Department of Microbiology and Infectious Diseases, Université de Sherbrooke, 3001 12ème Avenue Nord, Sherbrooke, Quebec, Canada.
BMC Infect Dis. 2010 Dec 30;10:363. doi: 10.1186/1471-2334-10-363.
Oral vancomycin (125 mg qid) is recommended as treatment of severe Clostridium difficile infection (CDI). Higher doses (250 or 500 mg qid) are sometimes recommended for patients with very severe CDI, without supporting clinical evidence. We wished to determine to what extent faecal levels of vancomycin vary according to diarrhoea severity and dosage, and whether it is rational to administer high-dose vancomycin to selected patients.
We recruited hospitalized adults suspected to have CDI for whom oral vancomycin (125, 250 or 500 mg qid) had been initiated. Faeces were collected up to 3 times/day and levels were measured with the AxSYM fluorescence polarization immunoassay.
Fifteen patients (9 with confirmed CDI) were treated with oral vancomycin. Patients with ≥ 4 stools daily presented lower faecal vancomycin levels than those with a lower frequency. Higher doses of oral vancomycin (250 mg or 500 mg qid) led to consistently higher faecal levels (> 2000 mg/L), which were 3 orders of magnitude higher than the MIC90 of vancomycin against C. difficile. One patient receiving 125 mg qid had levels below 50 mg/L during the first day of treatment.
Faecal levels of vancomycin are proportional to the dosage administered and, even in patients with increased stool frequency, much higher than the MIC90. Patients given the standard 125 mg qid dosage might have low faecal levels during the first day of treatment. A loading dose of 250 mg or 500 mg qid during the first 24-48 hours followed by the standard dosage should be evaluated in larger studies, since it might be less disruptive to the colonic flora and save unnecessary costs.
口服万古霉素（125mg，qid）被推荐用于治疗严重的艰难梭菌感染（CDI）。对于非常严重的 CDI 患者，有时会推荐使用更高剂量（250 或 500mg，qid），但缺乏支持临床证据。我们希望确定粪便中万古霉素的水平在多大程度上根据腹泻的严重程度和剂量而变化，以及对选定的患者给予高剂量万古霉素是否合理。
我们招募了疑似患有 CDI 的住院成人患者，这些患者已经开始接受口服万古霉素（125、250 或 500mg，qid）治疗。每天采集粪便 3 次以上，并使用 AxSYM 荧光偏振免疫测定法测量水平。
15 名患者（9 名确诊为 CDI）接受了口服万古霉素治疗。每天排≥4 次粪便的患者粪便中万古霉素水平低于排粪频率较低的患者。更高剂量的口服万古霉素（250mg 或 500mg，qid）导致粪便水平持续升高（>2000mg/L），比万古霉素对艰难梭菌的 MIC90 高 3 个数量级。1 名接受 125mg，qid 剂量的患者在治疗的第一天粪便水平低于 50mg/L。
粪便中万古霉素的水平与给予的剂量成正比，即使在粪便频率增加的患者中，也远高于 MIC90。给予标准 125mg，qid 剂量的患者在治疗的第一天可能会出现低水平的粪便。在更大的研究中，应该评估在最初的 24-48 小时内给予 250mg 或 500mg，qid 的负荷剂量，然后给予标准剂量，因为这可能对结肠菌群的干扰较小，并节省不必要的成本。
