title: Prophylactic Vancomycin Drops Reduce the Severity of Early Bacterial Keratitis in Keratoprosthesis.
abstract: BACKGROUND
  Artificial cornea transplantation, keratoprosthesis, improves vision for patients at high risk of failure with human cadaveric cornea. However, post-operative infection can cause visual loss and implant extrusion in 3.2-17% of eyes. Long-term vancomycin drops are recommended following keratoprosthesis to prevent bacterial keratitis. Evidence, though, in support of this practice is poor. We investigated whether prophylactic vancomycin drops prevented bacterial keratitis in an animal keratoprosthesis model.
  
  
  METHODS
  Twenty-three rabbits were assigned either to a prophylactic group (n = 13) that received vancomycin 1.4% drops 5 times/day from keratoprosthesis implantation to sacrifice, or a non-prophylactic group (n = 10) that received no drops. All rabbits had Staphylococcus aureus inoculation into the cornea at 7-12 days post-implantation and were sacrificed at predetermined time-points. Prophylactic and non-prophylactic groups were compared with slit-lamp photography (SLP), anterior segment optical coherence tomography (AS-OCT), and histology, immunohistochemistry and bacterial quantification of excised corneas. Corneal vancomycin pharmacokinetics were studied in 8 additional rabbits.
  
  
  RESULTS
  On day 1 post-inoculation, the median SLP score and mean±SEM AS-OCT corneal thickness (CT) were greater in the non-prophylactic than the prophylactic group (11 vs. 1, p = 0.049 and 486.9±61.2 vs. 327.4±37.1 μm, p = 0.029 respectively). On days 2 and 4, SLP scores and CT were not significantly different. Immunohistochemistry showed a greater CD11b+ve/non-CD11b+ve cell ratio in the non-prophylactic group (1.45 vs. 0.71) on day 2. Bacterial counts were not significantly different between the two groups. Corneal vancomycin concentration (2.835±0.383 μg/ml) exceeded minimum inhibitory concentration (MIC) for Staphylococcus aureus only after 16 days of vancomycin drops. Two of 3 rabbits still developed infection despite bacterial inoculation after 16 days of prophylactic drops.
  
  
  CONCLUSIONS
  Prophylactic vancomycin drops provided short-term benefit, but did not prevent infection. Achieving MIC in the cornea was not sufficient to prevent Staphylococcus aureus keratitis. Patients should continue to be counselled regarding the risk of infection following keratoprosthesis.
authors.affiliation: Singapore Eye Research Institute, Singapore; Singapore National Eye Centre, Singapore.
authors.forename: Aris
authors.initials: A
authors.lastname: Konstantopoulos
authors.affiliation: Singapore Eye Research Institute, Singapore.
authors.forename: Xiao Wei
authors.initials: XW
authors.lastname: Tan
authors.affiliation: Singapore Eye Research Institute, Singapore.
authors.forename: Gwendoline Tze Wei
authors.initials: GT
authors.lastname: Goh
authors.affiliation: Singapore Eye Research Institute, Singapore.
authors.forename: Padmanabhan
authors.initials: P
authors.lastname: Saraswathi
authors.affiliation: Singapore Eye Research Institute, Singapore.
authors.forename: Liyan
authors.initials: L
authors.lastname: Chen
authors.affiliation: Singapore Eye Research Institute, Singapore.
authors.forename: Chan Lwin
authors.initials: CL
authors.lastname: Nyein
authors.affiliation: Singapore Eye Research Institute, Singapore.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Singapore Eye Research Institute, Singapore.
authors.forename: Roger
authors.initials: R
authors.lastname: Beuerman
authors.affiliation: Singapore Eye Research Institute, Singapore; Singapore National Eye Centre, Singapore; Department of Clinical Sciences, Duke-NUS Graduate Medical School, Singapore.
authors.forename: Donald Tiang Hwee
authors.initials: DT
authors.lastname: Tan
authors.forename: Jod S
authors.initials: JS
authors.lastname: Mehta
authors.affiliation: Singapore Eye Research Institute, Singapore; Singapore National Eye Centre, Singapore; Department of Clinical Sciences, Duke-NUS Graduate Medical School, Singapore; Nanyang Technological University, Singapore.
authors.forename: Jod
authors.initials: J
authors.lastname: Mehta
mesh_terms: D000818:Animals; D000869:Anterior Eye Segment / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D003315:Cornea / Q000473:pathology; D015818:Eye Infections, Bacterial / Q000188:drug therapy* / Q000382:microbiology / Q000517:prevention & control*; D005137:Eye, Artificial; D007150:Immunohistochemistry; D007634:Keratitis / Q000188:drug therapy* / Q000382:microbiology* / Q000517:prevention & control; D008826:Microbial Sensitivity Tests; D009883:Ophthalmic Solutions / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D011817:Rabbits; D066167:Slit Lamp; D041623:Tomography, Optical Coherence; D014640:Vancomycin / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D009883:Ophthalmic Solutions; D014640:Vancomycin