Efflux-Mediated Resistance to Fluoroquinolones in Gram-Positive Bacteria and the Mycobacteria

The fluoroquinolone (FQ) group of antimicrobial agents is increasingly popular in the treatment of a variety of gram-negative infections, against which they are often highly effective. FQs are traditionally less active against gram-positive pathogens, although they are clinically useful against Mycoplasma pneumonia and have been employed in the treatment of drug-resistant mycobacterial infections (5), as well as infections caused by Staphylococcus aureus, Enterococcus faecalis, and penicillin-resistant Streptococcus pneumoniae (reviewed in references 6 and 24). With the development of newer FQs exhibiting enhanced activity against gram-positive bacteria (18, 35, 43, 62) it is likely, too, that this class of compounds will see more frequent use against these organisms. Still, it is clear that FQ use promotes FQ resistance, which is already a problem in methicillin-resistant S. aureus (MRSA), and has, in fact, been reported in all gram-positive pathogens for which FQ use has occurred. As with gram-negative pathogens, FQ resistance in gram-positive organisms usually results from target site mutations (gyrA DNA gyrase and parC or grlA topoisomerase IV) or active export of the agents via efflux pumps (24, 32). This review focuses on efflux mechanisms of FQ resistance, their distribution and clinical significance in gram-positive pathogens, the possible natural function(s) of these, and finally, the therapeutic potential of efflux pump inhibitors.