Topical levofloxacin 1.5% overcomes in vitro resistance in rabbit keratitis models

Abstract

Purpose: To determine whether topical levofloxacin 1.5% will successfully treat both levofloxacin-resistant and susceptible Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA) in rabbit keratitis models.

Methods: For levofloxacin-resistant and susceptible SA, respectively, 32 New Zealand White (NZW) rabbits were intrastromally injected with 1000 colony-forming units (CFU). After 4 hr, the corneas of eight rabbits were homogenized to determine onset CFU/ml. Twenty-four rabbits were divided into three treatments: levofloxacin, vancomycin (cefazolin for levofloxacin-susceptible SA) and saline. Twenty-one drops were administered over 5 hr. One hour post-treatment, the corneas were homogenized for CFU/ml. For levofloxacin-resistant and susceptible PA, respectively, 32 NZW rabbits were intrastromally injected with 1000 CFU. After 16 hr, the corneas of eight rabbits were homogenized for CFU/ml. Twenty-four rabbits were divided into three treatments: levofloxacin, tobramycin (ciprofloxacin for levofloxacin-susceptible PA) and saline. Nineteen drops were administered over 8 hr. One hour post-treatment, the corneas were homogenized for CFU/ml. The CFU/ml data were analysed for sterilization and non-parametrically for reduction.

Results: Levofloxacin 1.5% significantly reduced more (p < 0.05) levofloxacin-resistant SA than vancomycin; was equivalent to cefazolin (p > 0.05) for levofloxacin-susceptible SA; was equivalent to tobramycin for levofloxacin-resistant PA; was equivalent to ciprofloxacin for levofloxacin-susceptible PA; and significantly reduced more SA and PA than saline and onset. Levofloxacin 1.5% sterilized the corneas in the levofloxacin-resistant and susceptible PA groups (32/32) and levofloxacin-susceptible SA group (16/16), but not the levofloxacin-resistant SA group (0/16).

Conclusion: Levofloxacin 1.5% was effective for reducing SA and PA in the rabbit keratitis models regardless of in vitro resistance.

Fig. 1

Bar graph compares the anti-bacterial activity of levofloxacin 1.5% (IQUIX^®) to vancomycin 5% and saline for levofloxacin-resistant, vancomycin-susceptible Staphylococcus aureus.

Fig. 2

Bar graph compares the anti-bacterial activity of levofloxacin 1.5% (IQUIX^®) to cefazolin 5% and saline for levofloxacin-susceptible, cefazolin-susceptible Staphylococcus aureus.

Fig. 3

Bar graph compares the anti-bacterial activity of levofloxacin 1.5% (IQUIX^®) to tobramycin 1.4% and saline for levofloxacin-resistant, tobramycin-susceptible Pseudomonas aeruginosa.

Fig. 4

Bar graph compares the anti-bacterial activity of levofloxacin 1.5% (IQUIX^®) to ciprofloxacin 0.3% and saline for levofloxacin-susceptible, ciprofloxacin-susceptible Pseudomonas aeruginosa.