A Randomized Placebo-controlled Double-blinded Trial of the Treatment of MRSA Throat Carriage With Either Standard Decolonization Therapy or Standard Decolonization Therapy Combined With Oral Clindamycin

The bacterium Staphylococcus aureus frequently colonizes the human skin and mucous membranes. Longitudinal studies usually divide S. aureus carriers into either persistent or intermittent carriers, but because the number of samplings, the follow-up periods and the study populations differ between studies, the designation of carrier state is inconsistent. It has been estimated that around 20 % of a population are persistent carriers, 60 % are intermittent carriers and 20 % are non-carriers. S. aureus is an opportunistic pathogen that can become invasive and cause a large spectrum of infections. S. aureus is frequently the cause of skin and soft tissue infections e.g. wounds, furuncles and abscesses, and can also cause urinary tract infections and pneumonia. If it enters the bloodstream, it can lead to metastatic infections e.g. endocarditis, arthritis, osteomyelitis and meningitis. Furthermore, S. aureus is a common pathogen in surgical site infections and in infections related to foreign bodies, such as catheters and prostheses.

Antibiotic resistance in bacteria is an increasing challenge worldwide and is also seen in S. aureus. The first methicillin resistant Staphylococcus aureus (MRSA) were seen in 1961 just one year after the antibiotic methicillin was introduced. For several decades MRSA was mainly a hospital-associated bacterium, but since the mid 1990's it has become increasingly prevalent in the community where it often affects children and younger adults. MRSA can cause the same types of infections as the methicillin susceptible S. aureus, but often only colonizes the mucosa. When colonization is confirmed, the person is called a carrier of MRSA and there is a risk of both a wide spectrum of infections and spread of MRSA to others. The Danish Health Authority has published a National guideline on how to prevent the spread of MRSA and keep the prevalence of MRSA low in Denmark, especially in the health care setting. The finding of MRSA both in samples from clinical infections and in screening samples for MRSA carriage is notifiable and has to be reported to the Danish Patient Safety Authority and Statens Serum Institut, in order to monitor the number of MRSA positive persons in Denmark, potential outbreaks and risk factors for MRSA acquisition. Furthermore, the guideline recommends that MRSA carriers and their household members undergo a five day topical decolonization treatment consisting of nasal mupirocin ointment 2 % three times daily in the nostrils (mupirocin is an antibiotic usually active against MRSA) and chlorhexidine body wash 4 % once daily. Unfortunately, many patients are still MRSA carriers after completing the treatment and especially throat carriers are difficult to clear.

MRSA carriers have routinely been treated since 2009. Our current guideline recommends adding antibiotics to the standard regimen, clindamycin being our first line choice, on the second or third eradication attempt if the patient is a throat carrier and the isolate is clindamycin susceptible. To our knowledge, the only randomized, controlled trial including clindamycin for treatment of MRSA carriage, is a Swedish study that showed a significant effect of standard treatment plus the antibiotic rifampicin in combination with either clindamycin or sulfamethoxazole/trimethoprim compared to standard treatment alone in long-term MRSA carriers. As most of our patients are healthy individuals without infections, adding systemic antibiotics to the decolonization treatment must be considered thoroughly. There is a risk of side effects in the individual patient and prudent use of antibiotics in the era of a rising incidence of antimicrobial resistance is crucial to avoid selection of further resistance. Our group has recently published a retrospective study describing the MRSA treatment data of 164 patients treated in 2013. The study confirmed that throat carriers had a higher treatment failure rate but adding clindamycin to the first eradication attempt did not significantly increase the success rate. However, as there had been no randomization of patients the scientific evidence is low and the fact that there are no published studies using clindamycin as the only antibiotic for MRSA throat carriers, implies the need for a randomized trial on this subject.

Aim To investigate whether a significantly higher number of MRSA throat carriers become MRSA free when adding the oral antibiotic clindamycin to the standard regimen.

Primary endpoint: MRSA negative swabs at 1 month Secondary endpoint: MRSA negative swabs after 6 months