Key messages
-
Early treatment of meticillin-resistant Staphylococcus aureus (MRSA) (a type of bacteria which are resistant to some antibiotics) infection in people with cystic fibrosis (CF) seems possible, but we are unsure about the effectiveness of current routine treatment.
-
Longer-term implications of treatment are not clear.
-
Research is needed to assess MRSA infection and treatment in the age of cystic fibrosis transmembrane conductance regulator (CFTR) modulators (drugs that fix the broken protein made by the CF gene so salt and water can move correctly across cells and help move mucus from the lungs).
What is cystic fibrosis (CF)?
CF is an inherited condition which causes thick mucus to build up in the lungs and other organs. It is very difficult for people with CF to cough up this thick mucus, making it an ideal breeding ground for germs (including MRSA), and making them more prone to chest infections. CF worsens over time. Although there is currently no cure, many people with CF can lead active and full lives.
What is MRSA and how is it treated?
MRSA (meticillin-resistant Staphyloccocus aureus) are bacteria which cause infection that is treated with antibiotics. However, MRSA are resistant to some types of antibiotics, making the infection hard to treat. They are sometimes called 'superbugs' and infection with MRSA is particularly worrying for people with CF, as it is thought that MRSA can cause more damage than other bacteria which are not resistant to antibiotics.
MRSA is usually treated with a combination of antibiotics, taken orally (by mouth) or inhaled, alongside decontamination treatment (antibiotic creams applied to the skin and nasal cavities).
What did we want to find out?
We wanted to know whether treatment with antibiotics:
-
can get rid of MRSA infection in the lungs of children or adults with CF;
-
does not cause infection with other resistant bacteria;
-
does not cause unwanted effects.
What did we do?
We looked for studies that investigated antibiotics (oral or inhaled) to treat MRSA infections in people with CF.
-
Studies had to compare antibiotic treatment with either no treatment, placebo (sham treatment) or other type of antibiotics.
-
People had to have CF and current infection with MRSA.
What did we find?
We found five studies which recruited 410 people with CF and a diagnosed MRSA infection. Studies took place in Italy or North America and lasted from eight weeks to six months. People in the studies (equal numbers of males and females) were young (average age ranged from 11 to 25 years).
Oral antibiotics compared to no treatment (2 studies, 106 people)
One group of people with CF were treated with oral antibiotics (trimethoprim, sulfamethoxazole and rifampicin or co-trimoxazole and rifampicin), plus decontamination treatment; the other group received no treatment.
-
Oral antibiotics may clear MRSA. One trial stopped early due to clear benefits of antibiotics, but some people cleared the infection with no treatment. In six months, there was no difference between groups in the number of people who still had MRSA.
-
Antibiotics may increase lung function.
-
There may be little to no difference between groups in quality of life, frequency of flare-ups of the disease (although one study reported fewer people taking antibiotics were admitted to hospital in the first six months), unwanted effects of treatment, or changes in weight.
Inhaled antibiotics compared to placebo (2 studies, 251 people)
Both studies compared a standard dose of vancomycin (an inhaled antibiotic) to placebo (a dummy drug) and one study also compared a standard dose of vancomycin to a high dose.
-
Inhaled antibiotics probably make no difference to lung function compared to placebo (2 studies), but results from one study indicated that inhaled antibiotics probably lead to a small increase after 20 weeks.
-
A standard dose of vancomycin probably makes no difference to the frequency of flare-ups compared to placebo (2 studies);
-
One study reported a longer time to the next flare-up with the lower dose of vancomycin;
-
One study reported a decrease in MRSA bacteria levels with a higher dose of vancomycin for up to one month;
-
Neither study reported any differences in quality of life or unwanted effects.
Oral plus inhaled antibiotics compared to oral antibiotics plus placebo (1 study, 25 people)
One study compared a combination of oral plus inhaled antibiotics to inhaled antibiotics plus placebo.
-
We are uncertain if either treatment made any difference to MRSA clearance;
-
There may be few or no differences between groups in lung function, quality of life or unwanted effects;
-
The study did not report changes in weight or frequency of flare-ups.
What are the limitations of the evidence?
Our confidence in the results ranged from high to very low. This was due to potential issues with the trial designs (people knew which treatment they were receiving), or because there were small numbers of people in each trial and many of them dropped out.
How up to date is this evidence?
This review updates our previous review published in 2022. The evidence is current to 28 April 2026.
Read the full abstract
Cystic fibrosis is an inherited recessive disorder of chloride transport that is characterised by recurrent and persistent pulmonary infections from resistant organisms that result in lung function deterioration and early mortality in sufferers.
Meticillin-resistant Staphylococcus aureus (MRSA) has emerged not only as an important infection in people who are hospitalised, but also as a potentially harmful pathogen in cystic fibrosis. Chronic pulmonary infection with MRSA is thought to confer on people with cystic fibrosis a worse clinical outcome and result in an increased rate of lung function decline. Clear guidance for MRSA eradication in cystic fibrosis, supported by robust evidence, is urgently needed. This is an update of a previous review.
Objectives
To evaluate the effectiveness of antibiotic treatment designed to eradicate MRSA, to determine whether eradication confers better clinical and microbiological outcomes for pwCF, and to ascertain whether attempts at eradicating MRSA lead to increased acquisition of other resistant organisms (including Pseudomonas aeruginosa), increased adverse effects from drugs, or both.
Search strategy
We searched the Cochrane CF's Trials Register, PubMed, MEDLINE and three trials registries; handsearched article reference lists; and contacted experts in the field. We last searched Cochrane CF's Trials Register and the trials registries on 28 April 2026.
Selection criteria
Randomised controlled trials (RCTs) or quasi-RCTs of any combinations of topical, inhaled, oral or intravenous antimicrobials primarily aimed at eradicating MRSA compared with placebo, standard treatment or no treatment.
Data collection and analysis
We used standard methodological procedures expected by Cochrane and used the GRADE methodology to assess the certainty of the evidence.
Main results
The review includes three RCTs with 135 participants with MRSA infection. Two trials compared active treatment versus observation only and one trial compared active treatment with placebo.
Active treatment versus observation
In both trials (106 participants), active treatment consisted of oral trimethoprim and sulfamethoxazole combined with rifampicin. One trial administered this combination for two weeks alongside nasal, skin and oral decontamination and a three-week environmental decontamination, while the second trial administered this drug combination for 21 days with five days intranasal mupirocin. Both trials reported successful eradication of MRSA in people with cystic fibrosis, but they used different definitions of eradication.
One trial (45 participants) defined MRSA eradication as negative MRSA respiratory cultures at day 28, and reported that oral trimethoprim and sulfamethoxazole combined with rifampicin may lead to a higher proportion of negative cultures compared to control (odds ratio (OR) 12.6 (95% confidence interval (CI) 2.84 to 55.84; low-certainty evidence). However, by day 168 of follow-up, there was no difference between groups in the proportion of participants who remained MRSA-negative (OR 1.17, 95% CI 0.31 to 4.42; low-certainty evidence).
The second trial defined successful eradication as the absence of MRSA following treatment in at least three cultures over a period of six months. We are uncertain if the intervention led to results favouring the treatment group as the certainty of the evidence was very low (OR 2.74, 95% CI 0.64 to 11.75). There were no differences between groups in the remaining outcomes for this comparison: quality of life, frequency of exacerbations or adverse effects (all low-certainty evidence) or the change from baseline in lung function or weight (both very low-certainty evidence). The time until next positive MRSA isolate was not reported. The included trials found no differences between groups in terms of nasal colonisation with MRSA.
While not a specific outcome of this review, investigators from one study reported that the rate of hospitalisation from screening through day 168 was lower with oral trimethoprim and sulfamethoxazole combined with rifampicin compared to control (rate ratio 0.22, 95% CI 0.05 to 0.72; P = 0.01).
Nebulised vancomycin with oral antibiotics versus nebulised placebo with oral antibiotics
The third trial (29 participants) defined eradication as a negative respiratory sample for MRSA at one month following completion of treatment. No differences were reported in MRSA eradication between treatment arms (OR 1.00, 95% CI 0.14 to 7.39; low-certainty evidence). No differences between groups were seen in lung function or adverse effects (low-certainty evidence), in quality of life (very low-certainty evidence) or nasal colonisation with MRSA. The trial did not report on the change in weight or frequency of exacerbations.
Authors' conclusions
Early eradication of MRSA is possible in pwCF; evidence from one trial suggested active MRSA treatment may result in a higher proportion of MRSA-negative respiratory cultures after one month compared with observation. However, longer follow-up showed treatment may make little or no difference in the proportion of participants remaining MRSA-negative. One trial of nebulised antibiotics alone compared to placebo reported a decrease in MRSA CFUs with a higher antibiotic dose. The longer-term clinical consequences of any treatment option – in terms of lung function, mortality and cost of care – remain unclear.
We judged the evidence to range from high to very low-certainty, due to potential biases from trial design, high attrition rates and small sample sizes. While early eradication of respiratory MRSA in pwCF may be possible, the currently available evidence does not demonstrate that routine treatment of respiratory MRSA in pwCF is effective. Research is needed to assess MRSA infection and treatment in the age of modulator therapies.
Funding
The 2025 update was undertaken as part of Cochrane CF funding from the UK CF Trust and the CF Foundation.
Registration
Protocol (2012) DOI: 10.1002/14651858.CD009650.
Original review (2013) DOI: 10.1002/14651858.CD009650.pub2.
Review updates: (2015) DOI: 10.1002/14651858.CD009650.pub3; (2018) DOI: 10.1002/14651858.CD123456.pub4; (2022) DOI: 10.1002/14651858.CD009650.pub5.
