A 38-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 stromal infiltration and hypopyon. Gram stain of corneal scrapings shows gram-positive cocci in clusters. What is the drug of choice for empirical topical therapy?

## Bacterial Corneal Ulcer — Empirical Topical Therapy **Key Point:** Fortified topical antibiotics (cefazolin + gentamicin) are the gold standard for empirical treatment of bacterial corneal ulcers with stromal involvement and hypopyon, pending culture and sensitivity results. ### Rationale for Fortified Cefazolin + Gentamicin 1. **Broad-spectrum coverage**: Cefazolin (3rd-generation cephalosporin) covers gram-positive cocci (including *Staphylococcus aureus*, *Streptococcus pneumoniae*) and some gram-negatives; gentamicin covers gram-negative rods (*Pseudomonas aeruginosa*, *Enterobacteriaceae*). 2. **High corneal penetration**: Fortified formulations (5% cefazolin, 1.4% gentamicin) achieve therapeutic corneal levels without systemic absorption. 3. **Synergistic effect**: The combination provides superior bactericidal activity for severe, sight-threatening infections. 4. **Hypopyon presence**: Indicates anterior chamber involvement and significant bacterial load — requires aggressive dual therapy. ### Dosing Protocol - **Frequency**: Every 1 hour while awake (initially), then taper as clinical improvement occurs. - **Duration**: 7–14 days depending on ulcer healing and culture results. **High-Yield:** Fortified antibiotics are **not** used for prophylaxis or mild conjunctivitis — reserve for **stromal ulcers with hypopyon or significant infiltration**. ### Comparison of Topical Agents in Bacterial Corneal Ulcer | Agent | Spectrum | Penetration | Indication | Limitation | |-------|----------|-------------|-----------|------------| | Fortified cefazolin + gentamicin | Gram-positive + gram-negative | Excellent (fortified) | Empirical severe bacterial ulcer | Requires compounding; frequent dosing | | Fluoroquinolone (moxifloxacin) | Broad-spectrum | Good | Mild–moderate, contact lens ulcers | Monotherapy inadequate for severe stromal disease | | Natamycin 5% | Fungal (Candida, Aspergillus) | Moderate | Fungal ulcer | No antibacterial activity | | Acyclovir 3% | Herpes simplex virus | Poor corneal penetration | HSV keratitis | No bacterial coverage | **Clinical Pearl:** In resource-limited settings where fortified antibiotics are unavailable, a fluoroquinolone (moxifloxacin or ofloxacin) may be used as a second-line option, but efficacy is lower for severe infections. **Warning:** Do not use fluoroquinolone monotherapy for hypopyon ulcers — risk of treatment failure and corneal perforation.