Data from: Adjunctive clindamycin for cellulitis: clinical trial comparing flucloxacillin with or without clindamycin for the treatment of limb cellulitis

OBJECTIVE. To compare flucloxacillin with clindamycin to flucloxacillin alone for the treatment of limb cellulitis. DESIGN. Parallel, double-blinded, randomised controlled trial. SETTING. Emergency department attendances and general practice referrals within twenty hospitals in England. INTERVENTIONS. Flucloxacillin, at a minimum of 500mg four times per day for five days, with clindamycin 300mg four times per day for two days given orally versus flucloxacillin given alone. MAIN OUTCOME MEASURES. The primary outcome was improvement at Day 5. This was defined as being afebrile with either a reduction in affected skin surface temperature or a reduction in the circumference of the affected area. Secondary outcomes included resolution of systemic features, resolution of inflammatory markers, recovery of renal function, reduction in the affected area, decrease in pain, return to work or normal activities and the absence of increased side-effects. RESULTS. 410 patients were included in the trial. No significant difference was seen in improvement at Day 5 for flucloxacillin with clindamycin (136/156, 87%) versus flucloxacillin alone (140/172, 81%) – OR 1.55 (95% CI 0.81 to 3.01) p=0.174. There was a significant difference in the number of patients with diarrhoea at Day 5 in the flucloxacillin with clindamycin allocation (34/160, 22%) versus flucloxacillin alone (16/176, 9%) – OR 2.7 (95% CI 1.41 to 5.07), p=0.002. There was no clinically significant difference in any secondary outcome measures. There was no significant difference in the number of patients stating that they had returned to normal activities at the Day 30 interview in the flucloxacillin with clindamycin allocation (99/121, 82%) versus flucloxacillin alone (104/129, 81%) – adjusted OR 0.90 (95% CI 0.44 to 1.84). CONCLUSIONS. The addition of a short course of clindamycin to flucloxacillin early on in limb cellulitis does not improve outcome. The addition of clindamycin doubles the likelihood of diarrhoea within the first few days.【研究目的】比较氟氯西林（flucloxacillin）联合克林霉素（clindamycin）与单用氟氯西林治疗肢体蜂窝织炎（limb cellulitis）的临床疗效。 【研究设计】平行组、双盲随机对照试验（randomised controlled trial）。 【研究场景】英格兰境内20家医院的急诊科就诊患者及全科医疗转诊患者。 【干预措施】试验组给予氟氯西林（每日四次，每次至少500mg，疗程5天）联合克林霉素（每日四次，每次300mg，疗程2天）口服给药，对照组仅给予氟氯西林口服给药。 【主要结局指标】主要结局为第5天的病情改善情况，定义为体温恢复正常，且受累皮肤温度降低或受累区域周长缩小。次要结局包括全身症状缓解、炎症标志物恢复正常、肾功能恢复、受累区域面积缩小、疼痛减轻、恢复工作或正常日常活动，以及未出现不良反应加重。 【研究结果】本试验共纳入410例患者。试验组（氟氯西林联合克林霉素）第5天病情改善率为87%（136/156），对照组（单用氟氯西林）为81%（140/172），组间差异无统计学意义（优势比（odds ratio, OR）1.55，95%置信区间（confidence interval, CI）0.81~3.01，p=0.174）。试验组第5天腹泻患者占比为22%（34/160），显著高于对照组的9%（16/176）（OR 2.7，95%CI 1.41~5.07，p=0.002）。其余次要结局指标均无临床意义上的显著差异。在第30天随访访谈中，试验组恢复正常活动的患者占比为82%（99/121），对照组为81%（104/129），校正后优势比为0.90（95%CI 0.44~1.84），组间无显著差异。 【研究结论】在肢体蜂窝织炎早期治疗中，于氟氯西林基础上加用短疗程克林霉素并不会改善治疗结局，但会使治疗前几日出现腹泻的风险增加一倍。