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A multifaceted approach that involves early debridement and control of infection is critical to successful and rapid burn wound healing. This pilot study was conducted in 15 adult patients with burns to assess the usefulness of early enzymatic debridement with a combination of collagenase ointment and polymyxin B sulfate/bacitracin spray versus silver sulfaldiazine cream in partial-thickness burns. Combination treatment with collagenase and polymyxin B sulfate/bacitracin resulted in significantly shorter time to achieve a clean wound bed than silver sulfadiazine (median 6 vs 12 days; p = 0.0012) and significantly more rapid wound healing than silver sulfadiazine (median 10 vs 15 days; p = 0.0007). These results are encouraging and justify implementation of a larger, multicenter, comparative study.