Department of Paediatric Respiratory Medicine, Cystic Fibrosis Center, WilhelminaChildren’s Hospital, University Medical Center Utrecht, The Netherlands.
Thorax. 2010 Oct;65(10):915-20. doi: 10.1136/thx.2009.126128. Epub 2010 Aug 20.
Initial pulmonary Pseudomonas aeruginosa infection in patients with cystic fibrosis (CF) is currently treated with intensive antibiotic therapy. At this stage, inflammation and tissue injury might have already occurred. Moreover, bacterial eradication is not always achieved. Prophylactic treatment against P aeruginosa seemed to have a preventive effect in retrospective studies. A study was undertaken to establish prospectively the effect of cycled prophylactic treatment on prevention of initial P aeruginosa infection in children with CF.
This 3-year triple-blind randomised controlled trial included 65 children with CF without P aeruginosa infection. Intervention existed of 3-monthly 3-week treatments with oral ciprofloxacin and inhaled colistin or both placebo controls. The primary outcome was P aeruginosa infection. Secondary outcomes were serum anti-Pseudomonas antibodies, pulmonary function, exacerbations, chest x-ray scores, inflammation parameters, respiratory pathogens and antimicrobial resistance.
There was no difference in acquisition of P aeruginosa infection between the control and treatment groups (annual incidence 14% vs 11%; HR 0.738, 95% CI 0.299 to 1.822). Anti-Pseudomonas antibodies emerged earlier in the control group, but this difference had disappeared after 3 years. Chronic infection was observed in 19% of controls and 12% of treated patients. Decline in pulmonary function and other clinical outcomes did not differ between the two groups. In the treatment group, significantly fewer Gram-positive bacteria and Enterobacteriaceae were observed but there were more non-P aeruginosa non-fermentative Gram-negative bacteria. Conclusions Three-monthly cycled anti-P aeruginosa prophylaxis does not reduce the risk of initial and chronic infection in P aeruginosa-negative children with CF of all ages. Shifts in bacterial colonisation demand caution. Trial Registration Number ISRCTN 11604593.
目前，囊性纤维化（CF）患者的初始铜绿假单胞菌肺部感染采用强化抗生素治疗。在这个阶段，炎症和组织损伤可能已经发生。此外，细菌的清除并不总是能实现。针对铜绿假单胞菌的预防性治疗在回顾性研究中显示出预防作用。本研究旨在前瞻性地确定铜绿假单胞菌周期性预防治疗对 CF 儿童初始铜绿假单胞菌感染的预防效果。
这项为期 3 年的三盲随机对照试验纳入了 65 名无铜绿假单胞菌感染的 CF 患儿。干预措施为每 3 个月进行为期 3 周的口服环丙沙星和吸入黏菌素治疗或两者安慰剂对照。主要结局是铜绿假单胞菌感染。次要结局包括血清抗铜绿假单胞菌抗体、肺功能、加重发作、胸部 X 光评分、炎症参数、呼吸道病原体和抗菌药物耐药性。
对照组和治疗组在获得铜绿假单胞菌感染方面无差异（年发病率分别为 14%和 11%；HR 0.738，95%CI 0.299 至 1.822）。对照组中抗铜绿假单胞菌抗体出现更早，但 3 年后这种差异已经消失。对照组中 19%的患儿发生慢性感染，治疗组为 12%。两组患者的肺功能和其他临床结局均无差异。在治疗组中，革兰阳性菌和肠杆菌科的数量明显减少，但非铜绿假单胞菌非发酵革兰阴性菌的数量更多。结论：对于所有年龄段的铜绿假单胞菌阴性 CF 患儿，每 3 个月进行铜绿假单胞菌周期性预防治疗并不能降低初始和慢性感染的风险。细菌定植的变化需要谨慎对待。试验注册号：ISRCTN 11604593。
