Use of -Lactamase-Producing Anaerobes to Prevent Ceftriaxone from Degrading Intestinal Resistance to Colonization

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Abstract
Six adult volunteers were given 1 g/d of intravenous ceftriaxone for 5 d (consecutive). Ceftriaxone and β-lactamaseactivities were assayed in fecal samples obtained before and during drug administration, and anaerobic bacteria, Enterobacteriaceae, and fungi were counted. In two volunteers, no fecal β-lactamase activity was detected, but ceftriaxone was present during treatment at concentrations of 1.8–2.0 mg/g of feces. Concomitantly, fecal counts of anaerobes in these volunteers dropped from 10.5to 10 colony-forming units (cfu)/g of feces, and those of Candida species increased more than 100-fold. However, in the feces of the four other volunteers, β-lactamase activity was high during ceftriaxone administration, but no ceftriaxone was detected. In these volunteers, ceftriaxone administration was not followed by any significant change in counts of anaerobes or Candida species. This appeared to be due to the intraintestinal hydrolysis of ceftriaxone by resident β-lactamase-producing anaerobes. In gnotobiotic mice associated with a human fecal flora containing no β-lactamase-producing anaerobes, it was possible to prevent the deleterious effects of ceftriaxone on intestinal microbial composition and on colonization resistance (against a strain of Candida albicans and one of ceftriaxone-resistant Enterobacter cloacae) by feeding the animals with an association of four β-lactamase-producing anaerobic strains.