When to Initiate Fortified Antibiotic Eyedrops
Fortified antibiotic eyedrops should be initiated for severe bacterial keratitis, specifically when there is deep stromal involvement or infiltrates larger than 2 mm with extensive suppuration, or when the infection is unresponsive to initial fluoroquinolone therapy. 1
Severity-Based Treatment Algorithm
Mild to Moderate Bacterial Keratitis
- Start with fluoroquinolone monotherapy (moxifloxacin 0.5%, gatifloxacin, or ofloxacin 0.3%) as first-line treatment 1
- Single-drug fluoroquinolone therapy has been shown to be as effective as fortified antibiotic combinations for non-severe infections 2, 3, 4
- Fourth-generation fluoroquinolones (moxifloxacin, gatifloxacin) provide better gram-positive coverage than earlier generations, though they are not FDA-approved specifically for bacterial keratitis 1
Severe Bacterial Keratitis - Immediate Fortified Antibiotics
Initiate fortified antibiotics immediately when:
- Deep stromal involvement is present 1, 2
- Infiltrate diameter exceeds 2 mm with extensive suppuration 1
- Impending or frank corneal perforation 1
- Infectious process extends to adjacent tissues (e.g., sclera) 1
Treatment Failure - Switch to Fortified Antibiotics
Consider fortified antibiotics when:
- No clinical improvement after 48-72 hours of fluoroquinolone therapy 1
- Clinical worsening despite appropriate initial therapy 1
- Culture results indicate resistant organisms (MRSA, multidrug-resistant Pseudomonas) 1
Recommended Fortified Antibiotic Combinations
Standard dual therapy regimens:
- Cefazolin 50 mg/ml + Tobramycin 14 mg/ml (or Gentamicin 14 mg/ml) for broad gram-positive and gram-negative coverage 1, 5
- Alternative: Vancomycin 15-50 mg/ml + Tobramycin 14 mg/ml for suspected MRSA 1
Special Circumstances Requiring Fortified Antibiotics
Methicillin-Resistant Staphylococcus aureus (MRSA)
- Fluoroquinolones are generally poorly effective against MRSA ocular isolates 1
- Vancomycin 15-50 mg/ml is the treatment of choice for confirmed or suspected MRSA keratitis 1
- MRSA prevalence in ocular isolates has been reported at 42% of staphylococcal isolates in recent studies 1
Multidrug-Resistant Pseudomonas aeruginosa
- Topical colistin 0.19% should be considered for resistant Pseudomonas 1
- Resistance to moxifloxacin in P. aeruginosa has increased dramatically in some regions (19% to 52% over 2 years in southern India) 1
Post-Refractive Surgery Infections
- Consider fortified antibiotics earlier due to higher risk of MRSA and atypical mycobacteria 1
- Nontuberculous mycobacteria associated with LASIK may require multi-agent fortified therapy 1
Critical Dosing Considerations
Initial intensive dosing for severe cases:
- Instill fortified antibiotics every hour around the clock for the first 48 hours 1
- Some protocols recommend loading doses every 5-15 minutes initially 2, 6
- After 48 hours, taper based on clinical response 1
Important Caveats
Preparation Requirements
- Fortified antibiotics must be prepared by a compounding pharmacy that is a member of the Pharmacy Compounding Accreditation Board and designated as FDA 503A and/or 503B facility 1
- Proper sterile technique is essential during preparation 1
- Refrigerate all fortified preparations and shake well before instillation 1
Toxicity Concerns
- Aminoglycosides and vancomycin can retard epithelial healing 5
- Aminoglycosides may cause corneal and conjunctival toxicity 5
- Monitor closely for adverse effects, especially with prolonged use 5
Risk Factors for Fluoroquinolone Resistance
Consider fortified antibiotics earlier if patient has:
- Recent fluoroquinolone use 1, 2
- Recent hospitalization 1, 2
- Advanced age 1, 2
- Recent ocular surgery 1, 2