What is the recommended topical treatment for gram-negative infections?

Topical Treatment for Gram-Negative Infections

For gram-negative infections amenable to topical therapy, use topical antibiotics with gram-negative activity such as polymyxin B, aminoglycosides (gentamicin, tobramycin), or fluoroquinolones (ciprofloxacin), which achieve tissue concentrations 100-1000 times higher than systemic therapy. 1

Primary Topical Agents for Gram-Negative Coverage

Polymyxin B (First-Line for Topical Use)

• Polymyxin B has bactericidal action against almost all gram-negative bacilli except the Proteus group 2
• For ophthalmic infections caused by Pseudomonas aeruginosa, use a concentration of 0.1-0.25% (10,000-25,000 units/mL), administered 1-3 drops every hour initially 2
• Polymyxin B increases bacterial cell membrane permeability, leading to cell death 2
• All gram-positive bacteria, fungi, and gram-negative cocci are resistant to polymyxin B 2

Aminoglycosides (Alternative Topical Agents)

• Aminoglycosides (gentamicin, tobramycin, neomycin) are effective against a broad spectrum of gram-negative organisms including P. aeruginosa 3
• Neomycin is limited by toxicity to topical preparations only 3
• Gentamicin and tobramycin have excellent gram-negative coverage and are commonly used in topical formulations 3

Fluoroquinolones (Preferred for Ear Infections)

• Topical ciprofloxacin/hydrocortisone is highly effective for acute otitis externa caused by gram-negative organisms 1
• Fluoroquinolones provide excellent Pseudomonas coverage in topical formulations 1

Site-Specific Recommendations

Acute Otitis Externa

• Topical therapy alone (without systemic antibiotics) is the treatment of choice for uncomplicated acute otitis externa 1
• Topical preparations should contain antibiotics active against gram-negative organisms (polymyxin B or fluoroquinolones) 1
• Topical therapy delivers antibiotic concentrations of approximately 3000 µg/mL (0.3% solution), vastly exceeding systemic levels 1
• Do NOT prescribe systemic antimicrobials as initial therapy for diffuse, uncomplicated acute otitis externa 1

Ophthalmic Infections

• For P. aeruginosa eye infections, dissolve 500,000 polymyxin B units in 20-50 mL sterile water to achieve 10,000-25,000 units/mL concentration 2
• Subconjunctival injection of up to 100,000 units/day may be used for corneal and conjunctival Pseudomonas infections 2
• Avoid total systemic and ophthalmic instillation exceeding 25,000 units/kg/day 2

Diabetic Foot Infections (Mild)

• Limited data support topical antimicrobial therapy for mildly infected open wounds with minimal cellulitis 1
• Most mild infections can be treated with agents covering aerobic gram-positive cocci, but in warm climates, gram-negative isolates (especially P. aeruginosa) are more prevalent and may require broader coverage 1

Critical Considerations

When Topical Therapy is Insufficient

• Severe infections require systemic therapy with broad-spectrum agents active against gram-negative organisms 1
• Extension beyond the local site mandates systemic antimicrobials 1
• Polymyxin-based combination therapy should be considered for multidrug-resistant strains requiring systemic treatment 4, 5

Pseudomonas Coverage

• P. aeruginosa is a particularly problematic pathogen requiring specifically targeted coverage 1
• Polymyxin B and fluoroquinolones provide reliable anti-pseudomonal activity in topical formulations 2
• In countries with warm climates or patients soaking their feet, empiric anti-pseudomonal therapy is advisable 1

Resistance Patterns

• Polymyxins (polymyxin B, colistin) are increasingly used as last-line options for multidrug-resistant gram-negative bacteria 6, 7
• Extended-spectrum β-lactamase (ESBL) producing organisms are alarmingly prevalent and may require carbapenem-sparing topical regimens when feasible 1

Common Pitfalls

• Avoid prescribing systemic antibiotics for infections that can be adequately treated with topical therapy alone - this increases adverse effects (rashes, diarrhea, allergic reactions) and promotes resistance 1
• Do not assume P. aeruginosa isolated from wounds is always pathogenic; it may be a colonizer, especially in northern climates where prevalence is <10% 1
• Polymyxin B loses 50% of its activity in the presence of serum, making topical application more effective than systemic use for localized infections 2
• Neomycin should never be used systemically due to toxicity; restrict to topical/irrigating preparations only 3
• Avoid combining nephrotoxic drugs with polymyxins due to increased renal injury risk 4