Question 17

Are there any differences among the fluoroquinolones in terms of their ability to select for resistance?

Cross-resistance among the fluoroquinolones means that if an isolate is resistant to ciprofloxacin, there is also an increase in resistance to other fluoroquinolones. However, the extent to which this occurs does depend on the individual fluoroquinolone. In the past it was thought that moxifloxacin might have superior activity against 1^st-step S. pneumoniae mutants due to preferential binding to DNA gyrase. Recent evidence has shown that levofloxacin achieves similar rates and extent of bacterial kill in a range of S. pneumoniae isolates. A recent Italian study investigated the ability of different fluoroquinolones to select for resistance in S. pneumoniae and calculated the frequencies of spontaneous single-step mutations at plasma and ELF peak and trough concentrations (22). Multi-step selection of resistance was also evaluated. Results confirmed that levofloxacin and moxifloxacin had the lowest rates of mutations. In the multi-step analysis ciprofloxacin and prulifloxacin selected for the highest number of resistant strains.

Another group of researchers have investigated the number of mutagenic steps required for S. pneumoniae strains to develop resistance to different fluoroquinolones. They found that more steps were required for levofloxacin and moxifloxacin to select resistant pneumococcal strains compared to ciprofloxacin, gemifloxacin trovafloxacin and clinafloxacin (23). This study also analysed the mutagenic potential of each fluoroquinolone by calculating the number of induced revertants/μg quinolone/plate using E.coli and Salmonella mutation reversion assays. Results confirmed that levofloxacin and moxifloxacin have less mutagenic potency than other fluoroquinolones (Table 6) (23).

Table 6. Mutagenic potency of fluoroquinolones in Escherichia coli and Salmonella

Quinolone	Mutagenic potency (No. of induced mutants/mg/plate)
	Escherichia coli	Salmonella
Levofloxacin	3,401	5,279
Moxifloxacin	3,360	7,071
Ciprofloxacin	5,423	6,279
Clinafloxacin	7,070	16,034
Gemifloxacin	5,689	16,884
Trovafloxacin	6,060	17,742

Adapted from reference (23).