anti-infectives

Treating Ocular Infection

Should the new anti-infectives replace your old stand-bys? Before changing your prescribing preferences, check this refresher course.

KIMBERLY K. REED, O.D., F.A.A.O., Ft. Lauderdale, Fla.

A patient came to our clinic on a Monday morning after having visited the emergency department of a local hospital over the weekend with complaints of a red eye. She brought along the three medications prescribed by the emergency department doctor. Two of them were the same antibiotic — one a generic and the other a brand name drug — each to be instilled four times a day. The third drop was a close cousin of the first two, to be instilled twice a day. The patient was understandably confused and also unhappy that she'd had to pay for three medications. To make matters worse, she had a simple viral conjunctivitis and didn't even need an antibiotic.

Clinically significant PEK (SPK) deserves treatment with a prophylactic antibiotic, regardless of the underlying cause.

Many healthcare providers have a knee-jerk reaction to prescribe an antibiotic for virtually any red eye they see, despite knowing that many of these cases are not bacterial in nature.¹ Two common rationales are that the doctor is “covering all the bases” or that he believes “the patient expects something.” Neither reason has merit. More importantly, prescribing unnecessary antibiotics is far from a harmless – or inexpensive – practice. In this article, I discuss I the four categories of ocular infection: bacterial, viral, fungal and parasitic. For all of these conditions, the overarching premise is to identify what's causing the problem, eradicate that problem, and then clean up the consequences, all while protecting the cornea.

Bacterial eye disease

Probably the most common manifestation of bacterial eye infection is what we call “staph bleph,” although Staphylococcus aureus, the bug after which this condition is named, is a less common culprit than are other organisms.² That point is academic, however, because the other leading bacterial causes of the dry, flaky, brittle scales on an often thickened and inflamed lid margin and eyelashes have characteristics similar to those of S aureus and are generally susceptible to the same antibiotics.

When a bacterial infection involves only the eyelashes, removing the antigen may be as simple as having the patient perform lid hygiene morning and night. This will loosen and remove the debris that harbors the bacteria and often is sufficient to alleviate all symptoms. For stubborn cases, applying an antibiotic ointment to the lid margins with a clean fingertip or clean cotton swab twice a day is advisable to prevent more serious infection, such as conjunctivitis or ulceration of the lid margins. Some of the newer ocular antibiotics are formulated as viscous gels, and many practitioners are seeing excellent results with these products.³ Check the drug's Web site or the package insert for the recommended dosage.

Acute bacterial conjunctivitis has been described as “routine,” “uncommon,” “garden-variety” and “over-diagnosed.” These conflicting descriptions may come from the fact that the prevalence of bacterial conjunctivitis depends largely upon the population being studied. For instance, bacterial infections are far more common in urban areas than in rural areas, where viral infections predominate. Children with “pinkeye” are more often infected with bacteria than are adults.

“Staphylococcal” blepharitis with flakes and debris among lashes. Lid hygiene is often sufficient therapy, but an antibiotic ointment or viscous gel applied to the lash margin will help eradicate the bacteria.

What bacteria are responsible? Gram-positive infections — S aureus, Streptococcus pneumoniae and Staphylococcus epidermidis — are found mostly in adults, while gram-negative organisms, such as Haemophilus influenzae, are more common in children. This is important to recognize, so that appropriate anti-infective therapy can be selected.

Choosing the best

How do you choose the best antibiotic for your patient? First, make sure the drug you are considering is approved for the age of your patient. Some drugs are approved for children one-year and older, while others are approved for use in patients six years and older. Second, be sure to prescribe an antibiotic with broad-spectrum coverage. This is especially important if you're not taking cultures to determine the specific bacterium present, which is rarely done in routine cases.

Finally, consider cost and compliance issues. A patient who is likely to forget doses or whose work or school schedule makes frequent instillation of drops inconvenient would benefit from a less-frequent dosing regimen. Consider also that no matter how efficacious the antibiotic you prescribe may be, if the patient doesn't buy it because it is too expensive, the efficacy of that drug is zero.

Many practitioners consider antibiotic treatment for blepharitis and bacterial conjunctivitis optional. In fact, one study found bacterial conjunctivitis resolved in about 3.5 days with treatment and about 5.5 days without treatment.⁴ Remember that patients should be informed of the risks and benefits of non-treatment as well as treatment.

One condition for which treatment is required to maximize visual outcome is bacterial keratitis, which includes bacterial corneal ulcers. Keratitis refers to infection and inflammation of the cornea. This often takes the form of superficial punctate keratitis (SPK) or punctate epithelial keratitis, either in focal areas or diffusely distributed across the cornea. Ulcers are a specific type of keratitis that involve large areas of missing epithelium. Although severe SPK can be treated with an appropriate antibiotic in the dosing schedule recommended for conjunctivitis, the standard of care in treating true corneal ulcers dictates that a fourth-generation fluoroquinolone be prescribed. Usually, a loading dose of frequent drops for the first hour or two is recommended, followed by a schedule of 1 drop every 30 minutes to 2 hours for the first day during waking hours. An antibiotic ointment can be applied at night, or the patient can be instructed to wake up during the night to instill drops two or more times. Ancillary treatment may include cycloplegics and cold compresses. Daily follow-up is required until the cornea heals.

Viral eye disease

In contrast to bacterial infections, most viral infections are self-limited. That way of thinking may change, however, because several agents are being studied for use in all types of viral eye disease, including simple adenoviral conjunctivitis.

The two viral diseases that benefit from specific antiviral therapy are herpes simplex and herpes zoster. When ocular involvement is seen with either of these diseases, it means that the patient has, at some time in the past, been infected with the virus, usually transferred through direct contact of the skin, mouth or other mucus membrane. The characteristic conjunctivitis, keratitis, uveitis and blepharitis with simplex and zoster infections signal a reactivation of virus organisms that have remained dormant in the nerve ganglion for cranial nerve V supplying the eye and adnexa. These infections can be serious — herpes simplex keratitis is the leading cause of corneal blindness in developed countries — and the inflammatory response that goes with them can further compromise the patient's long-term prognosis.

Oral antiviral agents are effective against simplex and zoster viral infections. When prescribing, bear in mind that the differences in cost between the older drugs and the newer ones, as well as between generic and brand names, can be staggering. A recent price check at one national web-based drugstore showed a price difference of just over $300 when comparing an older generic oral anti-viral to a newer brand-name anti-viral. While there may be advantages to newer drugs with respect to a reduced dosing frequency and possibly slightly higher efficacy, the cost of the newer drug may be prohibitive to the patient.

Topical antiviral medications are usually recommended for treatment of active herpes simplex keratitis. Many of the older drops and ointments used for this purpose, for example, tri-fluridine 1% drops, are fairly toxic to the cornea. Newer medications (e.g. cidofovir gel, recently FDA-approved for the treatment of herpetic dendritic ulcers) may be less toxic without sacrificing therapeutic benefit. Again, in general, new medications are usually more costly than older medications that may have gone off patent and are now available in generic form.

If you are tempted to prescribe an antibiotic or an antibiotic-steroid combination for viral eye disease, try to resist the temptation, except under certain circumstances. This advice does not apply, for example, when there is clinically significant corneal epithelial staining with a more severe viral infection, which would put the patient at risk for secondary bacterial infection. We rely on the body's immune system to fight self-limited infections; however, when the immune system is preoccupied with fighting a viral disease, it is less able to ward off other types of infection. In these cases, a prophylactic antibiotic is advisable in the dosage approved for conjunctivitis therapy. Use steroid-antibiotic combination therapy only when significant staining and moderate to severe inflammation exist. Some conditions, such as epidemic keratoconjunctivitis, have peculiarities that make steroid use far more complex than in ordinary circumstances, requiring careful monitoring and a protracted tapering schedule.

Managing fungal and parasitic disease

Despite the widely publicized outbreaks related to contact lens solution contamination in recent years, infections with fungi and parasites are rare. Corneal infections with these types of organisms generally carry a poor prognosis, with a significant number of patients ultimately requiring corneal transplantation due to permanent corneal scarring.

Fungal eye disease is far more common in tropical regions than in colder climates, because the warm, moist conditions facilitate proliferation of the organism without a natural purge due to freezing. Fungal keratitis is frequently misdiagnosed initially as bacterial keratitis because the early clinical characteristics are similar. Only later in the disease process do certain differentiating characteristics appear. Feathery borders (indistinct edges that may appear to “bleed” out of the original central lesion) and satellite lesions (usually smaller secondary areas of corneal epithelial disruption adjacent to the larger ulcer) are strong indicators of fungal involvement. The patient may report a history of trauma 3 to 5 days prior to the appearance of clinical symptoms. Often the trauma involved yard work, horseback riding, outdoor sports or other activities associated with injuries from plant-based objects. In most cases of fungal keratitis, it is advisable to comanage with an infectious disease specialist, because cultures using specialty media are often required to direct treatment. Treatment usually lasts for several weeks and involves topical and oral antifungal agents along with topical antibiotic therapy aimed at eradicating the fungi's food source: bacteria.

Equally challenging to treat are parasitic infections of the cornea and conjunctiva. Acanthamoeba are parasites that can be found in water, air, soil, cooling systems, HVAC systems and elsewhere. Generally, the organism is not a threat to humans under normal circumstances; however, patients who have poor contact lens care habits, those who swim in contaminated pools, spas or natural water reservoirs, or those who are immunocompromised or who have a compromised corneal epithelium are susceptible to infection.

Lower palpebral follicles, characteristic of viral conjunctivitis. In the absence of corneal staining, these patients should not be treated with an antibiotic.

The acanthamoeba parasite exists in two forms: a free-living amoeba, which is fairly susceptible to antimicrobial therapy, and a hardy double-walled cyst, which is quite resistant. Moreover, the organism can remain in the cystic form for months to years, so treatment must continue long-term to ensure eradication.

No specific topical or oral anti-acanthamoeba therapies exist. The primary treatment is a topical antiseptic. Topical anti-fungal and antibiotic agents are often used as adjunctive management to kill the food source for the acanthamoeba organisms.

Stepwise process to resolution

The first step in managing any ocular infection is removing the antigen, which can be as simple as lid scrubs for a discrete bacterial infection or as complex as long-term therapy for a cystic acanthamoeba parasite. Regardless of the infection, our guiding principle throughout the treatment process is to protect the cornea. Also remember that an at-risk cornea — a cornea with significant epithelial compromise in the form of SPK or small erosions — usually requires prophylactic antibiotic therapy even if the underlying cause is not bacterial.

As optometrists, we have an important role not only to select the proper treatments for our patients' various conditions, but also to consider the patient as a person, not just an eye condition. Doing so will not only result in good clinical outcomes, but it is also the single most important factor in cultivating a long-lasting relationship with patients. OM

1. Rose PW, Ziebland S, Harnden A, et al. Why do general practitioners prescribe antibiotics for acute infective conjunctivitis in children? Qualitative interviews with GPs and a questionnaire survey of parents and teachers. Fam Pract 2006 Apr; 23(2): 226-232.
2. Groden LR, Murphy B, Rodnite J, et al. Lid flora in blepharitis. Cornea 1991 Jan; 10(1):50-53.
3. Luchs J. Efficacy of topical azithromycin ophthalmic solution 1% in the treatment of posterior blepharitis. Adv Ther 2008 Sep;25(9):858-870.
4. Everitt HA, Little PS, Smith PW. A randomized controlled trial of management strategies for acute infective conjunctivitis in general practice. BMJ 2006 Aug12;333(7563):321.

Dr. Reed is an associate professor of Optometry at Nova Southeastern University College of Optometry in Ft. Lauderdale, Fla. She teaches courses in ocular disease and ocular pharmacology, and lectures and writes frequently in the areas of anterior segment ocular disease and nutrition.