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

Summary

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.

Conditions

• Nasal and Pharyngeal Microbiome

Interventions

DRUG

Gentamicin Ophthalmic

4 drops daily in both eyes for 7 ± 1 days

DRUG

Ciprofloxacin Ophthalmic

4 drops daily in both eyes for 7 ± 1 days

DRUG

Povidone Ophthalmic

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

Sponsors & Collaborators

• Medical University of Vienna

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

45 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2019-08-12

Primary Completion

2023-08-28

Completion

2023-08-28

Countries

• Austria

Study Locations