What is the antimicrobial spectrum and mechanism of action of Neosporin (bacitracin, neomycin, polymyxin B) ointment?

Neosporin Ointment: Antimicrobial Spectrum and Mechanism of Action

Antimicrobial Spectrum

Neosporin (triple-antibiotic ointment containing neomycin, polymyxin B, and bacitracin) provides broad-spectrum coverage against the most common wound pathogens, including Staphylococcus aureus, coagulase-negative staphylococci, Pseudomonas aeruginosa, Escherichia coli, and other Enterobacteriaceae. 1, 2

Gram-Positive Coverage

• Staphylococcus aureus: At 1:100 dilution of ointment concentration, only 5% resistance observed, with 95% susceptibility maintained despite decades of over-the-counter use in the United States 2
• Methicillin-resistant S. aureus (MRSA): 98% susceptibility demonstrated in Australian surveillance data 2
• Coagulase-negative staphylococci: 100% susceptibility at therapeutic concentrations 2
• Enterococcus faecalis: Covered through synergistic neomycin/polymyxin B activity 1

Gram-Negative Coverage

• Pseudomonas aeruginosa: 100% susceptibility, with synergistic activity from both neomycin/bacitracin and bacitracin/polymyxin B combinations 1, 2
• Enterobacteriaceae (E. coli and others): 100% susceptibility maintained 2

Clinical Resistance Patterns

• Mupirocin-resistant organisms remain susceptible: All mupirocin-resistant S. aureus (5%) and coagulase-negative staphylococci (47%) were inhibited by triple-antibiotic ointment, making it an effective alternative when mupirocin resistance is present 2
• Stable susceptibility over time: No significant variation in resistance patterns observed from 1997-2002 in U.S. surveillance despite extensive over-the-counter availability 2

Mechanisms of Action

The three components work through distinct mechanisms that complement each other and produce synergistic antibacterial effects. 1

Neomycin (Aminoglycoside)

• Mechanism: Binds to the 30S ribosomal subunit, causing misreading of mRNA and inhibiting bacterial protein synthesis 1, 3
• Primary targets: Gram-negative bacteria and some gram-positive organisms 1
• Synergistic interactions: Demonstrates synergy with bacitracin against S. aureus and P. aeruginosa (FIC index <0.5), and with polymyxin B against E. faecalis 1

Polymyxin B (Polypeptide)

• Mechanism: Disrupts bacterial cell membrane integrity by binding to lipopolysaccharides in the outer membrane of gram-negative bacteria, causing leakage of intracellular contents 1, 3
• Primary targets: Gram-negative bacteria, particularly Pseudomonas species 1
• Synergistic interactions: Works synergistically with bacitracin against P. aeruginosa and with neomycin against E. faecalis 1

Bacitracin (Polypeptide)

• Mechanism: Inhibits bacterial cell wall synthesis by interfering with dephosphorylation of the lipid carrier that transports peptidoglycan precursors across the cell membrane 1, 3
• Primary targets: Primarily gram-positive bacteria, with some gram-negative activity 1
• Synergistic interactions: Synergistic with neomycin against S. aureus and P. aeruginosa, and with polymyxin B against P. aeruginosa 1

Three-Drug Synergy

• Enhanced efficacy: The three-drug combination achieves FIC values <1 for all common wound pathogens (S. aureus, E. faecalis, P. aeruginosa), indicating synergistic rather than merely additive effects 1
• Depth of penetration: Eradicates resident bacteria through 25 layers of stratum corneum and prevents overnight repopulation, though bacteria return within one week 4
• Complementary coverage: The distinct mechanisms ensure that organisms resistant to one component remain susceptible to the others, explaining the low overall resistance rates 1, 2

Clinical Relevance

Appropriate Use Contexts

• Minor wound prophylaxis: Reduces incidence of staphylococcal and streptococcal infections in minor skin trauma 5
• Hemodialysis catheter exit sites: Polysporin (bacitracin/polymyxin B, without neomycin) application associated with 75-93% reduction in catheter-related bloodstream infections, with bacteremia rates <1.0/1,000 catheter days maintained over 6 years without resistance development 6

Critical Safety Limitations

• Neomycin contact sensitivity: Occurs in 13-30% of patients with chronic otitis externa on patch testing, making it a significant concern for prolonged or repeated use 7, 8
• Ototoxicity risk: Should never be used with non-intact tympanic membranes (perforations or tympanostomy tubes) due to potential inner ear damage from aminoglycoside exposure 7, 8
• Systemic absorption concerns: Systemic side effects occur only with improper massive exposure, but risk increases with application to large surface areas or compromised skin barriers 5

Common Pitfalls to Avoid

• Assuming aminoglycoside cross-resistance: Neomycin resistance patterns differ significantly from gentamicin, tobramycin, and amikacin—none of these commonly tested parenteral aminoglycosides accurately predict neomycin resistance 2
• Using in ear infections without confirming tympanic membrane integrity: Always verify intact tympanic membrane before prescribing neomycin-containing preparations for otitis externa 7, 8
• Overlooking allergic contact dermatitis: Worsening symptoms 48-96 hours after initiating therapy may indicate neomycin allergy rather than treatment failure 7, 9