Article Date: 8/1/2012

CooperVision Launches Multifocal Daily Disposable
infection

The Drugs for the Bugs

All the currently available antibiotics for ocular infection are relevant.

Kimberly K. Reed, O.D., F.A.A.O.,
Fort Lauderdale, Fla.

During the past several decades, we have seen a tremendous increase in the understanding of the pathogenesis of infectious and inflammatory disease, and the pharmacological industry has responded by developing newer and more advanced medications. But is newer always better? It depends on the patient.

As an example, I recently examined a 56-year-old female patient who had been in our clinic twice previously with fairly severe mixed blepharitis. Specifically, she had thickened lid margins, meibomian gland dysfunction, flakes and debris on her upper and lower lashes, and ocular surface inflammation, including punctate staining of the inferior cornea OU. At her previous visits, I prescribed an antibiotic-steroid combination drop to eradicate her signs and symptoms.
At this visit, she confessed she couldn't afford to fill the prescription. So, I offered the patient another option: a combination antibiotic-steroid drop available generically for a very low cost. She filled the prescription and was able to get her condition under control.

In this patient's case, and with many others, having a second, third or even fourth treatment option on hand is necessary, so you can meet your patients' individual needs. For this reason, it's essential we're aware of all the currently available antibiotics, regardless of their age. And, bear in mind that while the problem of drug resistance has many different facets, overuse of antibiotics is certainly one of the primary causes. When the “latest, greatest” big guns are used to treat even low-grade infections, the risk of increasing resistance to these agents is higher. Sometimes, using the older, tried-and-true drugs ends up being more clinically effective and economical.

Here's a review of the currently available antibiotics for ocular infection, their most common uses and dosing recommendations. Remember that while side effects are possible with any topical medication, they are far more common with the oral versions of these drugs. That said, as with any therapy, be sure to let patients know about possible side effects as well as what to do if they occur.

The aminoglycosides

Tobramycin, gentamicin and neomycin make up this group of antibiotics. Tobramycin and gentamicin are available in drop and ointment forms and are widely available generically. They are effective against many gram-negative organisms that can cause conjunctivitis and keratitis, such as Pseudomonas, Serratia, and Hemophilus influenzae (H. flu), as well as streptococcal species of bacteria. This makes them moderately broad-spectrum, and thus, a good choice for mild-to-moderate bacterial infections of the lids, cornea and conjunctiva, especially when patient cost is an issue.

This patient had moderate corneal staining, more concentrated inferiorly, often seen in more severe cases of staphylococcal blepharitis.

Solutions are dosed q.i.d., and ointments are dosed b.i.d. to q.i.d., usually for seven-to-10 days regardless of formulation and based on the condition's severity. Ointments are a great choice if the patient requires overnight coverage for a more significant infection, such as a severe keratitis, and in pediatric conjunctivitis, or if your patient has an infection of the eyelids or adnexa.

Keep in mind that neomycin is not available as a single-ingredient medication. It is found in combination with other antibiotics and/or steroids in solution and ointment form. Its most notorious feature is that it is associated with a relatively high incidence of allergic reactions in the forms of lid swelling, crusting, “weeping” and profound itching. Therefore, if you choose to prescribe a drug that contains neomycin, be sure to first educate the patient of this possibility.

The macrolides

This group of antibiotics includes erythromycin, azithromycin and clarithromycin. Practitioners routinely use only the first two.

Erythromycin is topically only available as an ointment, and is primarily effective against gram-positive organisms — think staph.-related blepharitis. It's available generically and since it is approved for infants, is a common choice for the pediatric population. Its dosing is b.i.d. to q.i.d. usually for seven-to-10 days. Erythromycin is a common prophylaxis against ophthalmia neonatorum.

Azithromycin is available topically as a viscous eye drop. It is bacteriostatic as opposed to bactericidal, and although it's FDA-approved only for conjunctivitis, practitioners have frequently prescribed it off-label for mixed blepharitis. Because the antibiotic has excellent intrinsic anti-inflammatory properties, it's a good option for inflammation control when you don't want to prescribe a steroid. Azithromycin is dosed at b.i.d. for days one and two and then q.d. for the following five days.

The polypeptides

These antibiotics, polymixin B, bacitracin and gramicidin, interfere with either bacterial cell membrane or cell wall structure.

Polymixin B is found in combination antibiotic ointments and as a combination drop with trimethoprim (classified as a pyrimidine). It is effective against gram-negative organisms, such as pseudomonas and some enterobacteria infections of the cornea, conjunctiva and lids/lashes.

Of note: Trimethoprim has been shown in several studies as strongly effective against methicillin-resistant staphylococcus aureus (MRSA).1 This makes this combination drug a good choice in hospital and assisted-living settings, where MRSA tends to be prevalent. Dosing of the drop is q3h usually for seven-to-10 days, which you should take into consideration for patients who might have difficulty with a relatively high-dosing schedule.

This patient had significant corneal staining, necessitating the use of a prophylactic antibiotic to discourage a bacterial superinfection.

Bacitracin is also an ointment, but it works against gram-positive infections, such as staph. blepharitis. An ointment combination of polymixin B and bacitracin used b.i.d. to q.i.d. for seven-to-10 days displays a broad spectrum of activity against a variety of organisms. As an ointment, it is not a preferred conjunctivitis treatment for most adults due to the nuisance of temporary blurred vision. But it is useful for dermatologic conditions, such as ulcerated lid margins associated with blepharitis, or for prophylactic coverage of herpes zoster ophthalmicus lesions.

Gramicidin is found only in combination with other solutions. It has a nearly identical activity spectrum to bacitracin, and they are often interchanged with each other in ointment and solution formulations, respectively.

The sulfonamides

These “sulfa drugs” are available both systemically and topically. Topical sulfacetamide sodium drops and ointment can be prescribed as a stand-alone therapy or in combination with other antibiotics and/or steroids.

Historically, sulfacetamide/steroid combination drugs were used effectively to treat blepharitis because of the spectrum of coverage against gram-positive S. aureus. They fell out of favor, however, due to a relatively higher incidence of allergies, which can range from mild itching and rash to much more severe manifestations, including Stevens-Johnson syndrome.

With the advent of newer medications, like the aminoglycosides and fluoroquinolones, the sulfa drugs were largely ignored for the past two decades. Ironically, sulfacetamide is now making a relative “comeback” in some practices because sulfa derivatives are thought to be effective against Demodex, an intradermal mite implicated in causing and exacerbating many cases of blepharitis.2

Best bets for these drugs are cases of blepharitis that are poorly responsive to other firstline therapies. In these cases, practitioners prescribe a sulfacetamide/steroid combination ointment b.i.d. to q.i.d. on the lid margins usually for 10 days. Remember that sulfonamides are inactivated in the presence of mucopurulent discharge, so avoid them in bacterial conjunctivitis cases where discharge is a feature. (See photo on page 35.)

The fluoroquinolones

Ciprofloxacin, ofloxacin, levofloxacin, moxifloxacin, gatifloxacin and besifloxacin make up this group.

The first three are solution form — ciprofloxacin also comes in ointment form — and are currently the only antibiotics FDA-approved for the treatment of bacterial keratitis with ulcerations (aka bacterial corneal ulcers). They are dosed at q.i.d. usually for seven-to-10 days.

Moxifloxacin, gatifloxacin and besifloxacin are available in solution form and have been shown to provide a greater spectra of coverage, fewer side effects and improved dosing schedules when compared with the FDA-approved agents. With regard to the latter, b.i.d. and t.i.d. dosing options are available due to the incorporation of a drug vehicle that adds viscosity.

For instance, practitioners prescribe moxifloxacin either b.i.d. (the more viscous formulation) or t.i.d. (the less viscous formulation) throughout the treatment course, which typically lasts seven days. Practitioners prescribe gatifloxacin 0.3% q2h for days one and two, then q.i.d., while they prescribe the stronger 0.5% concentration q2h only for the first day, followed by b.i.d. to q.i.d. dosing for the next six days, depending on clinical response. Practitioners prescribe besifloxacin (also formulated in a viscous drop) t.i.d. usually for seven days for bacterial conjunctivitis. Of note, several recent papers have revealed that besifloxacin is more effective than other available topical antibiotics against MRSA.3

Although moxifloxacin, gatifloxacin and besifloxacin are not FDA approved for the treatment of corneal ulcers, practitioners have prescribed them off-label for this condition. Specifically, they dose these drugs more frequently than the recommended schedule for conjunctivitis. Generally, they prescribe a loading dose during the first one-to-two hours, and then have the patient use the drop q1h to q2h, depending on the condition's severity.

In addition, prescribing once or twice administration overnight is a common practice. Something to keep in mind: Both besifloxacin and gatifloxacin have demonstrated intrinsic anti-inflammatory activity. Also, gatifloxacin is preserved with benzalkonium chloride.

Clinical Pearls
AMINOGLYCOSIDES
• Gentamicin, Tobramycin, neomycin
• Solutions dosed q.i.d.
• Allergies common with neomycin
• Broad spectrum, generics are cost-effective

MACROLIDES
• Erythromycin is oral and topical, good for lids and kids
• Azithromycin: good dosing profile and topical viscous drop shows anti-inflammatory activity

POLYPEPTIDES
• Good supporting players in combination with other antibiotics and steroids
• Bacitracin is available as a stand-alone ointment and is useful in gram-positive lid disease

SULFONAMIDES
• Allergy to sulfa drugs is common
• In non-allergic patients, good choice for staph. blepharitis due to activity against Demodex

FLUOROQUINOLONES
• Classic drugs are dosed q.i.d., and three enjoy FDA approval for corneal ulcers
• Newer generations have higher viscosity or higher drug concentration allowing less frequent dosing and are standard of care for bacterial corneal ulcer treatment (off label)

Everything old should be new again

In summary, the “old timers” are still available and are often the best choice for patients who have specific clinical conditions and/or financial constraints.

On the other hand, the new or more recent drugs generally offer excellent broad-spectrum coverage against most common ocular pathogens in children and adults, with relatively fewer potential side effects than the “classic” drugs. Anti-inflammatory activity is a plus, if steroid use is too risky to the patient or they are otherwise contraindicated. The bottom line: Knowing which drug to offer as first line therapy is essential; but having a deep “bench” of available treatment options is equally important for those times when the first choice isn't feasible. OM

This patient displayed mild mucopurulent discharge, which collected on the inferior lid margin.

1. Asbell PA, Colby, KA, Deng S., et al. Ocular TRUST: nationwide antimicrobial susceptibility patterns in ocular isolates. Am J Ophthalmol. 2008 Jun;145(6):951-958. Epub 2008 Mar 28.
2. Czepita D, Ku na-Grygiel W, Czepita M, Grobelny A. Demodex folliculorum and Demodex brevis as a cause of chronic marginal blepharitis. Ann Acad Med Stetin. 2007;53(1):63-7; discussion 67.
3. Haas W, Gearinger LS, Usner DW, et al. Integrated analysis of three bacterial conjunctivitis trials of besifloxacin ophthalmic suspension, 0.6%: etiology of bacterial conjunctivitis and antibacterial susceptibility profile.Clin Ophthalmol. 2011;5:1369-79. Epub 2011 Sep 21.

Dr Reed is an associate professor at the Nova Southeastern University College of Optometry in Fort Lauderdale, Fla., a prolific author on eye health and a frequent continuing education lecturer. In addition, she writes OM's Nutrition column. E-mail Dr. Reed at kimreed@nova.edu, or send comments to optometricmanagement@gmail.com.


Optometric Management, Volume: 47 , Issue: August 2012, page(s): 31 - 35