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Meta-Analysis
. 2012 Nov 14;11(11):CD002203.
doi: 10.1002/14651858.CD002203.pub4.

Macrolide antibiotics for cystic fibrosis

Kevin W Southern  1 , Pierre M Barker, Arturo Solis-Moya, Latifa Patel
Affiliations
Meta-Analysis

Macrolide antibiotics for cystic fibrosis

Kevin W Southern et al. Cochrane Database Syst Rev. .

Update in

Abstract

Background: Macrolide antibiotics may have a modifying role in diseases which involve airway infection and inflammation, like cystic fibrosis.

Objectives: To test the hypotheses that, in people with cystic fibrosis, macrolide antibiotics: 1. improve clinical status compared to placebo or another antibiotic; 2. do not have unacceptable adverse effects. If benefit was demonstrated, we aimed to assess the optimal type, dose and duration of macrolide therapy.

Search methods: 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.We contacted investigators known to work in the field, previous authors and pharmaceutical companies manufacturing macrolide antibiotics for unpublished or follow-up data (May 2010).Latest search of the Group's Cystic Fibrosis Trials Register: 29 February 2012.

Selection criteria: Randomised controlled trials of macrolide antibiotics compared to: placebo; another class of antibiotic; another macrolide antibiotic; or the same macrolide antibiotic at a different dose.

Data collection and analysis: Two authors independently extracted data and assessed risk of bias. Seven groups were contacted and provided additional data which were incorporated into the review.

Main results: Ten of 31 studies identified were included (959 patients). Five studies with a low risk of bias examined azithromycin versus placebo and demonstrated consistent improvement in forced expiratory volume in one second over six months (mean difference at six months 3.97% (95% confidence interval 1.74% to 6.19%; n = 549, from four studies)). Patients treated with azithromycin were approximately twice as likely to be free of pulmonary exacerbation at six months, odds ratio 1.96 (95% confidence interval 1.15 to 3.33). With respect to secondary outcomes, there was a significant reduction in need for oral antibiotics and greater weight gain in those taking azithromycin. Adverse events were uncommon and not obviously associated with azithromycin, although a once-weekly high dose regimen was associated with more frequent gastrointestinal adverse events. Treatment with azithromycin was associated with reduced identification of Staphylococcus aureus on respiratory culture, but also a significant increase in macrolide resistance.

Authors' conclusions: This review provides evidence of improved respiratory function after six months of azithromycin. Data beyond six months were less clear, although reduction in pulmonary exacerbation was sustained. Treatment appeared safe over a six-month period; however, emergence of macrolide resistance was a concern. A multi-centre trial examining long-term effects of this antibiotic treatment is needed, especially for infants recognised through newborn screening.

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Conflict of interest statement

None known.

Figures

1
1
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Funnel plot of comparison: 1 Azithromycin versus placebo, outcome: 1.1 Relative change in FEV1 (% predicted).
4
4
Forest plot of comparison: 1 Azithromycin versus placebo, outcome: 1.1 Relative change in FEV1 (% predicted).
5
5
Funnel plot of comparison: 1 Azithromycin versus placebo, outcome: 1.5 Free of pulmonary exacerbation.
1.1
1.1. Analysis
Comparison 1 Azithromycin versus placebo, Outcome 1 Relative change in FEV1 (% predicted).
1.2
1.2. Analysis
Comparison 1 Azithromycin versus placebo, Outcome 2 Absolute change in FEV1 (% predicted).
1.3
1.3. Analysis
Comparison 1 Azithromycin versus placebo, Outcome 3 Percentage change in FVC.
1.4
1.4. Analysis
Comparison 1 Azithromycin versus placebo, Outcome 4 Free of pulmonary exacerbation.
1.5
1.5. Analysis
Comparison 1 Azithromycin versus placebo, Outcome 5 Mild adverse effects of antibiotic treatment.
1.6
1.6. Analysis
Comparison 1 Azithromycin versus placebo, Outcome 6 Admission to hospital.
1.7
1.7. Analysis
Comparison 1 Azithromycin versus placebo, Outcome 7 Acquisition of Pseudomonas aeruginosa.
1.8
1.8. Analysis
Comparison 1 Azithromycin versus placebo, Outcome 8 Acquisition of Staphylococcal aureus.
1.9
1.9. Analysis
Comparison 1 Azithromycin versus placebo, Outcome 9 Eradication of Staphylococcal aureus present at baseline.
1.10
1.10. Analysis
Comparison 1 Azithromycin versus placebo, Outcome 10 Acquisition of macrolide‐resistant Staphylococcal aureus.
1.11
1.11. Analysis
Comparison 1 Azithromycin versus placebo, Outcome 11 Acquisition of MRSA.
1.12
1.12. Analysis
Comparison 1 Azithromycin versus placebo, Outcome 12 Acquisition of Haemophilus influenzae.
1.13
1.13. Analysis
Comparison 1 Azithromycin versus placebo, Outcome 13 Acquisition of macrolide‐resistant Haemophilus influenzae.
1.14
1.14. Analysis
Comparison 1 Azithromycin versus placebo, Outcome 14 Acquisition of non‐tuberculous mycobacterium.
1.15
1.15. Analysis
Comparison 1 Azithromycin versus placebo, Outcome 15 Need for additional oral antibiotics.
1.16
1.16. Analysis
Comparison 1 Azithromycin versus placebo, Outcome 16 Number of courses of oral antibiotics.
1.17
1.17. Analysis
Comparison 1 Azithromycin versus placebo, Outcome 17 Number of days of additional oral antibiotics.
1.18
1.18. Analysis
Comparison 1 Azithromycin versus placebo, Outcome 18 Need for intravenous antibiotics.
1.19
1.19. Analysis
Comparison 1 Azithromycin versus placebo, Outcome 19 Number of courses of intravenous antibiotics.
1.20
1.20. Analysis
Comparison 1 Azithromycin versus placebo, Outcome 20 Number of days of intravenous antibiotics.
1.21
1.21. Analysis
Comparison 1 Azithromycin versus placebo, Outcome 21 Development of allergic bronchopulmonary aspergillosis.
1.22
1.22. Analysis
Comparison 1 Azithromycin versus placebo, Outcome 22 Change in BMI z score.
1.23
1.23. Analysis
Comparison 1 Azithromycin versus placebo, Outcome 23 Change in weight.
1.24
1.24. Analysis
Comparison 1 Azithromycin versus placebo, Outcome 24 Change in total quality of life score (CFQ‐R).
1.25
1.25. Analysis
Comparison 1 Azithromycin versus placebo, Outcome 25 Change in physical domain of CFQ‐R QoL score.
1.26
1.26. Analysis
Comparison 1 Azithromycin versus placebo, Outcome 26 Change in psychosocial domain of CFQ‐R QoL score.
1.27
1.27. Analysis
Comparison 1 Azithromycin versus placebo, Outcome 27 Change in body image domain of CFQ‐R QoL score.
1.28
1.28. Analysis
Comparison 1 Azithromycin versus placebo, Outcome 28 Change in respiratory symptom domain of CFQ‐R QoL score.
1.29
1.29. Analysis
Comparison 1 Azithromycin versus placebo, Outcome 29 Change in eating disorder domain of CFQ‐R QoL score.
1.30
1.30. Analysis
Comparison 1 Azithromycin versus placebo, Outcome 30 Change in problems with body weight domain of the CFQ‐R QoL score.
1.31
1.31. Analysis
Comparison 1 Azithromycin versus placebo, Outcome 31 Change in CRP.
2.1
2.1. Analysis
Comparison 2 Weekly versus daily azithromycin, Outcome 1 Relative change in FEV1 (% predicted).
2.2
2.2. Analysis
Comparison 2 Weekly versus daily azithromycin, Outcome 2 Days to first pulmonary exacerbation.
2.3
2.3. Analysis
Comparison 2 Weekly versus daily azithromycin, Outcome 3 Adverse events.
2.4
2.4. Analysis
Comparison 2 Weekly versus daily azithromycin, Outcome 4 Days in hospital.
2.5
2.5. Analysis
Comparison 2 Weekly versus daily azithromycin, Outcome 5 Number of hospital admissions.
2.6
2.6. Analysis
Comparison 2 Weekly versus daily azithromycin, Outcome 6 Acquisition of azithromycin‐resistant Staphylococcal aureus.
2.7
2.7. Analysis
Comparison 2 Weekly versus daily azithromycin, Outcome 7 Change in CRP.
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References

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Kessaris 2003 {published data only}
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Ordonez 2001 {published data only}
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Pirzada 1999 {published and unpublished data}
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Pukhalsky 2001 {published data only}
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Radionovitch 2005 {published and unpublished data}
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Rubin 2003 {published data only}
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Shmarina 2004 {published data only}
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References to studies awaiting assessment

Elmasry 2010 {published data only}
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