Treatment of Serious Staphylococcal Infections with a High Likelihood of MRSA

Empiric treatment of severe staphylococcal soft-tissue infections should be with an agent that has proven efficacy against MRSA, at least until antibiotic susceptibilities are available. Constitutive resistance to erythromycin is common among HA-MRSA strains and in certain geographic regions. Inducible clindamycin resistance is increasing in prevalence in both CA-MRSA and HA-MRSA strains. In addition, the use of ciprofloxacin (Cipro, Proquin XR) and even the newer quinolones is limited by the emergence of resistance. Interestingly, TMP-SMX (Bactrim, Septra) remains active against both MSSA and MRSA strains. Anecdotally, TMP-SMX also is commonly used to treat MRSA-complicated skin and skin-structure infections. In situations where streptococcal infections cannot be excluded, cephalexin, penicillin, or clindamycin should be administered.

Vancomycin has been traditionally used as the workhorse antibiotic to treat all MRSA infections; however, numerous problems have emerged. With the increased use of vancomycin, strains of S. aureus have appeared that are resistant to vancomycin with minimum inhibitory concentrations (MICs) of >16 mcg/mL (vancomycin-resistant S. aureus [VRSA]). Although these organisms are uncommon in the United States, vigorous control measures are required to prevent them from joining vancomycin-resistant enterococci (VRE) as major nosocomial pathogens. Vancomycin-intermediate S. aureus (VISA) with MICs of 2 to 4 mcg/mL and heteroresistant strains with MICs of 4 to 16 mcg/mL have also appeared. Heteroresistance can be detected only in broth culture in the presence of a very large inoculum (107 colony-forming units [CFUs] per milliliter). There also is mounting evidence that over the course of 3 to 4 decades of vancomycin use, MICs have gradually increased, even in sensitive strains. This development has relevance to the treatment of skin and soft-tissue infections, because tissue levels of vancomycin may reach only 2 to 4 mcg/mL owing to limited tissue penetration of this antibiotic. In the past, MRSA strains commonly had MICs of 0.1 to 0.5 mcg/mL, values considerably below achievable tissue levels of vancomycin (Vanco-cin). As suggested, at the present time and in the future, we may encounter strains with MICs of 1 to 2 mcg/mL, which may account for the greater failure rate of vancomycin in the treatment of a variety of infections including those involving the skin and soft tissue.

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  • Category: Infectious diseases