In Vitro Time-Kill of Common Ocular Pathogens with Besifloxacin Alone and in Combination with Benzalkonium Chloride.

BACKGROUND

Besifloxacin ophthalmic suspension 0.6% (/%) contains benzalkonium chloride (BAK) as a preservative. We evaluated the in vitro time-kill activity of besifloxacin, alone and in combination with BAK, against common bacteria implicated in ophthalmic infections.

METHODS

The activity of besifloxacin (100 µg/mL), BAK (10, 15, 20, and 100 µg/mL), and combinations of besifloxacin and BAK were evaluated against isolates of ( = 4), ( = 3), ( = 2), and ( = 2) in time-kill experiments of 180 min duration. With the exception of one isolate, all of the staphylococcal isolates were methicillin- and/or ciprofloxacin-resistant; one isolate was ciprofloxacin-resistant. The reductions in the viable colony counts (log CFU/mL) were plotted against time, and the differences among the time-kill curves were evaluated using an analysis of variance. Areas-under-the-killing-curve (AUKCs) were also computed.

RESULTS

Besifloxacin alone demonstrated ≥3-log killing of (<5 min) and (<120 min), and approached 3-log kills of . BAK alone demonstrated concentration-dependent killing of , and , and at 100 µg/mL produced ≥3-log kills in <5 min against these species. The addition of BAK (10, 15, and 20 µg/mL) to besifloxacin increased the rate of killing compared to besifloxacin alone, with earlier 3-log kills of all species except and a variable impact on . The greatest reductions in AUKC were observed among (8-fold) and (≥5-fold). Similar results were found when the isolates were evaluated individually by their resistance phenotype.

CONCLUSIONS

In addition to confirming the activity of 100 µg/mL BAK as a preservative in the bottle, these data suggest that BAK may help besifloxacin to achieve faster time-kills on-eye in the immediate timeframe post-instillation before extensive dilution against bacterial species implicated in ophthalmic infections, including drug-resistant . Greater killing activity may help prevent resistance development and/or help treat resistant organisms.