The Effect of Antibiotic Eye Drops on the Nasal Microbiome in Healthy Subjects

The Effect of Antibiotic Eye Drops on the Nasal Microbiome in Healthy Subjects, a Phase II Study

Ophthalmic topical antibiotics are commonly prescribed in clinical practice for several indications such as bacterial conjunctivitis, keratitis, blepharitis, dacryocystitis and also as prophylaxis. Aminoglycosides (i.e. gentamicin) and fluoroquinolones (i.e. ciprofloxacin) are among the most frequently used substance classes.

There is evidence that topical non-antibiotic eye drops might have an effect on the nasopharyngeal mucosal flora. This seems logical due to the anatomical connection through the nasolacrimal duct and the fact that up to 80% of topically administered drug diffuse into the systemic circulation through the highly vascularized nasopharyngeal mucosa. However, in the literature no data on the effect of antibiotic eye drops on the nasal or pharyngeal microbiome are currently available.

Recently, new, non-culture based techniques for assessment of the bacterial microbiome have been developed, so-called "next-generation sequencing" (NGS). NGS utilizes universal primers targeting the 16S rRNA gene, which is ubiquitous across most bacteria. With this technique, it is possible to gain information about a wide range of the bacterial microbiome and not only on pre-selected species.

In the present study, NGS will be used to investigate the effect of antibiotic eye drops on the nasal and pharyngeal microbiome. For this purpose, healthy subjects will be randomized to either receive eye drops containing gentamicin, ciprofloxacin or topical lubricants as control. As secondary outcome, prevalence of bacterial resistance genes, as well as signs and symptoms of ocular surface damage will be assessed.

The study will be carried out in 2 parts. Since both formulations of topical antibiotics contain benzalkonium chloride which also has a potential effect on the nasal and pharyngeal mucosal flora, it is unknown how much benzalkonium chloride would contribute to changes in the nasal microbiome after administration of topical antibiotics. To overcome this problem, first a pilot study in 20 subjects will be performed in which subjects will be randomized to receive either eye drops containing gentamicin, ciprofloxacin, preservative-containing topical lubricants or preservative-free topical lubricants. Based on the results of this pilot study, the control for the main part of the study will be chosen, depending on the effect on the bacterial microbiome. The results of the pilot study could also provide useful data to adjust the sample size for the main study part. In the main study, 60 subjects will be randomized to receive gentamicin, ciprofloxacin or lubricant eye drops. The same examinations as described above will be performed after 1 week treatment as well as 1 week and 3 months after treatment.

Study Overview

• Status: Completed
• Conditions: Nasal and Pharyngeal Microbiome
• Intervention / Treatment: Drug: Gentamicin Ophthalmic; Drug: Ciprofloxacin Ophthalmic; Drug: Povidone Ophthalmic; Drug: Povidone and Benzalkonium Chloride Ophthalmic

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Department of Clinical Pharmacology, Medical University of Vienna

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Men and women aged between 18 and 45 years
• Normal ophthalmic findings
• Tear Break Up Time >10 seconds
• Schirmer I Test > 10mm/5min
• Ametropia ≤ 6 diopters
• No use of topical eye or nasal drops in the last 3 months

Exclusion Criteria:

• Regular use of medication, abuse of alcoholic beverages or drugs
• Participation in a clinical trial in the 3 weeks preceding the study
• Treatment in the previous 3 weeks with any drug (except intake of hormonal contraceptives)
• Treatment with topical or systemic antibiotics within 8 weeks before inclusion
• Symptoms of a clinically relevant illness in the 3 weeks before the first study day
• History or presence of gastrointestinal, liver or kidney disease, or other conditions known to interfere with distribution, metabolism or excretion of study drugs
• Known hypersensitivity to any of the components of the IMP under investigation or other study medication
• Pregnant or breast-feeding women
• Women of childbearing potential (neither menopausal, nor hysterectomized, nor sterilized) not using effective contraception (i.e. oral contraceptives, intra-uterine device, contraceptive implant or condoms)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Gentamicin eye drops; 4 drops daily in both eyes for 7 ± 1 days	Drug: Gentamicin Ophthalmic; 4 drops daily in both eyes for 7 ± 1 days
Experimental: Ciprofloxacin eye drops; 4 drops daily in both eyes for 7 ± 1 days	Drug: Ciprofloxacin Ophthalmic; 4 drops daily in both eyes for 7 ± 1 days
Active Comparator: Povidone eye drops unpreserved; 4 drops daily in both eyes for 7 ± 1 days	Drug: Povidone Ophthalmic; 4 drops daily in both eyes for 7 ± 1 days
Active Comparator: Povidone eye drops preserved; 4 drops daily in both eyes for 7 ± 1 days	Drug: Povidone and Benzalkonium Chloride Ophthalmic; 4 drops daily in both eyes for 7 ± 1 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nasal bacterial microbiome	16S rRNA gene sequencing	change after 1 week treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharyngeal bacterial microbiome	16S rRNA gene sequencing	change after 1 week treatment
Antibiotic resistance gene prevalence		change after 1 week treatment
Minimum inhibitory concentrations for gentamicin and ciprofloxacin		change after 1 week treatment
Tear film thickness		change after 1 week treatment

Collaborators and Investigators

• Sponsor: Medical University of Vienna

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2019
• Primary Completion (Actual): August 28, 2023
• Study Completion (Actual): August 28, 2023

Study Registration Dates

• First Submitted: December 29, 2021
• First Submitted That Met QC Criteria: March 10, 2022
• First Posted (Actual): March 18, 2022

Study Record Updates

• Last Update Posted (Actual): May 16, 2025
• Last Update Submitted That Met QC Criteria: May 13, 2025
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Anti-Bacterial Agents; Anti-Infective Agents; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Topoisomerase Inhibitors; Topoisomerase II Inhibitors; Protein Synthesis Inhibitors; Anti-Infective Agents, Local; Cytochrome P-450 CYP1A2 Inhibitors; Plasma Substitutes; Blood Substitutes; Povidone; Ciprofloxacin; Gentamicins; Benzalkonium Compounds
• Other Study ID Numbers: OPHT-240518

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No