Benzalkonium chloride enhances antibacterial activity of gatifloxacin and reduces its propensity to select for fluoroquinolone-resistant strains.

Objective: To assess the impact of benzalkonium chloride (BAK) on the minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC) of gatifloxacin against Gram-positive pathogens in comparison to gatifloxacin and moxifloxacin alone, moxifloxacin plus BAK, and/or levofloxacin.

Methods: The MIC was measured following incubation of 10(5) colony-forming units (CFU)/mL of coagulase-negative staphylococci (CNS; n = 20), methicillin-susceptible Staphylococcus aureus (MSSA; n = 20), and methicillin-resistant S. aureus (MRSA; n = 20) with gatifloxacin, levofloxacin, or moxifloxacin. When present, BAK was added from 3.125 microg/mL to 6.25 microg/mL. The MPC was measured following incubation of 10(10) CFU/mL of MRSA (n = 9) and a commercially available MSSA strain with gatifloxacin or moxifloxacin in the absence and presence of BAK at concentrations from 7 microg/mL to 10 microg/mL.

Results: CNS was more susceptible to gatifloxacin (MIC(90) = 2 microg/mL) than levofloxacin (MIC(90) = 8 microg/mL) or moxifloxacin (MIC(90) = 4 microg/mL). MSSA was more susceptible to moxifloxacin (MIC(90) = 1 microg/mL) than gatifloxacin (MIC(90) = 4 microg/mL) or levofloxacin (MIC(90) = 4 microg/mL). MRSA were resistant to gatifloxacin, levofloxacin, and moxifloxacin. In the presence of BAK, however, the MIC(90) of gatifloxacin and moxifloxacin against CNS, MSSA, and MRSA was < or =0.008 microg/mL. Gatifloxacin and moxifloxacin had similar MPCs against MRSA (> or =4 microg/mL). In the presence of BAK, the MPC of gatifloxacin and moxifloxacin against MRSA ranged from < or =0.004 microg/mL to 0.125 microg/mL.

Conclusions: BAK substantially lowered the MIC and MPC of gatifloxacin and moxifloxacin against Gram-positive staphylococci compared to gatifloxacin alone, moxifloxacin alone, and/or levofloxacin. These findings suggest that the presence of BAK in the ophthalmic formulation of gatifloxacin (Zymar) may serve to enhance the potency of gatifloxacin and decrease its propensity to select for fluoroquinolone-resistant S. aureus strains.