Fecal concentration of intravenous vancomycin preparation after oral administration in an experimental model:...

Clostridioides difficile (C. difficile) infection is the main cause of nosocomial diarrhea. First-line treatment is oral vancomycin, but that presentation is not commercially available in Latin America. Our aim was to determine the fecal concentration of the oral administration of the conventional dose of an intravenous vancomycin preparation (VCM), in an experimental model.

A preclinical trial was conducted on 18 male mice (Balb/c strain), in three batches. The following doses of VCM were administered: 125 mg in batch A; 500 mg in batch B; and VCM-placebo in batch C. After receiving the doses, the mice were placed in metabolic cages, by batch. Feces were collected and the fecal concentration of VCM was analyzed through high pressure liquid chromatography 2, 4 and 6 h after drug administration.

The 125 mg dose of VCM reached the minimum inhibitory concentration (MIC) for C. difficile, without reaching the minimum bactericidal concentration (MBC₉₀), at 2, 4, and 6 h (521, 688, and 280 mg/L, respectively). Likewise, the 500 mg dose of VCM reached the MIC at 2 h, increased gradually, and reached MBC₉₀ between 4 and 6 h, in feces (1,062 and 1,779 mg/L, respectively), ANOVA, p = 0.0005.

The fecal concentration of vancomycin was dependent on the intragastric dose administered. Only the 500 mg dose of VCM reached therapeutic concentration for C. difficile (MIC and MBC₉₀), in the mice. We suggest starting a dose of 500 mg QID for achieving therapeutic concentration against C. difficile, as soon as 4 h after the first dose.