Bacitracin

Bacteria build their cell walls with the help of a lipid carrier, undecaprenyl pyrophosphate, that ferries wall building blocks across the cell membrane and must be recycled after each trip. Bacitracin, bridged by a metal ion such as zinc, forms a tight complex with the pyrophosphate end of this carrier and blocks its recycling, so the cell runs out of free carrier and cannot keep building wall¹. A high-resolution crystal structure published in 2013 showed the antibiotic completely enclosing the pyrophosphate group, flanked by zinc and sodium ions². Its activity is mainly against Gram-positive bacteria, including streptococci; in combination products it is paired with polymyxin B, which targets Gram-negative bacteria⁵.

Its injectable form was first approved in the US in 1948⁶. A key randomized, double-blind trial from 1996 assigned 922 people having outpatient skin surgery to bacitracin ointment or plain white petrolatum for wound care³. Infection rates were low in both groups and not statistically different (0.9% with bacitracin, 2.0% with petrolatum), although all of the Staphylococcus aureus infections occurred in the petrolatum group. Four bacitracin users (0.9%) developed allergic contact dermatitis, compared with none on petrolatum, and wound healing did not differ at any measured time point³. The authors concluded that plain petrolatum was an effective, lower-allergy choice for wounds after outpatient surgery. On the laboratory side, the mechanism was worked out in the 1970s¹ and refined with atomic-level structural detail in 2013², which the authors suggest could guide the design of new antibiotics².

Topical bacitracin is sold over the counter in the US as a first-aid antibiotic for minor cuts, scrapes and burns, and is an ingredient in FDA-approved prescription eye ointments^4,5. In 2020 FDA asked makers of bacitracin for injection to withdraw it, after an advisory committee judged that its benefits did not outweigh its risks, which include kidney toxicity and anaphylactic reactions; in 2022 FDA formally determined it had been withdrawn for those reasons⁶.

The over-the-counter label says not to use it in the eyes, over large areas of the body, or on deep or puncture wounds, animal bites or serious burns without asking a doctor, and to stop and seek advice if a rash or other allergic reaction appears or use runs past one week⁴. Allergic contact dermatitis is the best-documented problem with skin use³. The withdrawn injectable form carried risks of kidney toxicity and anaphylactic reactions⁶.

1. Stone & Strominger, Proc Natl Acad Sci USA 1971PubMed
2. Economou et al., Proc Natl Acad Sci USA 2013PubMed
3. Smack et al., JAMA 1996PubMed
4. FDA label: Bacitracin ointment (OTC Drug Facts)FDA label (DailyMed)
5. FDA label: Bacitracin zinc and polymyxin B ophthalmic ointmentFDA label (DailyMed)
6. FDA notice, Federal Register 2022 (bacitracin for injection)federalregister.gov