Pharmaceutical failure mechanism of the worldwide ReNu with MoistureLoc-related fusarium keratitis epidemic of 2004-2006

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Abstract

Purpose

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.

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