Prophylactic antibiotics for cystic fibrosis

Staphylococcus aureus causes pulmonary infection in young children with cystic fibrosis (CF). Prophylactic antibiotics are widely prescribed in the hope of preventing infection with Staphylococcus aureus and lung damage. Antibiotics also have adverse effects and long-term use might lead to chronic infection with organisms like Pseudomonas aeruginosa.

To assess the effect of continuous oral antibiotic prophylaxis compared to 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 the colonisation of the respiratory tract with organisms, e.g. Pseudomonas aeruginosa.

We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group trials register, comprising references identified from comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings. Companies manufacturing anti-staphylococcal antibiotics were approached for unpublished data. Most recent search of the Group's register: March 2003.

Randomised trials of continuous oral prophylactic antibiotics (given for at least one year) compared to intermittent antibiotic therapy given "as required," in people with CF of any disease severity.

The reviewers assessed trials for eligibility and methodological quality and extracted data.

Four studies, totalling 303 participants (139 boys) aged zero to seven years on enrollment, were included. 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 tests. We found no significant effect on nutrition, hospital admissions, additional courses of antibiotics or adverse effects. There is 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 a trend towards a higher rate from four to six years. However, as the duration of the studies reviewed has been of six years or less, conclusions cannot be drawn about the long-term effects of prophylaxis.

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. Future work should explore whether choice of prophylactic antibiotic or duration of treatment might influence infection with Pseudomonas aeruginosa.