A comparison of single and combined intravenous drug therapy for people with cystic fibrosis

Elphick HE, Tan AA

Published Online:

December 7, 2011

Cystic fibrosis is a serious genetic disease that affects cells in the exocrine glands (sweat glands and others). People with cystic fibrosis have a greater risk of chronic lung infections. They receive antibiotics by injection to treat these. The antibiotics are either a single drug or a combination of drugs. Both the choice of antibiotic and the use of single or combined therapy vary. We looked for randomised controlled trials which compared a single intravenous antibiotic with a combination of that antibiotic plus one other in people with cystic fibrosis. We included eight trials with a total of 356 people. Six of these were published before 1988. They were single centre trials with poor methodological quality. A range of drugs was used in the trials. This made it difficult to combine and analyse the results. We did not find any differences between the two therapies for lung function, symptom scores, adverse effects or bacteriological outcome measures. We conclude that there is not enough evidence to compare the different therapies. More research is needed, particularly for adverse effects.

Abstract (click to read)

Background:

Choice of antibiotic, and the use of single or combined therapy are controversial areas in the treatment of respiratory infection 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 CF requires further evaluation.

Objectives:

To assess the effectiveness of single compared to combination intravenous antibiotic therapy for treating people with CF.

Search strategy:

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: 24th August 2011.

Selection criteria:

Randomised controlled trials (RCTs) comparing a single intravenous antibiotic with a combination of that antibiotic plus a second antibiotic in people with CF.

Data collection and analysis:

Two authors independently assessed trial quality and extracted data.

Main results:

Twenty-seven trials were identified, of which eight trials (356 participants) comparing a single 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.

This record should be cited as:

Elphick HE, Tan AA. Single versus combination intravenous antibiotic therapy for people with cystic fibrosis. Cochrane Database of Systematic Reviews 2005, Issue 2. Art. No.: CD002007. DOI: 10.1002/14651858.CD002007.pub2

Assessed as up to date:

November 3, 2011

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Primary Review Group:

Cystic Fibrosis and Genetic Disorders Group

Health topics:

Genetic disorders > Cystic fibrosis > Antibiotic treatment

Lungs & airways > Cystic fibrosis > Antibiotic treatment

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Independent high-quality evidence for health care decision making

A comparison of single and combined intravenous drug therapy for people with cystic fibrosis

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