Standard versus biofilm antibiotic testing to guide antibiotic treatment in cystic fibrosis

Review question

We reviewed evidence to see whether it is better to test antibiotics on Pseudomonas aeruginosa bacteria (bugs) grown in a layer of slime (a biofilm) or on those grown in liquid, when deciding which antibiotics to use for treating a flare up of symptoms in people with cystic fibrosis. We wanted to know if either method would lead to better antibiotic choices with better clinical outcomes.

Background

Long-term lung infection is the main cause of death in people with cystic fibrosis. Antibiotic treatments for these infections have helped people with cystic fibrosis live longer. Doctors usually choose which antibiotics to use after on testing them against bacteria grown from samples taken from the infected person. These bacteria are grown in a liquid in the laboratory; but in real life bacteria such as Pseudomonas aeruginosa do not grow in liquid in the lungs of people with cystic fibrosis, instead they grow in a slime layer called a biofilm. Laboratory testing of antibiotics against Pseudomonas aeruginosa grown in a biofilm rather than in a liquid may give results that lead to better antibiotic choices with better clinical outcomes when treating pulmonary infections in people with cystic fibrosis.

Search date

We last looked for evidence on 19 June 2017.

Study characteristics

We included two trials, one run in the USA (in people who were clinically stable) and one run in Canada (in people who were having an exacerbation or respiratory flare up). A total of 78 people from these trials gave sputum samples. Bacteria from these samples were grown in either a liquid (34 samples) or biofilm (44 samples) with an equal chance of being grown in either one. Neither the individuals or their clinicians knew before or during the trial which method had been used for the sample from each person. A mixture of adults and children took part in the trials, with the average age being around 20 to 30 years. There were an equal number of men and women in both trials. Around half the people in the trials had two copies of the delta F508 gene and there were almost equal number of these in each group. Average lung function in both groups was similar.

Key results

The main outcome of both trials was the decrease in the amount of bacteria in the sputum of people in each group after antibiotic treatment. There was no difference in the levels of bacteria found in the sputum or in the improvement in lung function between the two groups in either trial. In both trials, there was a similar number of individuals in each group who had either a mild or moderate side effect. There were no serious side effects reported by anyone in either study. The evidence does not show that one method of testing is better than the other and that people receiving antibiotics chosen on the basis of either method have equal chances of any side effects.

Quality of the evidence

The quality of the evidence was quite good as people had equal chances of being in either group and they did not know which testing group they were in. This means we don't think the trial results would have been affected because of this.

Authors' conclusions: 

The current evidence is insufficient to recommend choosing antibiotics based on biofilm antimicrobial susceptibility testing rather than conventional antimicrobial susceptibility testing in the treatment of Pseudomonas aeruginosa pulmonary infections in people with cystic fibrosis. Biofilm antimicrobial susceptibility testing may be more appropriate in the development of newer, more effective formulations of drugs which can then be tested in clinical trials.

Read the full abstract...
Background: 

The antibiotics used to treat pulmonary infections in people with cystic fibrosis are typically chosen based on the results of antimicrobial susceptibility testing performed on bacteria traditionally grown in a planktonic mode (grown in a liquid). However, there is considerable evidence to suggest that Pseudomonas aeruginosa actually grows in a biofilm (or slime layer) in the airways of people with cystic fibrosis with chronic pulmonary infections. Therefore, choosing antibiotics based on biofilm rather than conventional antimicrobial susceptibility testing could potentially improve response to treatment of Pseudomonas aeruginosa in people with cystic fibrosis. This is an update of a previously published Cochrane Review.

Objectives: 

To compare biofilm antimicrobial susceptibility testing-driven therapy to conventional antimicrobial susceptibility testing-driven therapy in the treatment of Pseudomonas aeruginosa infection in people with cystic fibrosis.

Search strategy: 

We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Most recent search: 19 June 2017.

We also searched two ongoing trials registries and the reference lists of relevant articles and reviews. Most recent searches: 24 August 2017 and 05 September 2017.

Selection criteria: 

Randomized controlled trials of antibiotic therapy based on biofilm antimicrobial susceptibility testing compared to antibiotic therapy based on conventional antimicrobial susceptibility testing in the treatment of Pseudomonas aeruginosa pulmonary infection in people with cystic fibrosis.

Data collection and analysis: 

Both authors independently selected trials, assessed their risk of bias and extracted data from eligible trials. Additionally, the review authors contacted the trial investigators to obtain further information. The quality of the evidence was assessed using the GRADE criteria.

Main results: 

The searches identified two multicentre, randomized, double-blind controlled clinical trials eligible for inclusion in the review with a total of 78 participants (adults and children); one trial was done in people who were clinically stable, the other in people experiencing pulmonary exacerbations. These trials prospectively assessed whether the use of biofilm antimicrobial susceptibility testing improved microbiological and clinical outcomes in participants with cystic fibrosis who were infected with Pseudomonas aeruginosa. The primary outcome was the change in sputum Pseudomonas aeruginosa density from the beginning to the end of antibiotic therapy.

Although the intervention was shown to be safe, the data from these two trials did not provide evidence that biofilm susceptibility testing was superior to conventional susceptibility testing either in terms of microbiological or lung function outcomes. One of the trials also measured risk and time to subsequent exacerbation as well as quality of life measures and did not demonstrate any difference between groups in these outcomes. Both trials had an overall low risk of bias and the quality of the evidence using GRADE criteria was deemed to be moderate to high for the outcomes selected.

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