Children with cystic fibrosis (CF) are subject to pulmonary Staphylococcus aureus infections that can cause permanent lung injury. Damage results from thickened mucosal secretions that cause progressive airway obstruction, scarring, and tissue destruction. The debilitated bronchopulmonary system is then subject to other infections, notably from Pseudomonas aeruginosa. Preventing early S. aureus infection may delay subsequent infections and damage. Stutman and colleagues used a long-term, multi-center, double-blind, placebo-controlled study to look at the value of antibiotic prophylaxis in preventing S. aureus infection and delaying subsequent bronchopulmonary disease in children with CF.
Children four to 24 months of age who had CF and no radiologic evidence of pulmonary disease were enrolled. Based on initial respiratory cultures, participants were divided into the following three groups: (1) those positive for S. aureus, (2) those positive for P. aeruginosa, with or without S. aureus, and (3) those with no evidence of either pathogen.
Children in each group randomly received a five- to seven-year course of either oral cephalexin (80 to 100 mg per kg per day in three divided doses) or placebo. Quarterly evaluations included a history, physical examination, and throat culture. Pulmonary function testing was conducted at each quarterly examination until consecutive testing revealed no significant change in forced expiratory volume in one second (FEV1). Annual examinations included a hemogram, urinalysis, serum chemistry tests, and a chest radiograph. Study medications were given continuously but were discontinued for the duration of treatment when an antibiotic was given for an intercurrent illness. Children who were removed from the study medication for more than six weeks were removed from the study. A total of 119 children completed the study.
Children who were treated with cephalexin had a decrease in the frequency of S. aureus and an increase in the frequency of P. aeruginosa. There were no differences in any clinical outcome, such as days of hospitalization, radiographic or anthropometric scores, or pulmonary function tests. Participants who had more than one positive culture for P. aeruginosa had more frequent pulmonary symptom exacerbations, cough, and sputum production.
The authors conclude that long-term antibiotic treatment of young children with CF is not recommended. Although antibiotic treatment suppressed infection with S. aureus, the incidence of P. aeruginosa infection was higher among the children who received antibiotic therapy. Cephalexin treatment did not delay pulmonary disease or improve any clinical outcome.
In an accompanying editorial, Burns notes that these findings may also imply that aggressive treatment of P. aeruginosa infection may encourage colonization by a resistant strain or an even more virulent organism. Caution in the early treatment of pulmonary bacterial infection is recommended in children with CF until more is known about the microbiologic and clinical outcomes of such treatment.