Metronidazole + Neomycin Sulphate + Polymyxin B + Nystatin

Approved Indications:

A. Topical Ear (Otic) Infection – Complex/Mixed Etiology

• Otitis externa with mixed bacterial (Gram-positive/negative) and fungal involvement
• Postoperative ear wounds (e.g., canaloplasty, mastoidectomy) to prevent or treat mixed infections

B. Topical Wound or Skin Applications

• Mixed superficial bacterial-fungal skin infections, especially in moist intertriginous areas
• Peristomal dermatitis with confirmed bacterial and fungal components

Off-Label / Clinically Accepted Uses:

• Mixed dermal ulcers or erosions with polymicrobial colonization
• Secondary prevention in chronic otorrhea after tympanoplasty or tympanomastoid surgery

Formulations: Otic solution, cream, or ointment

Adults & Children (≥2 years oral equivalent)

• Otic Solution:
• Instill 3–4 drops into affected ear 3–4 times daily
• Duration: 7–14 days, depending on clinical response
• Topical Cream/Ointment:
• Apply thin film to clean, dry affected area 3–4 times daily
• Duration: 1–2 weeks or per clinical judgment

Pediatrics (<2 years):

• Use with caution; liberal guidance only under specialist review

Elderly:

• Same dosing; careful administration in ear canal with limited dexterity

Renal/Hepatic Impairment:

• No systemic dosing adjustment necessary; minimal systemic absorption

• Metronidazole: Activated in low-oxygen environments to generate free radicals that damage DNA of anaerobic bacteria.
• Neomycin Sulphate: Aminoglycoside that binds 30S bacterial ribosomal subunit, interrupting protein synthesis in Gram-negative and select Gram-positive bacteria.
• Polymyxin B: Disrupts Gram-negative bacterial cell membranes via interaction with lipopolysaccharides, causing cell lysis.
• Nystatin: Binds ergosterol in fungal cell membranes, creating destructive pores and inducing fungal cell death.
• Combined action ensures broad-spectrum activity against anaerobic bacteria, Gram-negative and Gram-positive aerobes, and Candida species commonly found in external ear and moist skin infections.

• Absorption: Minimal systemic absorption with topical or otic application unless skin is ulcerated or ear drum is unsealed.
• Distribution: Primarily localized at application site.
• Metabolism:
• Metronidazole undergoes hepatic metabolism if absorbed.
• Neomycin, polymyxin B, and nystatin remain largely unabsorbed systemically.
• Half-life: Negligible systemic presence; otic solution cleared via ear canal drainage.
• Excretion: Metronidazole metabolites urinary; others via feces or unattached debris.

• Pregnancy:
• Topical/otic route yields minimal systemic absorption.
• Metronidazole: Category B—safe with topical use in pregnancy.
• Nystatin: Generally safe (polyenes are category A/B).
• Neomycin/Polymyxin B: Minimal systemic absorption; topical use considered acceptable.
• Lactation:
• Excretion into breast milk is negligible. Safe if avoiding nipple contact and washing before breastfeeding.

• Primary Class: Broad-spectrum topical antimicrobial combination
• Subclasses: Nitroimidazole, Aminoglycoside, Polymyxin, Polyene antifungal

• Known allergy to any component (neomycin, polymyxin B, metronidazole, nystatin)
• Perforated tympanic membrane unless product labeling confirms suitability
• Otitis media with liver disease unless using otic-only formulations
• Neonates (risk of ototoxicity with aminoglycosides)

• Ototoxicity: Aminoglycoside risk increased if tympanic membrane perforated—use only if indicated and monitor hearing
• Nephrotoxicity: Minimal topical absorption unlikely to cause systemic effects
• Contact Dermatitis: Rare allergic reactions; discontinue if rash or itching present
• Fungal Overgrowth: Prolonged use may encourage resistant non-Candida organisms

Common (Topical):

• Mild local irritation or burning at application site
• Temporary ear itching or fullness
• Transient dry skin or mild pruritus with skin cream

Rare/Serious:

• Contact dermatitis or allergic reactions
• Transient hearing changes if product reaches middle ear with perforated drum
• Rare ototoxicity with prolonged use in ear

• Otic/topical route: Minimal systemic interaction
• Theoretical Considerations:
• Metronidazole: Additive effects with other topical irritants or ototoxic agents
• Avoid concurrent otic solutions containing aminoglycosides to minimize ototoxicity risk

• 2023 AAP Otitis Externa Guidelines: Only use aminoglycoside-containing eardrops when bacterial cultures confirm susceptible organisms and tympanic membrane is intact.
• 2024 FDA Safety Alert: Increased monitoring advised with neomycin-based otics in patients with known or suspected tympanic perforation.
• CDC SSTI Guidelines: Support combination antimicrobials for mixed bacterial–fungal skin infections when first-line therapies aren’t appropriate.

• Temperature: Store at 20°C to 25°C (68°F to 77°F); excursions allowed to 15°C–30°C
• Light & Humidity: Keep in original tightly closed container, protected from light and moisture
• Freezing: Protect from freezing
• Otic: Warm to body temperature before administration by holding bottle in palm briefly
• Cream/Ointment: Use applicator or gloves; close container tightly after each use