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

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

doi:10.52794/hujpharm.1728695

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

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

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

Details

Primary Language

English

Subjects

Pharmaceutical Microbiology

Journal Section

Research Article

Authors

Ongun Mehmet Saka
0000-0002-8726-6391
Türkiye

Gülsüm Ece Meraki
0009-0005-1407-622X
Türkiye

Gizem İnan This is me
0009-0008-9327-9018
Türkiye

Müjde Eryılmaz ^*
0000-0003-3760-1996
Türkiye

Publication Date

March 1, 2026

Submission Date

June 27, 2025

Acceptance Date

October 17, 2025

Published in Issue

Year 2026 Volume: 46 Number: 1

DOI

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

IZ

https://izlik.org/JA55WF69MN

Cite

RIS / Bibtex

APA

Saka, O. M., Meraki, G. E., İnan, G., & Eryılmaz, M. (2026). Microbial Contamination in Multi-Dose Ophthalmic Solutions: A Study on Patient-Used Eye Drops. Hacettepe University Journal of the Faculty of Pharmacy, 46(1), 39-47. https://doi.org/10.52794/hujpharm.1728695

AMA

1.Saka OM, Meraki GE, İnan G, Eryılmaz M. Microbial Contamination in Multi-Dose Ophthalmic Solutions: A Study on Patient-Used Eye Drops. HUJPHARM. 2026;46(1):39-47. doi:10.52794/hujpharm.1728695

Chicago

Saka, Ongun Mehmet, Gülsüm Ece Meraki, Gizem İnan, and Müjde Eryılmaz. 2026. “Microbial Contamination in Multi-Dose Ophthalmic Solutions: A Study on Patient-Used Eye Drops”. Hacettepe University Journal of the Faculty of Pharmacy 46 (1): 39-47. https://doi.org/10.52794/hujpharm.1728695.

EndNote

Saka OM, Meraki GE, İnan G, Eryılmaz M (March 1, 2026) Microbial Contamination in Multi-Dose Ophthalmic Solutions: A Study on Patient-Used Eye Drops. Hacettepe University Journal of the Faculty of Pharmacy 46 1 39–47.

IEEE

[1]O. M. Saka, G. E. Meraki, G. İnan, and M. Eryılmaz, “Microbial Contamination in Multi-Dose Ophthalmic Solutions: A Study on Patient-Used Eye Drops”, HUJPHARM, vol. 46, no. 1, pp. 39–47, Mar. 2026, doi: 10.52794/hujpharm.1728695.

ISNAD

Saka, Ongun Mehmet - Meraki, Gülsüm Ece - İnan, Gizem - Eryılmaz, Müjde. “Microbial Contamination in Multi-Dose Ophthalmic Solutions: A Study on Patient-Used Eye Drops”. Hacettepe University Journal of the Faculty of Pharmacy 46/1 (March 1, 2026): 39-47. https://doi.org/10.52794/hujpharm.1728695.

JAMA

1.Saka OM, Meraki GE, İnan G, Eryılmaz M. Microbial Contamination in Multi-Dose Ophthalmic Solutions: A Study on Patient-Used Eye Drops. HUJPHARM. 2026;46:39–47.

MLA

Saka, Ongun Mehmet, et al. “Microbial Contamination in Multi-Dose Ophthalmic Solutions: A Study on Patient-Used Eye Drops”. Hacettepe University Journal of the Faculty of Pharmacy, vol. 46, no. 1, Mar. 2026, pp. 39-47, doi:10.52794/hujpharm.1728695.

Vancouver

1.Ongun Mehmet Saka, Gülsüm Ece Meraki, Gizem İnan, Müjde Eryılmaz. Microbial Contamination in Multi-Dose Ophthalmic Solutions: A Study on Patient-Used Eye Drops. HUJPHARM. 2026 Mar. 1;46(1):39-47. doi:10.52794/hujpharm.1728695