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A Bacterial Corneal Ulcer Threatens Vision

Noncompliance may have caused this anomaly.

Optometric Management October 1, 2007
anti-infectives

A Bacterial Corneal Ulcer Threatens Vision

Contact-lens non-compliance may have caused this anomaly.

ERNEST BOWLING, O.D., M.S., F.A.A.O., DIPL., Summerville, Ga.

A 27-year-old woman presented complaining of eye pain, redness, photophobia and discharge of one-week duration O.S. Her last exam was one-month prior, at which time her regular O.D. renewed her prescription for extended-wear weekly replacement contact lenses.

During the case history portion of the exam, the patient admitted to non-compliance with both her wear- and replacement schedule.

Her past ocular history did not reveal any other abnormalities, and her past medical and family histories were both unremarkable.

Exam Findings

The patient's entering visual acuity (VA) was 20/40 O.D., O.S. Refraction and pinhole did not improve her VA.

On exam, her best-corrected-visual acuity (BCVA) was 20/30 O.D. with -7.25D and 20/40 O.S. with -6.50D O.D. correction.

Intraocular pressures (IOPs) via tonometry were 12mm Hg O.D. and 10mm Hg O.S.

Slit-lamp exam revealed 5mm of corneal neovascularization 360° O.D. and a corneal ulcer 3mm in diameter encroaching on the visual axis O.S. (see figure 1.)

The patient's anterior chamber was deep and quiet O.U.

Diagnosis

I diagnosed this patient with a presumed infectious keratitis.

Discussion

For years, the standard of care for infectious keratitis was topical fortified antibiotics.1 Following a large study that revealed second-generation fluoroquinolones were effective in the management of bacterial keratitis, both ciprofloxacin (Ciloxan, Alcon) and oflaxacin (Ocuflox, Allergan) gained FDA indications for bacterial keratitis. Practitioners chose to use these second-generation drugs, as they facilitated treatment (pharmacists had to compound fortified antibiotics, whereas ciprofloxacin and oflaxacin were commercially available).2

The Danger in Systemic Antibiotic Use
Because more and more optometrists are becoming comfortable with prescribing oral antibiotics, we need to remember that it's only a matter of time before systemic fourth-generation fluoroquinolones experience bacterial resistance. One recent study reported bacterial resistance to both topical moxifloxacin and topical gatifloxacin in post-LASIK cases.6 (Patients who are resistant to systemic antibiotics inevitably develop resistance to topical antibiotics.)
You can take two steps to limit resistance to these evolving and adaptable organisms:
  1. Never taper antibiotics. If you need to control an infection with antibiotics, a short-term, high-dosage prescription is preferable. This is because you want to kill all the illness-causing bacteria, leaving no bacterial survivors. Any bacteria that survive a mild dose are likely to be somewhat resistant. Sub-clinical dosing accomplishes nothing, save giving the microbe another chance to mutate and develop resistance. So, use the antibiotics for a very short and defined period of time, then discontinue the medication.
  2. Complete a proper differential diagnosis. If you're unsure of the presentation, don't prescribe an antibiotic. For instance, if you prescribe an antibiotic for a viral infection, such as epidemic keratoconjunctivitis (EKC), you will not kill the viruses, but you will introduce a selective pressure on bacteria in the body, inadvertently selecting the patient for antibiotic-resistant bacteria. The bottom line: Take care when prescribing antibiotics.

Figure 1: The patient's corneal ulcer O.S. at initial presentation.

The third generation fluoroquinolone, levofloxacin (Levaquin, Ortho-McNeil, Inc.), in a 1.5% concentration is also indicated for the treatment of bacterial keratitis.

Today, the topical fourth-generation fluoroquinolones moxifloxacin (Vigamox, Alcon) and gatifloxacin (Zymar, Allergan) are often used in the treatment of bacterial ulcers, off-label. Practitioners decided to switch to the fourth-generation fluroquino-lones because they offer a broader spectrum of action than the second- and third-generation drugs, and second-generation fluoroquinolone resistance is on the rise.

As fourth-generation fluoroquinolones provide a broader spectrum of action than their predecessors, we've long assumed these drugs are superior, despite the fact that researchers have not conducted any studies comparing these generations of drugs in the management of bacterial keratitis. That is, until now.

One recently published study compared the topical fourth-generation fluoroquinolone moxifloxacin with the topical second-generation ciprofloxacin hydrochloride in treating in-vivo Pseudomonas aeruginosa keratitis and compared topical moxifloxacin with vancomycin in the treatment of ciprofloxacin-resistant, methicillin-resistant Staphylococcus aureaus (MRSA) keratitis in rabbits. The results revealed that topical moxifloxacin and ciprofloxacin hydrochloride had similar efficacy in treating the P. aeruginosa keratitis and that the topical moxifloxacin and vancomycin had similar efficacy in treating the ciprofloxacin-resistant MRSA.3

In addition, in one clinical trial that compared the bacteriologic and clinical efficacy of gatifloxacin with ciprofloxacin in the treatment of a gram-positive Staphylococcus corneal ulcer in 104 patients, results showed that gatifloxacin had better action than ciprofloxacin both in vitro and in vivo.4

Both studies reveal the efficacy of two important drugs in eradicating two powerful organisms. In the case of MRSA, for years, researchers had thought it was a nosocomial or a hospital-acquired infection and therefore assumed it was limited to hospitals, nursing homes and extended-care facilities. Recently, however, reports have surfaced of MRSA infections in several endophthalmitis cases that had no nosocomial connection. This indicates that what was once a microbe confined to a limited area has made the jump, apparently successfully, to the general population.5

In addition, since Staphylococcus organisms are currently the leading cause of keratitis worldwide and have a growing antibiotic resistance to fluoroquinolones, it's essential we have an anti-infective in our treatment arsenal that can eradicate these dangerous bugs.4 (See "The Danger in Systemic Antibiotic Use,")

Recently, reports have surfaced of MRSA infections in several end-ophthalmitis cases that had no nosocomial connection.

Management

I gathered cultures from the patient's cornea, conjunctiva, contact lens and contact-lens case in sheep blood agar (SBA), chocolate agar, sabouraud dextrose agar and thioglycolate broth. I also obtained a corneal gram stain.

The outbreak of several contact-lens infections within the last two years highlight the importance of corneal cultures when determining treatment.

I then prescribed moxifloxacin as an empiric treatment to be used every 30 minutes around the clock O.S. for 24 hours, while awaiting cultures and sensitivity. I then instructed the patient to return for follow-up the next day.

The patient complied with the 24-hour follow-up, at which time her epithelial defect had reduced from 3mm to 1mm in diameter. Corneal and conjunctival cultures revealed coagulase negative S. aureaus and Streptococcus Pneumoniae, while the contact lens and contact-lens case culture grew Serratia marcescens. At this visit, I discussed with the patient the importance of compliance with proper lens care and wear.

Both organisms responded to the moxifloxacin. As a result, I had the patient continue this therapy for two more days and asked her to present the day after she finished her final treatment. At the four-day follow-up, the ulcer had totally resolved, and her vision returned to normal. She has since been referred back to her regular practitioner. OM

Corneal and conjunctival cultures revealed coagulase negative S. aureaus and Streptococcus Pneumoniae.
  1. Lin CP, Boehnke M. Effect of fortified antibiotic solutions on corneal epithelial wound healing. Cornea 2000 Mar;19:204-6.
  2. Hyndiuk RA, Eiferman RA, Caldwell DR, et al. Comparison of ciprofloxacin ophthalmic solution 0.3% to fortified tobramycin-cefazolin in treating bacterial corneal ulcers. Ciprofloxacin Bacterial Keratitis Study Group. Ophthalmology. 1996 Nov;103(11):1854-62.
  3. Aliprandis E, Ciralsky J, Lai H, et al. Comparative efficacy of topical moxifloxacin versus ciprofloxacin and vancomycin in the treatment of P. aeruginosa and cipro-floxacin-resistant MRSA Keratitis in Rabbits. Cornea. 2005 Mar; 24(2):201-205.
  4. Parmar P, Salman A, Kalavathy CM, et al. Comparison of topical gatifloxacin 0.3% and ciprofloxacin 0.3% for the treatment of bacterial keratitis. Am J Ophthalmol. 2006 Feb;141(2):282-286.
  5. Solomon R, Donnenfeld ED, Perry HD, et al. Methicillin-resistant Staphylococcus aureus infectious keratitis following refractive surgery. Am J Ophthalmol. 2007 Apr; 143(4): 629-634.
  6. Moshirfar M, Mirzaian G, Feiz V, Kang PC. Fourth-generation fluoroquinolone-resistant bacterial keratitis after refractive surgery. J Cataract Refract Surg. 2006 Mar;32(3):515-8.

Dr. Bowling is an associate professor and director of the primary eyecare service at the University of Alabama at Birmingham School of Optometry. E-mail him at ernie50@uab.edu.

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