Dr. James Roberts' two-part feature story on MRSA in Emergency Medicine News (2006;28: 32 and 2006;28: 23) was timely, coming just as we are beginning to recognize that methicillin-resistant Staphylococcus aureus, or MRSA, is replacing good old regular MSSA that we came to expect long ago to be resistant to penicillin (due to beta-lactamase production). Until recently, MRSA showed up mainly from patients with chronic conditions who acquired it in hospitals and nursing homes. Next came reports of an increased proportion of staph isolates among those cultured in microbiology labs that appeared community-acquired, that is, not hospital-acquired, and because nursing homes and surgery centers were outside the hospital per se, these were called community-associated MRSA, CA-MRSA. Next, clusters of MRSA skin infections were reported associated with incarceration, intravenous drug use, and contact sports.
You will soon be reading about what really matters: A significant proportion of all patients' skin and soft tissue infections in various outpatient settings, including EDs, are now due to MRSA, to the extent that MRSA appears to be replacing MSSA as the most common cause of (culturable) skin and soft tissue infections. A report by Frazee and colleagues in Annals of Emergency Medicine (2004;45:311, and on the Annals web site, www.annemergmed.com/article/PIIS0196064404015057/fulltext) and our accompanying editorial address this important development. We also report a similar local experience in an upcoming edition of Emerging Infectious Diseases. As part of Emergency ID NET, our CDC collaborative network of 11 major emergency departments to research emerging infectious diseases, we have witnessed that these local reports now reflect a national phenomenon. Staph has changed in a big way, and this has major implications for emergency practice.
Because knowledge about CA-MRSA is evolving rapidly, we would like to offer a few new insights different from Dr. Roberts' discussion. Because of this major change in staph susceptibility and epidemiology, despite a lack of clinical comparative antimicrobial trials (establishing an in vivo correlation with in vitro resistance or superiority of one therapy over another), a different approach to empirical therapy of various staph-associated infections is necessary. For life-threatening infections, such as severe sepsis/septic shock, endocarditis, and severe skin and soft tissue infections, vancomycin should be included as part of an empirical antimicrobial regimen. Fortunately, vancomycin is nearly universally active against MRSA (excluding rare reports of vancomycin intermediate susceptibility S. aureus, i.e., VISA).
For outpatient treatment, several choices are likely to be ineffective and should be avoided. These include, besides the anti-staphylococcal penicillins such as naf-, oxa-, and dicloxacillin, all cephalosporin regimens such as cephalexin (Keflex) and ceftriaxone (Rocephin), to which MRSA is resistant. Amoxicillin/clavulanic acid (Augmentin) is also inactive against MRSA and is overly broad and expensive. We also do not recommend fluoroquinolones, even the newer formulations with extended Gram-positive activity such as levo-, gati-, moxi, and gemifloxacin, for several reasons. Previously, resistance rapidly emerged to ciprofloxacin, to which MRSA currently demonstrates high rates of resistance, including among CA strains.
MRSA resistance rates to newer fluoroquinolones tend to be lower than to ciprofloxacin, but minimal inhibitory concentrations (MICs) are close to achievable drug levels and a large proportion of isolates have only intermediate susceptibility (and micro reports indicating only “S” or “R” can be misleading), and in some areas, resistance rates to drugs like levofloxacin are already high. The potential for patients and communities to acquire resistance to these drugs is concerning and their ultimate clinical effectiveness is questionable. There is some evidence that the addition of rifampin to a fluoroquinolone may augment activity and forestall the development of resistance. Finally, like Augmentin, new fluoroquinolones are costly and overly broad for the vast majority of patients with infections likely to be caused by only staph or Streptococcus pyogenes, or Group A strep.
Unfortunately, the recommended new empirical oral regimens that better target CA-MRSA, all pose some problematic tradeoffs. TMP/SMX and rifampin is an inexpensive BID regimen uniformly active against MRSA that has been used successfully to eliminate MRSA carriage; however, the TMP/SMX component of this two-drug regimen has poor activity against strep. Clindamycin has good activity against MRSA and strep, but even the generic formulation is expensive, raises concerns about GI side effects, and has shown resistance among about 10 percent of CA-MRSA isolates, with reports of increased resistance developing on therapy. Perhaps helpful in this decision is evidence that cellulitis is more often associated with strep as opposed to abscesses and purulent wound infections that are more often infected by staph. Finally, there is no evidence that uncomplicated abscesses due to MRSA respond less well to incision and drainage alone than MSSA abscesses. Only one oral antibiotic has universal activity against CA-MRSA and strep, linezolid (Zyvox), which is prohibitively expensive (more than $100 a day). Confronted with this choice, patients may choose amputation!
Because none of the newly recommended or old antimicrobial therapies are uniformly active against all MRSA and strep strains, and resistance patterns may be changing, initial cultures (and more certain follow-up) should now be more routinely considered, especially in more compromised patients and those with more severe infections.
The implications of the emergence of CA-MRSA go further. Hospitals currently have isolation policies for patients infected or known to be colonized with MRSA, sometimes contributing to backlogged admissions tying up rooms in the ED. Now these policies make no sense; patients with skin and soft tissue infections are being admitted to non-isolation beds only until MRSA grows out one to two days later. Unless we plan to isolate all of the many patients admitted for these infections, we should assume that MRSA has probably replaced MSSA as typical flora and use isolation precautions appropriate to prevent exposure to infected fluids, rather than place patients in single-bed isolation rooms based on the presence of MRSA. So much the better for our overcrowded EDs.
CA-MRSA is no longer emerging; it has emerged.
David Talan, MD
Gregory Moran, MD
Los Angeles, CA
The authors are the principal investigators in the Olive View-UCLA Department of Emergency Medicine/Division of Infectious Diseases, and have been awarded a five-year, $9 million grant from the National Institutes of Health to study the use of off-patent antibiotics for treating uncomplicated skin and soft tissue infections. The study will be conducted at Olive View-UCLA, Johns Hopkins University, Maricopa Medical Center in Phoenix, Truman Medical Center and the University of Missouri in Kansas City, and Temple University Medical Center in Philadelphia.