While I have never had a patient have corneal infection or any other infection after LASIK, cataract surgery, or any other surgery to date (thanks be to God!), I see many corneal ulcers from patients who use contact lenses or are referred to me from other eyeMDs or optometrist. Eye infections are very scary as we have all seen such infections destroy an eyeball completely. It is important to treat these aggressively and as fast as possible.
We do get many referrals from other optometrists and eyeMDs who started treating with standard topical fourth-generation fluoroquinolones like below, only to have the infection not improve or get worse. The patient then comes to us with a greater risk of permanent vision loss.
List of topical fourth-generation fluoroquinolones:
1. Besifloxacin 0.6%: (Bescivance): this is the best of the bunch in my opinion.
2. Moxifloxacin 0.5% (Vigamox),
3. gatifloxacin 0.3% (Zymar)
4. levofloxacin: 1.5% (Iquix,)
How to Culture the Cornea:
1. Stop all steroids
2. Stop all contact use
3. Take cultures: Corneal scraping should be prepared on the appropriate culture media: Saboraud agar (A) for fungal culture; chocolate agar (B) for aerobes; blood agar (C) and thioglycolate broth (D) for aerobes and anaerobes; viral transport media (E) for viral and Chylamydia culture and sterile saline (F) to transport specimens that require plating in the lab with otherwise unavailable media. Glass slides (G) should be used to create smears for microbial stains: GRAM and GIEMSA stains. (see Reference 1)
4. Start fortified antibiotics: topical fourth-generation fluoroquinolone is a common first-line therapy because it is readily available and covers most commonly encountered bacteria, but I prefer to treat with fortified antibiotics as it kills the organism usually better and faster: there is less doubt it will get better (aside from rare fungal or Acanthamoeba infections).
Start Combination therapy of Fortified Antibiotics
a. Aminoglycoside antibiotics used in fortified drops are Tobramycin or Gentamicin 1.4%
b. Cephalosporin: Cefazolin 5%
The frequency of drops depends upon the severity, but it is usual to start half-hourly drops all through 24 h (that means little sleeping) for most patients. A loading dose of a drop every 5 min for the first 30 min is used in severe ulcers. The frequency is reduced based on the clinical response.
List of fortified antibiotics for corneal infection:
- Aminoglycoside antibiotics used in fortified drops are Tobramycin or Gentamicin: I prefer Tobramycin as it is less toxic and irriating to the cornea/eye. They give an excellent Gram- negative coverage and are also active against staphylococci and some streptococci but not against pneumococci. They are however epitheliotoxic. Fortification is done by adding 80 mg/2 ml of antibiotic injection to 5 ml of commercially available antibiotic eye drops (0.3%) to get a concentration of 1.35%.
- Cephalosporin: The most commonly used cephalosporin in fortified drops is cefazolin. It gives good coverage for non-penicillinase producing Gram- positive bacteria. It is prepared by adding 5 ml of water for injection, to Injection Cefazolin 250 mg. The drops are refrigerated and should be discarded if they discolor to yellow or after a week, whichever is earlier.
- Vancomycin (50 mg/ml): It is useful for Gram-positive infections including methicillin-resistant staphylococci (MRSA). Empirical use is not recommended since it will escalate drug resistance.
- Amikacin (40-100 mg/ml): It is useful for infections due to Gram-negative organisms resistant to tobramycin and gentamicin. It is also used in infections due to atypical mycobacteria and Nocardia
- Methicillin (50 mg/ml): It is useful for penicillinase producing Staphylococci.
- Cotrimoxazole (Trimethoprim 16 mg/ml + sulfamethoxazole 80 mg/ml): It is recommended for Nocardia infections. The intravenous preparation is used directly as eye drops.
- Anti-pseudomonas antibiotics: Piperacillin (7 mg/ml), ceftazidime (50 mg/ml), cefoperazone and imipenem may be used in multidrug-resistant infections.
- Clarithromycin (10-40 mg/ml): Useful in atypical mycobacterial infections.
1. I start the following:
Tobramycin and Cefazolin q 5 min alternating x 5 then every 30 min alternating around the clock. Once improved, every 1hr alternating around the clock. When vision is improving, can allow patient to sleep more by using Bacitracin ointment from 11pm to 3am or so and using drops every 30min-1hr depending on how severe infection was & how quickly patient is improving. It is important not to taper (decrease frequency) too quickly but to also be aware of the toxicity these fortified drops (especially Gentamicin if using) can be to the cornea directly aside from the infection present.
2. If it is a very bad infection or the patient is immunocompromised, I start Vancomycin instead of the Cefazolin.
5. If patient does not improve in 48-72 hrs or gets worse:
a. we will sometimes reculture the cornea/wound
b. get PCR
c. do confocal microscopy looking for Acanthamoeba: it used to be impossible to get a Confocal unless you were at Harvard. We are getting a confocal microscope in a few weeks to help us with our dry eye patients and for this reason as well.
d. keep praying it gets better.
BUT NOW THERE IS A NEW WAY WHICH WILL EVENTUALLY REPLACE THE STANDARD WAY: see below.
6. Once ulcer is healed, we start steroid drops to try to decrease scar tissue as best possible.
7. If scar tissue inhibits vision significantly and does not go away, we recommend a corneal transplant.
Sandra Lora Cremers, MD, FACS
NEW WAY WHICH WILL EVENTUALLY REPLACE THE STANDARD WAY
It is not available yet for most eyeMDs. Being close to the NIH, we hope to be able to use this very so on if needed.
New RNA amplification techniques called Meta genomic deep sequencing allows the surgeon to look for the bacteria–the living organisms’ RNA and not the dead organisms’ DNA and amplify the culprit’s genome. A computer then subtract out the patient’s normal genomic RNA sequence and any DNA data (which is of old dead tissue) and matches the bad bug/bacteria to the organism causing the infection. This is a much faster technique than PCR.
When suspect Fungal:
The combined systemic and topical administration of voriconazole has successfully been used to treat keratomycosis. Because no voriconazole eye drop product is commercially available, we prepared a sterile eye drop solution (10 mg/ml). Voriconazole remains stable over 30 days, providing an eye drop solution suitable for use for the topical treatment of fungal keratitis.
Voriconazole, a more recent azole antifungal, is available commercially for systemic administration in the form of oral and IV formulations. It has an excellent broad spectrum of antifungal activity and is active against species that are known to be resistant to the other antifungal agents commonly used in fungal keratitis.28 Voriconazole is increasingly being used, orally in particular, against fungal keratitis. Oral voriconazole is highly bioavailable (96%) and has demonstrated good penetration into the different parts of the eye,66,67 with sufficient concentrations achieved to cover a wide range of keratitis-causative fungi.28However, oral voriconazole can be associated with side effects as well as significant drug interactions.68Topical voriconazole eye drops, manufactured extemporaneously and used in an off-label manner, have also been prescribed for the treatment of keratitis, with promising results.69 With topical administration, voriconazole demonstrated good penetration through the cornea into the aqueous humour,69 without compromising intraocular safety.70