Heyland Daren K, Dodek Peter, Muscedere John, Day Andrew, Cook Deborah
Kingston General Hospital and Queen's University, Kingston, ON, Canada.
Crit Care Med. 2008 Mar;36(3):737-44. doi: 10.1097/01.CCM.0B013E31816203D6.
To compare a strategy of combination therapy with a strategy of monotherapy with broad-spectrum antibiotics for suspected late ventilator-associated pneumonia.
Randomized trial.
Twenty-eight intensive care units in Canada and the United States.
The study included 740 mechanically ventilated patients who developed suspected ventilator-associated pneumonia after 96 hrs in the intensive care unit. Patients known to be colonized or infected with Pseudomonas or methicillin-resistant Staphylococcus aureus or who were immunocompromised were excluded from the study.
As initial unblinded therapy, patients were allocated to receive meropenem (1 g every 8 hrs) and ciprofloxacin (400 mg every 12 hrs) or meropenem alone. Before starting antibiotics, patients were also randomized to bronchoalveolar lavage with quantitative cultures or endotracheal aspirates. When culture results were available, physicians were encouraged to adjust antibiotics. Adequacy of antibiotics was defined as the organism present in the enrollment culture having in vitro susceptibility to one or more of the study antibiotics.
Baseline characteristics and etiologies of ventilator-associated pneumonia were similar in the two groups. There was no difference in 28-day mortality between the combination and monotherapy groups (relative risk = 1.05, 95% confidence interval 0.78-1.42, p = .74). Duration of intensive care unit and hospital stay, clinical and microbiological treatment response, emergence of antibiotic-resistant bacteria, isolation of Clostridium difficile in stool, and fungal colonization were also similar in the two groups. In a subgroup of patients who had infection due to Pseudomonas species, Acinetobacter species, and multidrug-resistant gram-negative bacilli at enrollment (n = 56), the adequacy of initial antibiotics (84.2% vs. 18.8%, p < .001) and microbiological eradication of infecting organisms (64.1% vs. 29.4%, p = .05) was higher in the combination group compared with the monotherapy group, but there were no differences in clinical outcomes.
For critically ill patients who have suspected late ventilator-associated pneumonia and who are at low risk for difficult-to-treat gram-negative bacteria, monotherapy is associated with similar outcomes compared with combination therapy. For those patients at high risk of difficult-to-treat gram-negative bacteria, combination therapy is safe and may be associated with better microbiological and clinical outcomes.
比较联合治疗策略与广谱抗生素单药治疗策略用于疑似晚发性呼吸机相关性肺炎的疗效。
随机试验。
加拿大和美国的28个重症监护病房。
本研究纳入了740例在重症监护病房机械通气96小时后发生疑似呼吸机相关性肺炎的患者。已知感染铜绿假单胞菌或耐甲氧西林金黄色葡萄球菌或免疫功能低下的患者被排除在研究之外。
作为初始非盲法治疗，患者被分配接受美罗培南（每8小时1克）和环丙沙星（每12小时400毫克）或仅接受美罗培南治疗。在开始使用抗生素之前，患者还被随机分为接受定量培养的支气管肺泡灌洗或气管内吸出物检查。当获得培养结果时，鼓励医生调整抗生素。抗生素的充足性定义为入组培养中存在的病原体对一种或多种研究抗生素具有体外敏感性。
两组呼吸机相关性肺炎的基线特征和病因相似。联合治疗组和单药治疗组的28天死亡率无差异（相对风险=1.05，95%置信区间0.78-1.42，p=0.74）。两组在重症监护病房和医院的住院时间、临床和微生物学治疗反应、耐药菌的出现、粪便中艰难梭菌的分离以及真菌定植情况也相似。在入组时因铜绿假单胞菌属、不动杆菌属和多重耐药革兰阴性杆菌感染的患者亚组（n=56）中，联合治疗组初始抗生素的充足性（84.2%对18.8%，p<0.001）和感染病原体的微生物学清除率（64.1%对29.4%，p=0.05）高于单药治疗组，但临床结局无差异。
对于疑似晚发性呼吸机相关性肺炎且治疗难治革兰阴性菌风险较低的重症患者，与联合治疗相比，单药治疗的结局相似。对于那些治疗难治革兰阴性菌风险较高的患者，联合治疗是安全的，可能会带来更好的微生物学和临床结局。
