Community-acquired methicillin-resistant Staphylococcus aureus: time to address the problem

In the USA, methicillin-resistant Staphylococcus aureus (MRSA) has been endemic in hospitals and long-term care facilities (LTCF) for the past 40 years. More recent concern surrounds the prevalence of community-acquired (CA)-MRSA and its impact on the disease burden of skin and soft-tissue infections [1,2]. It is estimated that between 50 and 78% of all S. aureus isolates are MRSA, and that up to 40% of all adult MRSA cases are community-acquired. CA-MRSA outbreaks have been reported in school settings, fitness clubs, professional and college athletic teams, and other community settings, thus making the task facing clinicians and public health officials much more daunting [3–5].

At large urban community hospitals across the USA there has been a dramatic increase in the prevalence of MRSA skin infections (cellulitis, furuncles and abscesses) among both HIV-positive and -negative patients. Many of these patients have no history of recent hospital admissions or LTCF stays, and thus represent CA-MRSA infections. Unfortunately, the epidemiologic surveillance has not been able to keep up with the anecdotal reports of the disease burden facing many of this country’s community hospitals, thus many clinicians and scientists alike have been grappling with the question of an official protocol regarding prevention and treatment approaches to this disease. Despite this dilemma, it is imperative to propose interim recommendations and guidelines to assist medical and public health officials’ handling of the prevention, treatment and research and policy facets of this burgeoning epidemic.

Prevention

Much of the debate about effective prevention of community MRSA infections centers on the origins of CA-MRSA and the predominant modes of transmission between individuals. Charlebois and colleagues reviewed computer databases from clinical settings in San Francisco, CA, USA, from 1992–1999 to identify community onset infections caused by MRSA [4]. While the authors found that most (58%) CA-MRSA emerged from strains in hospitals or LTCF, they also discovered that 20 out of the 35 isolates derived from a small subsample of intravenous drug users and did not match more than 600 clinical isolates. While these findings are not generalizable, they do suggest two things:

•	There is a link between hospital-acquired (HA)-MRSA and CA-MRSA strains
•	New CA-MRSA strains, possibly originating from hospitals and LTCF, are now developing in the community and have their own distinct and diverse genetic traits

The clinical importance of nasal carriage of MRSA remains controversial. While studies have demonstrated high prevalence of MRSA nasal carriage in school children, others have noted a lower than expected MRSA nasal carriage rate among physicians and nonphysicians [6,7]. Whether these rates of MRSA nasal carriage translate into clinically significant disease remains unproven, and the utility of prevention efforts involving treating MRSA nasal carriers as a community intervention for the development of skin disease has yet to be ascertained.

These findings suggest that nasal carriage of MRSA may not be as widespread in the community as originally thought, and more importantly, may not predict clinically significant illness. However, skin-to-skin contact appears to be the main mode of transmission of CA-MRSA, and should be the primary focus on which prevention efforts lie. Thus, focus on preventing the spread of HA- and CA-MRSA should stress the importance of hand washing when in contact with other individuals or public-used facilities [6,8]. While many public health advocates emphasize proper hand-washing techniques in medical facilities among staff, this same approach has not been enforced in public facilities where CA-MRSA may be easily transmitted, such as schools, gyms, sports training facilities and correctional facilities [3,5].

Treatment

Research on the characteristics of strains of CA-MRSA has revealed distinctions from HA-MRSA strains [3,9–11]:

•	Resistance to most β-lactam antibiotics
•	Presence of staphylococcal cassette chromosome (SCC) mec gene intravenous allele for methicillin resistance
•	Presence of Panton–Valentine leukocidin genes
•	Increased susceptibility to a broader array of antibiotics
•	Increased virulence

With these factors being identified, we potentially have the basis on which to recommend specific antibiotic therapy for the treatment of CA-MRSA skin infections.

Despite this, the approach to treating these infections in the clinical setting has proved challenging. While vancomycin has long been the gold standard for treating MRSA skin infections, its drawbacks include cost, potential toxicity, required intravenous administration, and reports of slow cure rates and failures [101]. Alternatives to vancomycin include bactrim (trimethoprim–sulfamethoxazole), clindamycin, flouroquinolones, tetracyclines, macrolides, third-generation cephalosporins, rifampin and linezolid [12,13].

Among these various alternatives, bactrim appears to be the most promising, both from a susceptibility and cost stand-point. CA-MRSA strains have been found to be 98–100% susceptible to bactrim, and the cost is estimated at US$45.00 for 30 tablets, compared with US$1178.37 for 20 linezolid tablets. However, there has yet to be a consensus for bactrim dosing for MRSA skin infections, with anecdotal reports citing treatment effectiveness with one tablet twice-daily dosing, while others advocate as much as two bactrim tablets three-times daily for more serious skin infections. Similarly, depending on the provider and medical facility preference, duration of treatment can range from 7 to 14 days, based on the severity of infection. Finally, topical treatments for CA-MRSA infections are available, such as bactroban ointment, but may only be effective in treating mild folliculitis outbreaks suspected to be CA-MRSA.

Unfortunately, no definitive clinical trials testing the comparative effectiveness of certain dosing regimens of bactrim between each other or against other antibiotics in treating CA-MRSA skin infections exist at this point. Moreover, the benefits of dosing of medications such as bactrim (and others) in treating CA-MRSA skin infections must be weighed against the increased likelihood of side effects and drug interactions with increased dosing requirements.

Research & policy

To date, a firm research and policy agenda regarding CA-MRSA is lacking, as the medical and public health communities have been trying to catch up with the epidemic that has been worsening during the past decade. We are aware of the outbreaks existing in emergency rooms, schools, public facilities and professional sports teams. We have seen media reports in newspapers and on the television citing anecdotal reports of rare cases of death from untreated CA-MRSA infections in both healthy young and elderly individuals with comorbid illnesses. Moreover, research has documented the need for more strict policies and enforcement of hand-washing precautions, increased regulation of antibiotic prescription practices, and more funding for studies examining prevalence rates and resistance profiles of specific geographic CA-MRSA strains. Yet federal and state programs and policies have been glaringly deficient in providing direction in the research, prevention and treatment of these infections.

There is much work to be carried out with the CA-MRSA epidemic both in the USA and worldwide. Regrettably, available evidenced-based medicine has been unable to keep up with the rapid community progression of these skin infections. However, this does not mean that the medical, scientific and public health communities should sit by idly awaiting definitive empiric studies to direct our actions. On a research front, future studies are needed to determine CA-MRSA prevalence in specific communities, regional susceptibility profiles and relative treatment effectiveness of various antibiotic regimens, including dosing and duration. Prevention of CA-MRSA should continue strict enforcement of hand-washing policies among hospital and medical facility personnel, with extension of these policies to include public facilities where close skin-to-skin contact between patrons is anticipated.

Treatment of CA-MRSA would benefit from official recommendations from the US Centers of Disease Control and Prevention and other federal organizations that can guide clinicians and public health officials on proper and cost-effective management strategies and prevention of various CA-MRSA skin infections. These recommendations should be inclusive of current available knowledge of CA-MRSA treatment, with the acknowledgment that guideline modifications may come in the future when new information is obtained. Finally, from a policy perspective, federal funding must be prioritized for future research on CA-MRSA, and individual state and county health departments should direct local medical facilities on continued enforcement of prudent antibiotic prescription policies to avoid further perpetuation of the epidemic. Without the disciplined involvement of medical and public health officials from every angle, the CA-MRSA epidemic will continue unabated.