title: Topical levofloxacin 1.5% overcomes in vitro resistance in rabbit keratitis models.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  Levofloxacin 1.5% was effective for reducing SA and PA in the rabbit keratitis models regardless of in vitro resistance.
authors.affiliation: Department of Ophthalmology/Microbiology, The Eye & Ear Institute of Ophthalmology/Microbiology, University of Pittsburgh, Pittsburgh, PA 15213, USA. kowalskirp@upmc.edu
authors.forename: Regis P
authors.initials: RP
authors.lastname: Kowalski
authors.forename: Eric G
authors.initials: EG
authors.lastname: Romanowski
authors.forename: Francis S
authors.initials: FS
authors.lastname: Mah
authors.forename: Robert M Q
authors.initials: RM
authors.lastname: Shanks
authors.forename: Y J
authors.initials: YJ
authors.lastname: Gordon
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D002437:Cefazolin / Q000008:administration & dosage; D002939:Ciprofloxacin / Q000008:administration & dosage; D015169:Colony Count, Microbial; D003319:Corneal Stroma / Q000382:microbiology; D003320:Corneal Ulcer / Q000188:drug therapy* / Q000382:microbiology; D004195:Disease Models, Animal; D024881:Drug Resistance, Bacterial; D015818:Eye Infections, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D064704:Levofloxacin; D015242:Ofloxacin / Q000008:administration & dosage*; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification / Q000502:physiology; D011817:Rabbits; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000302:isolation & purification / Q000502:physiology; D014031:Tobramycin / Q000008:administration & dosage; D014640:Vancomycin / Q000008:administration & dosage
chemical_list: D000900:Anti-Bacterial Agents; D002939:Ciprofloxacin; D064704:Levofloxacin; D014640:Vancomycin; D015242:Ofloxacin; D002437:Cefazolin; D014031:Tobramycin
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