1 Division of Child Health, Obstetrics & Gynaecology, University of Nottingham, and.
2 Nottingham Children's Hospital, Nottingham, United Kingdom.
Ann Am Thorac Soc. 2018 Jan;15(1):42-48. doi: 10.1513/AnnalsATS.201705-376OC.
Consensus is lacking regarding antistaphylococcal antibiotic prophylaxis use for young children with cystic fibrosis. Prophylaxis is recommended in the United Kingdom, but it is recommended against in the United States.
To test the hypothesis that antistaphylococcal antibiotic prophylaxis is associated with a decreased risk of Staphylococcus aureus acquisition but no increased risk of Pseudomonas aeruginosa acquisition.
We undertook a longitudinal observational study of children with cystic fibrosis who were recruited from birth (or from their first registry entry in the period) and followed until the age of 4 years (1,500 d) using 2000-2009 data from the UK Cystic Fibrosis Trust and Cystic Fibrosis Foundation registries. Children were excluded if they had a positive culture result for S. aureus or P. aeruginosa, or if they were receiving inhaled antibiotics, at the first encounter. Time to first S. aureus and P. aeruginosa detection in the UK/U.S. cohorts was compared using a Cox proportional hazards model. A UK-based analysis compared the same for those receiving flucloxacillin with those who received no prophylaxis. We included the following covariates: sex, age at registry entry, dornase alfa use, genotype, and center size.
The primary analysis comprised 1,074 UK and 3,677 U.S. children. The risk of first detection was greater in U.S. children than in UK children for S. aureus (hazard ratio [HR], 5.79; 95% confidence interval [CI], 4.85, 6.90; P < 0.001) and P. aeruginosa (HR, 1.92; 95% CI, 1.65, 2.24; P < 0.001). In the UK analysis, we compared 278 children receiving flucloxacillin and 306 receiving no prophylaxis. Flucloxacillin was not associated with a reduced risk of S. aureus detection (HR, 1.22; 95% CI, 0.74, 2.0; P = 0.43), but it was associated with an increased risk of P. aeruginosa detection (HR, 2.53; 95% CI, 1.71, 3.74; P < 0.001). None of the covariates significantly affected the risk estimate in either analysis.
The risk of first detection of S. aureus and P. aeruginosa was greater in the United States than in the United Kingdom. In the United Kingdom, the risk of first P. aeruginosa detection was increased among those receiving flucloxacillin compared with those who received no prophylaxis. These observational findings should be examined in randomized controlled trials.
对于患有囊性纤维化的幼儿,使用抗葡萄球菌抗生素预防的共识尚未达成。在英国,预防被推荐,但在美国则被反对。
检验以下假设,即抗葡萄球菌抗生素预防与降低金黄色葡萄球菌(金黄色葡萄球菌)获得风险相关,但与铜绿假单胞菌(铜绿假单胞菌)获得风险增加无关。
我们对囊性纤维化信托基金和囊性纤维化基金会登记处的 2000-2009 年英国儿童囊性纤维化登记资料进行了一项纵向观察性研究,对出生时(或登记期间首次登记时)招募的儿童进行了研究,并随访至 4 岁(1500 天)。如果在第一次就诊时儿童有金黄色葡萄球菌或铜绿假单胞菌的阳性培养结果,或正在接受吸入性抗生素治疗,则将其排除在外。使用 Cox 比例风险模型比较了英国/美国队列中首次检测到金黄色葡萄球菌和铜绿假单胞菌的时间。英国的一项分析比较了接受氟氯西林与未接受预防的儿童的情况。我们纳入了以下协变量:性别、登记时的年龄、脱氧核糖核酸酶 alfa 用药、基因型和中心规模。
主要分析包括 1074 名英国和 3677 名美国儿童。与英国儿童相比,美国儿童金黄色葡萄球菌(危险比[HR],5.79;95%置信区间[CI],4.85,6.90;P<0.001)和铜绿假单胞菌(HR,1.92;95%CI,1.65,2.24;P<0.001)的首次检测风险更高。在英国分析中,我们比较了 278 名接受氟氯西林和 306 名未接受预防的儿童。氟氯西林与金黄色葡萄球菌检测风险降低无关(HR,1.22;95%CI,0.74,2.0;P=0.43),但与铜绿假单胞菌检测风险增加有关(HR,2.53;95%CI,1.71,3.74;P<0.001)。在这两种分析中,没有协变量显著影响风险估计。
与英国相比,美国首次检测到金黄色葡萄球菌和铜绿假单胞菌的风险更高。在英国,与未接受预防的儿童相比,接受氟氯西林的儿童首次检测到铜绿假单胞菌的风险增加。这些观察性发现应在随机对照试验中进行检查。