The effect of metronidazole on wound healing in rats

Metronidazole is gaining increasing acceptance as a perioperative antimicrobial agent. We studied the effect of metronidazole on wound healing in Sprague-Dawley rats, which received seven daily intraperitoneal injections of either metronidazole, 20 mg/kg/day, (simulating a therapeutic course) or equivalent volumes of physiologic saline solution. On the second day of treatment 25 treated rats and 20 control rats had full-thickness circular skin defects created on the back and standardized midline celiotomy incisions. The fascial incisions were closed with staples, and the abdominal skin was closed with silk sutures. On the seventh postoperative day all rats were put to death. The breaking strength of 1 cm wide segments of skin and fascial celiotomy wounds was measured, and the contraction of the open back wounds was computed. There was no significant difference in wound contraction or skin wound breaking strength, but fascial wound breaking strength was lower in treated rats than in control rats (283 versus 548 gm mean; 2 p < 0.001). To determine whether metronidazole permanently altered or only temporarily delayed fascial wound healing, 39 additional rats treated with metronidazole and 40 control rats underwent celiotomies as described above on the second day of a 7-day course of treatment. Fascial wound breaking strength was measured 2, 3, and 5 weeks after operation. The wound breaking strength in rats treated with metronidazole remained significantly lower than that of control rats at 2 and 3 weeks (860 versus 1005 gmm at 2 weeks and 1071 versus 1369 gm at 3 weeks; both 2 p < 0.05), but at 5 weeks there was no significant difference between treated and control groups (1358 versus 1399 gm). Metronidazole apparently interferes with early fascial wound healing, but the wounds of treated rats ultimately attain the same strength as untreated controls.