THERAPEUTIC INSIGHTS
The Right Stuff
How to choose the appropriate topical antibiotic therapy for ocular infections.
By John Smay, O.D., Midwest City, Okla.

Today's primary care optometrist has a large arsenal of antibiotics to choose from when confronted with bacterial infections. Making the correct therapeutic choice lies in your understanding of the different classes of antibiotics available, their mechanisms of action, spectrum of coverage and potential side effects.

Once you're armed with this knowledge, you can make the appropriate drug choice to combat the various types of ocular infections that you'll encounter.

Proper protocol

To choose the appropriate antibiotic for each particular patient case, follow these steps:

• Make the correct diagnosis. Know what you're treating before you begin therapy. For instance, treatment for an infectious corneal ulcer differs from that for a sterile infiltrate.
• Decide which bacterial organism is most likely causing the problem. You may decide this through clinical experience or through culturing.
• Consider the severity of the infection and the level of threat to vision.
• Choose the drug most likely to kill the bacteria. Begin treatment with an adequate dosage for an effective length of time.

Clinically, you can use a small number of specific antibiotics to treat most ocular conditions. Therefore, you don't need to know the details of every topical antibiotic drop available, but you should familiarize yourself with the properties of those that you choose to use most often.

Classifications of antibiotics

Antibiotics are often classified into five basic groups according to their mechanisms of action.

1. The first group of drugs inhibits bacterial cell-wall synthesis. It includes such drugs as bacitracin and cephalosporins.
2. The second group disrupts the bacterial cell membrane. Polymyxin B is the most common ocular medication in this class.
3. The third group inhibits bacterial protein synthesis. It includes aminoglycosides (neomycin, gentamicin, tobramycin), tetracyclines, erythromycin and chloramphenicol.
4. The fourth group works by inhibiting folic acid synthesis. Humans get folic acid from their diets, but bacteria must synthesize it. Drugs that work in this fashion include sulfonamides and trimethoprim.
5. The last and newest group of drugs disrupts bacterial DNA synthesis. This class consists of fluoroquinolones.

Antibiotics are also classified according to their spectrums of effectiveness (broad or narrow), and according to which type of bacteria they're primarily effective against (Gram-positive or Gram-negative).

Knowing the classification of a drug is clinically helpful when your primary treatment choice fails or when you want to combine medications. For instance, if a bacterial conjunctivitis doesn't initially respond to tobramycin, it's unlikely that it will respond to another aminoglycoside. You should choose a different class of drug as the second therapy.

When using a combination of antibiotics, the two drugs should complement each other. To illustrate, if you use a drug that's more effective against Gram-negative bacteria and works by inhibiting protein synthesis, you may want to combine it with a drug that inhibits cell-wall synthesis and is most effective against Gram-positive bacteria.

Fluoroquinolones

Fluoroquinolones are the broadest-spectrum, most clinically effective antibiotics commercially available to us.

Four are currently available in ophthalmic solution: ciprofloxacin HCl 0.3% (Ciloxan), ofloxacin 0.3% (Ocuflox), norfloxacin 0.3% (Chibroxin) and the newest drug, levofloxacin 0.5% (Quixin).

All fluoroquinolones disrupt bacterial DNA synthesis by binding the enzyme DNA gyrase. Levofloxacin is the L-isomer of ofloxacin, which may bind with greater affinity to DNA gyrase, and so may have a greater antimicrobial effect.

• Comparing ciprofloxacin and ofloxacin. Clinically, ofloxacin and ciprofloxacin are currently the most commonly used fluoroquinolones. They're the only antibiotics with an indication for the treatment of bacterial corneal ulcers and conjunctivitis at a nonfortified concentration of 0.3% (Quixin is currently indicated for the treatment of bacterial conjunctivitis). Bacterial resistance to these drugs is rare but increasing, and the risk of corneal toxicity is low. In our clinic, we primarily use fluoroquinolones to treat moderate and severe bacterial conjunctivitis and corneal ulcers.
  Keep in mind that fluoro-quinolones aren't generically available so they're a relatively expensive treatment option. For less severe conjunctivitis, and for prophylactic use, other less expensive antibiotics may offer a better choice.
  The effectiveness of ofloxacin and ciprofloxacin is nearly equivalent in the clinic. However, ofloxacin is more soluble and penetrates into the anterior chamber and deep corneal layers more easily than ciprofloxacin. This may be useful if you need prophylaxis in the anterior chamber for post-cataract surgery patients, for example, or if you need good penetration into a deep corneal infection.
  You'll sometimes see cipro-floxacin precipitates form in the cornea after a few days of therapy because of the drug's lower solubility. These precipitates don't seem to hinder the healing process and may provide a reservoir of the drug to the cornea. They'll disappear once you discontinue therapy.
  Clinical studies indicate that ciprofloxacin may have a broader spectrum of coverage than ofloxacin and that the time required to kill most of the bacteria on the corneal surface is also shorter than with ofloxacin. This may make ciprofloxacin your drug of choice for prophylactic treatments such as inserting punctal plugs or eliminating the corneal bacterial flora before cataract surgery.
• Treating ulcers. Bacterial corneal ulcers are probably the most vision-threatening bacterial infection that we'll face on a routine basis. Because they have potential for serious vision loss, we need to aggressively treat them.
  For most peripheral and mid-peripheral ulcers of small to moderate size (2 mm or less), I treat with an initial therapy of ciprofloxacin or ofloxacin every 15 to 30 minutes for the first 6 hours, then every 30 minutes or hourly for the next 24 to 48 hours. The dosage is then tapered over the next 7 to 10 days as the ulcer heals.
  Start treatment with frequent instillation to get therapeutic levels of the drug to the infection site quickly. You won't be sorry that you used too much antibiotic on an ulcer, but you may regret not using enough.
  Adjunctive therapy usually includes a cycloplegic agent such as homatropine 5% q.i.d. This helps control the anterior chamber reaction that'll typically develop, and improves patient comfort. When prescribing a cycloplegic agent, remember that the mydriatic effect you'll see in an infected eye is much less than what you'd expect to see in a "normal" eye, so prescribe an adequate dose.
  You can also prescribe poly-myxin B sulfate and bacitracin zinc (Polysporin) for instillation up to q.i.d. It works well with fluoroquinolones to provide around-the-clock antibacterial activity.
  Remember that any time a person has an infectious corneal ulcer, the eye isn't only infected but also inflamed. Therefore, I'll usually have the patient take an oral nonsteroidal anti-inflammatory drug (NSAID), such as ibuprofen 400 mg, every 4 to 6 hours to help control the inflammatory process and help increase patient comfort.
  When treating an infectious corneal ulcer, pay attention to the patient's subjective complaints. If your therapy plan is effective, she'll usually report that her eye feels much better even though the objective appearance may not seem dramatically different. Often the objective clinical healing appearance will lag behind the subjective improvement in pain.
  Before initiating therapy, culture larger, deeper and more centrally located ulcers. With these more severe cases, alternate a fortified antibiotic like cefazolin 50 mg/ml with a fluoroquinolone or fortified tobramycin.

Our tried-and-true antibiotic

Probably the most commonly used antibiotic in our clinic is the combination drug polymyxin B sulfate and trimethoprim sulfate (Polytrim). Polymyxin B is primarily effective against Gram-negative bacteria, while trimethoprim is considered a broad-spectrum antibiotic effective against Gram-positive and Gram-negative bacteria. The combination of these drugs makes a highly effective broad-spectrum therapy.

We use this combination antibiotic for many purposes. It's our drug of choice for prophylaxis after corneal and conjunctival abrasions or burns and foreign body removal. Plus, it's effective in treating most mild-to- moderate cases of conjunctivitis.

Polytrim's risk of toxicity is low. It's approved for use in children as young as 2 months.

Trimethoprim sulfate has been used orally to treat acute exacerbations of bronchitis caused by Haemophilus influenzae and Streptococcus pneumoniae. Because these two bacteria are common culprits in pediatric conjunctivitis, the combination of polymyxin B sulfate and trimethoprim sulfate is a safe and generally effective drug for treating this condition.

The recommended dosage for mild-to-moderate conjunctivitis is 1 drop every 3 hours, up to 6 times a day.

Also, when treating conjunctivitis, remember to have your patients rinse their eyes with saline to remove as much mucopurulent debris as possible. This will enhance the effectiveness of the drop.

Aminoglycosides

These drugs, which inhibit bacterial protein synthesis, include neomycin, gentamicin and tobramycin. Of these, tobramy-cin probably has the broadest spectrum and least potential for toxicity and allergic reaction.

We often use the antibiotic steroid combination tobramycin 0.3% with dexamethasone 0.1% (TobraDex). It's indicated when your patient has ocular inflammation and he's at risk for bacterial infection.

This is an effective treatment for inflammations secondary to bacterial exotoxins. These include sterile peripheral infiltrates and phylectenular reactions. You should quickly see a dramatic response when you dose this medication q.i.d. for these conditions.

In cases where you need prophylaxis or when a patient has a case of mild-to-moderate adult conjunctivitis, you can use to-bramycin 0.3% alone as a substitute for the combination poly- myxin B sulfate and trimethoprim sulfate. Toxicity is a potential problem, but it's usually rare with short-term therapy.

Ointments

We mainly use ophthalmic antibiotic ointments in our practice for treating blepharitis, adjunctive therapy for corneal ulcers or severe conjunctivitis, and rarely when patching an eye. We use bandage contact lenses and topical NSAIDs in place of eye patches.

The most commonly used ointment in our office is poly-myxin B sulfate and bacitracin zinc (Polysporin).

Bacitracin is effective against Gram-positive bacteria and complements the Gram-negative spectrum of polymyxin B. The combination makes a good broad-spectrum ointment.

Most eyelid infections, such as blepharitis, are caused by Gram-positive organisms such as Staphylococcus aureus and Staphylococcus epidermidis. They typically respond well to polymyxin B sulfate and bacitracin zinc, but remember to include proper lid hygiene.

For the first 2 weeks, I usually have the patient do lid scrubs and warm compresses t.i.d. or b.i.d. followed by an application of polymyxin B sulfate and bacitracin zinc to the lashes and lid margin.

If this brings the condition under control, I'll have him continue indefinitely with lid scrubs to prevent recurrences. For stubborn blepharitis, or cases resistant to polymyxin B sulfate and bacitracin zinc, ciprofloxacin 0.3% ointment is a good second option to try.

Polymyxin B sulfate and bacitracin zinc also make a good adjunctive therapy for corneal ulcers. You can dose this combination as a nighttime therapy to provide around-the-clock antibacterial coverage. Have your patient use this therapy during the day with a fluoroquinolone or fortified antibiotic if his ulcer is severe.

Familiarize and customize

With all the options available, choosing an antibiotic can pose a challenge. You must consider many factors such as efficacy of a drug, potential for allergic reactions, bacterial resistance and cost of the medication.

However, by understanding the mechanism by which a drug works, which type of bacteria a drug is effective against and which drugs work well in combination, you can begin to establish your favorite drugs for treating the conditions you commonly see in practice.

Dr. Smay practices primary care optometry in a four-doctor group practice in Midwest City, Okla. He's a 1996 graduate of Northeastern State College of Optometry in Tahlequah, Okla. He completed an ocular pathology residency at the Western Oklahoma Eye Center.

Dr. Christensen has a partnership practice in Midwest City, Okla. He's a diplomate in the Cornea and Contact Lens Section of the American Academy of Optometry. He's also a member of National Academies of Practice.