Effects of broad-spectrum antibiotics on colonization of gastrointestinal tracts of mice by Candida albicans

Abstract

Three-month-old, male, Crl:CD1 (ICR) BR mice were fed chow containing Candida albicans or regular chow. Subsequently, both groups were given either antibiotics or normal saline for 10 days. Stool cultures were performed immediately before administration, at the end of antibiotic administration, and 1 week after the discontinuation of antibiotics, to determine the effect on the concentration of C. albicans in the stools. The stools of mice fed C. albicans and given antibiotics had substantially higher Candida counts than those of control mice fed C. albicans and given saline. Significantly higher candidal concentrations were observed in the stools of mice given chloramphenicol compared with those of mice given ciprofloxacin, sulfamethoxazoletrimethoprim, and ampicillin. No mice developed histopathological evidence of local gastrointestinal invasion or disseminated candidiasis. In this mouse model, Candida colonization increases substantially after the administration of antimicrobial agents with broad spectra and anaerobic activities.Patients with cancer are at risk of developing disseminated candidiasis (3, 11). The gastrointestinal (GI) tract is the source of dissemination in many cases (3, 10). The administration of broad-spectrum antibiotics is associated with an increase in the concentration of Candida organisms in the GI lumen and hence may increase the risk of disseminated candidiasis (3, 14). We have previously described a mouse model of sustained GI colonization by Candida albicans (15). In the present study, we report on the effects of five antimicrobial agents on the level of GI colonization by C. albicans in the this mouse model. These agents were selected because of their frequent use in outpatient therapy, an approach that has gained increased interest recently.Groups of 50 Crl:CD1 (ICR) BR mice, 3 months old and weighing approximately 25 g each (Charles River Laboratories, Wilmington, Mass.), were used with each antibiotic. Thirty of the mice were fed chow containing C. albicans for 2 weeks. Details of the preparation of this chow have been reported previously (15). The remaining 20 were fed regular chow which did not contain C. albicans. GI colonization by C. albicans was verified 1 week after the end of the special diet period by stool cultures, as described previously (14,15). Subsequently, 20 mice of each group colonized with C. albicans received subcutaneous injections of the study antibiotics for 10 days. The antimicrobial agents used in this study were amoxicillinclavulanate, chloramphenicol, ciprofloxacin, sulfamethoxazoletrimethoprim, and ampicillin and were supplied by their commercial manufacturers. The dosage schedules were equivalent to those for humans and were calculated by the method of * Corresponding author. Mailing address:

Development of an Orogastrointestinal Mucosal Model of Candidiasis with Dissemination to Visceral Organs

“…We found the inclusion of a broad-spectrum antibiotic regimen necessary to reduce the potential misinterpretation of deaths as being due to C. albicans, as demonstrated by early experiments, where deaths were not apparently due to C. albicans but rather were due to a secondary bacterial infection. The effects of various immunosuppressive regimens, antibiotics, and other factors on gut colonization and in some instances dissemination and course of disease have been previously reported by other investigators (10,14,19,22,26,30,31,33,34,36,37,47). Although candidal infection of other critical organs not studied, such as brain or heart, could be an alternative explanation to bacterial infection or immunosuppressant toxicity as a cause of death in our studies, progressive infections in other organs are not seen after intravenous challenge with Candida (6,12,23,38) or suggested by gross pathological examinations.…”

Erreger- und Resistenzspektrum einer chirurgischen ITS im systematischen 10-Jahres-Vergleich 1996-2005 im Rahmen des mikrobiologischen Routinemonitorings

“…Da die Mehrzahl der Candidämien auf eine Translokation über die Darmschleimhaut zurückgeführt wird, ist der durch Eliminierung der endogenen gastrointestinalen mikrobiellen Flora das Wachstum von Candida spp. begünstigende, zunehmende Einsatz der Breitspektrumantibotika kritisch zu sehen [14]. Zusätzlich prädispo-nierend für Candidämien auf chirurgischen Intensivstationen ist das Vorherrschen der 2 häufigsten Risikofaktoren: " Malignome zu 13 %, " bauchchirurgische Eingriffe zu 14 % [15].…”

Effects of vancomycin, teicoplanin, linezolid, quinupristin-dalfopristin, and telithromycin on murine gut colonization byCandida albicans

“…Agents with broad spectrum of activity including anaerobes, and/or high intestinal concentrations cause substantial increases in the yeast gut flora. On the other hand, antibiotics with narrower spectrum or with low concentrations in the GI contents are associated with small increases [12]. Glycopeptides are active against Gram-positive aerobic bacteria and to a lesser degree against Grampositive anaerobes.…”