Antecedent use of fluoroquinolones is associated with resistance to moxifloxacin in Clostridium difficile

Abstract

Objective. Moxifloxacin is characterized by high activity against Gram-positive cocci and some Gram-positive and -negative anaerobes, including Clostridium difficile. This study investigates the role of prior quinolone use in relation to patterns of susceptibility of C. difficile to moxifloxacin. Methods. Sixty-three clinical isolates of C. difficile were investigated for toxigenicity, susceptibility to moxifloxacin, and mutations in the DNA gyrase gene. The medical histories for 50 of these patients were available and used to identify previous fluoroquinolone use. Results. Thirty-three (52.4%) strains showed resistance to moxifloxacin (MICs ≥ 16 mg/L). All moxifloxacin-resistant strains harbored a mutation at amino acid codon Ser-83 of gyrA. Forty-five isolates (71.4%) were toxigenic; all moxifloxacin-resistant strains were in this group. Resistance to moxifloxacin was associated with prior use of fluoroquinolones (P-value 0.009, chi-square). Conclusions. Although the use of moxifloxacin to treat C. difficile-associated diarrhea is not likely to be common, these data show a relationship between antecedent fluoroquinolone use and resistance to moxifloxacin in C. difficile isolates, and raise questions regarding selection pressure for resistance placed on colonizing bacteria exposed to fluoroquinolones. Mutations in gyrA are involved in moxifloxacin resistance.