Testing antibiotics in combination for acute infections of Pseudomonas aeruginosa in cystic fibrosis

The main cause of death in people with cystic fibrosis is due to chronic lung infection. People with cystic fibrosis now live longer due to the aggressive use of antibiotics to treat lung infections. Traditionally, antibiotics are chosen based on the results of laboratory testing of each antibiotic separately against the bacterium (or bug) that is found in the lungs of someone with cystic fibrosis. Antibiotics tested in combination may have activity against a bacterium even if ineffective when tested alone. It is unclear, however, if choosing antibiotics to treat lung infections caused by Pseudomonas aeruginosa (P. aeruginosa) in people with cystic fibrosis, based on the results of testing antibiotics in combination is better than choosing antibiotics based on the results of testing antibiotics separately.

The search identified one study that tried to answer this question and was eligible for inclusion in the review. It was a multicentre, randomised, double-blind controlled clinical study. The study looked at whether using the results of testing antibiotics in combination versus testing antibiotics separately improved clinical outcomes in people with CF with lung infections. The study randomised 132 people with cystic fibrosis, the majority of whom had lung infections with P. aeruginosa. The study investigators were able to provide us with the data for those infected only with P. aeruginosa for the time until next lung infection. Choosing antibiotics to treat P. aeruginosa lung infections in people with CF based on results of testing antibiotics in combination did not lead to a longer time until the next lung infection compared to choosing antibiotics based on results of testing antibiotics separately.

The study was limited by the fact that it was not designed to specifically look at people with cystic fibrosis with P. aeruginosa infections. In addition, choosing antibiotics to treat lung infections in cystic fibrosis based on testing antibiotics in combination may be helpful only in those who have already failed antibiotic therapy based on testing antibiotics separately. Future studies addressing these concerns will require international collaboration due to the limited number of people with cystic fibrosis who meet these criteria.

Authors' conclusions: 

The current evidence, limited to one study, shows that there is insufficient evidence to determine effect of choosing antibiotics based on combination antimicrobial susceptibility testing compared to choosing antibiotics based on conventional antimicrobial susceptibility testing in the treatment of acute pulmonary exacerbations in people with CF with chronic P. aeruginosa infection. A large international and multicentre trial is needed to further investigate this issue.

The only trial included in the review was published in 2005, and we have not identified any relevant trials up to September 2011. We therefore do not plan to update this review until new trials are published, although we will search the Group's Cystic Fibrosis Trials Register on a two-yearly cycle.

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Background: 

Antibiotic therapy for acute pulmonary exacerbations in people with cystic fibrosis (CF) is usually chosen based on the results of antimicrobial susceptibility testing of individual drugs. Combination antimicrobial susceptibility testing assesses the efficacy of drug combinations including two or three antibiotics in vitro and can often demonstrate antimicrobial efficacy against bacterial isolates even when individual antibiotics have little or no effect. Therefore, choosing antibiotics based on combination antimicrobial susceptibility testing could potentially improve response to treatment in people with CF with acute exacerbations.

Objectives: 

To compare antibiotic therapy based on conventional antimicrobial susceptibility testing to antibiotic therapy based on combination antimicrobial susceptibility testing in the treatment of acute pulmonary exacerbations in people with CF and chronic infection with P. aeruginosa.

Search strategy: 

We identified relevant trials from the Group's Cystic Fibrosis Trials Register.

Latest search: 08 July 2013.

Selection criteria: 

Randomised and quasi-randomised controlled trials of antibiotic therapy based on conventional antimicrobial susceptibility testing compared to antibiotic therapy based on combination antimicrobial susceptibility testing in the treatment of acute pulmonary exacerbations in CF due to chronic infection with P. aeruginosa.

Data collection and analysis: 

Both authors independently selected trials, assessed their quality and extracted data from eligible studies. Additionally, the authors contacted the study investigators to obtain further information.

Main results: 

The search identified one study eligible for inclusion in the review. This study prospectively assessed whether the use of multiple combination bactericidal antibiotic testing (MCBT) improved clinical outcomes in participants with acute pulmonary exacerbations of CF who were infected with multiresistant bacteria. A total of 132 participants were randomised in the study. The study investigators provided data specific to the participants who were only infected with P. aeruginosa for the primary outcome: time until next pulmonary exacerbation. For "Time to next pulmonary exacerbation" in the participants specifically infected with only P. aeruginosa, the hazard ratio was 0.82, favouring the control group (95% CI 0.44 to 1.51) (P = 0.52). The data did not provide evidence that combination susceptibility testing was superior to conventional susceptibility testing.