Antibiotic therapy for the treatment of methicillin-resistant Staphylococcus aureus (MRSA)-infected or colonised non surgical wounds

Non surgical wounds include chronic skin ulcers (such as pressure sores or diabetic ulcers), burns and traumatic wounds. Methicillin-resistant Staphylococcus aureus (MRSA) can be present in 7% to 30% of such wounds, and the MRSA may spread into the bloodstream, causing a life-threatening illness. A proportion of the wounds in which MRSA was present show signs of infection such as redness, pain, and pus discharge. The presence of MRSA without infection is called colonisation. It is not clear whether antibiotics should be used in MRSA colonised non-surgical wounds. The antibiotic that has to be used in MRSA-infected wounds is also not clear. We tried to find this out by performing a thorough search of the medical literature for studies that compared different antibiotic treatments for MRSA-infected or MRSA-colonised non surgical wounds. We included only randomised controlled trials, as, if they are conducted properly, they provide the best information. We included all relevant randomised controlled trials irrespective of the language in which the study was reported, the year of publication, and the number of people included in them. Two review authors independently identified the trials and extracted the relevant information in order to decrease the chance of an error occurring during this process.

We identified three trials that provided some information on this topic. A total of 47 people with MRSA-infected diabetic foot infections were randomised to six different antibiotic treatments (choice of treatment determined by a method similar to coin tossing). The only outcome reported was the eradication of MRSA. The trials reported none of the other outcomes that are important for patients and healthcare funders, such as death, quality of life, length of hospital stay, use of healthcare resources and time to complete wound healing. Each trial compared different antibiotics, and in each comparison there was no difference in the effectiveness of the antibiotics in eradicating MRSA. The three trials were very small and had a number of design faults, so it is still not possible to say which antibiotic is the most effective in eradicating MRSA from non-surgical wounds. Because there were no trials at all comparing the use of antibiotics with no antibiotic we do not know whether using antibiotics at all makes a difference for people with MRSA-colonised non-surgical wounds. Further well-designed randomised controlled trials are necessary to determine the best treatment for non surgical wounds containing or infected with MRSA.

Authors' conclusions: 

We found no trials comparing the use of antibiotics with no antibiotic for treating MRSA-colonised non-surgical wounds and therefore can draw no conclusions for this population. In the trials that compared different antibiotics for treating MRSA-infected non surgical wounds, there was no evidence that any one antibiotic was better than the others. Further well-designed RCTs are necessary.

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Background: 

Non surgical wounds include chronic ulcers (pressure or decubitus ulcers, venous ulcers, diabetic ulcers, ischaemic ulcers), burns and traumatic wounds. The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) colonisation (i.e. presence of MRSA in the absence of clinical features of infection such as redness or pus discharge) or infection in chronic ulcers varies between 7% and 30%. MRSA colonisation or infection of non surgical wounds can result in MRSA bacteraemia (infection of the blood) which is associated with a 30-day mortality of about 28% to 38% and a one-year mortality of about 55%. People with non surgical wounds colonised or infected with MRSA may be reservoirs of MRSA, so it is important to treat them, however, we do not know the optimal antibiotic regimen to use in these cases.

Objectives: 

To compare the benefits (such as decreased mortality and improved quality of life) and harms (such as adverse events related to antibiotic use) of all antibiotic treatments in people with non surgical wounds with established colonisation or infection caused by MRSA.

Search strategy: 

We searched the following databases: The Cochrane Wounds Group Specialised Register (searched 13 March 2013); The Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2); Database of Abstracts of Reviews of Effects (2013, Issue 2); NHS Economic Evaluation Database (2013, Issue 2); Ovid MEDLINE (1946 to February Week 4 2013); Ovid MEDLINE (In-Process & Other Non-Indexed Citations, March 12, 2013); Ovid EMBASE (1974 to 2013 Week 10); EBSCO CINAHL (1982 to 8 March 2013).

Selection criteria: 

We included only randomised controlled trials (RCTs) comparing antibiotic treatment with no antibiotic treatment or with another antibiotic regimen for the treatment of MRSA-infected non surgical wounds. We included all relevant RCTs in the analysis, irrespective of language, publication status, publication year, or sample size.

Data collection and analysis: 

Two review authors independently identified the trials, and extracted data from the trial reports. We calculated the risk ratio (RR) with 95% confidence intervals (CI) for comparing the binary outcomes between the groups and planned to calculate the mean difference (MD) with 95% CI for comparing the continuous outcomes. We planned to perform the meta-analysis using both fixed-effect and random-effects models. We performed intention-to-treat analysis whenever possible.

Main results: 

We identified three trials that met the inclusion criteria for this review. In these, a total of 47 people with MRSA-positive diabetic foot infections were randomised to six different antibiotic regimens. While these trials included 925 people with multiple pathogens, they reported the information on outcomes for people with MRSA infections separately (MRSA prevalence: 5.1%). The only outcome reported for people with MRSA infection in these trials was the eradication of MRSA. The three trials did not report the review's primary outcomes (death and quality of life) and secondary outcomes (length of hospital stay, use of healthcare resources and time to complete wound healing). Two trials reported serious adverse events in people with infection due to any type of bacteria (i.e. not just MRSA infections), so the proportion of patients with serious adverse events was not available for MRSA-infected wounds. Overall, MRSA was eradicated in 31/47 (66%) of the people included in the three trials, but there were no significant differences in the proportion of people in whom MRSA was eradicated in any of the comparisons, as shown below.

1. Daptomycin compared with vancomycin or semisynthetic penicillin: RR of MRSA eradication 1.13; 95% CI 0.56 to 2.25 (14 people).
2. Ertapenem compared with piperacillin/tazobactam: RR of MRSA eradication 0.71; 95% CI 0.06 to 9.10 (10 people).
3. Moxifloxacin compared with piperacillin/tazobactam followed by amoxycillin/clavulanate: RR of MRSA eradication 0.87; 95% CI 0.56 to 1.36 (23 people).

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