Review question
We reviewed the evidence about the different effects of using a single intravenous (given directly into a vein) antibiotic compared to using a combination of intravenous antibiotics in people with cystic fibrosis infected with Pseudomonas aeruginosa.
Background
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, often due to bacteria called Pseudomonas aeruginosa. They receive antibiotics, either a single drug or a combination of different drugs, given into a vein to treat these infections. 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 another one in people with cystic fibrosis. This is an updated version of the review.
Search date
The evidence is current to: 07 October 2020.
Study characteristics
We included eight trials with a total of 356 people. Six of these were published before 1988, were each based in a single centre and used a range of different drugs. These factors made it difficult to combine and analyse the results.
Key results
We did not find any differences between the two therapies for lung function, bacteriological outcomes, side effects or symptom scores. We do not think that there is enough evidence to compare the different therapies properly. More research is needed, particularly looking at side effects of treatment.
Quality of the evidence
We judged the certainty of the evidence to be low to moderate. Six of the included trials were quite old (published between 1977 and 1988). They did not include many people and had flaws in the way the people taking part were put into the different treatment groups. Overall, the quality of the trials' design was poor.
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.
The 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 CF requires further evaluation. This is an update of a previously published review.
To assess the effectiveness of single compared to combination intravenous anti-pseudomonal antibiotic therapy for treating people with CF.
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: 07 October 2020.
We also searched online trials registries on 16 November 2020.
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.
Two authors independently assessed trial quality and extracted data. We assessed the certainty of the data using GRADE.
We identified 59 trials, of which we included eight trials (356 participants) comparing a single anti-pseudomonal agent to a combination of the same antibiotic and one other. 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.
There was considerable heterogeneity amongst these trials, leading to difficulties in performing the review and interpreting the results. 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 and the certainty of the evidence ranged from low to moderate.
The review did not find any differences between monotherapy and combination therapy in either the short term or in the long term for the outcomes of different lung function measures, bacteriological outcome measures, need for additional treatment, adverse effects, quality of life or symptom scores.