Bacitracin
bacitracin A, bacitracin zinc, BAC
Bacitracin is a cyclic peptide antibiotic described in 1945, produced by a Bacillus strain isolated in 1943 from the wound of a patient named Margaret Tracy, from whom it takes its name. It blocks bacterial cell wall building by trapping the lipid carrier that shuttles peptidoglycan subunits across the membrane. It survives today almost entirely as a topical agent; the injectable form was withdrawn on safety grounds.
Mechanism
Bacitracin binds undecaprenyl pyrophosphate, the pyrophosphorylated form of the C55 lipid carrier that ferries peptidoglycan building blocks across the cytoplasmic membrane. Binding requires a divalent metal ion, normally zinc, which is why commercial preparations are usually formulated as bacitracin zinc. The complex of bacitracin, zinc and undecaprenyl pyrophosphate is stable, so the lipid carrier cannot be dephosphorylated and recycled back to its active undecaprenyl phosphate form. The supply of carrier is finite and rapidly exhausted, cell wall synthesis stops, and the bacterium dies. Because it targets the carrier rather than an enzyme active site, cross-resistance with beta-lactams and glycopeptides is not expected.
The same lipid carrier is used in the synthesis of teichoic acids, capsular polysaccharide and other envelope polymers, so bacitracin has broad effects on Gram-positive envelope biogenesis. Its spectrum covers staphylococci, streptococci, Clostridium species and Neisseria, with most Gram-negative organisms intrinsically resistant because the peptide cannot cross the outer membrane. In the laboratory, disc susceptibility to bacitracin remains a classical presumptive test for group A streptococci. Resistance in Bacillus and some staphylococci is mediated by BcrABC-type ABC transporters that efflux the peptide and by increased undecaprenyl pyrophosphate phosphatase expression.
What the research shows
The modern story of bacitracin is one of retreat. For the injectable product, an FDA Antimicrobial Drugs Advisory Committee reviewed the evidence in April 2019 and voted almost unanimously that the benefits of intramuscular bacitracin do not outweigh its risks. Its only approved indication had been staphylococcal pneumonia and empyema in infants, a use that had effectively vanished from practice because safer alternatives exist. The FDA requested market withdrawal in January 2020, and subsequently determined formally that the product was withdrawn for reasons of safety or effectiveness, meaning no generic version can be approved. These are regulatory actions rather than published studies and carry no bibliographic identifier.
For topical use, the key randomised comparison remains the 1996 double-blind study by Smack and colleagues in JAMA, in which 922 ambulatory dermatological surgery patients with 1249 wounds were randomised to white petrolatum or bacitracin ointment. This audit corrected the draft's account, which reported only the null infection comparison. Overall postprocedure infection occurred in 13 patients (1.5%): nine (2.0%) in the petrolatum group and four (0.9%) in the bacitracin group, not a significant difference. However, Staphylococcus aureus was responsible for eight infections in the petrolatum group and none in the bacitracin group, a significant difference. Against that, four bacitracin patients (0.9%) and no petrolatum patients developed allergic contact dermatitis. Healing did not differ. The authors concluded that white petrolatum is a safe and effective wound-care ointment with a minimal risk of induced allergy, which is the basis for several dermatology bodies preferring it for routine clean wound care. Bacitracin was named Allergen of the Year by the American Contact Dermatitis Society in 2003, and it is a recognised, if uncommon, cause of anaphylaxis after topical application to open wounds.
Bacitracin retains genuine value in the microbiology laboratory as a presumptive identification test, and interest persists in its mechanism because undecaprenyl pyrophosphate is an attractive and underexploited antibacterial target.
Evidence assessment
Mixed evidence
Retained as mixed, but for corrected reasons. Applying the tiering rule mechanically would give bacitracin a strong rating because topical products hold approved labelling in the United States; that would misrepresent a legacy over-the-counter monograph as a modern efficacy dossier. Only one clinical study in this record survived verification: the 1996 randomised trial of white petrolatum against bacitracin ointment in dermatological surgery (PMID 8805732, 922 patients, 1249 wounds). Its result is genuinely mixed and the draft reported only half of it. Overall infection rates did not differ significantly (2.0% with petrolatum against 0.9% with bacitracin), but Staphylococcus aureus infections occurred in eight petrolatum patients and none given bacitracin, a statistically significant difference; conversely four bacitracin patients and no petrolatum patients developed allergic contact dermatitis. Meanwhile the injectable product, the only formulation ever approved for systemic infection, was judged by an FDA advisory committee in 2019 to have benefits that do not outweigh its risks, and was withdrawn. The three regulatory entries in this record carry no citable identifier and are marked unverified accordingly.
Tiers are applied consistently across the library and re-checked when new trials read out. Read the grading method.
Key studies
Infection and allergy incidence in ambulatory surgery patients using white petrolatum vs bacitracin ointment. A randomized controlled trial Preclinical only
Mixed result. Overall postprocedure infection occurred in 13 patients (1.5%), nine (2.0%) with white petrolatum against four (0.9%) with bacitracin, not a significant difference. Staphylococcus aureus caused eight infections in the petrolatum group and none in the bacitracin group (p=0.004). Conversely, four bacitracin patients (0.9%) and no petrolatum patients developed allergic contact dermatitis. Healing did not differ. The authors concluded white petrolatum is a safe and effective wound-care ointment with minimal risk of induced allergy.
FDA Antimicrobial Drugs Advisory Committee review of bacitracin for injection Preclinical only
The committee voted almost unanimously that the benefits of bacitracin for intramuscular injection do not outweigh its risks, citing nephrotoxicity and anaphylactic reactions and the availability of safer alternatives for the sole approved indication of staphylococcal pneumonia and empyema in infants.
FDA request for voluntary withdrawal of all bacitracin for injection applications Preclinical only
The FDA requested that all application holders voluntarily request withdrawal of approval for bacitracin for injection, concluding that the potential problems associated with the product were sufficiently serious that it should be removed from the market.
Determination that bacitracin for injection was withdrawn from sale for reasons of safety or effectiveness Preclinical only
The FDA determined that bacitracin for injection was withdrawn for reasons of safety or effectiveness, which prevents approval of abbreviated applications referencing it.
Safety
Systemic bacitracin causes nephrotoxicity, which was the principal reason for withdrawal of the injectable product, and can cause anaphylaxis. Topical bacitracin is generally well tolerated but is a notable contact sensitiser, producing allergic contact dermatitis that is often mistaken for worsening wound infection. Anaphylaxis following topical application to open wounds or mucosa has been reported and is the reason some guidelines advise against its use on large or deep wounds. Ototoxicity and neuromuscular blockade were described with systemic use. Irrigation of surgical wounds with bacitracin solutions has been associated with anaphylactic reactions.
Regulatory status
| Jurisdiction | Status |
|---|---|
| United Kingdom | Bacitracin is not marketed in the UK as a general over-the-counter topical antibiotic in the way it is in the United States. Historical combination preparations containing bacitracin have been discontinued, and UK practice discourages routine topical antibacterial prophylaxis of minor wounds in favour of cleaning and simple dressings. Any current availability is very limited and specialist. Bacitracin is not available as a systemic medicine in the UK. |
| United States | Topical bacitracin ointment is available without prescription under the FDA over-the-counter monograph for first aid antibiotics, alone and in combination with neomycin and polymyxin B. Bacitracin for injection is no longer available: the FDA requested voluntary withdrawal from all application holders on 31 January 2020 following an April 2019 advisory committee vote that its benefits do not outweigh the risks of nephrotoxicity and anaphylaxis. Federal Register notices subsequently completed the withdrawal of the abbreviated applications, and the FDA formally determined that bacitracin for injection was withdrawn for reasons of safety or effectiveness. The specific Federal Register citations were not independently confirmed in this audit pass and no docket number is asserted here. |
| WADA (sport) | Not prohibited. Bacitracin does not appear on the WADA Prohibited List in or out of competition. |
Questions
The best randomised evidence gives a mixed answer, and it is worth stating both halves. In a double-blind trial of 922 dermatological surgery patients, overall infection rates did not differ significantly between white petrolatum and bacitracin ointment. However, Staphylococcus aureus infections occurred in eight petrolatum patients and none given bacitracin, a significant difference, while allergic contact dermatitis occurred in four bacitracin patients and none given petrolatum. The trial authors concluded that white petrolatum is a safe and effective wound-care ointment with minimal allergy risk, and several dermatology bodies now recommend it for routine clean wound care on that basis. Bacitracin was named Allergen of the Year by the American Contact Dermatitis Society in 2003.
Because it caused kidney damage and anaphylaxis, and its only approved use, treating staphylococcal pneumonia and empyema in infants, had been superseded by safer drugs. An FDA advisory committee in 2019 voted almost unanimously that the benefits did not outweigh the risks. The FDA then requested voluntary withdrawal from all application holders and subsequently determined formally that the product had been withdrawn for reasons of safety or effectiveness, which blocks approval of any generic version.
Both interfere with cell wall building, but at different points. Penicillins inhibit the transpeptidase enzymes that cross-link peptidoglycan strands once the building blocks have arrived outside the membrane. Bacitracin acts earlier, binding the undecaprenyl pyrophosphate lipid carrier that ferries those building blocks across the membrane, and preventing it from being recycled. Because the carrier pool is small, synthesis stops quickly. The different target means bacitracin does not share cross-resistance with beta-lactams.