Smyth Alan R, Walters Sarah
Department of Child Health, School of Clinical Sciences & Nottingham Respiratory BRU, University of Nottingham, Nottingham,UK. 2c/o CFGD Group, Institute of Child Health, University of Liverpool, Liverpool, UK.
Cochrane Database Syst Rev. 2012 Dec 12;12:CD001912. doi: 10.1002/14651858.CD001912.pub2.
Staphylococcus aureus causes pulmonary infection in young children with cystic fibrosis (CF). Prophylactic antibiotics are prescribed hoping to prevent such infection and lung damage. Antibiotics have adverse effects and long-term use might lead to infection with Pseudomonas aeruginosa.
To assess continuous oral antibiotic prophylaxis to prevent the acquisition of Staphylococcus aureus versus no prophylaxis in people with CF, we tested these hypotheses. Prophylaxis: 1. improves clinical status, lung function and survival; 2. causes adverse effects (eg diarrhoea, skin rash, candidiasis); 3. leads to fewer isolates of common pathogens from respiratory secretions; 4. leads to the emergence of antibiotic resistance and colonisation of the respiratory tract with Pseudomonas aeruginosa.
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, comprising references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. Companies manufacturing anti-staphylococcal antibiotics were contacted.Most recent search of Register: 02 August 2012.
Randomised trials of continuous oral prophylactic antibiotics (given for at least one year) compared to intermittent antibiotics given 'as required', in people with CF of any disease severity.
The authors assessed studies for eligibility and methodological quality and extracted data.
We included four studies, totaling 401 randomised participants aged zero to seven years on enrolment. Fewer children receiving anti-staphylococcal antibiotic prophylaxis had one or more isolates of Staphylococcus aureus. There was no significant difference between groups in infant or conventional lung function. We found no significant effect on nutrition, hospital admissions, additional courses of antibiotics or adverse effects. There was no significant difference in the number of isolates of Pseudomonas aeruginosa between groups, though there was a trend towards a lower cumulative isolation rate of Pseudomonas aeruginosa in the prophylaxis group at two and three years and towards a higher rate from four to six years. As the studies reviewed lasted six years or less, conclusions cannot be drawn about the long-term effects of prophylaxis.
AUTHORS' CONCLUSIONS: Anti-staphylococcal antibiotic prophylaxis leads to fewer children having isolates of Staphylococcus aureus, when commenced early in infancy and continued up to six years of age. The clinical importance of this finding is uncertain. Further research may establish whether the trend towards more children with CF with Pseudomonas aeruginosa, after four to six years of prophylaxis, is a chance finding and whether choice of antibiotic or duration of treatment might influence this.
金黄色葡萄球菌可导致患有囊性纤维化（CF）的幼儿发生肺部感染。通常会开具预防性抗生素以预防此类感染和肺部损伤。抗生素有不良作用，长期使用可能导致铜绿假单胞菌感染。
为评估持续口服抗生素预防措施与不进行预防措施相比，对CF患者预防金黄色葡萄球菌感染的效果，我们对以下假设进行了验证。预防措施：1. 改善临床状况、肺功能和生存率；2. 引起不良作用（如腹泻、皮疹、念珠菌病）；3. 减少呼吸道分泌物中常见病原体的分离株；4. 导致抗生素耐药性的出现以及呼吸道被铜绿假单胞菌定植。
我们检索了Cochrane囊性纤维化和遗传疾病研究组试验注册库，其中包括通过全面电子数据库检索、相关期刊手工检索以及会议论文摘要集确定的参考文献。我们还联系了生产抗葡萄球菌抗生素的公司。注册库的最新检索时间为2012年8月2日。
对任何疾病严重程度的CF患者进行的随机试验，比较持续口服预防性抗生素（至少服用一年）与按需服用的间歇性抗生素。
作者评估了研究的合格性和方法学质量，并提取了数据。
我们纳入了四项研究，共有401名年龄在0至7岁的随机参与者入组。接受抗葡萄球菌抗生素预防的儿童中，分离出一株或多株金黄色葡萄球菌的人数较少。两组在婴儿期或传统肺功能方面无显著差异。我们发现对营养、住院次数、额外的抗生素疗程或不良作用没有显著影响。两组之间铜绿假单胞菌分离株的数量没有显著差异，尽管在预防组中，在两年和三年时铜绿假单胞菌的累积分离率有降低趋势，而在四年至六年时有升高趋势。由于所审查的研究持续时间不超过六年，因此无法得出关于预防措施长期效果的结论。
在婴儿期早期开始并持续至六岁时，抗葡萄球菌抗生素预防措施可使分离出金黄色葡萄球菌的儿童人数减少。这一发现的临床重要性尚不确定。进一步的研究可能会确定，在预防四年至六年之后，CF患儿中铜绿假单胞菌感染人数增加的趋势是否只是偶然现象，以及抗生素的选择或治疗持续时间是否会影响这一趋势。
