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Cellulitis is an acute spreading infection of the skin extending to the deep subcutaneous tissue characterized by pain, swelling, erythema and warmth. Cellulitis in the non-neutropenic patient, in the absence of bite wounds, salt or fresh water exposure, and coexisting ulcers is usually caused by Gram-positive pathogens, the most common being the beta-hemolytic streptococci and S .aureus, including methicillin-sensitive (MSSA) and methicillin-resistant (MRSA) strains. Empiric therapy for management of cellulitis has traditionally included antibiotics with activity against beta-hemolytic streptococci and MSSA such as penicillinase-resistant penicillins or first generation cephalosporins, unless the patient was known to have a previous MRSA infection or in cases of severe systemic toxicity.
Over the past decade there has been a steady rise in the incidence of community-acquired methicillin-resistant S. aureus (CA-MRSA). A recent study  documented a nearly three-fold increase in the incidence of skin and soft tissue infections (SSTIs) presenting to Emergency Departments in this country concurrent with the emergence of CA-MRSA. A study published in 2006 from the Grady Health System found that 72% of community-acquired S. aureus skin and STI were caused by MRSA .
The USA 300 clone of CA-MRSA predominates in this country and differs from hospital acquired MRSA in several important ways. CA-MRSA is found in patients without the traditional risk factors for MRSA, is usually more susceptible to different antibiotic classes, has a unique chromosomal cassette containing a smaller resistance gene thought to result in more efficient transmission, and usually contains a virulence factor, Panton-Valentine leukocidin (PVL) . PVL produces cytotoxins, causing tissue necrosis and leukocyte destruction, which can result in serious infections such as necrotizing fasciitis and pyomyositis. However, most CA-MRSA associated infections are purulent or pustular skin lesions and SSTIs.
Outbreaks of CA-MRSA have been documented in inmates of correctional facilities, athletes, military personnel, intravenous drug abusers, homosexual men, homeless persons, in healthy children, and in specific populations including Alaskan Natives, Native Americans and Pacific Islanders. The current epidemic extends to populations not traditionally infected with MRSA such patients with diabetes, HIV-infection, ESRD on hemodialysis, those receiving prior antibiotics, and in recently hospitalized and/or nursing home patients . A recent prospective study of patients hospitalized with MRSA found that there were no clinical or epidemiological risk factors that could reliably distinguish between community-acquired MRSA and MSSA .
Given the increasing incidence of CA-MRSA SSTIs and the inability to reliably identify CA-MRSA, alternative regimens have been recommended for the treatment of suspected and/or confirmed CA-MRSA infection. In the outpatient setting, these include sulfamethoxazole-trimethoprim, clindamycin, doxycycline, and linezolid. Clindamycin has the potential advantage of also decreasing production of staphylococcal toxins, but increasing resistance to clindamycin has been documented and the microbiology lab should test for inducible resistance using the double-disk D-test. Increasing resistance to doxycycline in CA-MRSA has also been reported . For hospitalized patients, recommended parenteral agents for the treatment of suspected CA-MRSA cellulitis include vancomycin, linezolid, daptomycin and tigecycline. Although vancomycin remains the gold standard, increasing resistance to vancomycin has been documented and strains with heteroresistance to vancomycin may also develop resistance to daptomycin. Linezolid, like clindamycin, has the ability to impair toxin production in more serious SSTI and limited resistance to linezolid has been documented to date . Several promising investigational agents include dalbavancin and telavancin (lipoglycopeptides), oritavacin (a semisynthetic glycopeptides), and ceftobiprole, a broad-spectrum third generation cephalosporin .
Given the current epidemic of CA-MRSA skin and soft tissue infections and the inability to distinguish MRSA from MSSA by risk factors and/or clinical presentation, the clinician should initiate treatment for MRSA with one of the recommended oral or parenteral antibiotics. It is also important to attempt confirmation of the etiologic agent of cellulitis, which is not usually done secondary to the low yield of cultures. All abscesses and pustules should be aspirated and sent for culture. Bullae should be unroofed and the base swabbed and sent for culture. Establishing the susceptibility of S. aureus isolates in even a small proportion of patients will enable the provider to switch to a narrower spectrum agent if CA-MRSA is ruled out, decreasing the resistance pressure that is driving this current epidemic.
Reviewed by Howard Leaf MD, Assistant Professor, NYU Division of Infectious Diseases and Immunology
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