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Meta-Analysis
. 2017 Apr 18;4(4):CD001912.
doi: 10.1002/14651858.CD001912.pub4.

Prophylactic anti-staphylococcal antibiotics for cystic fibrosis

Alan R Smyth  1 , Margaret Rosenfeld  2
Affiliations
Meta-Analysis

Prophylactic anti-staphylococcal antibiotics for cystic fibrosis

Alan R Smyth et al. Cochrane Database Syst Rev. .

Update in

Abstract

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.

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Conflict of interest statement

ARS declares relevant activities of membership of a MPEX steering committee, advisory board member (Vertex, Gilead and MPEX), lectures paid for by Gilead and Novartis.

MR declares no known conflict of interest.

Clarification statement added from Alan Smyth, Co‐ordinating Editor on 19 February 2020: This review was found by the Cochrane Funding Arbiters, post‐publication, to be noncompliant with the Cochrane conflict of interest policy, which includes the relevant parts of the Cochrane Commercial Sponsorship Policy. It will be updated by February 2021. The update will have a majority of authors and lead author free of conflicts.

Figures

1.1
1.1. Analysis
Comparison 1 Anti‐staphylococcal prophylaxis versus 'as required' treatment, Outcome 1 Lung function (% predicted).
1.2
1.2. Analysis
Comparison 1 Anti‐staphylococcal prophylaxis versus 'as required' treatment, Outcome 2 Number of children from whom S aureus isolated at least once.
1.3
1.3. Analysis
Comparison 1 Anti‐staphylococcal prophylaxis versus 'as required' treatment, Outcome 3 Z score weight.
1.4
1.4. Analysis
Comparison 1 Anti‐staphylococcal prophylaxis versus 'as required' treatment, Outcome 4 Z score length.
1.5
1.5. Analysis
Comparison 1 Anti‐staphylococcal prophylaxis versus 'as required' treatment, Outcome 5 Number of children requiring admission (annualised rates).
1.6
1.6. Analysis
Comparison 1 Anti‐staphylococcal prophylaxis versus 'as required' treatment, Outcome 6 Days in hospital (annualised rates).
1.7
1.7. Analysis
Comparison 1 Anti‐staphylococcal prophylaxis versus 'as required' treatment, Outcome 7 Number of children receiving additional antibiotics.
1.8
1.8. Analysis
Comparison 1 Anti‐staphylococcal prophylaxis versus 'as required' treatment, Outcome 8 Days of additional antibiotics.
1.9
1.9. Analysis
Comparison 1 Anti‐staphylococcal prophylaxis versus 'as required' treatment, Outcome 9 Number of children from whom H influenzae isolated at least once.
1.10
1.10. Analysis
Comparison 1 Anti‐staphylococcal prophylaxis versus 'as required' treatment, Outcome 10 Number of children from whom P aeruginosa isolated at least once.
1.11
1.11. Analysis
Comparison 1 Anti‐staphylococcal prophylaxis versus 'as required' treatment, Outcome 11 Adverse effects: mean number of days experiencing adverse effect.
1.12
1.12. Analysis
Comparison 1 Anti‐staphylococcal prophylaxis versus 'as required' treatment, Outcome 12 Shwachman score.
1.13
1.13. Analysis
Comparison 1 Anti‐staphylococcal prophylaxis versus 'as required' treatment, Outcome 13 Chrispin‐Norman Score.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Chatfield 1991 {published and unpublished data}
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References to studies excluded from this review

Ballestero 1992 {published data only}
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Feigelson 1993 {published data only}
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Harrison 1985 {published data only}
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Kerrebijn 1984 {published data only}
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Loening‐Baucke 1979 {published data only}
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    1. Loening‐Baucke V, Mischler EH, Myers MG. Cephalexin compared to placebo in the management of patients with cystic fibrosis [abstract]. 19th Annual Meeting Cystic Fibrosis Club Abstracts. 1978:69.
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Nolan 1982 {published data only}
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References to ongoing studies

CF START 2016 {published data only}
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References to other published versions of this review

Smyth 2003
    1. Smyth AR, Walters S. Prophylactic anti‐staphylococcal antibiotics for cystic fibrosis. Cochrane Database of Systematic Reviews 2003, Issue 3. [DOI: 10.1002/14651858.CD001912] - DOI - PubMed
Smyth 2014
    1. Smyth AR, Walters S. Prophylactic anti‐staphylococcal antibiotics for cystic fibrosis. Cochrane Database of Systematic Reviews 2014, Issue 11. [DOI: 10.1002/14651858.CD001912.pub3] - DOI - PubMed

MeSH terms