Clostridium difficile infection (CDI) is the first cause of nosocomial diarrhea in industrial countries. Oral vancomycin is an important component of CDI treatment. Higher doses are used for patients with severe CDI, but without clear clinical evidence.
The aim of this study to determine if the fecal levels of vancomycin vary according to diarrhea severity and dosage.
Adults presenting with unformed stools and receiving oral vancomycin for less than 24 hours were included. Feces were collected up to 3x/day when feasible. Vancomycin serum levels were measured at days 1 and 3. Levels were measured with the AxSYM fluorescence polarization immunoassay system (Abbott), with an adapted protocol for feces.
A total of 13 patients (9F/4M) with a mean age of 67.8 (SD17.6) years, experienced 14 distinct CDI episodes, and were treated with oral vancomycin four times daily for CDI suspicion. CDI was confirmed by toxin detection or endoscopy in 8 patients. Patients received a total of 455 doses, distributed as followed: 125mg (224;49%), 250mg (92;20%) and 500mg (139;31%). As depicted in figure 1, patients receiving 500mg doses presented in average higher fecal concentrations than patients with lower doses (6165.8 µg/ml vs. 1701.8 µg/ml; p= 0.0002). Additionally patients with an average of less than three stools daily presented a mean concentration higher than patients with more important diarrhea (3959.3 µg/ml vs. 1549.2 µg/ml, p= 0.0004). In only 3 patients, detectable serum vancomycin levels were found on day 3 (0.8 µg/ml).
Patients with severe diarrhea presented lower concentration of fecal vancomycin. Higher dosage was associated with increased fecal levels. Consequently, a dosage of 500mg four times daily should be considered in patients with severe CDI. Compared to reported CMI90 for vancomycin vs. C.difficile, any dosage in our study lead to fecal concentrations exceeding outrageously this limit.