Background. Postoperative infection of intestine with methicillin-resistant
Staphylococcus aureus (MRSA) is fatal in some cases. The object of this st
udy was to establish a mouse model for the infection, providing a useful to
ol for investigating mechanisms in the progression of infection.
Methods. Mice were pretreated with cyclophosphamide, injected orally or dir
ectly into jejunum with MRSA prepared from a postoperative patient, and the
n given 5 daily doses of antibiotics. Forty-eight hours after the injection
, bacterial translocation and serum endotoxin levels were examined. Macroph
age depletion was carried out by the administration of liposome-encapsulate
d dichloromethylene diphosphate (Cl2MDP), 4 days before MRSA injection.
Results. Injection into the jejunum but not oral administration of MRSA ind
uced enteritis with diarrhea and resulted in death in most cyclophosphamide
-treated mice. Translocation of MRSA in mesenteric lymph nodes and liver wa
s observed, concomitantly with E. coil infection. Endotoxin-resistant C3H/H
eJ mice infected with MRSA survived longer than endotoxin-sensitive C3H/He
mice, but also died within a week after MRSA injection. Selective depletion
of macrophages induced infection in mice that were not pretreated with cyc
lophosphamide,
Conclusion. We established a mouse model for the fatal MRSA infection which
induced enteritis with diarrhea, that will be a useful tool for investigat
ing the mechanisms for sometimes fatal MRSA infection of the intestine in p
ostoperative patients. The presence off. coli or endotoxin seemed to play a
major role in the mortality of mice in the early days of MRSA-induced ente
ritis, but other factors, probably from MRSA, in the later days. Phagocytes
were quite important for protection against thee MRSA infection. (C) 2001
Academic Press.