Antibiotic prophylaxis in infants and young children with cystic fibrosis: a randomized controlled trial. Prognosis in cystic fibrosis treated with continuous flucloxacillin from the neonatal period. Neonatal screening for cystic fibrosis in Wales and the West Midlands: clinical assessment after five years of screening.
To evaluate whether antistaphylococcal prophylaxis in infants and young children with cystic fibrosis (CF) would suppress the acquisition of Staphylococcus aureus and delay the onset of the manifestations of bronchopulmonary disease.
                A 7-year, multicenter, double-blind, placebo-controlled study of continuous antistaphylococcal therapy. Otherwise healthy children <2 years of age with CF were randomly assigned to be treated with daily cephalexin (80-100 mg/kg/day) or placebo. Clinical, microbiologic, laboratory, radiographic, and anthropometric outcomes were evaluated.
                Of 209 children enrolled, 119 completed a 5- to 7-year course of therapy. Mean age at enrollment was 15.6 and 14.1 months in the cephalexin and placebo groups, respectively. Respiratory cultures from children treated with cephalexin were significantly less likely to be positive for S aureus (6.0% vs 30.4%; P <.001). They were, however, much more likely to be positive for Pseudomonas aeruginosa (25.6% vs 13.5%; P <.009). These differences became apparent in the first year after enrollment and persisted over the duration of the study. In contrast to these microbiologic differences, there were no differences in clinical outcome measures, including radiographic (Brasfield score, 23.4 vs 23.2) or anthropometric scores or pulmonary function.
                Although long-term prophylaxis with cephalexin successfully delayed the acquisition of S aureus, it enhanced colonization with P aeruginosa and did not lead to clinically significant improvement in major health outcomes. These data do not support routine antistaphylococcal prophylaxisin otherwise healthy infants and young children with CF. All newborn infants in East Anglia are screened for cystic fibrosis by blood immunoreactive trypsin assay at 7 days. Thirty eight infants with cystic fibrosis were randomised to treatment with either continuous oral flucloxacillin 250 mg/day (group P, n = 18) or with episodic antimicrobials as clinically indicated (group E, n = 20). Their progress was monitored from diagnosis to 24 months by a nurse coordinator who visited all infants regularly, at home and in hospital, to collect anthropometric, dietary, clinical, and microbiological data. Mean (range) age of confirmation of diagnosis was 5.7 weeks (1-14 weeks). There was no significant difference in birth weight, genotype, immunoreactive trypsin concentration, neonatal history, symptoms at diagnosis, pancreatic enzyme supplementation, or parental smoking history between the groups. Infants in group E had more frequent cough and a greater number of Staphylococcus aureus isolates than infants in group P. More infants of group E were admitted to hospital, had higher admission rates during the second year (19 v 5), for longer periods (6.4 v 2.2 days), despite receiving more than double the number of courses of antibiotics than group P infants (in addition to flucloxacillin). Continuous prophylactic flucloxacillin from early diagnosis of cystic fibrosis is associated with improved clinical progress during the first two years of life. Screening of the newborn for cystic fibrosis by measurement of immunoreactive trypsin has been undertaken on alternate weeks in Wales and the West Midlands for five years since 1985 to evaluate the possible clinical benefits of early diagnosis. Patients detected by screening and those diagnosed by clinical symptoms alone were assessed annually for differences in clinical, anthropometric, and biochemical variables. Fifty eight infants not considered to be at risk of cystic fibrosis (they did not present with meconium ileus and do not have a sibling with cystic fibrosis) have been detected by screening and they have been compared with 44 children who were diagnosed clinically. This latter group includes nine children whose screening was negative but who were recognised subsequently to have cystic fibrosis. The mean age at diagnosis of the screened group was significantly lower than that of the group diagnosed clinically. Excluding admissions for diagnostic tests for cystic fibrosis, the screened group spent a significantly shorter time in hospital during the first year of life. The results of all other comparisons made between the screened group and those diagnosed clinically were similar up to the age of 4 years.
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.