿米卡星与单纯静脉注射（IV）美罗培南和阿米卡星治疗革兰阴性MDRO引起的VAP的疗效和安全性。
对90例VAP患者进行了一项随机非盲对照试验。患者被随机分为三组，每组人数相等：第一组接受静脉注射阿米卡星20mg/kg/24小时和美罗培南2g，静脉滴注30分钟，每8小时一次。第二组除每8小时雾化吸入阿米卡星25mg/kg/天外，其余与第一组相同。第三组接受静脉注射阿米卡星20mg/kg/24小时、每8小时雾化吸入阿米卡星25mg/kg/天，以及美罗培南2g用240ml生理盐水稀释后，静脉滴注3小时，每8小时一次。主要结局是VAP的临床结局。次要结局包括微生物学结局、VAP相关死亡率、机械通气（MV）持续时间、ICU住院时间和肾毒性。
与第一组相比，第二组和第三组的临床治愈率更高（第二组为53.33%，第三组为66.67%，第一组为26.67%，P = 0.007）。与第一组相比，第二组的机械通气天数显著减少（分别为5.32±1.86天和7.3±2.1天，P<0.001），ICU住院天数减少（分别为11.87±2.6天和15.3±3.1天，P<0.001）。与第二组相比，第三组的机械通气天数显著减少（分别为4.22±1.32天和5.32±1.86天，P = 0.011），ICU住院天数显著减少（分别为9.21±1.17天和11.87±2.6天，P<0.001）。在肾毒性或死亡率方面，所有组具有可比性。
对于革兰阴性MDRO引起的VAP患者，在全身抗生素治疗中添加雾化阿米卡星可能具有疗效优势，美罗培南延长输注的使用可改善危重症患者的临床结局。
