Involvement of endotoxin in the mortality of mice with gut-derived sepsis due to methicillin-resistant Staphylococcus aureus.
MRSA causes a wide diversity of diseases, ranging from benign skin infections to life-threatening diseases, such as sepsis. However, there have been few reports of the pathophysiology and mechanisms of sepsis resulting from the gut-derived origin of MRSA. Therefore, we established a murine model of gut-derived sepsis with MRSA and factors of MRSA sepsis that cause deterioration. We separated mice into four groups according to antibiotic treatment as follows: (i) ABPC 40 mg/kg; (ii) CAZ 80 mg/kg; (iii) CAZ 80 mg/kg + endotoxin 10 microg/mouse; and (iv) saline-treated control groups. Gut-derived sepsis was induced by i.p. injection of cyclophosphamide after colonization of MRSA strain 334 in the intestine. After the induction of sepsis, significantly more CAZ-treated mice survived compared with ABPC-treated and control groups. MRSA were detected in the blood and liver among all groups. Endotoxin levels were significantly lower in the CAZ-treated group compared to other groups. Inflammatory cytokine levels in the serum were lower in the CAZ-treated group compared to other groups. Fecal culture showed a lower level of colonization of E. coli in the CAZ-treated group compared to other groups. In conclusion, we found that CAZ-treatment ameliorates infection and suppresses endotoxin level by the elimination of E. coli from the intestinal tract of mice. However, giving endotoxin in the CAZ-treated group increased mortality to almost the same level as in the ABPC-treated group. These results suggest endotoxin released from resident E. coli in the intestine is involved in clinical deterioration resulting from gut-derived MRSA sepsis.
The Third Department of Surgery, Toho University Ohashi Medical Center, 2-17-6 Ohashi, Meguro-ku, Tokyo 153-8515, Japan.
Masashi
M
Uramatsu
Tetsuya
T
Matsumoto
Kazuhiro
K
Tateda
Kazutoshi
K
Shibuya
Shuichi
S
Miyazaki
Tetsuya
T
Horino
Masaaki
M
Tanabe
Yoshinobu
Y
Sumiyama
Shinya
S
Kusachi
Keizo
K
Yamaguchi
D000818:Animals; D016470:Bacteremia / Q000401:mortality*; D015169:Colony Count, Microbial; D005260:Female; D007420:Intestine, Large / Q000382:microbiology; D008070:Lipopolysaccharides / Q000097:blood / Q000502:physiology*; D055624:Methicillin-Resistant Staphylococcus aureus; D051379:Mice; D008807:Mice, Inbred BALB C; D013203:Staphylococcal Infections / Q000401:mortality*; D015996:Survival Rate
D008070:Lipopolysaccharides