High frequency of single-step resistance mutations in Nocardia farcinica exposed to quinolones

U.S. Jensen, J.D. Knudsen, K. Schønning

Author address: 

Hvidovre, DK


Objectives: Nocardia farcinica infections often require prolonged antibiotic therapy and perorally administered agents are desirable. Isolates commonly display in vitro susceptibility to quinolones when tested by disc diffusion methodology. In the present study, we investigated the activity of three different quinolones (ciprofloxacin, levofloxacin and moxifloxacin) against N. farcinica and assessed the robustness of their activity by determining the frequency of single step resistant mutants when exposed to inhibitory concentrations of quinolones. Methods: 10 isolates of N. farcinica were used in the study; correct identification to the species level was verified by 16S rDNA sequencing. MICs of ciprofloxacin, levofloxacin and moxifloxacin against N. farcinica as well as S. aureus ATCC 25923 and E. coli CCUG 17620 were determined by the agar dilution method using inocula of approximately 10.000 CFU and 48 h of incubation. Single step mutation frequencies were determined by heavily inoculating selective agar plates containing quinolone at a concentration of 4x MIC and counting resistant colonies after 5 days incubation. Inoculum was quantified by seeding a dilution series of the inoculum employed on unselective plates and counting colonies after 48 h of incubation and frequencies were calculated by dividing the number of resistant colonies by the number of CFU present in inoculum. Results: When MICs were determined by agar dilution method all quinolones displayed roughly the same potency against N. farcinica isolates (MICs between 0.25 and 4). As expected moxifloxacin were the most potent quinolone against S. aureus. However, all three quinolones selected for single step resistant mutants, the frequency of which was higher for ciprofloxacin (~108722;6) than for levofloxacin (108722;7-108722;8), which again was higher than for moxifloxacin (108722;8-108722;9). However, even for moxifloxacin the frequency against N. farcinica was comparable to the single step mutation frequency of ciprofloxacin against S. aureus (10-9). Conclusions: Although quinolones may exhibit activity against N. farcinica, N. farcinica is capable of rapid development of resistance. Therefore, quinolones should probably be avoided, at least as single agents, in the treatment of Nocardia infections.

abstract No: 


Full conference title: 

16th European Congress of Clinical Microbiology and Infectious Diseases
    • ECCMID 16th (2006)