Reports of Post-keratoplasty Infections for Eye Bank-prepared and Non-Eye Bank-prepared Corneas: 12 Years of Data From a Single Eye Bank.

PURPOSE: To examine postoperative reports of infection rates for eye bank-prepared and non-eye bank-prepared corneas from January 1, 2006 to December 31, 2017, from a single eye bank. METHOD: A retrospective review of reported fungal and bacterial infections with corneal transplant surgeries using corneas distributed by our eye bank was conducted. The reported number of infections for corneas that underwent eye bank preparation (pre-cut and pre-stripped corneas) and for those distributed without eye bank preparation was quantified. The potential association between infection rates in tissue prepared by the eye bank and those in corneas that had no additional eye bank processing was also examined. RESULTS: Four of 17,035 corneas distributed during the study period were associated with fungal infections (1 eye bank-prepared and 3 non-eye bank-prepared corneas) and were attributed to the tissue after investigation by eye bank medical directors. There was no ascending trend of infections reported with eye bank-prepared corneas in the first 3 years (2 of 1054 corneas, 0.19%) compared with that in the last 3 years of the study period (6 of 3500 corneas, 0.17%; P = 0.901) when the eye bank distributed 3 times more prepared corneas than non-eye bank-prepared corneas. A significant increase in the numbers of reported infections for non-eye bank-prepared corneas was observed between these 3-year intervals (0.1% in the first 3 years to 1.58% in the last 3 years; P = 0.001). CONCLUSIONS: Reports of infections remained low despite increased use of eye bank-prepared tissue. These results suggest that factors other than eye bank tissue preparation should be considered when investigating potential sources of pathogen contamination in donor corneas.

Pre-systemic elimination of tilidine: localization and consequences for the formation of the active metabolite nortilidine.

The therapeutic activity of tilidine, an opioid analgesic, is mainly related to its active metabolite nortilidine. Nortilidine formation mainly occurs during the high intestinal first-pass metabolism of tilidine by N-demethylation. Elimination of the active nortilidine to the inactive bisnortilidine is also mediated by N-demethylation and is supposed to take place in the liver, probably at a smaller rate. The aim of this study was the investigation of the pre-systemic elimination of tilidine using grapefruit juice (GFJ) as an intestinal CYP3A4 inhibitor and efavirenz (EFV) as a CYP3A4 activator. A randomized, open, placebo-controlled, cross-over study was conducted in 12 healthy volunteers using 100 mg tilidine solution p.o., regular strength GFJ 250 mL (3 times at 12-hr intervals) and EFV 400 mg (12 hr before tilidine administration). Tilidine, nortilidine and bisnortilidine in plasma and urine were quantified by a validated LC/MS/MS analysis. GFJ did not change any pharmacokinetic parameter of tilidine and its metabolites, which suggests that intestinal CYP3A4 does not contribute to the first-pass metabolism of tilidine. No effect of EFV on the pharmacokinetics of the active nortilidine was observed except a significant reduction of the terminal elimination half-life by 15%. Overall elimination (renal and metabolic clearances) was unaffected by every treatment. CYP3A4 does not seem to play a major role in tilidine first-pass and overall metabolism. Other unknown metabolites and their enzymes responsible for their formation have to be investigated as they account for the majority of renally excreted metabolites.