Faecal pharmacokinetics of orally administered vancomycin in patients with suspected Clostridium difficile infection

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.Clostridium difficile infection (CDI) is the main cause of nosocomial diarrhoea in industrialized countries. Recently, an increase in CDI incidence was observed in North America and Europe due to the emergence of an apparent toxin hyper-producing strain (NAP1/BI/027) [1-6]. For many years, metronidazole was preferred to vancomycin as the first-line treatment of CDI because of its lower cost, lower selection pressure for the emergence of vancomycin-resistant pathogens, and because it was considered as effective as vancomycin for most patients [7-12]. Oral vancomycin was recommended only for the most severe cases and for those relapsing after a course of metronidazole, based on its extremely high faecal levels, which are several hundred times higher than the MIC90 of vancomycin against C.