title: Effects of low levels of ciprofloxacin on a chemostat model of the human colonic microflora.
abstract: To study the utility of an in vitro model system for assessing the effect of low concentrations of a fluoroquinolone (FQ) drug on the ecology of the human intestinal microflora, chemostats containing human fecal flora were exposed to 0.43, 4.3, and 43microg of ciprofloxacin (CI) per milliliter. Prior to and during drug exposure, we assayed short-chain fatty acids (SCFA), bacterial populations, and the relative levels of susceptibility of these populations to CI and trovafloxacin (TV), a newer related FQ with increased activity against anaerobes. The degree to which CI affected the chemostat ecology was measured statistically by comparing observed data with the corresponding predicted "no effect" level. No changes in total SCFA were observed; only butyrate was significantly higher at the intermediate and high-dose levels. Enterococci counts and the levels of susceptibility to CI among enterococci were also unaffected. Escherichia coli counts decreased in a dose-dependent manner. Susceptibility levels in E. coli followed no interpretable pattern. Bacteroides fragilis group (BfG) counts decreased significantly following exposure to 43 and 4.3microg/mL CI. Ciprofloxacin susceptibility among the BfG in these chemostats was not determined because the BfG counts were too low (less than 30 colonies per plate) when undiluted chemostat samples were plated. However, within 2 days of exposure to 0.43microg/mL CI, the percentage of BfG resistant to 4microg/mL CI increased to over 95%. Before exposure, all BfG were susceptible to both CI (2microg/mL) and TV (0.25microg/mL). All BfG isolated during exposure were resistant to both CI (4microg/mL) and TV (2microg/mL). Resistance selection in the BfG was unexpected as the MIC(90) of CI for B. fragilis is 8microg/mL. Since the average colon flora is about 20% B. fragilis and other bacteroides, CI may impact the human gut flora even at subtherapeutic levels.
authors.affiliation: TechLab, Inc., 1861 Pratt Drive, Blacksburg, Virginia, 24060-6364, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Carman
authors.forename: M A
authors.initials: MA
authors.lastname: Woodburn
mesh_terms: D000890:Anti-Infective Agents / Q000009:adverse effects*; D001421:Bacteria, Anaerobic / Q000187:drug effects / Q000502:physiology; D001441:Bacteroides fragilis / Q000187:drug effects / Q000502:physiology*; D018929:Cell Culture Techniques; D002939:Ciprofloxacin / Q000009:adverse effects*; D003106:Colon / Q000187:drug effects / Q000382:microbiology*; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000187:drug effects / Q000502:physiology*; D005243:Feces / Q000382:microbiology; D011157:Population Dynamics
chemical_list: D000890:Anti-Infective Agents; D002939:Ciprofloxacin