Highlighting the Microbial Contamination of the Dropper Tip and Cap of In-Use Eye Drops, the Associated Contributory Factors, and the Risk of Infection: A Past-30-Years Literature Review

Abstract

The sterility of eye drop content is a primary concern from manufacturing until opening, as well as during handling by end users, while microbial contamination of the dropper tip and cap are often disregarded. The contamination of these sites during drug administration represents a risk of microbial transmission and ocular infection. In this review, we aim to assess microbial contamination of the dropper tip and cap of in-use eye drops, the associated contributory factors, and the risk of infection. We conducted a literature search of the MEDLINE, PubMed, and Cochrane Central databases. A total of 31 out of 1503 studies were selected. All the studies conducted in different settings that documented microbiologically contaminated in-use eye drops were included. Our review showed that microbial contamination of the dropper tip and cap of in-use eye drops ranged from 7.7 to 100% of the total contaminated tested samples. Documented contributory factors were conflicting across the literature. Studies investigating the association between eye infection and microbial contamination of the dropper tip and cap were scarce. New technologies offer a promising potential for securing the long-term sterility of eye drop content, tips, and caps, which could benefit from more research and well-defined study protocols under real-life scenarios.

Multidrug-Resistant Pseudomonas aeruginosa Keratitis Associated With Artificial Tear Use

“…Contaminations may also cause severe infections. Contaminated trypan blue has led to endophthalmitis, and contaminated steroid and glaucoma drops and contact lens solutions have been associated with infectious keratitis . Artificial tears have not yet been associated with keratitis, although contamination has been reported …”

Reactions to serum eye drops—New Zealand experience and review of the literature

“…These infections may be due to contamination during manufacturing or, more often, while the patient uses them. 16,17 Infections with SED are possible, but we have not found such a case in NZ or in published literature despite the fact that eyes with OSD may be at particular risk. Stringent processes, including filtration, and bacterial culture before release, are generally used to manufacture SED.…”

Association of Serious Adverse Effects With the Contamination of Ocular Medications—A Global Perspective

“…Numerous studies have reported the rate of contamination of various ocular medications at different settings of drop administration, the effect of preservatives on bottle sterility, and the effect of duration of usage on the rate of contamination. The microbial contamination rate of eye drops varied from 2.3% to 73% . Contamination of the dropper tip of a multidose formulation drop is more common than contamination of the residual content of the bottle.…”

“…Contamination of the dropper tip of a multidose formulation drop is more common than contamination of the residual content of the bottle. Multidose preservative-free formulations have a higher risk of contamination compared with eye drops with preservatives . Educating patients on the appropriate use of eye drops should reduce the risk of bottle tip contamination, especially in multidose preservative-free formulations.…”