Abstract
Studies were performed to optimize vancomycin (VCM) therapy for methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) infections in an experimental rat MRSA infection model. Wistar male rats were inoculated with viable MRSA (1.0×10<sup>9</sup>CFU/animal) after the administration of kanamycin (100mg/kg/day) and metronidazole (25mg/kg/day). These MRSA-bearing rats were then administered latamoxeF (LMOX, 80mg/kg/day) and cyclophosphamide (CY, 200mg/kg/day) to induced MRSA infections. VCM (80mg/kg/day) was then administered to treat the infections beginning on either day 2 (early) or 4 (late) after the initiation of LMOX administration. Fecal MRSA was isolated from MRSA-bearing rats at a mean concentration of 6.7×10<sup>3</sup> CFU/g 30 days after inoculation, which remained constant for the next 30 days. After LMOX and CY administration, intestinal MRSA growth significantly increased and MRSA was further isolated from the liver, spleen, kidneys, and blood. In rats treated with oral VCM early after LMOX, viable MRSA decreased in the intestinal tract and was not isolated from other organs. In the late VCM oral administration group, MRSA was isolated at greater than 10<sup>4</sup>CFU/g from the feces and also from the organs. However, both the growth of intestinal MRSA and translocations were inhibited with concomitant oral and parenteral VCM. These results suggest that LMOX administration to asymptomatic MRSA carriers may be a risk factor which induces abnormal proliferation of intestinal MRSA. These results also stress the importance of early VCM treatment for MRSA enterocolitis and the need for parenteral administration of VCM to prevent MRSA septicemia.
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