The Antibiogram and Outcomes of Antimicrobial Regimens in Microbial Keratitis: A Prospective Cohort Study

Bacterial Keratitis Clinical Trial

Official title:

Evaluation of Antibiogram Results and Clinical Response to Prescribed Antimicrobials in Microbial Keratitis Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05655689
• Other study ID #: ID 0106991
• Status: Completed
• Start date: December 31, 2021
• Est. completion date: January 1, 2023

Study information

• Verified date: November 2022
• Source: Alexandria University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study is an observational prospective cohort study which aims to generate an antibiogram and to assess the clinical responses and outcomes of microbial keratitis patients, treated with empiric topical antimicrobial therapies, with the main objective being to recommend the most effective empiric therapy. Microbial keratitis patients are attending the Cornea Outpatient Clinic at Alexandria Main University Hospital, Alexandria, Egypt.

Description:

The main objective of this observational study is to recommend the most effective empiric topical antimicrobial therapy in microbial keratitis, according to the current local antimicrobial resistance data and the clinical outcomes of patients with bacterial, fungal, and mixed bacterial and fungal keratitis being treated with different empiric topical antibiotics and antifungal therapies. In the study, test results of routinely performed culture and sensitivity on corneal scraping samples and on contact lenses in indicated severe, centrally located, and large ulcers are collected and analyzed. The sensitivity data is utilized to generate an antibiogram to describe the local prevalence of bacteria and fungi causing microbial keratitis and to investigate the prevalence of antimicrobial resistance. Results of the culture and sensitivity are often delayed, hence empiric broad- spectrum antimicrobial therapy is ideally started after corneal scraping, until laboratory test results are obtained. Broad-spectrum empiric therapy will be modified into a more selective culture- guided therapy if the causative agent and its antimicrobial sensitivity are identified. Empiric therapy continues in cases where the culture results are negative together with clinical improvement. Also, when patients have already been on empiric treatment before presenting to the clinic, corneal scraping and culture are not performed. In the study, microbial keratitis patients diagnosed as either bacterial, fungal, or mixed bacterial and fungal keratitis, taking the empiric topical antimicrobials, are observed. The study investigator 's role is to observe and study the clinical responses and treatment outcomes of microbial keratitis patients who are on different empiric antimicrobial therapies as part of the routine medical care. There is no assignment of any intervention to the study participants. The investigator does not intervene, and does not prescribe, recommend, or assign any intervention to the study participants. The clinical response of microbial keratitis patients, who are on different empiric antibiotics and antifungal eye drops, is studied by determining the primary and secondary outcomes. Measured outcomes include corneal ulcer healing, time to epithelialization, improvement in visual acuity, rates of surgical interventions and complications.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 123
• Est. completion date: January 1, 2023
• Est. primary completion date: January 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 90 Years

Eligibility

Inclusion Criteria:

• Patients diagnosed with bacterial keratitis either clinically or by culture.
• Patients diagnosed with fungal keratitis either clinically or by culture.
• Patients diagnosed with mixed bacterial and fungal keratitis either clinically or by culture.

Exclusion Criteria:

• Patients diagnosed with corneal abrasions and non-infectious corneal ulcers.
• Patients diagnosed with acanthamoeba keratitis as a single causative agent.
• Patients diagnosed with viral keratitis as a single causative agent.
• Patients who are noncompliant to treatment.

Related Conditions & MeSH terms

• Bacterial Keratitis
• Fungal Keratitis
• Keratitis

Intervention

Drug:
• Moxifloxacin Ophthalmic 0.5% Ophthalmic Solution
In the observational study, patients treated with topical antibiotic moxifloxacin 0.5% eye drops as part of routine medical care are observed. The investigator does not assign any specific intervention to the study participants.
• Ceftazidime 5% + vancomycin 5%
In the observational study, patients treated with topical fortified antibiotics ceftazidime 5% and vancomycin 5% eye drops as part of routine medical care are observed. The investigator does not assign any specific intervention to the study participants.
• Gentamicin 1.4% + vancomycin 5%
In the observational study, patients treated with the topical fortified antibiotics gentamicin 1.4% and vancomycin 5% eye drops as part of routine medical care are observed. The investigator does not assign any specific intervention to the study participants.
• Natamycin 5% Oph Susp
In the observational study, patients treated with the topical natamycin 5% antifungal eye drops as part of routine medical care are observed. The investigator does not assign any specific intervention to the study participants.
• Voriconazole 1%
In the observational study, patients treated with voriconazole 1% antifungal eye drops as part of routine medical care are observed. The investigator does not assign any specific intervention to the study participants.
• Natamycin 5% + voriconazole 1%
In the observational study, patients treated with the topical natamycin 5% and voriconazole 1% antifungals eye drops as part of routine medical care are observed. The investigator does not assign any specific intervention to the study participants.
• Natamycin 5%+ ceftazidime 5% + vancomycin 5%
In the observational study, patients treated with the topical natamycin 5% and antifungal and the fortified antibiotic ceftazidime 5% and vancomycin 5% eye drops as part of routine medical care are observed. The investigator does not assign any specific intervention to the study participants.
• Voriconazole 1% + ceftazidime 5% + vancomycin 5%
In the observational study, patients treated with the topical voriconazole 1% antifungal and the fortified antibiotics ceftazidime 5% and vancomycin 5% eye drops as part of routine medical care are observed. The investigator does not assign any specific intervention to the study participants.

Locations

Country	Name	City	State
Egypt	Cornea Outpatient Clinic at Alexandria Main University Hospital	Alexandria

Sponsors (1)

Lead Sponsor	Collaborator
Alexandria University

Country where clinical trial is conducted

Egypt, 

References & Publications (1)

Nayel AA, Hamdy NA, Massoud TH, Mohamed NM. A comparison of antimicrobial regimen outcomes and antibiogram development in microbial keratitis: a prospective cohort study in Alexandria, Egypt. Graefes Arch Clin Exp Ophthalmol. 2024 Jan 19. doi: 10.1007/s00417-023-06362-0. Online ahead of print. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Corneal ulcer healing	An ulcer is recognized as healed when there is a lack of epithelial defect, and no infiltrates. This is detected by the routine examination under the cobalt-blue light of the slit lamp biomicroscope. The absence of fluorescein staining when fluorescein is applied to the ulcer indicates an intact epithelium.	4 months from participation
Primary	The time to epithelialization	The time required to re-epithelialization of the corneal ulcer is measured in days.	4 months from participation
Primary	The antibiogram generation	The corneal scraping culture and sensitivity test results are collected to produce the local antibiogram. Antimicrobial susceptibility is determined using the standard agar disc-diffusion method (Kirby-Bauer) by measuring the zone of inhibition. For each isolate, percentage susceptibility to the antimicrobial is calculated by dividing the number of susceptible isolates by the total number of tested isolates.	4 months from participation
Secondary	The best spectacle-corrected visual acuity	The best spectacle-corrected visual acuity (BCVA) is routinely measured using the Snellen chart. The baseline (BCVA) and the post-treatment (BCVA) are recorded as decimal values of Snellen fractions. For patients with very low vision, the semiquantitative scale of counting fingers (CF), hand motion (HM), perception of light (PL) and no perception of light (NPL) is quantified by their conversion into the equivalent decimal values using the Freiburg Visual Acuity Test (FrACT). The improvement in (BCVA) is measured by finding the difference between the post-treatment BCVA and the baseline BCVA.	4 months from participation
Secondary	Surgical interventions	The percentage of surgical interventions is calculated. An example of surgical intervention is therapeutic penetrating keratoplasty (TKP)	4 months from participation
Secondary	Corneal perforations	The percentage of corneal perforations is calculated. Corneal perforations are routinely tested by the Seidel test on slit lamp biomicroscope examination with cobalt blue light.	4 months from participation
Secondary	Corneal melting	The percentage of corneal melting is calculated. Corneal melting is clinically diagnosed by the slit lamp biomicroscope examination.	4 months from participation
Secondary	Corneal opacities	The percentage of corneal opacities is calculated. The presence of corneal opacity is detected by the slit lamp biomicroscope examination.	4 months from participation