Key messages
– Intravenous (given into a vein) antibiotics are commonly used to treat flare-ups in symptoms of cystic fibrosis, but the assumption that exacerbations are due to more bacteria in the lungs has been questioned.
– We assessed many different antibiotics as single medicines or combinations of medicines as well as how they were given (intravenous, inhaled (breathed in) or oral (by mouth)). We found no difference in any clinical outcomes such as how well the lungs work or the time to the next flare-up between any type of treatment, except for people who responded early to treatment where a shorter duration of treatment may be appropriate.
What is cystic fibrosis and what are exacerbations?
Cystic fibrosis is an inherited condition in which the mucous the body produces is sticky and this affects how several organs in the body work. The lungs and the airways are probably the most affected organs in people with cystic fibrosis. The sticky mucous makes it difficult to cough up bacteria (germs) that can cause infections. It is thought that this can lead to flare-ups of lung disease, known as pulmonary exacerbations. These exacerbations can be treated with antibiotics (medicines that kill bacteria), but over time the germs may not be able to be cleared completely and the infections can last a long time (chronic).
What did we want to know?
We wanted to see what evidence there is for the current practice of using intravenous (given into a vein) antibiotics to treat people with cystic fibrosis who have an exacerbation. We wanted to know if it is better to give two different antibiotics than just one antibiotic and wanted to consider if any particular antibiotic combination is better than any other. We also wanted to know if intravenous antibiotics are any better than inhaled (breathed in using an aerosol) or oral (by mouth) antibiotics for treating pulmonary exacerbations in people with cystic fibrosis.
What did we do?
We looked for studies of people with cystic fibrosis who were in hospital because of an exacerbation and which compared a course of any dose of intravenous antibiotics (either just one antibiotic or combinations of different ones) to either a placebo (dummy treatment with no active medication), or to other intravenous antibiotics, or to inhaled antibiotics, or oral antibiotics. We did not look for studies that compared different doses of the same antibiotic.
We compared and summarised the results of the studies and rated our confidence in the evidence, based on factors such as study methods and sizes.
What did we find?
We found 45 studies involving 2810 people. Most studies were small, quite old, and lasted between three and 15 days. They often did not provide the information we were looking for. There were many different study designs; some studies compared either single intravenous antibiotics or a combination of different intravenous antibiotics with a placebo. Some studies compared single intravenous antibiotics to a combination of intravenous antibiotics or compared different intravenous combinations (different medicines or durations of treatment); other studies compared intravenous antibiotics to oral or inhaled antibiotics.
Key results
We found none of our compared antibiotics or antibiotic combinations to show better lung function. We found little information on the time to the next exacerbation and there was no clear treatment that was better for this either. One study in people who responded early to treatment showed that a shorter duration of antibiotics worked as well as a longer duration. Only one study reported on quality of life and showed no difference between inhaled plus intravenous antibiotics and a combination of two different intravenous antibiotics. The evidence was unclear for unwanted effects; most reported unwanted effects related to digestive or liver problems. We did not find any evidence for the effect of different treatments on bodyweight. We found limited evidence that more days of antibiotics were no better than fewer days.
What are the limitations of the evidence?
Our confidence in the results from the included studies ranged from high to very low and many studies were not fully reported. Some studies included people more than once, which made comparing treatments difficult. It was also often difficult to decide from the information given how well the studies were carried out – particularly with respect to how people were chosen and whether the people or doctors knew which treatment they were being given.
How up to date is this evidence?
This is an update of a previously published review. We last searched for evidence on 19 June 2024.
The evidence of benefit from administering IV antibiotics for pulmonary exacerbations in cystic fibrosis is often poor, especially in terms of size of studies and risk of bias, particularly in older studies. We are not certain whether there is any difference between specific antibiotic combinations, and neither is there evidence of a difference between the IV route and the inhaled or oral routes. There is limited evidence that shorter antibiotic duration in adults who respond early to treatment is not different to a longer period of treatment. There remain several unanswered questions regarding optimal IV antibiotic treatment regimens.
Cystic fibrosis is a multisystem disease characterised by the production of thick secretions causing recurrent pulmonary infection, often with unusual bacteria. Intravenous (IV) antibiotics are commonly used in the treatment of acute deteriorations in symptoms (pulmonary exacerbations); however, recently the assumption that exacerbations are due to increases in bacterial burden has been questioned. This is an update of a previously published review.
To establish whether IV antibiotics for the treatment of pulmonary exacerbations in people with cystic fibrosis improve short-term and long-term clinical outcomes.
We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews and ongoing trials registers.
Date of last search of Cochrane Trials Register: 19 June 2024.
Randomised controlled trials and the first treatment cycle of cross-over studies comparing IV antibiotics (given alone or in an antibiotic combination) with placebo, or inhaled or oral antibiotics for people with cystic fibrosis experiencing a pulmonary exacerbation. Studies comparing different IV antibiotic regimens were also eligible.
We assessed studies for eligibility and risk of bias, and extracted data. Using GRADE, we assessed the certainty of the evidence for the outcomes lung function % predicted (forced expiratory volume in one second (FEV1) and forced vital capacity (FVC)), time to next exacerbation and quality of life.
We included 45 studies involving 2810 participants. The included studies were mostly small, and inadequately reported, many of which were quite old. The certainty of the evidence was mostly low.
Combined intravenous antibiotics versus placebo
Data reported for absolute change in % predicted FEV1 and FVC suggested a possible improvement in favour of IV antibiotics, but the evidence is very uncertain (1 study, 12 participants; very low-certainty evidence). The study did not measure time to next exacerbation or quality of life.
Intravenous versus nebulised antibiotics
Five studies (122 participants) reported FEV1, with analysable data only from one study (16 participants). We found no difference between groups (moderate-certainty evidence). Three studies (91 participants) reported on FVC, with analysable data from only one study (54 participants). We are very uncertain on the effect of nebulised antibiotics (very low-certainty evidence). In one study, the 16 participants on nebulised plus IV antibiotics had a lower mean number of days to next exacerbation than those on combined IV antibiotics (low-certainty evidence), but we found no difference in quality of life between groups (low-certainty evidence).
Intravenous versus oral antibiotics
Three studies (172 participants) reported no difference in different measures of lung function. We found no difference in analysable data between IV and oral antibiotic regimens in either FEV1 % predicted or FVC % predicted (1 study, 24 participants; low-certainty evidence) or in the time to the next exacerbation (1 study, 108 participants; very low-certainty evidence). No study measured quality of life.
Intravenous antibiotic regimens compared
One study (analysed as two data sets) compared the duration of IV antibiotic regimens between two groups (split according to initial antibiotic response). The first part was a non-inferiority study in 214 early treatment responders to establish whether 10 days of IV antibiotic treatment was as effective as 14 days. Second, investigators looked at whether 14 or 21 days of IV antibiotics were more effective in 705 participants who did not respond early to treatment. We found no difference in FEV1 % predicted with any duration of treatment (919 participants; high-certainty evidence) or the time to next exacerbation (information later taken from registry data). Investigators did not report FVC or quality of life.
Other comparisons
We also found little or no difference in lung function when comparing single IV antibiotic regimens to placebo (2 studies, 70 participants), or in lung function and time to next exacerbation when comparing different single antibiotic regimens (2 studies, 95 participants). There may be a greater improvement in lung function in participants receiving combined IV antibiotics compared to single IV antibiotics (6 studies, 265 participants; low- to very low-certainty evidence), but probably no difference in the time to next exacerbation (1 study, 34 participants; low-certainty evidence). Four studies compared a single IV antibiotic plus placebo to a combined IV antibiotic regimen with high levels of heterogeneity in the results. We are very uncertain if there is any difference between groups in lung function (4 studies, 214 participants) and there may be little or no difference to being re-admitted to hospital for an exacerbation (2 studies, 104 participants). Nine studies (417 participants) compared combined IV antibiotic regimens with a great variation in drugs. We identified no differences in any measure of lung function or the time to next exacerbation between different regimens (low- to very low-certainty evidence).
There were mixed results for adverse events across all comparisons; common adverse effects included elevated liver function tests, gastrointestinal events and haematological abnormalities. There were limited data for other secondary outcomes, such as weight, and there was no evidence of treatment effect.