The Risk of Microbial Contamination in Multiple-Dose Preservative-Free Ophthalmic Preparations

Abstract

Multiple-dose ophthalmic preparations that do not contain preservatives carry high risks of microbial contamination. However, there are various types of hospital preparations, with different physicochemical properties. In the present study, we evaluated the association between physicochemical properties and microbial contamination in ophthalmic preparations. The investigated hospital preparations included ophthalmic preparations of physiological saline, 0.2% fluconazole, 0.5% vancomycin hydrochloride, and 2% cyclosporine. We investigated the microbial dynamics of each ophthalmic preparation and microbial contamination in ophthalmic preparations used by patients. Remarkable growth of Pseudomonas aeruginosa, Burkholderia cepacia, and Serratia marcescens was observed in ophthalmic preparations of physiological saline and 0.2% fluconazole. All tested microorganisms displayed decreased counts after inoculation in 0.5% vancomycin hydrochloride. In 2% cyclosporine, all investigated microorganisms were below the limit of detection after inoculation for 6 h. The microbial contamination rates of ophthalmic preparations used by patients were 16.7% (3/18 samples) for 0.5% vancomycin hydrochloride and 0% (0/30 samples) for 2% cyclosporine. All detected contaminants in 0.5% vancomycin hydrochloride were Candida spp., one of which was present at a level of 1 10 4 colony-forming units/mL. The storage method for in-use ophthalmic preparations should be considered on the basis of their physicochemical properties.

Ocular benzalkonium chloride exposure: problems and solutions

“…Their small size can make gripping and squeezing difficult, especially in patients with tremor or arthritis of the hands. Some of these obstacles can be overcome with multidose preservative-free formulations, but these are at risk of microbial contamination [ 103 ]. Systems to prevent microbial influx into multidose preservative-free formulations—such as the proprietary ABAK and COMOD systems—have been developed and are available for a limited number of drugs [ 3 ].…”

Approaches to the Search of the Optimum Packaging of Eye Drops

“…However, a large volume of eye drops packages (more than 5 ml) for multiple uses of medicines does not always allow maintaining the sterility of the solution for a long time if there are no preservatives in the composition itself [23].…”

Microbial contamination of multiple-dose preservative-free hospital ophthalmic preparations in a tertiary care hospital

“…In two reports of contamination of preservative-free hospital-prepared eye drops, 8.4% 4 and 16.7% 1 were found to be contaminated, and the bottles used by patients at home were more tainted than those used by medical staff in inpatient settings. 4 , 5 Another study showed there was no difference between contamination rates in eye drops administered by staff in outpatient departments and those instilled in wards using shared medications in multi-user settings; however, inter-patient transmission of microorganisms could have influenced the results.…”

“…It is well known that without preservatives, ophthalmic solutions may become contaminated. 1 It is possible that microbial contamination may alter the pH of preparations and reduce the eye drops' efficacy. 2 , 3 Therefore, maintaining sterility during eye drop use is a crucial measure.…”