N-chlorotaurine and its analogues N,N-dichloro-2,2-dimethyltaurine and N-monochloro-2,2-dimethyltaurine are safe and effective bactericidal agents in ex vivo corneal infection models

Acta Ophthalmol. 2012 Dec;90(8):e632-7. doi: 10.1111/j.1755-3768.2012.02501.x. Epub 2012 Sep 12.

Abstract

Purpose: N-chlorotaurine (NCT) and its analogues N-monochloro-2,2-dimethyltaurine (NVC-612) and N-dichloro-2,2-dimethyltaurine (NVC-422) are new anti-infectives for topical treatment for conjunctivitis. The aim of this study was to show that these compounds are safe in an EpiOcular model and effective in corneas infected ex vivo.

Methods: Corneal buttons were excised from porcine eyes. In 183 of the 229 corneas, erosion and artificial superficial stromal incision were induced. They were bathed in suspensions of Pseudomonas aeruginosa or Staphylococcus aureus for 24 hr at 37°C and incubated in solutions of the test substances at 37°C and pH 7.1. Subsequently, they were subjected to histology (n = 20) or homogenized followed by quantitative bacterial cultures (n = 209). Ocular irritation was tested using the EpiOcular™ tissue system (MatTek Corporation).

Results: Bacterial accumulations were detected histologically both on the corneal surface and also in the anterior third of the stroma of incised corneal buttons. All three test compounds at a concentration of 55 mm (equals 1% NCT) reduced the bacterial counts of P. aeruginosa and S. aureus by approximately 5 log10 after 60- and 120-min incubation, respectively. Significant killing was observed as early as after 5-min incubation. Also intrastromal bacteria were inactivated. In the EpiOcular™ tissue model, NCT, NVC-422 and NVC-612 had no or very low potential to irritate corneal tissue.

Conclusion: N-chlorotaurine, NVC-422 and NVC-612 are non-irritating in cornea and kill P. aeruginosa and S. aureus, even following penetration into the deeper corneal stromal layers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / toxicity
  • Colony Count, Microbial
  • Cornea / microbiology
  • Cornea / pathology
  • Disease Models, Animal*
  • Eye Infections, Bacterial / drug therapy*
  • Eye Infections, Bacterial / microbiology
  • Eye Infections, Bacterial / pathology
  • Keratitis / drug therapy*
  • Keratitis / microbiology
  • Keratitis / pathology
  • Pseudomonas Infections / drug therapy*
  • Pseudomonas Infections / microbiology
  • Pseudomonas Infections / pathology
  • Pseudomonas aeruginosa / drug effects
  • Pseudomonas aeruginosa / isolation & purification
  • Staphylococcal Infections / drug therapy*
  • Staphylococcal Infections / microbiology
  • Staphylococcal Infections / pathology
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / isolation & purification
  • Swine
  • Taurine / analogs & derivatives
  • Taurine / pharmacology
  • Taurine / toxicity
  • Treatment Outcome

Substances

  • Anti-Bacterial Agents
  • N-monochloro-2,2-dimethyltaurine
  • Taurine
  • N-chlorotaurine
  • NVC-422