Introduction: Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen causing 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 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.

Method: We separated mice into three groups according to the antibiotic treatment as follows, 1) ampicillin (ABPC) 40 mg/kg, 2) ceftazidime (CAZ) 80 mg/kg, and 3) saline-treated control groups. Gut-derived sepsis was induced by intraperitoneal injection of cyclophosphamide after colonization of MRSA strain 334 in the intestine. The survival of mice was monitored and various organs were obtained during the infection for further analysis.

Results: After the induction of sepsis, significantly more CAZ-treated mice survived in comparison with ABPC-treated and control group of mice. MRSA were detected in the blood and liver among all groups. Endotoxin levels were significantly lower in 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 CAZ-treated group compared to other groups.

Conclusion: We found that CAZ-treatment ameliorates the infection and suppresses endotoxin level by the elimination of E. coli from the intestinal tract of mice. These results suggest endotoxin release from the resident E. coli in the intestine is involved in clinical deterioration resulting from gut-derived MRSA sepsis.