Abstract: We included four studies, with a total of 401 randomised participants aged zero to seven years on enrolment; one study is ongoing. The two older included studies generally had a higher risk of bias across all domains, but in particular due to a lack of blinding and incomplete outcome data, than the two more recent studies. We only regarded the most recent study as being generally free of bias, although even here we were not certain of the effect of the per protocol analysis on the study results. Evidence was downgraded based on GRADE assessments and outcome results ranged from moderate to low quality. Downgrading decisions were due to limitations in study design (all outcomes); for imprecision (number of people needing additional antibiotics); and for inconsistency (weight z score). Fewer children receiving anti-staphylococcal antibiotic prophylaxis had one or more isolates of Staphylococcus aureus (low quality evidence). There was no significant difference between groups in infant or conventional lung function (moderate quality evidence). We found no significant effect on nutrition (low quality evidence), hospital admissions, additional courses of antibiotics (low quality evidence) or adverse effects (moderate quality evidence). There was no significant difference in the number of isolates of Pseudomonas aeruginosa between groups (low quality evidence), 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. 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.

Plain-language summary: The review includes four studies with 401 children; there were no adult studies. The children were put into groups at random and received either an oral antibiotic continuously as a prevention for at least one year or no antibiotic treatment to prevent infection with Staphylococcus aureus. All children could be given additional antibiotics if their doctor thought they needed them, based on symptoms and germs grown in their respiratory secretions. Studies lasted for a maximum of six years. The review found some evidence that giving regular antibiotics to young children (continued up to six years of age) leads to fewer infections with Staphylococcus aureus. For other outcomes in the review, there was no difference between giving regular antibiotics or not. Since none of the studies lasted longer than six years, we can't draw any conclusions about long-term use. Also, since all studies were in children, we can not comment on the use of these drugs in adults. Future research should look at patterns of antibiotic resistance and survival. All the studies were of variable quality and the quality of the evidence for different outcomes ranged from low to moderate. We judged that the two older studies had a higher risk of bias overall compared to the two newer studies. In particular this was because those taking part in the studies (or their parents or caregivers) would be able to guess which treatment they were receiving, and also one study did not state if anyone had dropped out and if so what the reasons were. Only the newest study seemed to be free of bias, although even here we were not certain if the study results were affected by the way the data were analysed. Further research might change the estimate of the size of the treatment effect and would certainly affect our confidence in the estimated effect.