Benzalkonium Chloride Enhances Antibacterial Activity of Gatifloxacin and Reduces its Propensity to Select for Fluoroquinolone-Resistant Strains

Abstract

Purpose:

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 10⁵ 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 μg/mL to 6.25 μg/mL. The MPC was measured following incubation of 10¹⁰ 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 μg/mL to 10 μg/mL.

Results:

CNS was more susceptible to gatifloxacin (MIC₉₀ = 2 μg/mL) than levofloxacin (MIC₉₀ = 8 μg/mL) or moxifloxacin (MIC₉₀ = 4 μg/mL). MSSA was more susceptible to moxifloxacin (MIC₉₀ = 1 μg/mL) than gatifloxacin (MIC₉₀ = 4 μg/mL) or levofloxacin (MIC₉₀ = 4 μg/mL). MRSA were resistant to gatifloxacin, levofloxacin, and moxifloxacin. In the presence of BAK, however, the MIC₉₀ of gatifloxacin and moxifloxacin against CNS, MSSA, and MRSA was ≤0.008 μg/mL. Gatifloxacin and moxifloxacin had similar MPCs against MRSA (≥4 μg/mL). In the presence of BAK, the MPC of gatifloxacin and moxifloxacin against MRSA ranged from ≤0.004 μg/mL to 0.125 μg/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.