Microbial Contamination in Multi-Dose Ophthalmic Solutions: A Study on Patient-Used Eye Drops

Year 2026, Volume: 46 Issue: 1, 39 - 47, 01.03.2026

Ongun Mehmet Saka , Gülsüm Ece Meraki , Gizem İnan Müjde Eryılmaz

https://doi.org/10.52794/hujpharm.1728695

https://izlik.org/JA55WF69MN

Abstract

Abstract
This study investigates the microbial contamination of patient-used ophthalmic solutions and assesses potential contamination sources. Fifty-five multi-dose ophthalmic solution samples were collected from patients after treatment. Sterility testing was performed using the direct inoculation method in accordance with the European Pharmacopoeia (Ph. Eur. 11.0). Contaminant microorganisms were identified at the species level using Matrix-Assisted Laser Desorption/Ionization–Time of Flight Mass Spectrometry (MALDI-TOF MS). Among the tested samples, only one sample (1.8%) exhibited microbial contamination. Two distinct bacterial species were identified: Micrococcus luteus and Dermacoccus nishinomiyaensis. The contamination was detected in an expired sample, highlighting the potential risk associated with using ophthalmic solutions beyond their shelf life. Although the contamination rate was low, this study underscores the importance of maintaining strict hygiene practices while using ophthalmic drugs. Educating patients on proper handling, storage, and adherence to expiration dates is crucial to minimizing contamination risks. Further studies with larger sample sizes and preservative-free formulations are recommended to comprehensively assess microbial contamination patterns in ophthalmic solutions. These findings provide valuable insights into contamination risks in ophthalmic solutions, emphasizing the necessity of stringent quality control and patient education to minimize microbial growth.

Keywords: Microbial contamination, Ophthalmic solutions, Sterility testing, Microbiological quality control, Antimicrobial preservatives

Keywords

Microbial contamination , Ophthalmic solutions , Sterility testing , Microbiological quality control , Antimicrobial preservatives

References

• 1. Eryılmaz M. İlaç keşfi ve geliştirilmesi sürecinde mikrobiyolojinin yeri. Alp M: İlaç Keşfi ve Geliştirilmesi, Akademisyen Kitabevi A.Ş., Ankara; 2021. 19-34 p.
• 2. Denyer SP, Hodges NA, Gorman SP, Gilmore BF. Hugo and Russell’s Pharmaceutical Microbiology, 8th edn. Wiley-Blackwell; 2011.
• 3. Sandle T. Pharmaceutical microbiology: Essentials for quality assurance and quality control, Woodhead Publishing, Cambridge, UK; 2016.
• 4. Jimenez, L. Microbial contamination control in the pharmaceutical industry. CRC Press; 2004.
• 5. Sutton S. Pharmaceutical quality control microbiology: A guidebook to the basics, PDA; 2007.
• 6. Wechsler ME, Carroll NJ, Klibanov AM, Mitragotri S. New strategies for ophthalmic drug delivery: Beyond eye drops. Nat Rev Drug Discov. 2019;18(8):618–639. https://doi.org/10.1038/s41573-019-0025-z
• 7. European Pharmacopoeia (Ph. Eur. 11.0). Sterility testing and microbial limit tests for pharmaceuticals. European Directorate for the Quality of Medicines (EDQM); 2022.
• 8. United States Pharmacopeia (USP-NF 2024). Microbiological examination of nonsterile products: Tests for specified microorganisms. United States Pharmacopeial Convention; 2024.
• 9. Kyei S, France D, Asiedu K. Microbial contamination of multiple-use bottles of fluorescein ophthalmic solution. Clin Exp Optom. 2019;102(1):30-34. https://doi.org/10.1111/cxo.12821
• 10. Chantra S, Hathaisaard P, Grzybowski A, Ruamviboonsuk P. Microbial contamination of multiple-dose preservative-free hospital ophthalmic preparations in a tertiary care hospital. Adv Ophthalmol Pract Res. 2022;2(1):100046. https://doi.org/10.1016/j.aopr.2022.100046
• 11. Iskandar K, Marchin L, Kodjikian L, Rocher M, Roques, C. 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. Pharmaceutics. 2022;14(10):2176. https://doi.org/10.3390/pharmaceutics14102176
• 12. Roquefeuil L, Iskandar K, Roques C, Marchin L, Guittard M, Poupet H, et al. Evaluating and managing the microbial contamination of eye drops: a two-phase hospital-based study. Pharmaceutics. 2024;16(7):933. https://doi.org/10.3390/pharmaceutics16070933
• 13. Kumar NM, Mah FS. Bacterial, Chlamydial, and mycobacterial infections. Albert, D., Miller, J., Azar, D., Young, L.H: Albert and Jakobiec’s Principles and Practice of Ophthalmology. Springer, Cham; 2021.
• 14. Feghhi M, Mahmoudabadi AZ, Mehdinejad M. Evaluation of fungal and bacterial contaminations of patient-used ocular drops. Med Mycol. 2008;46(1):17-21. https://doi.org/10.1080/13693780701487979
• 15. Seng P, Drancourt M, Gouriet F, La Scola B, Fournier PE, Rolain JM, et al. Ongoing revolution in bacteriology: routine identification of bacteria by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Clin Infect Dis. 2009;49(4):543-551. https://doi.org/10.1086/600885
• 16. Mugoyela V, Mwambete KD. Microbial contamination of nonsterile pharmaceuticals in public hospital settings Ther and Clin Risk Manag. 2010;6:443-448. https://doi.org/10.2147/TCRM.S12253
• 17. Joron C, Romeo B, Le Flèche-Matéos A, Rames C, El Samad Y, Hamdad F. Dermacoccus nishinomiyaensis as a cause of persistent paediatric catheter-related bacteraemia. Clin Microbiol Infect. 2019;25(8):1054-1055. https://doi.org/10.1016/j.cmi.2019.02.023
• 18. Shi X, Qiu S, Ji L, Lu H, Wu S, Chen Q, et al. Pathogenetic characterization of a Micrococcus luteus strain isolated from an infant. Front Pediatr. 2023;11:1303040. https://doi.org/10.3389/fped.2023.1303040
• 19. Triguy J, Tolin AL, Peña S, Ballester C, Gallardo A, Aguilar Fixman MJ. Dermacoccus nishinomiyaensis brain abscesses as the first manifestation of chronic granulomatous disease. Arch Argent Pediatr. 2023;121(4): e202202804. https://doi.org/10.5546/aap.2022-02804.eng
• 20. Goldstein MH, Silva FQ, Blender N, Tran T, Vantipalli S. Ocular benzalkonium chloride exposure: problems and solutions. Eye (Lond). 2022;36(2):361-368. https://doi.org/10.1038/s41433-021-01668-x
• 21. Nagstrup AH. The use of benzalkonium chloride in topical glaucoma treatment: An investigation of the efficacy and safety of benzalkonium chloride-preserved intraocular pressure-lowering eye drops and their effect on conjunctival goblet cells. Acta Ophthalmol. 2023;101(278):3-21. https://doi.org/10.1111/aos.15808
• 22. Hashim ZA, Celiksoy V. Pharmaceutical products microbial contamination; approaches of detection and avoidance. MID. 2024;6(1):159-170. https://doi.org/10.21608/mid.2024.266636.1785
• 23. Alsaleem AT, Obaid H AF, Alruwaili ROA, Alruwaili MMA, Alenezi RFM, Al Anazi FMJ, et al. Investigation of the microbial contamination of pharmaceutical products. LHEP. 2024;309-324.
• 24. Rahman MQ, Tejwani D, Wilson JA, Butcher I, Ramaesh K. Microbial contamination of preservative free eye drops in multiple application containers. Br J Ophthalmol. 2006;90:139–141. https://doi.org/10.1136/bjo.2005.078386