Treatment of Inflammatory Bowel Disease Associated E. coli with Ciprofloxacin and E. coli Nissle in the Streptomycin-Treated Mouse Intestine

Background: E. coli belonging to the phylogenetic group B2 are linked to Inflammatory Bowel Disease (IBD). Studies have shown that antimicrobials have some effect in the treatment of IBD, and it has been demonstrated that E. coli Nissle has prophylactic abilities comparable to 5-aminosalicylic acid (5-ASA) therapy in ulcerative colitis. The objective of this study was to test if ciprofloxacin and/or E. coli Nissle could eradicate IBD associated E. coli in the streptomycin-treated mouse intestine. Results: After successful colonization with the IBD associated E. coli strains in mice the introduction of E. coli Nissle did not result in eradication of either IBD associated strains or an E. coli from a healthy control, instead, co-colonization at high levels were obtained. Treatment of mice, precolonized with IBD associated E. coli, with ciprofloxacin for three days alone apparently resulted in effective eradication of tested E. coli. However, treatment of precolonized mice with a combination of ciprofloxacin for 3 days followed by E. coli Nissle surprisingly allowed one IBD associated E. coli to re-colonize the mouse intestine, but at a level 3 logs under E. coli Nissle. A prolonged treatment with ciprofloxacin for 7 days did not change this outcome. Conclusions: In the mouse model E. coli Nissle can not be used alone to eradicate IBD associated E. coli; rather, 3 days of ciprofloxacin are apparently efficient in eradicating these strains, but surprisingly, after ciprofloxacin treatment (3 or 7 days)

Inoculation of <i>E. coli</i> Nissle in mice pre-colonized with IBD associated <i>E. coli</i> or a control strain.

<p>Sets of three mice were used in each experiment. CFU of the inoculation suspension of IBD/control strain are shown at day 0 (∼10⁹ CFU/mouse). Blue arrow indicates the inoculation of <i>E. coli</i> Nissle strain at day 6 (∼10⁹ CFU/mouse). Each graph represents the CFU counts of three mice and bars represent Standard error of the means (SEM). Detection Limit (DL) at 20 CFU/g faeces.</p

Three days treatment with ciprofloxacin in mice pre-colonized with IBD associated <i>E. coli</i> or a control strain.

<p>Sets of three mice were used in each experiment. CFU counts of the inoculated strains from faecal samples of mice. CFU of the inoculation suspension is shown at day 0 (∼10⁹ CFU/mouse). Black arrow indicates the initiation of ciprofloxacin treatment from day 6–9 (0.2 mg/mouse) every 6 h. Detection limit 20 CFU/g faeces (dotted line). Each graph represents the CFU counts of three mice and bars represent SEM. Detection Limit (DL) at 20 CFU/g faeces.</p

Three days treatment with ciprofloxacin and a subsequent treatment with <i>E. coli</i> Nissle daily in mice pre-colonized with IBD associated <i>E. coli</i> or a control strain.

<p>Sets of three mice were used in each experiment. CFU counts of the inoculated strains from faecal samples of mice. CFU of the inoculation suspension is shown at day 0 (∼10⁹ CFU/mouse). Black arrow indicates the initiation of ciprofloxacin treatment from day 6–9 (0.2 mg/mouse) every 6 h. Blue arrow indicates initiation of inoculation with <i>E. coli</i> Nissle strain at high levels (∼10⁹ CFU/mouse) every day throughout the experiment. Each graph represents the CFU counts of three mice and bars represent SEM. Detection Limit (DL) at 20 CFU/g faeces.</p

Treatment with ciprofloxacin for 7 days followed by inoculation with <i>E. coli</i> Nissle.

<p>Sets of three mice were used in each experiment. CFU counts of the inoculated strains from faecal samples of mice. CFU of the inoculation suspension is shown at day 0 (∼10⁹ CFU/mouse). Black arrow indicates the initiation of ciprofloxacin treatment from day 6–13 (0.2 mg/mouse) every 6 h. Blue arrow indicates initiation of inoculation with <i>E. coli</i> Nissle strain at high levels (∼10⁹ CFU/mouse) every day throughout the experiment. IBD associated <i>E. coli</i> strain 2 was apparently eradicated by 7 days of treatment with ciprofloxacin; however, strain 2 once again reappeared under treatment with <i>E. coli</i> Nissle. Each graph represents the CFU counts of three mice and bars represent SEM. Detection Limit (DL) at 20 CFU/g faeces (dotted line).</p