People with cystic fibrosis are particularly susceptible to chest infections, some of which can become chronic. It’s important, therefore to try to find treatments for these infections and an updated Cochrane Review from the Cochrane Cystic Fibrosis and Genetic Disorders Group examines the evidence for the use of antibiotics. Alan Smyth, a Coordinating Editor for the Group, based in University of Nottingham in the UK, is one of the authors of this April 2017 review update. He tells us more in this podcast.
John: Hello, I'm John Hilton, editor of the Cochrane Editorial unit. People with cystic fibrosis are particularly susceptible to chest infections, some of which can become chronic. It’s important, therefore to try to find treatments for these infections and an updated Cochrane Review from the Cochrane Cystic Fibrosis and Genetic Disorders Group examines the evidence for the use of antibiotics. Alan Smyth, a Coordinating Editor for the Group, based in University of Nottingham in the UK, is one of the authors of this April 2017 review update. He tells us more in this podcast.
Alan: Cystic fibrosis, or CF, is an inherited condition which affects 10,000 people in the UK and around 70,000 worldwide. It causes difficulties in clearing mucus from the airways, which leads to recurrent chest infections. Some of these can become chronic and this frequently happens with a common germ called Pseudomonas aeruginosa. By their late teens, most people with CF will have chronic Pseudomonas infection in their lungs, which can lead to more frequent admissions to hospital, worsening cough and other symptoms, a deterioration in quality of life and a shorter life. When the infection appears for the first time, it can be eradicated with antibiotic treatment. However, once it’s gained a foothold, Pseudomonas is impossible to get rid of. For this reason, clinical teams that look after people with CF will check for Pseudomonas every time they see them and, if they find the infection, they will give antibiotics to eradicate it. Although eradication treatment is effective in the short term, Pseudomonas infection often recurs and chronic infection usually occurs eventually.
Our Cochrane Review aimed to see whether antibiotic strategies were effective in eradicating Pseudomonas and in preventing chronic infection. We wanted to compare different approaches to antibiotic therapy to see if one was better than another, and to look at any unwanted side effects. We considered trials in which intravenous, oral or inhaled antibiotics had been compared to placebo or no treatment and also head-to-head studies which compared one antibiotic combination with another. We found 7 eligible studies, with a total of 744 participants.
Three of the trials compared active treatment with placebo or no treatment. These were older and smaller than the other studies, but a meta-analysis of the two trials of inhaled tobramycin showed effective eradication two months after the start of treatment. The other trial tested inhaled colistin combined with oral ciprofloxacin and found that this reduced chronic Pseudomonas infection two years after eradication treatment.
More recent trials have compared differing durations of treatment or different antibiotic combinations. None of these have shown that any particular treatment is clearly better or worse than any other but, equally, none of them was large enough to say that one approach is as good as any other.
These trials included a comparison of 28 days of colistin with ciprofloxacin, which is widely used in Europe, versus the same duration of tobramycin with ciprofloxacin, which is preferred in the US. Eradication rates were similar for both regimens, but the prevalence of another germ causing lung infection in CF, Stenotrophomonas maltophilia, increased during the trial in both groups. Other studies have compared these drug combinations given for different time periods, and different ways of deciding when to use inhaled tobramycin.
In summary, we know that chronic Pseudomonas infection reduces the quality and the length of life of people with CF and that eradication therapy in general is beneficial. But, we don’t know if the different therapies have similar effects or whether one is clearly better than another. This needs further investigation and, if the CF community were able to use common outcome measures, this would allow meta-analysis of future trials, helping build an evidence base for future practice. In particular, we need to find out whether we can make eradication treatment less aggressive for some patients, whilst ensuring it is equally effective at eradicating the Pseudomonas, in order to get the benefits while reducing the burden of treatment and the potential harms.
John: You can find much more detail about the trials in Alan’s review, including the specific treatments that were compared in the head-to-head trials by going online to Cochrane library dot com and searching for the review with the words "Pseudomonas and cystic fibrosis".