Several recent outbreaks of Clostridium difficile-associated disease (CDAD) have been attributed to the emergence of an epidemic strain with increased resistance to
fluoroquinolone antibiotics. Some clinical studies have suggested that
fluoroquinolones with enhanced antianaerobic activity (i.e.,
gatifloxacin and
moxifloxacin) may have a greater propensity to induce CDAD than
ciprofloxacin and
levofloxacin do. We examined the effects of subcutaneous
fluoroquinolone treatment on in vitro growth of and toxin production by epidemic and nonepidemic C. difficile isolates in cecal contents of mice and evaluated the potential for these agents to inhibit
fluoroquinolone-susceptible isolates during treatment. When C. difficile isolates were inoculated into cecal contents collected 2 days after the final
antibiotic dose,
gatifloxacin and
moxifloxacin promoted significantly more growth and toxin production than
ciprofloxacin and
levofloxacin did. During treatment,
gatifloxacin and
moxifloxacin inhibited growth of
fluoroquinolone-susceptible but not
fluoroquinolone-resistant isolates.
Ciprofloxacin and
levofloxacin promoted growth of C. difficile when administered at higher doses (i.e., 20 times the human dose in mg/kg of
body weight), and
levofloxacin inhibited growth of
fluoroquinolone-susceptible, but not
fluoroquinolone-resistant, C. difficile isolates when administered in combination with
ceftriaxone. Thus,
fluoroquinolones with enhanced antianaerobic activity (i.e.,
gatifloxacin and
moxifloxacin) promoted C. difficile growth to a greater extent than did
ciprofloxacin and
levofloxacin in this model. However, our findings suggest that
fluoroquinolones may exert selective pressure favoring the emergence of epidemic
fluoroquinolone-resistant C. difficile strains by inhibiting
fluoroquinolone-susceptible but not
fluoroquinolone-resistant isolates during treatment and that agents such as
levofloxacin or
ciprofloxacin can exert such selective pressure when administered in combination with
antibiotics that disrupt the anaerobic microflora.