What is the initial treatment for a patient presenting with keratitis?

Initial Treatment of Keratitis

The initial treatment of keratitis depends critically on identifying the causative organism, with topical fluoroquinolone monotherapy (ofloxacin 0.3%, ciprofloxacin 0.3%, or levofloxacin 1.5%) as first-line empiric therapy for bacterial keratitis, topical natamycin for fungal keratitis, and antivirals for herpetic keratitis. 1, 2, 3

Bacterial Keratitis: First-Line Approach

Empiric Antibiotic Selection

• Topical fluoroquinolone monotherapy is as effective as fortified combination therapy for most cases of bacterial keratitis. 1, 2
• FDA-approved fluoroquinolones include ciprofloxacin 0.3%, ofloxacin 0.3%, and levofloxacin 1.5%. 1
• Single-drug fluoroquinolone therapy has demonstrated equivalent efficacy to fortified antibiotic combinations in clinical trials. 1, 2

Dosing Strategy Based on Severity

For central or severe keratitis (deep stromal involvement, infiltrate >2mm, extensive suppuration, or hypopyon):

• Loading dose: every 5-15 minutes initially 1, 2
• Maintenance: every hour around the clock 1
• Consider fortified antibiotics for large, visually significant infiltrates, especially with hypopyon 1

For peripheral or mild keratitis:

• Less aggressive dosing (4-6 times daily) may suffice 1
• Ointments may be useful at bedtime for less severe cases 1

Critical Diagnostic Steps

• Obtain corneal scrapes for smear and culture before initiating therapy in sight-threatening cases (central location, multifocal, melting, painful). 4, 3
• Gram stain results guide initial empiric selection while awaiting culture. 4
• Culture antibiogram results should modify therapy only if clinical response is inadequate at 48 hours. 1

Adjunctive Measures

• Cycloplegic agents are indicated when substantial anterior chamber inflammation is present to decrease synechiae formation and reduce pain. 1
• Avoid pressure patching in contact lens wearers due to increased risk of secondary infection. 2

Resistance Patterns and Pitfalls

Fluoroquinolone Resistance

• Resistance rates exceed 30% for Staphylococcus aureus and coagulase-negative staphylococci. 4
• Risk factors for resistance include recent fluoroquinolone use, hospitalization, advanced age, and recent ocular surgery. 1, 2
• Streptococci and anaerobes have variable susceptibility to fluoroquinolones. 1

Special Organism Considerations

Pseudomonas aeruginosa:

• May show increased inflammation in first 24-48 hours despite appropriate therapy—this is not treatment failure. 5
• Multidrug-resistant strains require alternative agents like topical colistin 0.19%. 5
• Modify therapy only if no improvement by 48 hours. 1, 5

Nocardia:

• Avoid corticosteroids entirely—outcomes are poor with steroid use. 1

Corticosteroid Timing (Bacterial Keratitis Only)

Do not use corticosteroids initially. 1

When to Add Corticosteroids

• After 2-3 days of progressive improvement on antibiotics (not 4+ days—earlier addition yields better visual outcomes). 1
• Only after pathogen identification and ruling out fungal infection. 1
• Only when epithelial defect is healing and/or ulcer is consolidating. 1
• Specifically beneficial for Pseudomonas keratitis and severe bacterial keratitis. 1, 5

Corticosteroid Monitoring

• Examine patient within 1-2 days after initiating steroids. 1
• Monitor intraocular pressure closely. 1
• Counsel patients about cataract and glaucoma risks. 1
• Patients already on topical steroids at presentation should have steroids reduced or eliminated until infection is controlled. 1

Fungal Keratitis

Topical natamycin 5% is the treatment of choice for fungal keratitis. 6, 3

Natamycin Dosing

• Initial: one drop hourly or every 2 hours. 6
• After 3-4 days: reduce to 6-8 times daily. 6
• Duration: 14-21 days or until resolution of active fungal keratitis. 6
• Gradually taper at 4-7 day intervals to ensure organism elimination. 6

Critical Fungal Keratitis Considerations

• Never use corticosteroids in fungal keratitis—associated with poor outcomes and increased risk of penetrating keratoplasty. 1
• Natamycin is indicated for Fusarium solani keratitis, fungal blepharitis, and conjunctivitis. 6
• Culture and susceptibility testing should guide therapy when possible. 6

Viral (Herpetic) Keratitis

Antiviral therapy is the cornerstone of treatment, with topical or systemic administration depending on depth and severity of involvement. 7, 8, 3

Treatment Strategy

• Epithelial keratitis: Topical antivirals with debridement and mydriatics. 7
• Stromal and endothelial keratitis: Antivirals plus topical corticosteroids. 7, 3
• Systemic antivirals for deep corneal involvement or severe disease. 7
• PCR testing confirms diagnosis in atypical cases. 3

Monitoring and Modification

Signs of Treatment Response (48-72 hours)

• Reduced pain and discharge 5
• Lessened eyelid edema and conjunctival injection 5
• Consolidation and sharper demarcation of infiltrate perimeter 5
• Decreased infiltrate density without progressive stromal loss 5
• Reduced anterior chamber inflammation and hypopyon 5
• Initial re-epithelialization 5
• Cessation of progressive corneal thinning 5

When to Modify Therapy

• Lack of improvement or stabilization by 48 hours mandates regimen modification. 1, 5
• Higher minimum inhibitory concentration correlates with worse outcomes. 1
• When improving, do not adjust therapy based solely on culture results. 1

Tapering Antibiotics

• Taper according to clinical response and organism virulence. 5
• Never taper below 3-4 times daily—subtherapeutic dosing increases resistance risk. 5
• Pseudomonas and other virulent organisms require more prolonged therapy. 5

Common Pitfalls to Avoid

• Premature discontinuation of antibiotics in Pseudomonas keratitis leads to treatment failure. 5
• Medication toxicity can mimic treatment failure (worsening inflammation, corneal melting). 5
• Confusing increased inflammation from steroid withdrawal with worsening infection. 1
• Using corticosteroids before organism identification or in Nocardia/fungal infections. 1
• Chronic prophylactic antibiotics promote resistant organism growth. 1