Question 25

What is the role of efflux in fluoroquinolone resistance?

The prevalence of fluoroquinolone-resistant S. pneumoniae is slowly rising as a consequence of the increased use of fluoroquinolone antibiotics to treat CAP. The hypothesis that increased expression of efflux pumps by S. pneumoniae may facilitate the emergence of fluoroquinolone resistance was tested by Louie et al. (79). A wild-type S. pneumoniae strain and a strain with overexpression of an efflux pump were treated for 10 days with ciprofloxacin or levofloxacin in the presence or absence of reserpine, an efflux pump inhibitor. Dosing schedules mimicked ciprofloxacin 750 mg twice daily and levofloxacin 500 or 750 mg once daily. Levofloxacin at 750 mg once daily, with and without reserpine, effectively eradicated both pathogens without selecting for fluoroquinolone resistance. This study demonstrated that ciprofloxacin is a better inducer of efflux pump expression than levofloxacin in both isolates. This is likely to result in ciprofloxacin resistance increasing at a higher rate than for levofloxacin.