Cochrane Database Syst Rev. 2026 Aug 27. 8
CD009650
Supported by the Cochrane Cystic Fibrosis Review Group
RATIONALE: Cystic fibrosis (CF) is a genetic disorder characterised by recurrent and persistent pulmonary infections from resistant organisms, resulting in deterioration of lung function and early mortality. Meticillin-resistant Staphylococcus aureus (MRSA) is an important infection in hospital patients and harmful to people with CF (pwCF). Chronic pulmonary MRSA infection may confer a worse clinical outcome on pwCF and result in a faster decline in lung function. Robust evidence clearly guiding MRSA eradication in CF is urgently needed. This is an updated 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 METHODS: 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.
ELIGIBILITY CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs of any combination of topical, inhaled, oral or intravenous antibiotics for treating MRSA compared with placebo, standard treatment or no treatment in pwCF, regardless of age or disease severity.
OUTCOMES: We planned to assess these outcomes at up to 12 months following therapy: eradication of MRSA from respiratory cultures, time until next positive MRSA isolate, quality of life (QoL), change from baseline in forced expiratory volume in one second (FEV1) % predicted, change in weight (kg), frequency of pulmonary exacerbations and adverse effects of treatment.
RISK OF BIAS: Using the original Cochrane risk of bias tool, we assessed individual domains and produced an overall risk of bias for each trial.
SYNTHESIS METHODS: We followed Cochrane's standard methodology, conducting fixed-effect meta-analyses or reporting narratively. We assessed evidence certainty using GRADE.
INCLUDED STUDIES: We included five RCTs (410 participants).
SYNTHESIS OF RESULTS: Oral antibiotics versus no treatment Two trials (106 participants) compared observation to oral trimethoprim plus sulfamethoxazole combined with rifampicin; in one trial for two weeks alongside topical decontamination and a three-week environmental decontamination, and in a second for 21 days alongside intranasal mupirocin (five days); 29 participants withdrew from the second trial by the end of follow-up. Oral antibiotics have little or no effect on any outcome reported below, in contrast to one study (45 participants) which was terminated early due to results clearly favouring treatment. In one trial defining eradication as negative MRSA respiratory cultures at day 28 and remaining so at day 168 (45 participants), treatment may result in more negative cultures than observation (odds ratio (OR) 12.6 (95% confidence interval (CI) 2.84 to 55.84; low-certainty). There may be little to no difference between groups by day 168 of follow-up (OR 1.17, 95% CI 0.31 to 4.42), and also in one trial defining successful eradication as no MRSA in at least three cultures over six months follow-up (OR 2.74, 95% CI 0.64 to 11.75; low-certainty). Treatment may result in an increase in FEV1 % predicted from baseline (MD 5.67%, 95% CI 1.43 to 9.90; 2 trials, 58 participants; low-certainty evidence). There may be little to no differences between groups in QoL, frequency of pulmonary exacerbations (although one study reported a lower hospitalisation rate through day 168 with treatment (P = 0.01)), adverse effects, or weight (all low-certainty evidence). Nebulised antibiotics versus placebo Two trials (275 participants randomised, 251 analysed) compared a standard dose of vancomycin (one trial additionally compared a high dose) to placebo. The multi-arm trial reported a decrease in MRSA colony forming units (CFUs) at each time point, up to one month. There were no differences in most lung function results in either trial, but treatment probably increased FEV1% predicted at 20 weeks (MD 3.55%, 95% CI 0.33 to 6.77; P = 0.03; 1 trial, 133 participants; moderate-certainty evidence). This trial also reported no difference in pulmonary exacerbation frequency, while the multi-arm trial reported a longer time to the next exacerbation with the lower vancomycin dose (no placebo data available). Evidence from both trials suggests that nebulised antibiotics may make little or no difference in QoL (high to low-certainty), or frequency of adverse outcomes or of exacerbations (low-to-moderate-certainty evidence). Oral antibiotics plus nebulised antibiotics (vancomycin) versus oral antibiotics plus placebo One trial (29 participants randomised, 25 participants analysed) compared combination antibiotic treatment (inhaled plus oral) to oral antibiotics plus inhaled placebo, defining eradication as a negative MRSA respiratory sample at one month following treatment. Combination antibiotic treatment may result in little or no difference in MRSA eradication at three months (OR 1.63, 95% CI 0.19 to 13.93; low-certainty evidence), lung function (no data available for analysis) or adverse effects (low-certainty evidence), in QoL (very low-certainty evidence) or nasal colonisation with MRSA.
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.