A 35-year-old farmer presents with a 3-day history of severe ocular pain, photophobia, and purulent discharge from the right eye. Slit-lamp examination reveals a central corneal ulcer with a white infiltrate and hypopyon. Gram stain of corneal scrapings shows gram-positive cocci in clusters. What is the drug of choice for empiric topical therapy?

## Bacterial Corneal Ulcer — First-Line Topical Therapy **Key Point:** Bacterial corneal ulcers require aggressive topical antibiotic therapy with fortified antibiotics (high-concentration, non-commercial formulations) to achieve adequate corneal penetration and therapeutic levels. ### Clinical Presentation Recognition The clinical triad of: - Central corneal infiltrate with hypopyon - Purulent discharge - Gram-positive cocci in clusters (Staphylococcus aureus) ...indicates **bacterial keratitis** requiring immediate fortified antibiotic therapy. ### Fortified Antibiotic Regimen | Feature | Fortified Cephalosporin + Aminoglycoside | Fluoroquinolone Monotherapy | |---------|------------------------------------------|---------------------------| | **Preparation** | Cefazolin 5% + Gentamicin 1.4% (fortified) | Ciprofloxacin 0.3% (commercial) | | **Corneal Penetration** | Excellent (high concentration) | Moderate (lower concentration) | | **Gram-positive Coverage** | Excellent | Good | | **Gram-negative Coverage** | Excellent | Excellent | | **Dosing Frequency** | Every 30 min–1 hour (day 1–2), then every 2 hours | Every 30 min–1 hour | | **First-Line Status** | **YES — Gold standard** | Alternative monotherapy | | **Indication** | Severe, sight-threatening ulcers | Mild-to-moderate ulcers | **High-Yield:** Fortified antibiotics are **NOT commercially available** — they must be prepared by the hospital pharmacy by diluting injectable antibiotics. This is the standard of care in India for moderate-to-severe bacterial keratitis. ### Why Fortified Cephalosporin + Aminoglycoside? 1. **Synergistic coverage:** Cephalosporin covers gram-positive cocci (including MRSA strains); gentamicin covers gram-negative rods and provides synergy. 2. **Superior corneal penetration:** Fortified formulations (5% cephalosporin, 1.4% gentamicin) achieve therapeutic levels in corneal tissue. 3. **Empiric broad-spectrum:** Covers the most common bacterial pathogens (Staphylococcus, Streptococcus, Pseudomonas, Moraxella) before culture results. 4. **Guideline standard:** Endorsed by American Academy of Ophthalmology (AAO) and Indian ophthalmology literature as first-line for moderate-to-severe keratitis. **Clinical Pearl:** The combination is applied **alternately** (not mixed) every 30 minutes to 1 hour during the acute phase, then tapered based on clinical response. Topical NSAIDs are **avoided** in the acute phase (risk of perforation). **Mnemonic:** **CFAG** = **C**ephalosporin + **F**ortified + **A**minoglycoside + **G**entamicin for **G**ram-positive keratitis.