Between 2004-2006, a worldwide epidemic of Fusarium keratitis occurred, traced to Bausch & Lomb’s ReNu with MoistureLoc contact lens solution (RML), containing the antimicrobial agent, alexidine dihydrochloride. Our previous studies indicated that heating RML (>42oC and ≤ 56oC) in its plastic (but not a glass) bottle resulted in decreased anti-Fusarium capability. The present study was undertaken to determine the exact mechanism of this antimicrobial failure.Methods
We investigated if: microbiologically and/or analytically (using Raman spectroscopy), an alexidine-neutralizing leachate emanates from heated ReNu bottles; the alexidine concentration (measured by liquid chromatography coupled with tandem mass spectroscopy) changes when stored in heated ReNu bottles; alexidine permeates into ReNu bottle walls and can be detected by Fourier transform infrared spectroscopy; non-alexidine antimicrobials fail in heated ReNu bottles; and/or, alexidine fails in heated non-ReNu bottles.Results
No leachates were identified microbiologically or analytically. The alexidine concentration was 2.8 times greater in room temperature- (vs. 56oC-) stored ReNu bottles. Alexidine deposited into the ReNu bottle wall 3.1 times greater in the heated (vs. room temperature-stored) container. Non-alexidine antimicrobials retain their anti-Fusarium capability after being heated in ReNu bottles and alexidine heated in non-ReNu bottles did not lose its anti-Fusarium activity.Conclusion
Alexidine permeates into the walls of heated ReNu plastic bottles, diminishing its concentration in solution and allowing Fusarium growth. This appears to be the mechanism of the RML-related Fusarium keratitis epidemic.