Antibiotic Concentration After Delivery to Middle Ear for Chronic Suppurative Otitis Media

Measuring Antibiotic Solution Concentration at the Tympanic Membrane Following Self-administration by Patients With Chronic Suppurative Otitis Media

The study team aims to elucidate the potential role of ototopical antibiotic concentration on outcomes in patients diagnosed with chronic suppurative otitis media (CSOM). Chronic suppurative otitis media (CSOM) is characterized by chronic inflammation of the middle ear with persistent discharge from a non-intact tympanic membrane. CSOM is notably associated with a significant burden of disease worldwide. Topical fluoroquinolones are first line therapy for CSOM and are advantageous as compared to oral or intravenous therapy in that these antibiotics avoid systemic side effects and have the potential to locally deliver high antibiotic concentrations, which were thought to be sufficient to overcome all bactericidal resistance to fluoroquinolones.

The investigators will measure antibiotic concentration in aspirates via liquid chromatography with tandem mass spectrometry (LC-MS/MS) from the middle ear of selected subjects with CSOM who are prescribed and instructed to self-administer ototopical ciprofloxacin. Enrolled subjects will be asked to return 3 to 10 days after initial visit to aspirate the middle ear and receive a follow-up evaluation. Furthermore, the subjects will be asked to keep logs of their medication use and to administer the ototopical medication one hour prior to their appointments. The measured ciprofloxacin concentrations will be correlated with clinical outcomes, primarily the time to symptom resolution. The guiding hypothesis is that patient self-administration of ciprofloxacin drops vary in antibiotic delivery with diluted concentrations significantly below the in vitro concentration of the prescribed solution and that these concentrations are below the bactericidal concentration of ciprofloxacin-resistant bacteria.

Study Overview

• Status: Completed
• Conditions: Chronic Suppurative Otitis Media
• Intervention / Treatment: Other: Aspiration of middle ear fluid following standard-of-care delivery of ciprofloxacin and dexamethasone suspension

• Study Type: Observational
• Enrollment (Actual): 3
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03766
      • Dartmouth Hitchcock Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Ten subjects will be accrued locally in the ENT clinic on 4F at tertiary care center Dartmouth-Hitchcock Medical Center in Lebanon, NH, using inclusion/exclusion criteria listed above.

Description

Inclusion Criteria:

• Adult patients greater than or equal to 18 years of age
• Diagnosis of Chronic Suppurative Otitis Media (CSOM)

Exclusion Criteria:

• Atypical presentation of CSOM or atypical anatomy of the ear
• Presence of additional ear pathophysiology beyond CSOM
• Adults unable to consent
• Individuals who are not yet adults (infants, children, teenagers)
• Pregnant women
• Prisoners
• Non-English speaking

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Chronic Suppurative Otitis Media group; Enrolled subjects with persistent otorrhea due to CSOM and prescribed with standard of care (prescription for antibiotic drops from a pharmacy of their choice with specific written instructions for self-administration).

Other: Aspiration of middle ear fluid following standard-of-care delivery of ciprofloxacin and dexamethasone suspension; Micro-aspirate of middle ear fluid will be taken from participants with a Juhn Tym-Tap specimen trap following standard-of-care delivery of ciprofloxacin 0.3% and dexamethasone 0.1% suspension. Samples will be analyzed to measure antibiotic concentration in the middle ear fluid.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of Ciprofloxacin	Antibiotic Delivery to the Middle Ear will be measured by Ciprofloxacin concentration Relevant concentration range is 2000 ng/mL to 2,000,000 ng/mL, which are the minimum inhibitory concentration and theoretical maximum concentration, respectively. Measured through LC-MS/MS, aspirate collected 3-10 days after initial visit.	3 to 10 days after initial visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Compliance to Treatment as measured by Daily Compliance + Symptom Log	The patient is given a medication and symptoms log to track administration of ototopical ciprofloxacin treatment (3 times per day for 10 days).	Starting after the initial visit, for 10 days
Persistence of Symptoms as measured by Daily Compliance + Symptom Log	The patient is given a medication and symptoms log to track status of symptoms, which include ear discomfort, ear discharge, ear fullness, hearing changes, and "other."	Starting after the initial visit, for 10 days. Afterwards, weekly surveys to monitor symptoms for a maximum followup of 12 weeks.

Collaborators and Investigators

• Sponsor: Dartmouth-Hitchcock Medical Center
• Investigators: Principal Investigator: James E Saunders, MD, Dartmouth-Hitchcock Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2022
• Primary Completion (Actual): July 14, 2022
• Study Completion (Actual): July 14, 2022

Study Registration Dates

• First Submitted: October 25, 2021
• First Submitted That Met QC Criteria: November 12, 2021
• First Posted (Actual): November 24, 2021

Study Record Updates

• Last Update Posted (Actual): August 1, 2023
• Last Update Submitted That Met QC Criteria: July 31, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: antibiotic resistance; csom; chronic suppurative otitis media; ototopical ciprofloxacin
• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation; Otorhinolaryngologic Diseases; Ear Diseases; Infections; Otitis; Otitis Media; Suppuration; Otitis Media, Suppurative; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 CYP1A2 Inhibitors; Dexamethasone; Ciprofloxacin
• Other Study ID Numbers: STUDY02001093

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