The use of intravenous antibiotics to treat pulmonary exacerbations in people with cystic fibrosis

Review question

Do intravenous antibiotics (antibiotics given via a vein) given to treat 'flare ups' of lung disease (pulmonary exacerbations) in people with cystic fibrosis improve clinical outcomes in the short term and the long term?

Background

We wanted to evaluate the evidence for the current practice of using intravenous antibiotics to treat people with cystic fibrosis who have a pulmonary exacerbation. We wanted to discover if it is better to give two antibiotics than just a single antibiotic and wanted to consider if any particular antibiotic combination is better than any other. We also wanted to discover if intravenous antibiotics are any better than inhaled or oral antibiotics in treating pulmonary exacerbations in people with cystic fibrosis.

Search date

We last searched for evidence on 27 July 2015.

Study characteristics

The review included 40 studies with 1717 people with cystic fibrosis. Studies compared intravenous antibiotics with placebo (dummy drug with no active medication) and also one antibiotic compared to two antibiotics given together. Specific antibiotic combinations were also compared as were intravenous antibiotics with antibiotics that were breathed in (inhaled) and antibiotics that were swallowed (oral). The studies lasted from three to 15 days, although most of the studies lasted for two weeks.

Key results

In the comparison between those people who were given just one antibiotic and those who were given two, it appeared that those receiving two antibiotics experienced a greater improvement in lung function, but when limited to only those studies that included a dummy drug, we did not see any difference. There was no effect upon the amount of time until the next exacerbation, weight, or adverse effects. No combination of antibiotics was any better than any other. The outcomes for people were the same irrespective of whether they were treated by intravenous, oral or inhaled antibiotics. None of the studies reported on quality of life.

Quality of the evidence

The quality of the included studies was often poor and many were not properly reported. Some studies included volunteers more than once which made comparing treatments difficult. It was also often difficult to decide from the information given how well the studies were carried out - particularly with respect to how volunteers were chosen and whether the volunteers or doctors could tell which treatment they were being given.

Authors' conclusions: 

The quality of evidence comparing intravenous antibiotics with placebo is poor. No specific antibiotic combination can be considered to be superior to any other, and neither is there evidence showing that the intravenous route is superior to the inhaled or oral routes. There remains a need to understand host-bacteria interactions and in particular to understand why many people fail to fully respond to treatment.

Read the full abstract...
Background: 

Cystic fibrosis is a multi-system disease characterised by the production of thick secretions causing recurrent pulmonary infection, often with unusual bacteria. Intravenous antibiotics are commonly used in the treatment of acute deteriorations in symptoms (pulmonary exacerbations); however, recently the assumption that exacerbations are due to increases in bacterial burden has been questioned.

Objectives: 

To establish if intravenous antibiotics for the treatment of pulmonary exacerbations in people with cystic fibrosis improve short- and long-term clinical outcomes.

Search strategy: 

We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews and ongoing trials registers.

Date of last search of Cochrane trials register: 27 July 2015.

Selection criteria: 

Randomised controlled trials and the first treatment cycle of cross-over studies comparing intravenous antibiotics (given alone or in an antibiotic combination) with placebo, inhaled or oral antibiotics for people with cystic fibrosis experiencing a pulmonary exacerbation.

Data collection and analysis: 

The authors assessed studies for eligibility and risk of bias and extracted data.

Main results: 

We included 40 studies involving 1717 participants. The quality of the included studies was largely poor and, with a few exceptions, these comprised of mainly small, inadequately reported studies.

When comparing treatment with a single antibiotic to a combined antibiotic regimen, those participants receiving a combination of antibiotics experienced a greater improvement in lung function when considered as a whole group across a number of different measurements of lung function, but with very low quality evidence. When limited to the four placebo-controlled studies (n = 214), no difference was observed, again with very low quality evidence. With regard to the review's remaining primary outcomes, there was no effect upon time to next exacerbation and no studies in any comparison reported on quality of life. There were no effects on the secondary outcomes weight or adverse effects. When comparing specific antibiotic combinations there were no significant differences between groups on any measure. In the comparisons between intravenous and nebulised antibiotic or oral antibiotic (low quality evidence), there were no significant differences between groups on any measure. No studies in any comparison reported on quality of life.

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