Bacitracin

Bacitracin requires zinc (Zn2+) for activity. The bacitracin-Zn2+ complex binds undecaprenyl pyrophosphate (C55-PP), the isoprenoid lipid carrier that shuttles peptidoglycan precursors from the cytoplasm to the periplasm during cell wall synthesis. After transferring the precursor, C55-PP must be dephosphorylated to C55-P to be recycled. Bacitracin traps C55-PP, preventing this regeneration and depleting the pool of functional carrier lipid. Cell wall synthesis halts with insufficient carrier available, leading to bacteriolysis. This mechanism is distinct from and complementary to beta-lactams, glycopeptides, and fosfomycin.

Bacitracin is active against Gram-positive organisms because it cannot penetrate the outer membrane of Gram-negatives to reach periplasmic C55-PP. Activity covers Streptococcus pyogenes (Group A strep), S. aureus, and most other Gram-positive pathogens including MRSA (though MIC values for MRSA are higher). The topical OTC use primarily targets Gram-positive skin pathogens causing impetigo, wound infections, and minor skin infections.

Bacitracin is a component of Neosporin (with neomycin and polymyxin B) and bacitracin-only ointments used for minor cuts, wounds, and burns. Clinical evidence supports reduction in wound infection rates and improved healing compared to no treatment. Contact allergy to neomycin (in combination products) is more common than to bacitracin itself. Bacitracin-only ointments are preferred for neomycin-sensitive patients.

Bacitracin disc susceptibility testing (0.04 units disc) is used clinically to presumptively identify Group A Streptococcus (uniformly susceptible) from other beta-hemolytic streptococci. This simple diagnostic test uses bacitracin as a selective inhibitor rather than a therapeutic agent. Resistance is uncommon in Group A strep, making this a reliable clinical test even though it does not represent antibiotic therapy.