We examined the effect of antibiotic treatment on establishment of intestinal colonization by Candida glabrata in adult mice. Subcutaneous ceftriaxone, piperacillin-tazobactam, clindamycin, and metronidazole promoted increased density of stool colonization, whereas cefepime, levofloxacin, and aztreonam did not. These findings suggest that antibiotics that inhibit intestinal anaerobes promote C. glabrata colonization.The gastrointestinal tract is a primary site of colonization by Candida species and is frequently a source for hematogenous dissemination in cancer patients (1). Antibiotics play a crucial role in the pathogenesis of Candida infections by inhibiting competing indigenous microflora, thereby facilitating acquisition and overgrowth of Candida species in the gastrointestinal tract and at other sites (1). Several studies suggest that antibiotics that inhibit obligate anaerobes in the intestinal tract may be more likely to promote overgrowth of C. albicans than those that do not (1,4,5,7,(8)(9)(10)(11), but little data regarding the effect of antibiotics on colonization with other Candida species are available. We used a mouse model to test the hypothesis that antibiotics with potent activity against intestinal anaerobes (piperacillin-tazobactam, metronidazole, ceftriaxone, and clindamycin) promote overgrowth of Candida glabrata, whereas agents with minimal activity against anaerobes (cefepime, levofloxacin, and aztreonam) do not.Four C. glabrata strains were used: ATCC 90030, MRL 191, A129, and A239. The fluconazole MICs for the strains were 32, 16, 0.5, and 4 g/ml, respectively. The experimental protocol was approved by the Cleveland Veterans Affairs Medical Center's Animal Care Committee. Female CF1 mice (Harlan Sprague-Dawley, Indianapolis, Ind.) weighing 25 to 30 g were used. To prevent cross-contamination, mice were housed in individual cages with filter tops. An initial experiment (four mice per group) was performed to examine the ability of the four C. glabrata strains to colonize the intestinal tract. Mice were treated daily with subcutaneous normal saline (0.2 ml) or piperacillin-tazobactam (8 mg in 0.2 ml of normal saline) for 2 days before and 6 days after orogastric inoculation of 10 8 CFU of C. glabrata with a stainless steel feeding tube (Popper & Sons, New Hyde Park, N.Y.). Piperacillin-tazobactam was chosen for the initial experiment because we have previously demonstrated that it inhibits anaerobes, facultative gram-negative bacilli, and enterococci in the stool of mice (2). Fresh stool samples were collected at baseline and 1, 3, and 6 days after inoculation of C. glabrata. For quantification of C. glabrata, serially diluted stool samples were plated onto Sabouraud dextrose agar (Becton, Dickinson, and Company, Sparks, Md.) containing piperacillin-tazobactam (16 g/ml) and incubated in room air at 37°C for 48 h. The lower limit of detection was ϳ2 log 10 CFU/g. Strains A239 and ATCC 90030 were chosen to evaluate the effect of different antibiotics on establishment of colonization because ...