Fortified antibiotic advance improves corneal infection treatment paradigm

Infectious keratitis, also known as corneal ulceration, is a painful,
vision-threatening condition. Most corneal ulcers are associated with contact lens (CL) wear, and they are often due to poor CL hygiene. But corneal ulcers can also be secondary to infected CL solution or infected CLs themselves. Historically, corneal ulcer management has been dictated by a treatment algorithm that considers the size and location of the ulcer and often includes performing a culture test of the infiltrate, then prescribing fluoroquinolones, fortified antibiotics or both. In a recent development, the acquisition and provision of fortified antibiotics has been simplified, resulting in a practice paradigm shift replete with potential vision-saving benefits.

Figure. Slit lamp photograph demonstrating a large, paracentral infiltrate with overlying epithelial defect secondary to contact lens overwear.(Image courtesy of Brian Shafer, MD)

Corneal ulcer management

If the corneal ulcer is peripheral and less than 1 mm, it is typically not vision threatening if managed appropriately. In a case like this, I skip the culture test and go straight to prescribing a fourth-generation fluoroquinolone, such as gatifloxacin or moxifloxacin, every hour for the first day and then tapering based on patient response to treatment. Conversely, when a patient presents with an ulcer greater than 1 mm and/or central in location (Figure), I perform a culture test to determine what pathogen is causing the infection and then recommend a fortified antibiotic for the patient as quickly as possible. Fortified antibiotics are compounded to deliver increased concentrations of medication to the cornea in situations where commercially available antibiotics may be insufficient to manage the infection.

Historically, the steps involved in carrying out the fortified antibiotic treatment plan were inefficient for the physician and burdensome to the patient. After we ordered the fortified antibiotic from a compounding pharmacy, the patient or their caregiver had to travel to the compounding pharmacy—sometimes up to 2 hours away—to retrieve the customised eye drops. This is a major problem because large, centrally located corneal ulcers can be vision threatening and progress rapidly, so timely administration of the medication is critical. In regions where access to fortified antibiotics is limited, we often start patients on commercially available topical treatment and spend hours searching for a pharmacy that may be able to deliver. Given the threat to vision in these cases, this placeholder treatment was insufficient.

Fortified antibiotic development

The recent development that has improved the treatment outlook for our patients who present with vision-threatening corneal ulcers is that we are now able to stock a fortified, high-concentration, compounded antibiotic—Fortisite (ImprimisRx, a Harrow company)—in our clinics for the immediate treatment of patients in need. Fortisite is a compounded combination of tobramycin 1.5% and vancomycin 5%, and it is distributed through an FDA-registered and FDA-inspected 503B outsourcing facility. The formula is tested for both potency and sterility before it is dispensed, and it is stable at refrigerated temperatures (5 °C) for up to 180 days. Because Fortisite is now available for in-office use from an FDA-registered 503B outsourcing facility, each bottle must comply with rigorous analytical testing protocols not required for local compounding pharmacies.

This is a complete game changer for my practice. Patients are often frightened when they are told that they have a large, vision-threatening ulcer. The last thing they want to hear is that they will need to travel to acquire the necessary fortified antibiotics. Now, when I identify a large central corneal ulcer and deliver the diagnosis, I can reduce their worries by getting them started on the appropriate treatment without delay.

There are important benefits associated with this advance. When a fortified antibiotic is called for, the delay in administering appropriate treatment is eliminated and the logistical burden on the patient is removed as well.

These advantages are more significant in some practices than others. For instance, in a large metropolitan area such as Philadelphia, Pennsylvania, where I practice, patients with corneal ulcers are often referred to tertiary medical centers because those facilities can create fortified antibiotics and/or perform the culture test. Stocking a fortified antibiotic in my clinic enables me to treat and retain these patients.

As a result of this development, corneal ulcers can be managed by an ophthalmologist in any outpatient private practice office. For practices that are either not comfortable with the 503B coding process or are unprepared to stock the medication in their clinic, there is an alternative that is still an improvement over having the patient travel to a compounding pharmacy. Eye care providers can order Fortisite directly through the ImprimisRx 503B pharmacy and have it shipped to the patient overnight. Therefore, even physicians who do not want to stock the fortified antibiotic can reduce the logistical burden on their patients and deliver the drug to them in an expedient manner.

No two corneal ulcers are alike, but if they are large and centrally located, the common denominator is that time is of the essence. Fortified antibiotics are used in these cases to stop a process that causes permanent damage and prevent vision loss. The ability of private practice ophthalmologists to immediately administer fortified antibiotic eye drops or have them delivered overnight to the patient is a giant step forward for both the practice and the patient.

Brian Shafer, MD | E: brian.shafer@shafervision.com

Brian Shafer

Dr Shafer is a refractive cataract, cornea and glaucoma surgeon. He is the founder and CEO of Shafer Vision Institute and adjunct assistant professor of ophthalmology at Perelman School of Medicine at the University of Pennsylvania. He is a consultant and speaker for Harrow.