What is the role of cefazolin in treating bacterial keratitis in a contact lens wearer?

Cefazolin in Bacterial Keratitis for Contact Lens Wearers

Cefazolin 50 mg/ml fortified topical solution is a critical component of combination antibiotic therapy for severe bacterial keratitis in contact lens wearers, particularly when combined with an aminoglycoside like tobramycin or gentamicin to provide comprehensive coverage against both gram-positive organisms (especially Staphylococcus species) and Pseudomonas aeruginosa.

When to Use Cefazolin-Based Fortified Therapy

Escalate to fortified cefazolin + aminoglycoside combination therapy when:

• Large corneal infiltrates are present 1, 2
• Central location of the ulcer threatens vision 1, 2
• Hypopyon is visible 1, 2
• Severe bacterial keratitis with significant stromal involvement 1

Start with fluoroquinolone monotherapy (moxifloxacin 0.5%, levofloxacin 1.5%, or ciprofloxacin 0.3%) only for small, non-central ulcers without hypopyon. 2

Preparation of Fortified Cefazolin 50 mg/ml

The American Academy of Ophthalmology provides specific compounding instructions: 1

1. Add 9.2 ml of artificial tears to a vial of cefazolin 1 g powder for injection
2. Dissolve completely, then take 5 ml of this solution and add it to 5 ml of artificial tears
3. Refrigerate and shake well before each instillation

Combination Therapy Rationale

Cefazolin must be combined with an aminoglycoside (tobramycin 14 mg/ml or gentamicin 14 mg/ml) because:

• Contact lens-associated keratitis is most commonly caused by Pseudomonas aeruginosa (the dominant gram-negative pathogen), which cefazolin does not adequately cover 3, 4
• Cefazolin provides robust gram-positive coverage, particularly against Staphylococcus species 4, 5
• The combination of cefazolin + tobramycin achieves 93% empiric coverage of bacterial keratitis isolates 5
• Cefazolin demonstrates superior potency against Staphylococcus aureus compared to cefuroxime 5

Evidence Hierarchy for Antibiotic Selection

Recent network meta-analysis data (2025) shows healing time rankings: 6

• Vancomycin + ceftazidime (fastest healing, SUCRA 83.8)
• Moxifloxacin monotherapy (SUCRA 83.1)
• Cefazolin + tobramycin (SUCRA 71.3)

However, cefazolin + tobramycin remains the standard fortified combination therapy recommended by the American Academy of Ophthalmology for severe cases requiring dual therapy. 1

Dosing Frequency

• Apply fortified cefazolin + aminoglycoside every 30-60 minutes around the clock initially for severe keratitis 2
• Taper frequency based on clinical response at 24-48 hour follow-up 2

Critical Adjunctive Measures

Immediately implement these concurrent interventions:

• Remove and discard contact lenses and cases permanently 2, 7
• Add cyclopentolate 1% or homatropine 5% three times daily to reduce pain and prevent synechiae 2
• Never patch the eye as this dramatically increases infection progression risk 2
• Obtain corneal scrapings for culture before starting antibiotics in sight-threatening cases 2

Resistance Patterns to Consider

Cefazolin shows significant resistance in certain organisms: 4, 8

• Bacterial keratitis isolates demonstrate high resistance to cephalosporins including cefazolin 4
• Streptococcus pneumoniae shows 100% resistance to gentamicin, making cefazolin the critical component for streptococcal coverage 8
• All gram-positive isolates remain vancomycin-sensitive, making vancomycin + ceftazidime an alternative for resistant cases 8, 6

When Cefazolin-Based Therapy May Be Insufficient

Consider vancomycin + ceftazidime instead of cefazolin + aminoglycoside when:

• Methicillin-resistant Staphylococcus aureus (MRSA) is suspected or confirmed (gentamicin provides 100% MRSA coverage in combination regimens) 5
• Treatment failure occurs after 48-72 hours on cefazolin + tobramycin 2
• Culture results show cefazolin resistance 4, 8

Common Pitfalls to Avoid

• Do not use cefazolin monotherapy for contact lens-related keratitis—Pseudomonas coverage is essential 3, 4
• Do not use ocular ointments as primary therapy due to poor corneal penetration 2
• Do not add topical corticosteroids initially as they delay healing and increase infection risk 2
• Do not allow water contact during treatment or future contact lens wear (swimming, showering, hot tubs) 1, 2, 7

Follow-Up Protocol

• Reassess within 24 hours of treatment initiation to detect early treatment failure 2
• If no improvement or worsening at 3-4 days, obtain repeat culture and sensitivity testing 7
• Monitor for complications requiring surgical intervention (corneal perforation, endophthalmitis) 4, 9