title: A comparison of invasive and cytotoxic Pseudomonas aeruginosa strain-induced corneal disease responses to therapeutics.
abstract: OBJECTIVE
  During corneal infection, cytotoxic Pseudomonas aeruginosa strains remain mostly extracellular, while invasive strains can enter corneal cells and replicate within them. We tested the hypothesis that ofloxacin, which easily penetrates host cell membranes, would be more effective than the less cell-permeable antibiotic tobramycin, for treatment of corneal infection by an invasive P. aeruginosa strain.
  
  
  METHODS
  A murine model of P. aeruginosa keratitis was used to compare the response to ofloxacin, tobramycin, prednisolone acetate, and non-preserved saline treatment, as well as combination antibiotic-corticosteroid therapy for infection caused by a cytotoxic strain (6206) and an invasive strain (PAO1). Treatment involved hourly eye drop administration for 12 hours.
  
  
  RESULTS
  As expected, tobramycin was less effective at eradicating viable bacteria from corneas infected with the invasive strain. Despite rapid sterilization of corneas in other antibiotic treated groups, disease progression occurred during the 12 hour treatment period. Both antibiotics hastened disease resolution over the next 7 days for infections caused by either strain. Corticosteroid use during the 12 hour treatment period was of little added benefit.
  
  
  CONCLUSIONS
  Differences between invasive and cytotoxic strain infections in their early response to the different therapeutic regimens did not translate to notable differences after 7 days, but the effects of antibiotics in halting disease progression were delayed for both strain types. These results suggest that successful management might be improved by addressing factors contributing to disease progression during sterilization of the cornea by antibiotics.
authors.affiliation: Morton D. Sarver Laboratory for Contact Lens and Cornea Research, School of Optometry, University of California, Berkeley, CA 94720-2020, USA.
authors.forename: Ellen J
authors.initials: EJ
authors.lastname: Lee
authors.forename: Tan N
authors.initials: TN
authors.lastname: Truong
authors.forename: Myra N
authors.initials: MN
authors.lastname: Mendoza
authors.forename: Suzanne M J
authors.initials: SM
authors.lastname: Fleiszig
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D003315:Cornea / Q000382:microbiology; D003320:Corneal Ulcer / Q000188:drug therapy* / Q000382:microbiology; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D015818:Eye Infections, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D015242:Ofloxacin / Q000627:therapeutic use; D011239:Prednisolone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification / Q000472:pathogenicity*; D014031:Tobramycin / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D005938:Glucocorticoids; C009935:prednisolone acetate; D011239:Prednisolone; D015242:Ofloxacin; D014031:Tobramycin