Analysis of 42 cases of septicemia caused by an epidemic strain of methicillin-resistant Staphylococcus aureus: Evidence of resistance to vancomycin

Recent case reports of vancomycin treatment failures in the United States, Japan, and France have prompted a retrospective analysis of 42 cases of sep ticemia caused by epidemic methicillin-resist ant Stapyhlococcus aureus str ain 15 (EMRSA-15), which is the most prevalent epidemic strain of methicill in-resistant S. aureus in the United Kingdom; all cases occurred in a teach ing hospital in Manchester, United Kingdom, between 1994 and 1998, Mortalit y was lowest (4%) in patients with rifampin-susceptible isolates treated wi th vancomycin and rifampin. It rose to 38% in patients who were treated wit h both antibiotics but in whom the organism became resistant to rifampin du ring therapy, and it reached 78% in patients who had rifampin-resistant iso lates or in whom rifampin was contraindicated (P < .0001; Fisher exact test , 2-tailed). All isolates were susceptible to vancomycin by conventional la boratory testing, but susceptibility was lost by growth in vancomycin in vi tro, becoming resistant at a minimum inhibitory concentration of 8 mg/L, Th is was associated with accumulation of cell-wall material. The deoxyribonuc leic acid fingerprint remained unchanged. This study suggests that rifampin played a key role in the prevention of deaths caused by an epidemic strain of methicillin-resistant S. aureus that readily gave rise to a subpopulati on with reduced susceptibility to vancomycin.