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Meta-Analysis
. 2016 Dec 1;12(12):CD002007.
doi: 10.1002/14651858.CD002007.pub4.

Single versus combination intravenous anti-pseudomonal antibiotic therapy for people with cystic fibrosis

Heather E Elphick  1 , Alison Scott  1
Affiliations
Meta-Analysis

Single versus combination intravenous anti-pseudomonal antibiotic therapy for people with cystic fibrosis

Heather E Elphick et al. Cochrane Database Syst Rev. .

Update in

Abstract

Background: Choice of antibiotic, and the use of single or combined therapy are controversial areas in the treatment of respiratory infection due to Pseudomonas aeruginosa in cystic fibrosis (CF). Advantages of combination therapy include wider range of modes of action, possible synergy and reduction of resistant organisms; advantages of monotherapy include lower cost, ease of administration and reduction of drug-related toxicity. Current evidence does not provide a clear answer and the use of intravenous antibiotic therapy in cystic fibrosis requires further evaluation. This is an update of a previously published review.

Objectives: To assess the effectiveness of single compared to combination intravenous anti-pseudomonal antibiotic therapy for treating people with cystic fibrosis.

Search methods: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Most recent search of the Group's Trials Register: 14 October 2016.

Selection criteria: Randomised controlled trials (RCTs) comparing a single intravenous anti-pseudomonal antibiotic with a combination of that antibiotic plus a second anti-pseudomonal antibiotic in people with CF.

Data collection and analysis: Two authors independently assessed trial quality and extracted data.

Main results: We identified 45 trials, of which eight trials (356 participants) comparing a single anti-pseudomonal agent to a combination of the same antibiotic and one other, were included.There was a wide variation in the individual antibiotics used in each trial. In total, the trials included seven comparisons of a beta-lactam antibiotic (penicillin-related or third generation cephalosporin) with a beta-lactam-aminoglycoside combination and three comparisons of an aminoglycoside with a beta-lactam-aminoglycoside combination. These two groups of trials were analysed as separate subgroups.There was considerable heterogeneity amongst these trials, leading to difficulties in performing the review and interpreting the results. The meta-analysis did not demonstrate any significant differences between monotherapy and combination therapy, in terms of lung function; symptom scores; adverse effects; and bacteriological outcome measures.These results should be interpreted cautiously. Six of the included trials were published between 1977 and 1988; these were single-centre trials with flaws in the randomisation process and small sample size. Overall, the methodological quality was poor.

Authors' conclusions: The results of this review are inconclusive. The review raises important methodological issues. There is a need for an RCT which needs to be well-designed in terms of adequate randomisation allocation, blinding, power and long-term follow up. Results need to be standardised to a consistent method of reporting, in order to validate the pooling of results from multiple trials.

PubMed Disclaimer

Conflict of interest statement

Dr Heather Elphick has no interests to declare.

Dr Alison Scott has no interests to declare.

Figures

1.1
1.1. Analysis
Comparison 1 Single versus combination, symptomatic regimen, Outcome 1 Mean FEV1 at end of course (% pred).
1.2
1.2. Analysis
Comparison 1 Single versus combination, symptomatic regimen, Outcome 2 Mean FVC at end of course (% pred).
1.3
1.3. Analysis
Comparison 1 Single versus combination, symptomatic regimen, Outcome 3 Mean RV at end of course (% pred).
1.4
1.4. Analysis
Comparison 1 Single versus combination, symptomatic regimen, Outcome 4 Mean TLC at end of course (% pred).
1.5
1.5. Analysis
Comparison 1 Single versus combination, symptomatic regimen, Outcome 5 Mean RV/TLC at end of course (% pred).
1.6
1.6. Analysis
Comparison 1 Single versus combination, symptomatic regimen, Outcome 6 Mean PFR at end of course (% pred).
1.7
1.7. Analysis
Comparison 1 Single versus combination, symptomatic regimen, Outcome 7 Mean MMEF at end of course (% pred).
1.8
1.8. Analysis
Comparison 1 Single versus combination, symptomatic regimen, Outcome 8 Mean Schwachman score at end of course.
1.9
1.9. Analysis
Comparison 1 Single versus combination, symptomatic regimen, Outcome 9 Number of Pseudomonas isolates eradicated at end of course.
1.10
1.10. Analysis
Comparison 1 Single versus combination, symptomatic regimen, Outcome 10 Mean change Pseudomonas density in cfu/g at end of course.
1.11
1.11. Analysis
Comparison 1 Single versus combination, symptomatic regimen, Outcome 11 Number adverse events.
1.12
1.12. Analysis
Comparison 1 Single versus combination, symptomatic regimen, Outcome 12 Number readmitted.
1.13
1.13. Analysis
Comparison 1 Single versus combination, symptomatic regimen, Outcome 13 Mean time to next course of antibiotics (weeks).
1.14
1.14. Analysis
Comparison 1 Single versus combination, symptomatic regimen, Outcome 14 Mean WBC count at end of course.
1.15
1.15. Analysis
Comparison 1 Single versus combination, symptomatic regimen, Outcome 15 Number resistant strains.
See this image and copyright information in PMC

Update of

References

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    1. Elphick HE, Tan AA. Single versus combination intravenous antibiotic therapy for people with cystic fibrosis. Cochrane Database of Systematic Reviews 2005, Issue 2. [DOI: 10.1002/14651858.CD002007.pub2] - DOI - PubMed
Elphick 2014
    1. Elphick HE, Jahnke N. Single versus combination intravenous antibiotic therapy for people with cystic fibrosis. Cochrane Database of Systematic Reviews 2014, Issue 4. [DOI: 10.1002/14651858.CD002007.pub3] - DOI - PubMed

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