Antibiotic prophylaxis in infants and young children with cystic fibrosis: a randomized controlled trial. Antibiotic prophylaxis in cystic fibrosis: inhaled cephaloridine as an adjunct to oral cloxacillin. Reducing antibiotic use in children: a randomized trial in 12 practices.
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. The effect of prophylactic antibiotics on bacterial colonization of the respiratory tract and on general progression of cystic fibrosis was studied in a two-year prospective study of 47 mildly to moderately affected patients. One group of patients received inhaled cephaloridine and the other received no inhaled antibiotic; both groups received cloxacillin orally. Carriage of Haemophilus influenzae was greater in the group not receiving inhaled antibiotic (55% vs 20%). Rates of carriage of Staphylococcus aureus (23%). Pseudomonas aeruginosa (greater than 90%). Pseudomonas cepacia (45%), and other organisms were similar in both groups. There were no significant differences between the two groups in incidence of respiratory tract infections or hospital admissions, clinical scores, radiologic scores, or rate of change of pulmonary function. Although continuous antistaphylococcal antibiotic prophylaxis may be successful in suppressing colonization with S. aureus, it may also contribute to the high rates of carriage of Ps. aeruginosa and Ps. cepacia observed in patients with cystic fibrosis. To test whether an educational outreach intervention for families and physicians, based on the Centers for Disease Control and Prevention (CDC) principles of judicious antibiotic use, decreases antimicrobial drug prescribing for children younger than 6 years old. Setting. Twelve practices affiliated with 2 managed care organizations (MCOs) in eastern Massachusetts and northwest Washington State. Patients. All enrolled children younger than 6 years old.
                Practices stratified by MCO and size were randomized to intervention or control groups. The intervention included 2 meetings of the practice with a physician peer leader, using CDC-endorsed summaries of judicious prescribing recommendations; feedback on previous prescribing rates were also provided. Parents were mailed a CDC brochure on antibiotic use, and supporting materials were displayed in waiting rooms. Automated enrollment, ambulatory visit, and pharmacy claims were used to determine rates of antibiotic courses dispensed (antibiotics/person-year) during baseline (1996-1997) and intervention (1997-1998) years. The primary analysis (for children 3 to <36 months and 36 to <72 months) assessed the impact of the intervention among children during the intervention year, controlling for covariates including patient age and baseline prescription rate. Confirmatory analyses at the practice level were also performed.
                The practices cared for 14 468 and 13 460 children in the 2 study years, respectively; 8815 children contributed data in both years. Sixty-two percent of antibiotic courses were dispensed for otitis media, 6.5% for pharyngitis, 6.3% for sinusitis, and 9.2% for colds and bronchitis. Antibiotic dispensing for children 3 to <36 months old decreased 0.41 antibiotics per person-year (18.6%) in intervention compared with 0.33 (11.5%) in control practices. Among children 36 to <72 months old, the rate decreased by 0.21 antibiotics per person-year (15%) in intervention and 0.17 (9.8%) in control practices. Multivariate analysis showed an adjusted intervention effect of 16% in the younger and 12% in the older age groups. The direction and approximate magnitude of effect were confirmed in practice-level analyses.
                A limited simultaneous educational outreach intervention for parents and providers reduced antibiotic use among children in primary care practices, even in the setting of substantial secular trends toward decreased prescribing. Future efforts to promote judicious prescribing should continue to build on growing public awareness of antibiotic overuse.
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.