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Community-acquired MRSA
Daniel Scheurich, M.D., and Keith Woeltje, M.D., Ph.D.
Dr. Scheurich is clinical fellow, Department of Medicine, and Dr. Woeltje is Associate Professor, Infectious Diseases, Washington University School of Medicine, St. Louis, MO. Within the past 12 months, Drs. Scheurich and Woeltje report no commercial conflicts of interest. Albert Einstein College of Medicine, CCME staff and interMDnet staff have nothing to disclose. Release Date: 04/13/2009 Termination Date: 04/13/2012 Estimated time to complete: 1 hour(s). Albert Einstein College of Medicine designates this enduring material for a maximum of 1 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Albert Einstein College of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. Learning Objectives
Upon completion of this Cyberounds®, the participant should be able to:
Staphylococcus aureus is a virulent organism that is the causative agent of a wide range of clinical disease, including skin and soft tissue infections (SSTI). Traditionally, there were two categories into which these infections fell: infections acquired in the community and those acquired in the health care setting. In this context, organisms causing community-acquired infections were typically susceptible to traditional antibiotics of choice, namely anti-staphylococcal penicillins, of which methicillin is the parent drug. These organisms are referred to as methicillin-sensitive Staphylococcus aureus (MSSA). Infections acquired in the hospital or other health care settings, in contrast, were often caused by strains of S. aureus that were frequently resistant to the beta-lactam antibiotics and were hence known as methicillin-resistant Staphylococcus aureus (MRSA). ... CA-MRSA infections have become epidemic in the US. Over the last decade there has been an increasing percentage of isolates from the community that are methicillin-resistant in patients without traditional risk factors for MRSA (such as hospitalization). The agent in these infections is now termed community-acquired MRSA (CA-MRSA). CA-MRSA infections have become epidemic in the US. Several recent series have examined the resistance patterns from S. aureus isolated from community-acquired infections and found the percentages that are methicillin-resistant range as high as 44-59%. (1) SSTI, including simple cellulitis, are primarily caused by group A streptococcus and S. aureus.(2) Cellulitis has been a challenge to characterize etiologically because causative organisms are difficult to culture from the site of infection and peripheral blood cultures are positive in only about 2% of patients.(3) Community onset SSTI has been treated historically with oral beta-lactam antibiotics. However, with the emergence of CA-MRSA, knowledge of the pathogenesis, presentation and treatment of SSTI, including antibiotic resistance patterns, is important to a wide range of physicians. This includes primary care doctors, emergency room physicians, surgeons and infectious disease specialists, all of whom are involved in the diagnosis and treatment of these infections. Virulence CA-MRSA strains are particularly adept at causing SSTI, generally presenting as cutaneous abscesses. There are several important genomic distinctions between CA-MRSA strains and historical healthcare-associated strains which may lend insights into the pathogenesis of CA-MRSA. Many CA-MRSA strains produce increased cell-surface binding proteins that may facilitate entry into non-phagocytic host cells. Pyrogenic supertoxins, encoded on the genome, may additionally help these organisms evade host immunity by preventing clonal proliferation of specific anti-staphylococcal T-cells. While these virulence factors are important in CA-MRSA pathogenicity, they do not completely explain their tendency to cause SSTI.(4) Arginine catabolic mobile element (ACME) is a genetic component found integrated into the bacterial chromosome of many CA-MRSA isolates. It elaborates gene products that aid in the utilization of arginine. While there are also non-mobile chromosomal gene products in S. aureus performing similar tasks, they are genetically distinct. ACME is not found in hospital strains of MRSA, epidemiologic evidence for its importance in the virulence of CA-MRSA. In addition, ACME is common in Staphylococcus epidermidis, a commensal of the skin, and so its elaboration as a mobile gene product in CA-MRSA may partially explain the skin tropism of the organism. The specific role of ACME in the pathogenesis of CA-MRSA has not been determined.(4) ... S. aureus can be a human commensal and can be recovered from the nares, axilla, vagina and groin of healthy subjects. Panton-Valentine leukocidin (PVL), a pore-forming leukocidin, is the most common virulence factor noted in association with CA-MRSA. Like ACME, it is epidemiologically implicated in the pathogenesis of CA-MRSA, for it is present in community-acquired strains but rarely seen with healthcare-associated strains. However, PVL-knockout strains can cause abscesses in laboratory animal models, and so the importance of PVL in CA-MRSA's tendency to cause purulent SSTI is uncertain.(4)(5) Conversely, CA-MRSA strains lacking phenol-soluble modulin (PSM) peptides have reduced ability to cause abscesses in mice, implicating PSM as an important virulence factor. PSM is also produced in hospital strains of MRSA but at much lower levels in vitro. Furthermore, similar peptides are elaborated in S. epidermidis, which may again contribute to the tendency of CA-MRSA to cause SSTI. (4) In addition to specific gene product virulence factors, regulation of gene production may be of importance in the virulence of CA-MRSA. Environmental or other factors may contribute to altered gene expression, leading to increased virulence and the organism's skin and soft tissue tropism.(4) Altered expression of gene products is another area in CA-MRSA pathogenicity which requires more study. Risk Factors for CA-MRSA Risk factors for colonization with and infections from CA-MRSA are poorly defined. In the initial stages of the epidemic, outbreaks were reported in military recruits, prison inmates, and participants in team and contact sports.(6) CA-MRSA is no longer seen exclusively in these groups of patients, however. ... Patients often present with a complaint of a 'spider bite', though often there is no history of a bite. Several large studies have examined whether risk for SSTI from CA-MRSA, as opposed to MSSA, is higher in African-Americans, younger patients, those with recent B-lactam antibiotic use, intravenous drug use, homelessness and those with a recent history of incarceration. The results of these studies are conflicting -- while there are risk factors for the development of SSTI due to CA-MRSA, as opposed to MSSA, there is no reliable way to distinguish the two based on risk factors alone.(7)(8)(9)(10) CA-MRSA should be suspected in all patients presenting from the community with SSTI. S. aureus can be a human commensal and can be recovered from the nares, axilla, vagina and groin of healthy subjects. Nasal carriage of S. aureus in healthy volunteers was found to be 23% in one study.(11) These rates may be higher in patients with exposure to health care facilities and with underlying medical illnesses, since CA-MRSA can be isolated from these same bodily areas in patients with and without a history of SSTI. Another study examined the rates of carriage of CA-MRSA in patients admitted to the hospital. Anterior nasal cultures were obtained from patients within 48 hours of hospitalization. This study found 7.3% of patients were colonized with MRSA. The study investigators were able to determine by molecular analysis that 30% of the MRSA isolates were CA-MRSA (2.2% of the total study population).(12) Analysis of data from the National Health and Nutrition Examination Survey (HANES), examining subjects who were not institutionalized, found a lower percentage of patients with nasal MRSA colonization (0.86%).(13) Patients who develop colonization with S. aureus during hospitalization are at risk for subsequent staphylococcal infection. Approximately 10% of patients who acquired MRSA colonization in a general inpatient population developed SSTI.(13) Those patients who become prevalent carriers (carriage for greater than one year) are also at risk for subsequent infection. Twenty-three percent (23%) of such carriers developed infection in one study.(14) Of the 38% of military recruits who were found to be colonized with CA-MRSA in another study, 3% of this subgroup subsequently developed SSTI.(15) ... CA-MRSA has been increasingly reported as the causative agent of nosocomial infections. |