Medications for Contact
Lens-Related Infection

BY WILLIAM TOWNSEND, O.D.
MAY 1996

Contact lens wearers may be more likely to develop ocular infections than non-wearers. These therapeutic drugs will enable you to provide optimum care for these patients.Contact lens patients are not immune to infection; if anything, they're more prone because they have more eye-hand contact than non-wearers. We're fortunate to have numerous medications at our disposal for treating these patients. Here are the most commonly used treatments for contact lens-related infection.

ANTIBIOTICS

There's a vast assortment of antibiotics that affect bacterial growth. Understanding how they work and identifying the causative organism in any given condition is imperative in designing a treatment plan.

Drugs Affecting Protein Synthesis

Like other cellular organisms, bacteria must carry out protein synthesis to sustain life and growth. Manufacture of proteins depends on replication of RNA patterns by ribosomes in the cell cytoplasm. Disrupting that process leads to bacteriostasis or cell death.

Aminoglycosides: Aminoglycosides bind irreversibly to the 30S unit of bacterial ribosomes and thereby inhibit protein synthesis. Other antibiotics such as tetracycline and chloramphenicol also inhibit protein synthesis by binding with bacterial ribosomes, but are bacteriostatic; aminoglycosides are bactericidal. The exact nature of this bactericidal mechanism remains elusive, but we do know that it is concentration dependent.

Gentamicin, which is derived from the actinomycete Micromonospora, has a broad spectrum of activity. It is especially effective against gram-negative bacteria and has limited activity against some gram-positive bacteria. Gentamicin is available in a 0.3% ophthalmic solution or ointment and is widely used to treat bacterial conjunctivitis. Gentamicin is also used in fortified concentrations of up to 50gm/ml as part of combination therapy for corneal ulcers. Unfortunately, widespread use has led to a number of resistant bacterial strains. Cases of bacterial conjunctivitis that are refractory to gentamicin usually respond well to tobramycin or a fluorinated quinolone. Gentamicin is relatively toxic to corneal epithelium and may cause a punctate keratitis.

Tobramycin is similar to gentamicin in antibacterial activity and pharmokinetic properties but is more active than gentamicin against Pseudomonas aeruginosa. Some cross resistance between these two drugs has been noted in certain bacterial strains. Tobramycin is available in 0.3% solution and ointment, as well as in combination with steroids. Because of its excellent anti-Pseudomonas properties, tobramycin is particularly useful for treating contact lens-related infectious keratitis. Like gentamicin, tobramycin can delay healing and cause a diffuse punctate keratitis. Because fortified tobramycin (11mg/ml) has a broad spectrum of activity, it's a good treatment for corneal ulcers.

Neomycin is a widely used aminoglycoside with activity against gram-positive and gram-negative organisms. Neomycin is rarely used systemically because it causes renal and ototoxicity. It is only available in combination with other medications to produce broad spectrum antibiotics. Neosporin is combined with polymyxin B (Statrol ointment and solution), or with polymyxin B and bacitracin (Neosporin ointment).

Neomycin has a relatively high rate (10 percent) of hypersensitivity reactions and practitioners prefer not to prescribe neomycin-containing medications.

Amakacin, a semisynthetic aminoglycoside, is not commercially available as an ophthalmic preparation. Fortified amakacin (6.7mg/ml) is used to treat contact lens-related ulcers caused by gentamicin/tobramycin-resistant organisms, particularly bacilli.

Tetracyclines: The tetracycline family is a group of drugs that are bacteriostatic and inhibit protein synthesis within bacterial cells. Once transported into the cell, the tetracyclines bind to the 30S subunit of ribosomes to prevent amino acids from attaching at that site. In addition to their antibacterial properties, they alter lipid metabolism and are effective treatments for acne, meibomitis, blepharitis and other complications associated with sebum-secreting glands.

Commonly prescribed members of this family include short-acting drugs such as tetracycline and oxytetracycline and longer acting compounds such as doxycycline and minocycline. Used systemically, these drugs treat chlamydial infection, trachoma, meibomitis and acne rosacea as well as canaliculitis due to Actinomyces israelii. Systemic use of tetracyclines is contraindicated in children under eight years of age and in pregnant females because it can retard bone and tooth growth. Calcium binds to and deactivates tetracyclines so patients should avoid calcium-based antacids or milk products when taking these drugs.

Erythromycin, Chloramphenicol and Clindamycin: These medications inhibit protein synthesis by binding to the 50S subunit of bacterial ribosomes. Erythromycin can be bactericidal or bacteriostatic. It is most commonly used to treat gram-positive bacteria. It has a spectrum of activity similar to that of penicillin. Unlike tetracycline, it has little effect on bone or tooth development and can be used to treat adult and pediatric chlamydial infections. It is also useful for treating cellulitis caused by staph and strep. Its limited effect on Haemophilus infections necessitates an additional antibiotic when treating cellulitis. Erythromycin is available in ophthalmic form as an ointment, Illotycin (Dista), that is particularly useful in treating staph lid disease, and has also been used as a prophylactic agent for the prevention of ophthalmia neonatorum.

Chloramphenicol is a bacteriostatic agent that is active against both gram-negative and gram-positive bacteria. Its broad spectrum of activity is offset by its unfortunate ability to cause aplastic anemia, a potentially fatal blood disorder that has been caused by systemic and even topical use of the drug. Bone marrow depression is also linked with chloramphenicol. Due to potential side effects associated with this medication, its use has declined and other medications have replaced it as a broad spectrum antibiotic. It's available in ophthalmic solution or ointment form as Chloromycetin (Parke-Davis).

Clindamycin is also a bacteriostatic drug that inhibits protein synthesis. Its ocular use is limited to treatment of Actinomyces israelii canaliculitis and ocular toxoplasmosis. Clindamycin is known to cause pseudomembranous colitis in adults, a serious and potentially fatal condition. It is available in systemic and topical forms, but not as an ophthalmic preparation.

Drugs Affecting DNA Synthesis

Fluorinated Quinolones: Recently, bacterial species resistant to almost all antibiotics have emerged. The fluorinated quinolones are active against many of these species. They inhibit the action of DNA gyrase and kill bacteria as well as inhibit their growth for up to six hours. Uncoiled bacterial DNA is as much as 300 times as long as the bacterial cell. Supercoiling of bacterial DNA is necessary to allow it to fit in the cells and is mediated by the enzyme DNA gyrase. Traditionally, corneal ulcers have been treated with a fortified antibiotic combination that included a cephalosporin and an aminoglycoside. A recent study compared ofloxacin to a combination of fortified tobramycin and cefazolin in the treatment of bacterial corneal ulcers. The results showed that the efficacy of ofloxacin was comparable and less toxic to the cornea.

Presently available ophthalmic preparations include ciprofloxacin (Ciloxan), ofloxacin (Ocuflox), and norfloxacin (Chibroxin). These medications are particularly useful in treating small to moderate-sized corneal ulcers off the visual axis. They are also effective for treating conjunctivitis refractory to other medications. To avoid the further development of resistant strains, reserve your fluoroquinolones for more severe infections that do not respond to other medications.

Drugs Affecting Folic Acid Synthesis

Unlike human cells, bacterial cells cannot absorb folic acid and must metabolize it from para-aminobenzoic acid (PABA). Drugs that thwart bacterial synthesis of folic acid include sulfonamides, pyrimethamine, and trimethoprim.

Sulfonamides were the first drugs used systemically to treat infection. They are analogs of PABA and competitively inhibit folic acid synthesis. Sulfonamides are bacteriostatic so the immune system must be operational to kill the infecting organism. Because PABA is abundant in any purulent discharge, infections that produce large amounts of pus will not respond to sulfonamides.

Because of their widespread use, there is considerable microbial resistance and hypersensitivity to sulfonamides so their usefulness is limited. In the past, sulfonamides were often used to treat blepharitis and conjunctivitis, but they have been largely supplanted by other drugs because of the high incidence of resistance in Staphylococcus epidermidis and Staph. aureus species. Many strep and haemophilus species are sensitive to sulfonamides, so they may be used for treating pediatric ocular infections.

Sodium sulfacetamide is available in solution form (10%, 15% and 30%) or in ointment form (10%). In most cases, there are other antibiotics that better meet the needs of the patient, and sulfonamides should be used only when other antibiotics are not available.

Pyrimethamine and trimethoprim: These drugs also interfere with folic acid synthesis through inhibition of the conversion of dihydrofolic acid to tetrahydrofolic acid. They are bacteriostatic, and are especially useful in treating infections caused by Strep. pneumonia and Haemophilus influenzae, the most common causative microorganisms in pediatric conjunctivitis.

Trimethoprim (0.1%) is available in combination with polymyxin B as Polytrim (Allergan). Polymyxin B kills Pseudomonas aeruginosa, and other gram-negative organisms not sensitive to Trimethoprim. Several studies have demonstrated the efficacy of trimethoprim in treating pediatric conjunctivitis caused by these organisms.

Drugs Affecting Cell Wall Metabolism

Unlike animal cells, bacteria possess a cell wall. This distinctive characteristic allows certain drugs to interfere with synthesis of the cell wall of bacteria while having minimal effect on human tissue.

Penicillins: Penicillins inhibit the final step in the synthesis of peptidoglycan. They are especially effective against gram-positive organisms whose cell wall structure is highly dependent on peptidoglycans for strength. Penicillins also have some activity against gram-negative organisms. Treponema pallidum and Neisseria gonorrhoeae are two important pathogens that are sensitive to penicillin G and V. These drugs are administered systemically, but fortified preparations have been used to treat infections and corneal ulcers caused by these organisms as well as streptococci, staphylococci and Corynebacterium. Fortified drop concentrations for topical ocular therapy are as follows: penicillin G: 333,000U/ml, carbenicillin: 6.2mg/ml, and oxacillin: 66mg/ml.

Cephalosporins: Like the penicillins, cephalosporins interfere with synthesis of the peptidoglycan layer of the bacterial cell wall. They are most effective against gram-positive bacteria primarily because beta lactamase produced by many gram-negative bacteria deactivate most cephalosporins. Cefazolin, a first-generation cephalosporin, is commonly prescribed for corneal ulcers. It has broad activity against staphylococcus, streptococcus, proteus, and haemophilus species. Although cephalosporins are not available in a commercially produced ophthalmic form, Cefazolin (Ancef) fortified to a strength of 50 mg/ml is used in combination with fortified gentamicin or tobramycin for treatment of corneal ulcers. Ceftriaxone, a third generation cephalosporin, has been used to systemically treat ophthalmia neonatorum caused by Neisseria gonorrhoeae.

Vancomycin: Vancomycin is usually reserved for bacteria that are resistant to other antibiotics. Systemic administration of vancomycin can result in nephrotoxicity as well as potentially permanent hearing loss. The bactericidal effect of vancomycin results from inhibition of cell wall synthesis. It interferes with peptidoglycan synthesis, which alters cell membrane permeability, and RNA synthesis. Vancomycin has little or no effect on gram-negative bacilli, but is very effective against gram-positive organisms such as staphyloccus and streptococcus as well as clostridium and neisseria. Selected strains of staph and strep are among the most resistant forms of bacteria known. The primary use of vancomycin in eye care is as a fortified drug used in combination therapy to treat corneal ulcers. Its great benefit is that it's active against organisms that are resistant to cephalosporins. When used to treat ulcerative keratitis, vancomycin is typically fortified to a concentration of 33mg/ml.

Bacitracin: Bacitracin inhibits formation of polysaccharide chains that make up part of the structure of peptidoglycans. As is the case with other antibiotics of this class, it's most effective against gram-positive organisms. It has the potential to cause renal damage, so it's used topically. Bacitracin is produced as an ointment.

Bacitracin is used to treat staph and lid disease. Because of its low toxicity as an ophthalmic preparation, it's used in combination with polymyxin B and neomycin (Neosporin) as a broad spectrum antibiotic ointment.

Drugs Affecting the Cell Membrane

The cell membranes of human and bacterial cells are similar so there are few drugs that affect the integrity of bacterial cell membranes.

Polymyxin B: Polymyxin B is a cationic detergent that causes increased cell permeability and loss of intracellular fluid, thus causing cell death. It is effective against gram-negative bacteria but is rarely used systemically because it may cause severe and sometimes permanent renal damage. It is only available in combination with other drugs such as Neosporin (polymyxin B, neomycin, and gramicidin) or Statrol (polymyxin B and neomycin). Polymyxin B is also used in combination ointments such as Polysporin (polymyxin B, bacitracin) or Mycetracin (polycyxin B, neomycin, bacitracin).

Gramicidin: Gramicidin increases cell membrane permeability, which in turn leads to cell death. Its activity is primarily against gram-negative bacteria. Gramicidin is produced in combination with other medications for broad spectrum activity (see Polymyxin B). These products are commonly prescribed for conjunctivitis and as a prophylactic antibiotic after corneal abrasion.

CONTROL OF INFLAMMATION DURING INFECTION

It is sometimes necessary to control pain and discomfort caused by inflammation that invariably accompanies infection. For this, we have two choices: nonsteroidal anti-inflammatory drugs and corticosteroids.

Topical NSAIDS diminish or relieve the prostaglandin-induced signs and symptoms of allergic eye disease. Prostaglandin, unlike histamine, is not stored in tissue, but must be synthesized through the cyclo-oxygenase pathway. NSAIDS work by blocking the cyclo-oxygenase pathway and preventing the formation of prostaglandin. While they display significant anti-inflammatory action, NSAIDS lack many of the undesirable side effects of steroids. They do not raise IOP, cause cataracts, or exacerbate existing ocular infection.

Corticosteroids:

• inhibit the early and late phases of inflammation;
• reduce vascular permeability thereby lessening associated edema and migration of polymorphonuclear neutrophils, macrophages and other leukocytes into the area of inflammation; and
• prevent the release of proteolytic enzymes and other destructive agents by granulocytes. By inhibiting the activity of phospholipase, corticosteroids block the conversion of arachidonic acid into prostaglandins, leukotrienes and other mediators.

The result is reduction of many of the signs and symptoms of long-term inflammation. In addition, by inhibiting fibroblast activity, corticosteroids reduce or prevent scar formation. These effects are especially desirable where tissue must remain clear for proper vision.

Use of corticosteroids should be tempered by a thorough understanding of the potential complications posed by their use. Because their immune suppressing effects are nonselective, they increase susceptibility to viral, bacterial and fungal infection. They also inhibit wound healing and migration of epithelial cells.

CONCLUSION

By understanding the mechanism of action of medications, we can better treat our contact lens patients' episodes of infection. Prudent prescribing of therapeutic agents allows us to minimize the degree of discomfort and damage caused by these conditions.

Dr. Townsend practices in Canyon, Texas, and he is a consultant at the Amarillo VA Medical Center. He lectures on therapeutics, diagnosis and management of ulcerative and non-ulcerative corneal disease, and common disease control in the optometric practice. He is an adjunct associate professor at the University of Houston College of Optometry.