Severe disease has also been described due to strains of CaMRSA. Francis described 4 patients with necrotizing pneumonia due to CaMRSA similar to the pediatric cases referred to above. The isolates from all 4 patients carried PVL and SCCmecA IV genes and were of the USA300 strain group (26). Of note, all 4 patients initially had influenza-like illnesses, demonstrating again the association between influenza and staphylococcal pneumonia. This also signifies these presentations were potentially vaccine preventable. Recently, necrotizing fasciitis caused by CaMRSA strains, all again characterized as having PVL genes, has been described (27). This new phenomenon expands the differential diagnosis of causes of this life-threatening soft-tissue syndrome and influences empirical antibiotic selection.
A 41-year-old with Crohn’s disease treated with infliximab undergoes ventral hernia repair. She has a past surgical history of multiple abdominal surgeries. Three weeks postoperatively she is readmitted with a superinfected hematoma requiring operative drainage. Cultures reveal MRSA, susceptible to erythromycin, clindamycin, vancomycin, gentamicin, tetracycline, and trimethoprim-sulfamethoxazole.
The work to date on this new aspect of resistance in S. aureus intimates a trend similar to that previously experienced with penicillin resistance. Penicillinase-producing strains, first recognized in 1944, became increasingly common among hospital isolates after the second World War (28,29). By the 1970s, penicillin-resistant staphylococci had become widespread in the Community as well. Currently, identification of a penicillin-susceptible S. aureus isolate is uncommon.
The potential for further increases in the prevalence of methicillin resistance among staphylococci lies with the SCCmecA complex. Acquisition of this determinant from another resistant clone of either S. aureus or a coagulase-negative staphylococcus is the necessary first step in the process of becoming methicillin resistant. Types I through III are large, and this has been an obstacle to frequent transfers to MSSA strains. The result of this dynamic is that hospital-acquired MRSA to this point has descended from a relatively small number of clones as compared with the wide heterogeneity seen in susceptible S. aureus (30). As mentioned above, SCCmecA IV is smaller and can therefore more easily insert into many different MSSA strains without a loss of fitness. In fact type IV strains have been shown in vitro to replicate faster than hospital MRSA strains (20). This may allow MRSA to begin to displace MSSA as the predominant community phenotype in a manner similar to that in which penicillin-susceptible S. aureus was replaced.
A similar phenomenon may occur in hospitals wherein a typical CaMRSA strain may become the predominant hospital clone. This has been described already in 1 hospital where SCCmecA IV became the major determinant of methicillin resistance in the hospital (31). The trend was identifiable by a “more susceptible” antibiogram of MRSA strains. Future epidemiological surveillance will be necessary as the potential exists for resistant strains to continue to cross the increasingly more permeable barrier between traditional healthcare and the community.
Increasing resistance to S. aureus has several implications for clinicians. Fundamental principles in the management of infectious syndromes become even more important, particularly source control of suppurative foci through debridement and drainage. An added benefit of such procedures is that they facilitate the establishment of a microbiological diagnosis. Clinicians and microbiologists will need to continue to work together closely so as to be aware of resistance trends in their community. In situations where the pathogen is not identified and treatment is prescribed empirically, follow-up is crucial.
Obviously, the emergence of CaMRSA has limited antibiotic choices. Clindamycin, trimethoprim-sulfamethoxazole, and doxycycline remain therapeutic options in the appropriate clinical situation. The severe clinical manifestations described above require consideration of empirical vancomycin in the treatment of patients presenting seriously ill with infectious syndromes that could be potentially due to S. aureus while awaiting culture results. The most extensive experience for inpatient use is with this agent. Linezolid, daptomycin, and quinupristin-dalfopristin are newer agents with activity against MRSA that have been reviewed elsewhere (32,33). Growing experience with these agents has provided options in situations where vancomycin cannot be used. It has also emphasized some of their limitations. Daptomycin and quinupristin-dalfopristin are only given parenterally, while linezolid can be given both orally and intravenously. Expense impacts the use of all three especially outside the hospital. Treatment-limiting cytopenias and peripheral and optic neuropathy have been described with linezolid when it is has been employed for extended courses of therapy. Daptomycin is inhibited by surfactant and therefore should not be used for suspected pulmonary infections. Quinupristin-dalfopristin’s use can be limited by disabling myalgias and the need for central venous access. More data about the use of these newer agents for invasive infections are needed before they can be considered superior to vancomycin.