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 septicemia caused by epidemic methicillin-resistant Staphylococcus aureus strain 15 (EMRSA-15), which is the most prevalent epidemic strain of methicillin-resistant S. aureus in the United Kingdom; all cases occurred in a teaching hospital in Manchester, United Kingdom, between 1994 and 1998. Mortality was lowest (4%) in patients with rifampin-susceptible isolates treated with vancomycin and rifampin. It rose to 38% in patients who were treated with both antibiotics but in whom the organism became resistant to rifampin during therapy, and it reached 78% in patients who had rifampin-resistant isolates or in whom rifampin was contraindicated (P<.0001; Fisher exact test, 2-tailed). All isolates were susceptible to vancomycin by conventional laboratory testing, but susceptibility was lost by growth in vancomycin in vitro, becoming resistant at a minimum inhibitory concentration of 8 mg/L. This was associated with accumulation of cell-wall material. The deoxyribonucleic 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 subpopulation with reduced susceptibility to vancomycin.
Burnie
J
J
Infectious Diseases Research Unit, University of Manchester, Central Manchester Healthcare Trust, Manchester, United Kingdom. jburnie@labmed.cmht.nwest.nhs.uk
Matthews
R
R
Jiman-Fatami
A
A
Gottardello
P
P
Hodgetts
S
S
D'arcy
S
S
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D004269:DNA, Bacterial / Q000235:genetics; D004196:Disease Outbreaks; D004352:Drug Resistance, Microbial; D018432:Drug Resistance, Multiple; D016521:Electrophoresis, Gel, Pulsed-Field; D005260:Female; D006801:Humans; D008712:Methicillin / Q000494:pharmacology*; D051379:Mice; D008826:Microbial Sensitivity Tests; D008854:Microscopy, Electron; D010406:Penicillins / Q000494:pharmacology*; D015995:Prevalence; D012189:Retrospective Studies; D012293:Rifampin / Q000494:pharmacology; D018805:Sepsis / Q000453:epidemiology / Q000382:microbiology* / Q000401:mortality; D013203:Staphylococcal Infections / Q000453:epidemiology / Q000382:microbiology* / Q000401:mortality; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000648:ultrastructure; D014640:Vancomycin / Q000494:pharmacology; D014774:Virulence / Q000235:genetics
D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D010406:Penicillins; D014640:Vancomycin; D008712:Methicillin; D012293:Rifampin