Fortified Eye Drops and Keratitis Regimens: Concentrations and Preparation
Last updated: October 2026
Concentrations, standard preparation methods and starter regimens for microbial keratitis. Always scrape and send cultures before starting, and follow your hospital pharmacy's aseptic protocol.
Safety: prepare fortified drops under aseptic conditions (ideally in pharmacy), label them with drug, concentration, date and "keep refrigerated", and replace them according to local stability rules (commonly within about 7 days). Check concentrations twice: these are 10–20 times stronger than commercial drops.
Antibacterial
| Drug | Concentration | Common preparation | Covers |
|---|---|---|---|
| Cefazolin (fortified) | 50 mg/mL (5%) | Add 9.2 mL of artificial tears or sterile saline to a 1 g vial (about 100 mg/mL); take 5 mL and add 5 mL more vehicle | Gram-positive |
| Vancomycin (fortified) | 25–50 mg/mL | Add 10 mL (for 50 mg/mL) or 20 mL (for 25 mg/mL) of vehicle to a 500 mg vial | Gram-positive including MRSA; use for resistant or severe cases |
| Tobramycin (fortified) | About 14 mg/mL (1.4%) | Add 2 mL of injectable tobramycin (40 mg/mL) to a 5 mL bottle of commercial 0.3% tobramycin drops | Gram-negative including Pseudomonas |
| Ceftazidime (fortified) | 50 mg/mL | As per pharmacy protocol (reconstitute vial to 50 mg/mL in vehicle) | Gram-negative (alternative to aminoglycoside) |
| Moxifloxacin 0.5% or gatifloxacin 0.3–0.5% | Commercial | Ready to use | Broad monotherapy for small, peripheral ulcers |
Antifungal
| Drug | Concentration | Preparation | Notes |
|---|---|---|---|
| Natamycin | 5% | Commercial suspension | First choice for filamentary fungi, especially Fusarium (MUTT I: better than topical voriconazole) |
| Voriconazole | 1% (10 mg/mL) | Reconstitute a 200 mg vial to 20 mL with sterile water or vehicle | Good for Aspergillus and as an add-on. Oral voriconazole added no benefit in MUTT II. |
| Amphotericin B | 0.15% (1.5 mg/mL) | Reconstitute a 50 mg vial in 10 mL sterile water (5 mg/mL), then dilute 3 mL of this with 7 mL of water | Yeasts (Candida). Protect from light. |
Acanthamoeba
- Biguanides: PHMB 0.02% or chlorhexidine 0.02%, often with a diamidine (propamidine 0.1%). Polihexanide 0.08% monotherapy is now licensed in Europe.
- Very frequent dosing at first (hourly day and night for 48 hours), then taper over months. Pain out of proportion and a ring infiltrate are the clues.
Starter regimen and taper
| Stage | Typical frequency |
|---|---|
| Loading | Every 5–15 minutes for the first hour (or a drop every 5 minutes for 5 doses) |
| Intensive phase | Hourly day and night for 24–48 hours (alternate the two fortified drops every 30 minutes) |
| When improving (smaller infiltrate, healing epithelium, less pain) | 2-hourly while awake, then 4-hourly, guided by culture and response |
| Fungal keratitis | Natamycin hourly while awake for 1–2 weeks, then taper slowly; continue for some weeks after apparent healing |
- Steroids: SCUT showed no overall benefit for bacterial keratitis; avoid them until the organism is known and improving (never in suspected fungal or Acanthamoeba keratitis).
- Add a cycloplegic for pain, and consider an oral anti-collagenase (doxycycline) and vitamin C for melting ulcers.
- Review daily at first. Worsening after 48–72 hours: re-scrape, consider a corneal biopsy or confocal microscopy, and think of fungus, Acanthamoeba, Nocardia or atypical mycobacteria.
Related: microbial keratitis work-up, intrastromal and intravitreal doses and dendrites and pseudo-dendrites.
Key sources
- Wills Eye Manual, 8th ed. Appendix: preparation of fortified antibiotics and antifungals
- Prajna NV et al. The Mycotic Ulcer Treatment Trial (MUTT I). JAMA Ophthalmol 2013;131:422–9
- Prajna NV et al. MUTT II: oral voriconazole. Ophthalmology 2016;123:1229–38
- Srinivasan M et al. The Steroids for Corneal Ulcers Trial (SCUT). Arch Ophthalmol 2012;130:143–50
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