Other symptoms warranting referral include nausea; vomiting; severe headache, which may indicate acute angle-closure glaucoma; or significant purulent discharge, which may be a symptom of hyperacute bacterial infection from gonorrhea or chlamydia.5,6 Patients may also present with an injury from their use of contact lenses, given that many wearers do not use or replace their lenses as directed.5
Of particular note, any patient who has fluorescein staining suggestive of dendritic branching ulceration should be immediately referred for evaluation of ocular herpes. A topical steroid should not be administered, because it could worsen the symptoms of ocular herpes, exacerbate ulceration, and increase intra-ocular pressure, potentially outweighing any benefit of treatment.5,6 Never use a topical ocular steroid for conjunctivitis; most primary-care clinicians lack advanced training, and microscopy is not available in daily practice.
Although bacterial conjunctivitis is usually self-limited,12,13 studies have shown the benefits of treatment with topical ophthalmic antibiotics.13 Such benefits include reducing the time to recovery, limiting spread of the infection to others, preventing the recurrence of infection, providing a quicker return to normal activities and decreasing the risk for sight-threatening complications.9,10,13 Patients with an inadequate response to therapy may have a more serious condition.10
Topical ophthalmic antibiotics are effective because their direct on-site delivery results in high concentrations of drug on the ocular surface. Bacterial cultures are not routinely done in primary care, and antibiotic treatment is generally empirical with a broad-spectrum antibiotic.10,14 The classes of antibiotics used in the treatment of bacterial conjunctivitis include aminoglycosides, polymyxin B combinations, macrolides, and fluoroquinolones.9,10
Differences in molecular structures among drug classes and compounds affect tear concentration and conjunctival tissue penetration, which in turn impact clinical efficacy. The newer fluoroquinolones attain greater conjunctival penetration than older antibiotics, and the more recently introduced fluoroquinolones penetrate the conjunctiva better than do older ones.15,16
Antibiotic formulation can also affect dosing frequency and drug distribution on the eye surface. For example, antibacterials in solutions or suspensions tend to be washed more rapidly from the ocular surface through tearing or rapid blinking, thus requiring frequent dosing. About 50% of an eye drop is lost from the eye almost immediately after application because it will exceed the conjunctival cul-de-sac’s maximum capacity of only 20 to 30 µl.
Petrolatum or oil-based ointments are more viscous, offering more prolonged residence time and less frequent dosing, but with the trade-off of blurry vision as a common side effect.17 The addition of such viscosity-enhancing agents as polyvinylpyrrolidone, polyvinyl alcohol, or carboxymethylcellulose to solutions or suspensions can dramatically increase a drug’s residence time. DuraSite (InSite Vision, Alameda, Calif.) is a recently developed polycarbophil-based mucoadhesive vehicle that is used in several topical antibiotic formulations.18,19
Some patients may be sensitive to the preservatives found in most antibiotic ophthalmic solutions, such as benzalkonium chloride (BAK), which is used in all topical antibiotic formulations except that of the fluoroquinolone moxifloxacin (Vigamox). Preservatives stabilize compounds and prevent contamination but may cause ocular irritation.20,21 Without using a biomicroscope, it is difficult to determine whether a patient’s worsening symptoms are attributable to treatment failure or sensitivity to eye drops. However, preservatives may enhance the activity of an antibiotic. In vitro comparisons of antibiotics with and without BAK showed that agents with BAK eradicated a greater percentage of bacteria more rapidly than those without.21-23 The risks and benefits of BAK as a preservative need to be studied further.22
Table 3 provides a review of the classes of antibiotics used in the treatment of bacterial conjunctivitis.24-33
Aminoglycosides. The aminoglycosides gentamicin and tobramycin (Tobrex) affect gram-negative and gram-positive bacteria,30,34 although these agents may have limited activity against streptococci.17,34 Both drugs require frequent administration,35 which may limit compliance.36 Studies comparing gentamicin with tobramycin did not find a significant difference between the two drugs in the percentages of patients achieving clinical cures and microbial eradication.27,37 Both provoke such mild-to-moderate ocular adverse events as edema, pruritus, burning, and chemosis.35,37,38
Polymyxin B formulations. The polymyxin B-based formulations include polymyxin B/trimethoprim, polymyxin B/bacitracin (Polysporin), and polymyxin B/bacitracin/neomycin.17 These combinations are not reliably bactericidal,17 and polymyxin B/trimethoprim provides what has been described as only fair coverage of S. pneumoniae.11 Monotherapy with polymyxin B is bactericidal for gram-negative bacteria, and trimethoprim, neomycin, and bacitracin are bactericidal for gram-positive and gram-negative pathogens. Combinations need to be administered as often as aminoglycosides, so patient compliance may be an issue.39,40
A double-masked clinical study comparing the polymyxin B/bacitracin combination (administered four times daily for seven days) with placebo found that patients receiving the combination treatment had significantly higher rates of clinical cure and bacterial eradication than those receiving placebo.28 Two clinical studies comparing different combinations of polymyxin B did not find significant differences in rates of clinical resolution or microbial eradication among the formulations.41 Polymyxin B trimethoprim has been shown to be slower in resolving the clinical signs and symptoms of bacterial conjunctivitis than the newer fluoroquinolone moxifloxacin. 39
Polymyxin B combinations have primarily moderate adverse events.39,40
Macrolides. The two macrolides used in the treatment of bacterial conjunctivitis—erythromycin and azithromycin (AzaSite)—are bacteriostatic agents.42 Erythromycin is usually recommended only for prophylaxis of neonatal conjunctivitis because the drug has limited activity against S. aureus.11,42 In vitro studies have shown that azithromycin is less active against gram-positive bacteria than erythromycin but has a broader spectrum of anti-infective activity against gram-negative pathogens, including H. influenzae.42 Azithromycin is administered less frequently than the aminoglycosides or polymyxin B combinations due to inclusion of DuraSite in the formulation (Table 3).
Clinical studies with azithromycin, applied twice daily on Days 1 and 2 and once daily on Days 3 to 5, have shown that the rates of clinical efficacy and bacterial eradication are similar to those of the aminoglycosides and polymyxin B combinations.18,43 Such adverse events as burning or stinging, eye irritation, headache, conjunctival hyperemia, and worsening bacterial conjunctivitis were seen in similar numbers of patients who received azithromycin, vehicle, or tobramycin in clinical studies.43,44