Ophthalmic Anti Infective Drugs

Ophthalmic anti infective drugs treat infections of the lids, conjunctiva, cornea and (with other routes) deeper structures. They include topical antibiotics, antivirals, antifungals and antiamoebic agents. Most acute bacterial conjunctivitis is mild and self-limiting; the greater danger is corneal infection (keratitis), which needs intensive treatment within hours.

Mechanism.

• Fluoroquinolones (ofloxacin, ciprofloxacin, levofloxacin, moxifloxacin) inhibit DNA gyrase and topoisomerase IV.
• Aminoglycosides (gentamicin, tobramycin) and chloramphenicol inhibit bacterial protein synthesis; fusidic acid inhibits elongation factor G; azithromycin and tetracycline bind the ribosome; cefuroxime inhibits cell wall synthesis.
• Aciclovir and ganciclovir inhibit viral DNA polymerase after viral thymidine kinase activation.
• Natamycin binds fungal ergosterol; voriconazole inhibits ergosterol synthesis.
• Polyhexanide and chlorhexidine disrupt amoebic membranes.

Pharmacokinetics. Drops reach the tear film at high concentration and enter the cornea; penetration to the aqueous is good for fluoroquinolones and poor for aminoglycosides through intact epithelium. Ointments prolong contact but blur vision. Frequent dosing (hourly) is needed for keratitis. Systemic absorption is small.

• Antibiotic drops and ointments: chloramphenicol 0.5 percent drops and 1 percent ointment; gentamicin 0.3 percent; tobramycin 0.3 percent; ofloxacin 0.3 percent; ciprofloxacin 0.3 percent; levofloxacin 0.5 percent; moxifloxacin 0.5 percent; fusidic acid 1 percent gel; azithromycin 1.5 percent; tetracycline 1 percent ointment; erythromycin 0.5 percent ointment.
• Fortified drops: cefuroxime 5 percent with gentamicin or tobramycin 1.5 percent, prepared by a pharmacy for severe keratitis.
• Antivirals: aciclovir 3 percent ointment; ganciclovir 0.15 percent gel; trifluridine 1 percent where available.
• Antifungals: natamycin 5 percent suspension; voriconazole 1 percent drops.
• Antiamoebic: polyhexanide 0.02 percent; chlorhexidine 0.02 percent.
• Antiseptic: povidone-iodine 2.5 percent for neonatal prophylaxis and pre-injection preparation.

Regimens.

• Acute bacterial conjunctivitis: usually clears in 5 to 7 days without treatment; if treated, chloramphenicol 0.5 percent one drop every 2 hours for 48 hours then four times daily, or fusidic acid 1 percent gel twice daily, continued for 48 hours after resolution.
• Bacterial keratitis (corneal ulcer): after corneal scraping for smear and culture, moxifloxacin 0.5 percent or levofloxacin 0.5 percent one drop every hour day and night for the first 24 to 48 hours, then every 2 hours while awake, tapering with healing; or fortified cefuroxime with gentamicin alternating hourly. Add a cycloplegic for pain.
• Fungal keratitis (common after plant-matter trauma): natamycin 5 percent one drop every hour while awake for 3 to 7 days, then every 2 to 4 hours, continued for 2 to 3 weeks; voriconazole 1 percent as alternative or add-on. Do not use steroids.
• Herpes simplex keratitis (dendritic ulcer): aciclovir 3 percent ointment five times daily until 3 days after healing, or ganciclovir 0.15 percent gel five times daily until healed, then three times daily for 7 days; add oral aciclovir for stromal disease and prophylaxis after recurrence.
• Acanthamoeba keratitis: polyhexanide 0.02 percent or chlorhexidine 0.02 percent hourly then tapered, over several months; specialist care.
• Trachoma: azithromycin 20 mg/kg as a single oral dose (maximum 1 g) for mass treatment, or tetracycline 1 percent eye ointment twice daily for 6 weeks.
• Ophthalmia neonatorum: gonococcal disease needs ceftriaxone 25 to 50 mg/kg by intramuscular injection once (maximum 125 mg); chlamydial disease needs oral erythromycin 50 mg/kg daily in four doses for 14 days; add saline irrigation.
• Neonatal prophylaxis: tetracycline 1 percent or erythromycin 0.5 percent ointment, or povidone-iodine 2.5 percent, once after birth.
• Blepharitis and stye: lid hygiene, with topical antibiotic ointment (for example azithromycin or erythromycin) for 2 to 4 weeks if staphylococcal.

Selection. Withhold antibiotic for mild, uncomplicated conjunctivitis in well adults. Treat all contact lens wearers, painful red eyes with reduced vision, and corneal opacities as keratitis until proven otherwise. Take scrapings before treatment where a laboratory exists; start broad treatment without delay if it does not.

Contraindications. Hypersensitivity; topical steroids alone in presumed infection; chloramphenicol in a personal history of marrow aplasia; neomycin-containing drops in neomycin allergy.

Effects. Stinging, transient blurring, allergic conjunctivitis and lid dermatitis (aminoglycosides, neomycin), epithelial toxicity and delayed healing with frequent fluoroquinolones, aminoglycosides and antiseptics, white corneal precipitates with ciprofloxacin, resistance with prolonged or low-dose use. Chloramphenicol drops carry a very rare reported risk of marrow aplasia; causality is unproven.

Interactions. Negligible when applied alone. Separate different drops by 5 minutes; remove contact lenses during treatment.

Monitoring. Review keratitis daily at first (ulcer size, hypopyon, pain, vision); change treatment on culture result or failure at 48 to 72 hours; review conjunctivitis if no improvement at 48 hours.

Special groups.

• Pregnancy and breastfeeding: chloramphenicol drops, fusidic acid and erythromycin are used; avoid tetracycline for prolonged courses.
• Children: chloramphenicol and fusidic acid are used from birth; fluoroquinolones are used when benefit is clear.
• Region: trachoma is endemic in parts of East Africa and drives corneal scarring (trichiasis needs surgery); fungal keratitis follows plant and animal-tail injury and use of traditional eye remedies; over-the-counter steroid-antibiotic drops cause worsening of herpetic and fungal keratitis, so refer all corneal ulcers urgently.