Topical versus Systemic Antimicrobial Therapy for Treating Mildly Infected Diabetic Foot Ulcers: A Randomized, Controlled, Double-Blinded, Multicenter Trial of Pexiganan Cream
Topical versus Systemic Antimicrobial Therapy for Treating Mildly Infected Diabetic Foot Ulcers: A Randomized, Controlled, Double-Blinded, Multicenter Trial of Pexiganan Cream
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DOI：
10.1086/593185
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发表时间：
2008-12-15
影响因子：
11.8
通讯作者：
Zasloff, Michael
中科院分区：
文献类型：
--
作者：
Lipsky, Benjamin A.;Holroyd, Kenneth J.;Zasloff, Michael
背景资料。糖尿病足部感染溃疡的局部抗菌治疗可以集中于创面，避免全身抗感染药物的不良反应。我们比较了门诊使用外用抗菌肽Pexiganan醋酸酯乳膏和口服氟喹诺酮类抗生素氧氟沙星治疗轻度感染的糖尿病足溃疡的疗效。在两个连续的双盲对照试验中(研究303和研究304)，我们随机选择患有轻度感染的糖尿病足溃疡的糖尿病患者接受活性外用药物或活性口服抗生素，外加各自的非活性安慰剂。令人感兴趣的主要结果是感染的临床治愈或改善。次要结果包括伤口病原体的根除和伤口愈合，这由半定量评分系统记录下来。总体而言，835名患者是随机的；每个治疗组的患者在人口统计学和临床特征方面都是相似的。尽管研究303没有证明等效性，但研究304和两个试验的综合数据显示，在临床改善率(85%-90%)、总的微生物清除率(42%-47%)和伤口愈合率方面，外用培西甘和口服氧氟沙星的结果相同(在95%的可信区间内)。恶化蜂窝组织炎(2%-4%)和截肢(2%-3%)的发生率在不同治疗组之间没有显著差异。接受氧氟沙星治疗的部分患者出现了对氧氟沙星的细菌耐药，而接受培克西甘治疗的患者对聚氧氟沙星没有明显的耐药性。在治疗患有轻度感染的足部溃疡的糖尿病患者中，外用聚己烷可能是口服抗生素治疗的有效替代方案，并可能降低选择抗菌素耐药细菌的风险。NCT00563394和NCT00563433。
Background. Topical antimicrobial therapy of infected diabetic foot ulcers can focus on the wound and avoid the adverse effects of systemic anti-infective agents. We compared the efficacy of outpatient treatment using an investigational topical antimicrobial peptide, pexiganan acetate cream, with the efficacy of systemic therapy using an oral fluoroquinolone antibiotic, ofloxacin, for mildly infected diabetic foot ulcers.Methods. In 2 consecutive, double-blind, controlled trials (study 303 and study 304), we randomized diabetic patients with a mildly infected diabetic foot ulcer to receive the active topical agent or active oral antibiotic, plus a respective inactive placebo. The primary outcome of interest was clinical cure or improvement of the infection. Secondary outcomes included eradication of wound pathogens and wound healing, which was documented by a semiquantitative scoring system.Results. Overall, 835 patients were randomized; those in each treatment arm were similar with regard to demographic and clinical characteristics. Although study 303 failed to demonstrate equivalence, study 304 and the combined data for the 2 trials demonstrated equivalent results (within the 95% confidence interval) for topical pexiganan and oral ofloxacin in clinical improvement rates (85%-90%), overall microbiological eradication rates (42%-47%), and wound healing rates. The incidence of worsening cellulitis (2%-4%) and amputation (2%-3%) did not differ significantly between treatment arms. Bacterial resistance to ofloxacin emerged in some patients who received ofloxacin, but no significant resistance to pexiganan emerged among patients who received pexiganan.Conclusions. Topical pexiganan might be an effective alternative to oral antibiotic therapy in treating diabetic patients with a mildly infected foot ulcer, and might reduce the risk of selecting antimicrobial-resistant bacteria.Clinical trials registration. NCT00563394 and NCT00563433.