Safety and efficacy of Intralipid emulsions of amphotericin B J Antimicrob Chemother 1997 ; 40 : 137 – 139

Sir, We describe a clinical strain of methicillin-resistant Staphylococcus aureus (MRSA) with reduced susceptibility to vancomycin (MIC 8 mg/L). The strain was isolated from a surgical wound infection which was refractory to vancomycin therapy. In May 1996, a 4 month-old male infant underwent heart surgery for pulmonary atresia. Two weeks following surgery, the infant became febrile and developed a purulent discharge from the sternal surgical incision site; culture of the purulent material yielded MRSA. The patient was treated with vancomycin (45 mg/kg daily) for 29 days, but fever and discharge of pus continued, and the Creactive protein (CRP) remained elevated (40 mg/L). The treatment was changed to a combination of vancomycin and arbekacin (an aminoglycoside approved for MRSA infection in Japan). After 12 days of this regimen, the purulent discharge subsided, the wound began to heal, and the CRP declined from 40 to 9 mg/L. The antimicrobial therapy was discontinued. However, 12 days later the surgical site appeared inflamed with the development of a subcutaneous abscess accompanied by a sudden onset of fever and a raised CRP level of 35 mg/L. Therapy was resumed with the combination of arbekacin and ampicillin/sulbactam which has been shown to have synergic activity against MRSA. After 6 days of therapy, the patient’s fever had subsided and CRP declined below detectable levels ( 3 mg/L). During the next few days, however, the CRP level fluctuated between 3 and 10 mg/L, suggesting persistence of infection. Debridement of the subcutaneous abscess was performed and the patient was discharged from the hospital after a further 17 days of therapy with arbekacin and ampicillin/ sulbactam. CRP remained below detectable levels. The MRSA strain (Mu50), which was isolated from the purulent discharge at the sternal incision site and from the debridement sample, had a vancomycin MIC of 8 mg/L by the broth microdilution method. Vancomycin has the most reliable antimicrobial activity against MRSA. The emergence of resistance to vancomycin in S. aureus has been predicted based on the high levels of resistance to vancomycin in enterococci and because transfer of the vanA-containing plasmid from enterococci into S. aureus has been demonstrated. S. aureus strain Mu50 did not carry vanA or vanB genes as judged by PCR amplification of DNA. The exact mechanism of the organism’s reduced susceptibility to vancomycin remains to be determined but it may be due to an intrinsic mechanism of augmented cell-wall synthesis. This is inferred from three findings (data not shown): the cell wall appeared twice as thick as the wall of control strains on electron microscopy; there was a three-fold increase in the production of both penicillin-binding protein (PBP) 2 and PBP2 as measured by Western blotting; and a three-fold increase, as judged by HPLC analysis, in production of cell wall murein precursors compared with vancomycin-susceptible MRSA strains (MIC 2 mg/L). Low-level vancomycin resistance (MICs 8–16 mg/L) has been reported in clinical isolates of coagulase-negative staphylococci, but Mu50 is the first clinical strain of S. aureus to demonstrate this level of vancomycin resistance. In Juntendo University Hospital, strains with reduced vancomycin susceptibility showing pulsed-field gel electrophoresis patterns identical or similar to Mu50, have now been found in 2% of all MRSA isolates. Prolonged vancomycin therapy or, as in this case, combination therapy with other antimicrobial agents is necessary for infections caused by such strains. The situation reinforces the recommendation of the Centers for Disease Control and others to test all strains of staphylococci for resistance to vancomycin, and to use vancomycin prudently. Further work on the population analysis and mechanisms of resistance in these strains is proceeding.