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Prophylactic anti-staphylococcal antibiotics for cystic fibrosis
Alan R Smyth1, Margaret Rosenfeld2
1Division of Child Health, Obstetrics & Gynaecology (COG), School of Medicine, University of Nottingham, Queens Medical Centre, Derby Road, Nottingham, UK, NG7 2UH.
Insights
Continuous prophylactic antibiotics in children with cystic fibrosis (CF) reduce Staphylococcus aureus isolates but do not significantly improve lung function or cause adverse effects. Long-term impacts and Pseudomonas aeruginosa trends require further investigation.
Area of Science:
- Pediatric Pulmonology
- Infectious Diseases
- Pharmacology
Background:
- Staphylococcus aureus is a common pulmonary pathogen in young children with cystic fibrosis (CF).
- Prophylactic antibiotics are used to prevent S. aureus infection and lung damage in CF patients.
- Long-term antibiotic use may lead to adverse effects and infection with Pseudomonas aeruginosa.
Purpose of the Study:
- To evaluate the efficacy and safety of continuous oral antibiotic prophylaxis for preventing Staphylococcus aureus acquisition in children with CF.
- To assess the impact of prophylaxis on clinical status, lung function, survival, adverse events, and pathogen colonization.
Main Methods:
- Systematic review and meta-analysis of randomized controlled trials.
- Searched Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register and other databases.
- Included four studies with 401 participants aged 0-7 years, focusing on continuous oral prophylactic antibiotics versus no prophylaxis.
Main Results:
- Fewer children receiving prophylaxis had Staphylococcus aureus isolates (low quality evidence).
- No significant differences were observed in lung function, nutrition, hospital admissions, or adverse effects.
- No significant difference in Pseudomonas aeruginosa isolates, with a trend towards higher rates after 4-6 years of prophylaxis.
Conclusions:
- Early-initiated anti-staphylococcal antibiotic prophylaxis reduces S. aureus isolates in young children with CF up to age six.
- The clinical significance of reduced S. aureus is uncertain, and long-term effects, including Pseudomonas aeruginosa trends, require further research.
Background:
Staphylococcus aureus causes pulmonary infection in young children with cystic fibrosis. Prophylactic antibiotics are prescribed hoping to prevent such infection and lung damage. Antibiotics have adverse effects and long-term use might lead to infection with Pseudomonas aeruginosa. This is an update of a previously published review.
Objectives:
To assess continuous oral antibiotic prophylaxis to prevent the acquisition of Staphylococcus aureus versus no prophylaxis in people with cystic fibrosis, we tested these hypotheses. Prophylaxis:1. improves clinical status, lung function and survival;2. causes adverse effects (e.g. diarrhoea, skin rash, candidiasis);3. leads to fewer isolates of common pathogens from respiratory secretions;4. leads to the emergence of antibiotic resistance and colonisation of the respiratory tract with Pseudomonas aeruginosa.
Search Methods:
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, comprising references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. Companies manufacturing anti-staphylococcal antibiotics were contacted.Most recent search of the Group's Register: 29 September 2016.
Selection Criteria:
Randomised trials of continuous oral prophylactic antibiotics (given for at least one year) compared to intermittent antibiotics given 'as required', in people with cystic fibrosis of any disease severity.
Data Collection And Analysis:
The authors assessed studies for eligibility and methodological quality and extracted data.
Main Results:
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.
Authors' Conclusions:
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.