| Healthcare (Hospital)-Associated MRSA versus Community-Associated MRSA As mentioned in the course introduction, MRSA infections fall into two general types: Healthcare-associated MRSA (HA-MRSA) Infections that occur in people who are, or have recently been, hospitalized. Community-acquired MRSA (CA-MRSA) Infections that are apparently acquired in the community There are a number of factors that distinguish HA-MRSA from CA-MRSA isolates. These factors are summarized in the table below. Factor HA-MRSA CA-MRSA Origin of strains Nosocomial infections Five isolates associated with healthcare settings: USA100, -200, -500, -600, -800 USA100 is the predominant isolate while USA 200 is the second most common isolate. USA700 has been isolated in both healthcare and community settings. Evolved from endemic methicillin susceptible S. aureus (MSSA) strains Two clones, USA300 and USA400, are associated with the majority of CA-MRSA infections in the United States. USA300 has emerged as the most prominent clone and is not found among hospital strains. Genetic lineage Isolates usually carry large SCCmec types I, II or III (34-67 kb) The larger size of SCCmecII and III permits the inclusion of other non-beta lactam resistance genes so that HA-MRSA strains tend to be multi-drug resistant Isolates carry a smaller SCCmec variant, predominantly type IV (24 kb), less often type V or variant VT. SCCmecIV (except for mecA) does not permit the inclusion of other non-beta lactam resistance genes so that CA-MRSA isolates exhibit resistance to only methicillin and erythromycin and are more often susceptible to other non-beta lactam antibiotics (eg., trimethoprim/sulfamethoxazole (SXT) and clindamycin). Affected population Largely affects older adults and people with weakened immune systems; those who have undergone surgical procedures are at increased risk. Healthy persons in the general population without established risk factors for MRSA acquisition Clinical syndromes Found at multiple sites, most commonly bloodstream infections, urinary tract infections (UTI) and respiratory tract infections Predominantly skin and soft tissue infections (SSTIs), such as abscesses, cellulitis, folliculitis and impetigo and a serious form of pneumonia Genes for Panton-Valentine Leukocidin (PVL) are associated with SCCmecIV; the clinical spectrum of infections caused by CA-MRSA is directly related to the presence of PVL genes, coding for the production of a cytotoxin that causes tissue necrosis and leukocyte destruction. | View Page |
| Future perspectives With MRSA becoming the new "normal" in many areas, clinicians will have to define the role of up to a dozen anti-MRSA drugs; alternatives to vancomycin, including older drugs like clindamycin, doxycycline and trimethoprim/sulfamethoxazole, and newer agents like linezolid and daptomycin for serious infections. There are also a number of drugs under development including enhanced glycopeptides – dalbavancin, oritavancin, telavancin, and anti-MRSA cephalosporins. | View Page |
| Clostridium difficile-associated Diarrhea Clostridium difficile-associated diarrhea (CDAD) is a unique hospital infection that occurs almost entirely in patients who have received previous antimicrobial treatment. Anaerobic gut flora are crucial to colonization resistance, so any disruption of the normal colonic flora (through illness, therapeutic procedures or, most commonly, antibiotic use) is essential to the pathogenesis of C. difficile infection. The association of CDAD with antibiotic use is significant. Early attention (1970s) focused on clindamycin but later on (1980s,1990s & continuing today) the cephalosporins, especially third generation, and broad spectrum penicillins (e.g., amoxycillin/ampicillin) were also implicated. The risk of CDAD is increased if C. difficile is resistant to the particular antimicrobial. In the case of clindamycin, C. difficile resistance is variable. Risk of infection due to a clindamycin-resistant strain increases with use of the drug. For the third generation cephalosporins, C. difficile is universally resistant; thus, any toxigenic strain is capable of causing CDAD during cephalosporin use. Other less commonly implicated antibiotics are the macrolides, e.g., erythromycin, azithromycin, clarithromycin. However, prolonged courses of any antibiotics will increase the risk of disease. Even those antibiotics used to treat colitis (metronidazole, for example) have sometimes been reported to cause CDAD.The fluoroquinolones have been in use since the 1980s. Ciprofloxacin was approved in 1987, but it is only in recent years with the emergence of the epidemic strain 027/NAP1/BI, which is resistant to the fluoroquinolones, that this class of drugs has been implicated in Clostridium difficile disease. The fluoroquinolones were initially considered to be low risk but their use has been increasing, both with hospital inpatients and in the community, and fluoroquinolones are now implicated as a risk factor for C. difficile infection. The newer fluoroquinolones, e.g., gatifloxacin, moxifloxacin, have better activity against anaerobes, but poor in vitro activity against C. difficile, thus increasing the likelihood of CDAD. The CDC now recommends that all fluoroquinolones, as a class, be used sparingly as each poses an increased risk for CDAD. | View Page |
| Risk Factors and Resistance Enterococci are largely commensal organisms that are opportunistic pathogens. Underlying disease, an immunocompromised state, age, lengthy hospital stays or long term care, invasive treatments, and/or prior antimicrobial therapy are factors that are associated with significant infections with these species. As noted previously, Enterococci are intrinsically resistant to many antibiotics. Intrinsic resistance affects not only beta lactams (including a broad range of cepahlosporins) and aminoglycosides, but also clindamycin and trimethoprim/sulfamethoxazole. The standard recommended therapy for systemic infections is a combination of either penicillin or vancomycin and an aminoglycoside (gentamicin or streptomycin). The goal of combination therapy is to achieve a synergistic bacteriocidal effect between the cell wall agent and the aminoglycoside.In recent decades, increasing resistance to other antibiotics through acquired resistance mechanisms has become a growing therapeutic and infection control problem. Of key concern are high level resistance (HLR) to aminoglycosides and increasing resistance to glycopeptides such as vancomycin. | View Page |
