| Summary: | Background: Besifloxacin ophthalmic suspension 0.6% (<i>w</i>/<i>v</i>%) 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 <i>Staphylococcus epidermidis</i> (<i>n</i> = 4), <i>Staphylococcus aureus</i> (<i>n</i> = 3), <i>Haemophilus influenzae</i> (<i>n</i> = 2), and <i>Pseudomonas aeruginosa</i> (<i>n</i> = 2) in time-kill experiments of 180 min duration. With the exception of one <i>S. aureus</i> isolate, all of the staphylococcal isolates were methicillin- and/or ciprofloxacin-resistant; one <i>P. aeruginosa</i> isolate was ciprofloxacin-resistant. The reductions in the viable colony counts (log<sub>10</sub> 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 <i>P. aeruginosa</i> (<5 min) and <i>H. influenzae</i> (<120 min), and approached 3-log kills of <i>S. aureus</i>. BAK alone demonstrated concentration-dependent killing of <i>S. epidermidis</i>, <i>S. aureus</i> and <i>H. influenzae</i>, 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 <i>P. aeruginosa</i> and a variable impact on <i>S. aureus</i>. The greatest reductions in AUKC were observed among <i>H. influenzae</i> (8-fold) and <i>S. epidermidis</i> (≥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 <i>S. epidermidis</i>. Greater killing activity may help prevent resistance development and/or help treat resistant organisms.
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