Therapeutics and Drug Brief
The Threat of Vancomycin-Resistant MRSA
Source: Hiramatsu K, J Antimicrob Chemother 1997;40:135-136.
A4-month-old male infant developed a wound infection caused by methicillin-resistant Staphylococcus aureus (MRSA) at the sternal incision two weeks after a radical operation for pulmonary atresia. In spite of vancomycin (VCM) administration at a dose of 45 mg/kg/d for 29 days, infection continued, and arbekacin (an aminoglycoside approved for MRSA infection in Japan) was added. After 12 days, the infection subsided and antimicrobial therapy was discontinued. However, 12 days later, subcutaneous abscess was noted, and a combination of arbekacin and ampicillin/sulbactam was started. Signs of infection initially subsided but subsequently increased, and debridement of the subcutaneous abscess was later required. The patient recovered and was discharged from the hospital after 17 days.
The MRSA strain (Mu 50) isolated from the purulent discharge from the sternal incision site and also from the debridement sample had a MIC of 8 mg/L for VCM, as confirmed by the broth microdilution method. The Mu 50 strain did not contain the van A or van B genes as judged by PCR amplification of DNA.
Comment by Jun Takezawa, MD
Because clinical isolates of coagulase-negative staphylococci with low-level resistance to VCM (MICs 8-16 mg/L) have been reported (N Engl J Med 1987;316:927-931), and because transfer of the van A containing plasmid from enterococci to Staphylococcus aureus has been accomplished in vitro (FEMS Microbiology Letters 1992;93:195-198), the eventual emergence of VCM-resistant MRSA has been predicted with great concern. Fortunately, the MRSA strain isolated in this case (Mu 50) did not carry the van A or van B genes, and it was not completely resistant to VCM (MIC > 32 mg/L). Although the exact mechanism of acquiring resistance to VCM in the present case is unknown, Hiramatsu and colleagues speculate that it occurred as a result of the organism's intrinsic mechanism of augmented cell-wall synthesis.
MRSA infection is one of the most common nosocomial infections in Europe, North America, and Japan. Although most MRSA strains remain sensitive to VCM, clinical isolates of MRSA that are intermediately resistant to VCM have now also been reported from Michigan and New Jersey (MMWR Morb Mortal Wkly Rep 1997;46:No. 35). In the Japanese university hospital in which the MRSA strain in this paper was identified, 2% of all MRSA isolates were found to be acquiring reduced VCM susceptibility. It has not been confirmed that transmission of the van A gene via plasmid from VCM-resistant enterococci (VRE) to MRSA occurs clinically, but if this does happen, the number of victims of VCM-resistant MRSA infection will definitely increase. Because overuse and misuse of antimicrobial agents are known to be responsible for the emergence of antimicrobial-resistant pathogens, hospital infection control teams should review and restrict the use of VCM following current guidelines (MMWR Morb Mortal Wkly Rep 1995;44:No. RR-12), and assure that patient care is provided according to the recommendations for multidrug-resistant organisms (Infect Control Hosp Epidemiol 1996;17:53-80).
The most accurate antimicrobial susceptibility test for staphylococci is determination of MIC using the methods of broth dilution, agar dilution, or agar-gradient diffusion (the current disk diffusion method is not acceptable). The bacteriology laboratory should confirm the genus and species of the organism, repeat the MIC determination, and inform the healthcare authorities of the presumptive staphylococcal strain with reduced susceptibility to VCM.
Dr. Takezawa is Director of Emergency and Intensive Care Medicine Professor, Department of Emergency Medicine Nagoya University School of Medicine, Nagoya, Japan.
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