Ciprofloxacin at low levels disrupts colonization resistance of human fecal microflora growing in chemostats

We studied the in vitro effects of a range of ciprofloxacin (CI) concentrations on the human intestinal flora's colonization resistance (CR) to Salmonella kedougou NCTC 12173. Four steady state microbial communities were established in chemostats using inocula from a single pool of human feces. Three chemostats were exposed to CI (0.1, 0.43 and 5 mug/mL, respectively); one served as a no-drug control. The CR of each community was tested by three successive daily challenges of 108 S. kedougou, each delivered in a 1 mL bolus. There was no colonization of the no-drug chemostat. Likewise, after exposure to only 0.1 mug/mL CI there was no loss of CR and S. kedougou did not colonize. Conversely, both the 0.43 and the 5 mug/mL-exposed floras suffered a loss of CR and these chemostats were colonized. S. kedougou overgrew faster and reached higher counts in the presence of 0.43 than it did in the presence of 5 mug/mL. One possible explanation is that CI had a dose-dependent effect on both the challenge strain and CR. Thus, at higher levels, even though CR was disrupted by CI, so too was the growth of the challenge strain. Since exposure to CI elicited a dose-dependent reduction in Escherichia coli counts [Reg. Pharmacol. Toxicol. 33 (2001) 276] our new data suggest that E. coli may contribute to the CR against salmonella. We further conclude that, even at fecal levels below those reached during therapy, CI may impact the human gut flora sufficiently to facilitate colonization by S. kedougou. (C) 2004 Elsevier Inc. All rights reserved.