Interventions (treatments) to clear meticillin-resistant Staphylococcus aureus (MRSA) from the lungs of people with cystic fibrosis

Review question

We looked for evidence for the effects of different ways of clearing meticillin-resistant Staphylococcus aureus (MRSA) from the lungs of people with cystic fibrosis.

Background

MRSA is the name given to particular bacteria which are resistant to some types of antibiotics. This is particularly worrying for people with cystic fibrosis, which is an inherited condition which amongst other things causes thick mucus to build up in the lungs. It is very difficult for people with cystic fibrosis to cough up this thick mucus, making it an ideal breeding ground for bacteria, including MRSA, and making these people more prone to chest infections. It is thought that MRSA can cause more damage than other bacteria, which are not resistant to antibiotics. We wanted to identify research evidence to support the best way for treating MRSA infections and also to see if this would improve the lives of people with cystic fibrosis. This is an update of a previously published review.

Search date

The evidence is current to: 27 July 2017.

Key results

We found two trials which included people with cystic fibrosis and a diagnosed MRSA infection. In one trial the active treatment was oral trimethoprim and sulfamethoxazole combined with rifampicin and some additional decontamination treatment and in the second trial it was oral co-trimoxazole and rifampicin with intranasal mupirocin; in both trials the comparison treatment was just observation and no active treatment. The results of these trials showed that clearing MRSA from the airways of people with CF is possible. Although a larger proportion of those who were treated became clear of MRSA in both trials, some of the individuals who were untreated also cleared MRSA spontaneously. Also, six months after treatment, the number of individuals who still had MRSA was not different between those who received treatment and those who did not.

In one of the trials, fewer people who were treated with antibiotics were admitted to hospital in the first 168 days. There were no other differences seen between the two groups (treated or untreated) in terms of their lung function, weight or chest exacerbations at six months.

Treating MRSA early in people with CF has been shown to be possible, but it is not clear what longer-term implications this will have.

Quality of the evidence

Using GRADE methodology, we judged the quality of the evidence we found to be very low to low for the different outcomes. This was due to potential issues from the trial design where people knew which treatment each of the participants were receiving (groups were either given medication or just observed) and because there were small numbers of people included in each trial. Also, one of the trials did not report all details clearly.

Authors' conclusions: 

Early eradication of MRSA is possible in people with cystic fibrosis, with one trial demonstrating superiority of active MRSA treatment compared with observation only in terms of the proportion of MRSA-negative respiratory cultures at day 28. However, by six months, the proportion of participants who remained MRSA-negative did not differ between treatment arms in either trial. Moreover, the longer-term clinical consequences in terms of lung function, mortality and cost of care, remain unclear.

Using GRADE methodology, we judged the quality of the evidence provided by this review to be very low to low, due to potential biases from the open-label design and unclear detail reported in one trial. Based on the available evidence, it is the opinion of the authors that whilst early eradication of respiratory MRSA in people with cystic fibrosis is possible, there is not currently enough evidence regarding the clinical outcomes of eradication to support the use of the interventions studied.

Read the full abstract...
Background: 

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 as, not only 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 people with cystic fibrosis with 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 treatment regimens designed to eradicate MRSA and to determine whether the eradication of MRSA confers better clinical and microbiological outcomes for people with cystic fibrosis. To ascertain whether attempts at eradicating MRSA can lead to increased acquisition of other resistant organisms (including P aeruginosa) or increased adverse effects from drugs, or both.

Search strategy: 

Randomised and quasi-randomised controlled trials were identified by searching the Cochrane Cystic Fibrosis and Genetic Disorders Group's Cystic Fibrosis Trials Register, PubMed, MEDLINE, clinical trial registries (Clinicaltrials.gov, WHO ICTRP, ISRCTN Registry), handsearching article reference lists and through contact with experts in the field.

Date of the last search of the Group's Cystic Fibrosis Trials Register: 27 July 2017.

Ongoing trials registries were last searched: 07 August 2017.

Selection criteria: 

Randomised or quasi-randomised controlled trials comparing any combinations of topical, inhaled, oral or intravenous antimicrobials with the primary aim of eradicating MRSA compared with placebo, standard treatment or no treatment.

Data collection and analysis: 

The authors independently assessed all search results for eligibility. They used the GRADE methodology to assess the quality of the evidence.

Main results: 

The review includes two trials with a total of 106 participants with MRSA infection. In both trials the active treatment was oral trimethoprim and sulfamethoxazole combined with rifampicin; however, 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. In both trials the control arm was observation only.

Both trials reported successful eradication of MRSA in people with CF as an outcome; however, the definition used for MRSA eradication differed. The first trial (n = 45) defined MRSA eradication as negative MRSA respiratory cultures at day 28, and reported that, when compared to control, oral trimethoprim and sulfamethoxazole combined with rifampicin may lead to a higher proportion of negative cultures, 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 in the proportion of participants who remained MRSA-negative in either treatment arm, OR 1.17 (95% CI 0.31 to 4.42) (low-quality evidence). In the second trial, successful eradication was defined as the absence of MRSA following treatment (oral co-trimoxazole and rifampicin with intranasal mupirocin or observation) in at least three cultures over a period of six months. At the time of reporting, 40 out of 61 participants had completed follow-up, but results showed no difference between groups. Eradication was achieved in 12 out 29 participants (41%) receiving active treatment, and in 9 out of 32 participants (28%) on the observation arm, OR 1.80 (95% CI 0.62 to 5.25) (very low-quality evidence).

With regards to this review's secondary outcomes, these were reported in the first trial only. The trial reports that no differences were observed between the two arms in terms of pulmonary exacerbations (from screening to day 28), nasal colonisation, lung function, weight or participant-reported outcomes. While not a specific outcome of this review, investigators 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 = 0.0102).

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