Continuing Education Activity

This educational initiative on topical bacitracin offers healthcare practitioners essential insights and resources for effectively utilizing this antibiotic in treating minor skin injuries such as cuts, scrapes, and burns. Bacitracin is a staple in both professional settings and home first aid kits, available as both a single-agent ointment and in a triple-therapy combination with neomycin and polymyxin B. The program outlines indications, mechanisms of action, safe administration practices, adverse effects, and contraindications, emphasizing proper patient education on the application and duration of treatment to optimize outcomes.

Key elements of this initiative include the emphasis on monitoring patients for signs of allergic reactions and educating healthcare providers on making informed decisions to minimize adverse effects. This educational activity seeks to enhance healthcare providers' capabilities in managing infections effectively treated with topical bacitracin, ultimately aiming to improve patient outcomes.

Objectives:

• Identify the indications for topical bacitracin.
• Evaluate the antimicrobial mechanism of action of bacitracin.
• Assess the potential adverse drug reactions of topically-applied bacitracin.
• Implement effective collaboration and communication among interprofessional team members to improve outcomes and treatment efficacy for patients who might benefit from bacitracin topical therapy.

Indications

Bacitracin, a topical antibiotic ointment, is commonly used by medical professionals and the general public to treat minor skin injuries such as cuts, scrapes, and burns.

The discovery of bacitracin dates back to 1945, stemming from the wound of a 7-year-old American girl named Margaret Tracey. The debris collected from her leg injury cultured several related cyclic polypeptides produced by a member of the Bacillus subtilis group, which led to the naming of the antibiotic.[1]

FDA-Approved Indications

The United States Food and Drug Administration (FDA) approved bacitracin in 1948 to prevent and treat acute and chronic localized skin infections. Bacitracin can be administered less frequently as an intramuscular (IM) injection to treat infantile streptococcal pneumonia and empyema.

Bacitracin is available as a single-agent ointment or combined with neomycin and polymyxin B into a triple-therapy ointment. The latter is available over the counter (OTC) at local pharmacies.[2] Additionally, the FDA has approved ocular bacitracin for treating superficial infections of the cornea and conjunctiva caused by susceptible organisms.

Off-Label Uses

The American Academy of Ophthalmology recommends using bacitracin for Pediculosis palpebrarum caused by Phthirus pubis. Forceps can remove adult lice and nits from the eyelids and eyelashes. If nits are firmly attached, the affected lashes may need to be epilated. A mild ophthalmic ointment such as bacitracin or erythromycin should be applied 2 to 3 times daily over 10 days to remove adult lice and nits completely.[3] In a randomized controlled trial, researchers evaluated the effectiveness of various topical agents against Propionibacterium acnes. The results indicated that a triple antibiotic ointment containing neomycin, bacitracin, and polymyxin B effectively inhibited bacterial growth.[4] The Infectious Diseases Society of America (IDSA) guidelines suggest that oral bacitracin may be considered for treating initial Clostridium difficile infections. However, alternative medications are preferred due to inadequate evidence and concerns about antimicrobial resistance.[5]

Mechanism of Action

Bacitracin is a mixture of several closely related cyclic polypeptide antibiotics that exhibit both bacteriostatic and bactericidal properties, depending on the drug's concentration and the microorganism's susceptibility.

It is effective against many gram-positive bacteria, including species of Staphylococcus, Streptococcus, Corynebacterium, Clostridium, and Actinomyces. Some gram-negative organisms, such as species of Neisseria, are also susceptible to bacitracin; however, most gram-negative organisms are resistant.[6][7]

Bacitracin is readily absorbed through denuded, burned, or granulated skin, functioning to inhibit the transfer of mucopeptides into the cell walls of various microorganisms. This action blocks bacterial cell wall synthesis and, ultimately, bacterial replication. Additionally, bacitracin inhibits proteases and other enzymes that alter bacterial cell membrane function. Specifically, it inhibits bacterial cell wall synthesis by preventing the dephosphorylation of the P-P-phospholipid carrier, which attaches the cell wall peptidoglycan precursor units to the cell membrane, resulting in bacterial cell lysis.[8] The stability of bacitracin is enhanced when complexed with zinc.[9]

Pharmacokinetics 

Absorption: Bacitracin is poorly absorbed systemically when applied in topical, ophthalmic, and oral formulations but achieves quick and complete absorption when administered intramuscularly. However, topical bacitracin can be absorbed through burned, denuded skin or areas with granulating tissue.

Distribution: Bacitracin is widely distributed throughout the body, reaching all major organs. Following intramuscular injection, it is present in ascitic and pleural fluids. Bacitracin exhibits minimal protein binding.

Metabolism: Bacitracin is primarily metabolized into smaller peptides and amino acids. The primary metabolite, des-amido-bacitracin, is microbiologically inactive. Additionally, catabolic peptides are formed during the metabolism process.

Excretion: Bacitracin is primarily excreted through the kidneys, with about 87% of an intramuscular dose eliminated through urine within 6 hours. Hydrolytic cleavage products, including di- and tripeptides, are found in urine and bile.

Administration

Available Dosage Forms and Strength

In the USA, bacitracin is available in topical and ophthalmic forms. The topical formulation is an ointment with a concentration of 500 units/g.

Adult Dosage

Topical: Bacitracin is primarily employed as a topical agent, applied directly to wounds or infected areas. Additionally, this antibiotic is available as an ophthalmic ointment formulated specifically for treating superficial infections of the conjunctiva and cornea.[10]

Before application, the skin should be cleaned gently using mild soap and water. After cleansing, sufficient ointment must be applied to cover the affected areas. Covering the wound with a sterile dressing may aid the healing process and prevent further contamination of the wound site.

Ophthalmic formulation: Bacitracin ointment should be applied directly into the conjunctival sac 1 to 3 times daily. In blepharitis cases, all scales and crusts must be removed, followed by a uniform ointment application over the lid margins. When applying the ointment directly to the infected eye, patients are advised to take appropriate precautions to prevent contamination.

Specific Patient Populations

Hepatic impairment: Edit this: Manufacturers do not provide any information regarding the dosage adjustment for bacitracin. Therefore, this medication should be used with caution.

Renal impairment: The parenteral formulations of bacitracin can cause nephrotoxicity and should be used with caution.

Pregnancy considerations: Topical bacitracin, previously classified as FDA pregnancy risk category C, has not been extensively studied for use during pregnancy or lactation. Current evidence does not indicate an increased risk of adverse fetal development. However, due to limited data, caution is advised. Healthcare providers should carefully weigh the risks versus benefits and consider alternative treatments when feasible to ensure the safety of both mother and infant. Further research is necessary to fully understand the safety profile of topical bacitracin during pregnancy and breastfeeding.[11]

Breastfeeding considerations: Topical and ophthalmic formulations of bacitracin generally exhibit minimal absorption through the skin, posing a low risk to nursing infants. Using water-soluble creams or gel products exclusively on breast tissue is recommended to reduce potential exposure from licking.[12]

Edit this: Topical and ophthalmic formulations of bacitracin generally exhibit minimal absorption through the skin, presenting a low risk to nursing infants. To mitigate potential exposure to mineral paraffin from licking, it is recommended that water-soluble creams or gel products be used exclusively on breast tissue.[12]

Pediatric patients: Bacitracin has received FDA approval for treating blepharitis and superficial infections affecting the conjunctiva or cornea.

Older patients: See adult dosage and administration.

Adverse Effects

When used topically as a single agent ointment or part of a triple therapy ointment, bacitracin and its drug formulation components may cause allergic contact dermatitis. Additionally, cases involving anaphylactic reactions to bacitracin have been reported.[13]

Common and mild adverse effects of bacitracin include:

• Fever
• Hives
• Itching
• Swelling of lips and face [2]
• Difficulty breathing
• Nausea
• Vomiting [14]
• Allergic contact dermatitis [15]

Contraindications

Topical bacitracin is contraindicated in anyone with hypersensitivity to bacitracin or its formulation components. Patients with known hypersensitivity to neomycin may also be sensitive to bacitracin. Anaphylactoid reactions have been reported.[13]

Warnings and Precautions

• Bacitracin application to an infection or wound caused by a viral or fungal infection may increase the risk of developing drug-resistant bacteria.
• Topical bacitracin use is recommended only for minor skin injuries and should not be used over larger areas of the body.
• Before using topical bacitracin, physician consultation is recommended for serious injuries such as burns, deep wounds, puncture wounds, or animal bites.[16][17]
• In 2020, the FDA prohibited the use of bacitracin-containing injections because of the potential for nephrotoxicity.[18][19][20]

Monitoring

Secondary infections may develop; topical bacitracin should not be used for more than 7 days unless directed by a physician. The area of application should be monitored. If symptoms worsen, bacitracin use should be stopped immediately, and a clinician should be contacted regarding further management.[13]

Allergy patch testing may be necessary if an adverse reaction occurs after using bacitracin, either as a single-agent ointment or as part of a triple-therapy ointment. There have been multiple reports of anaphylactoid reactions and anaphylaxis associated with its use.[21][22][21] Furthermore, MRGPRX2, which belongs to a novel subfamily of G protein-coupled receptors (GPCRs) known as MAS-related GPCRs (MRGPRs), has been identified as a potential mediator in non-immunoglobulin E (IgE)-mediated responses. A study has shown that bacitracin can trigger MRGPRX2-dependent activation of mast cells, suggesting that non-IgE-mediated mechanisms may contribute to pseudo-allergic drug hypersensitivity reactions. This finding offers insights into the mechanism behind bacitracin-induced allergic contact dermatitis, underscoring the need for more research to investigate and establish effective treatment options thoroughly.[23]

Toxicity

Signs and Symptoms of Overdose

No toxicity is reported with the topical use of bacitracin, either as a single agent or in a triple therapy ointment. However, the intramuscular (IM) route has been associated with nephrotoxicity and renal failure due to tubular and glomerular necrosis. Consequently, careful monitoring is essential for IM administration of bacitracin. Renal function should be assessed before, during, and after IM administration to ensure safety.

Management of Overdose

Patients' daily optimal fluid intake and urinary output should be closely monitored to prevent kidney injury. Concurrent use of nephrotoxic drugs such as streptomycin, kanamycin, polymyxin E, and neomycin should be avoided.[24][25]

Enhancing Healthcare Team Outcomes

Topical bacitracin has been widely available and recognized as a safe over-the-counter (OTC) topical antibiotic for the past 7 decades.[2] However, its increased use and adverse effects led to its designation as the "contact allergen of the year" in 2003 by the American Contact Dermatitis Society.[26] Between 2005 and 2006, it was identified as the sixth most common allergen in patch tests.[27][28]

All healthcare professionals should be vigilant about the potential risks of anaphylactoid reactions or anaphylaxis associated with bacitracin use. Individuals with confirmed contact dermatitis should avoid products containing bacitracin. Healthcare providers should advise patients to carefully read labels for bacitracin in ointments, creams, and other wound care products.

Healthcare providers should consider bacitracin as a potential cause when encountering a patient with a possible contact allergy, persistent dermatitis, or a non-healing wound, as bacitracin allergy may mimic cellulitis or superficial wound infection. A clinical indicator distinguishing an allergic reaction from an infectious process is the presence of itching in allergic responses, as opposed to worsening pain in infections. Collaboration between dermatologists and immunologists can provide insights into distinguishing allergic dermatitis from infection. In cases of anaphylaxis caused by bacitracin, emergency medicine physicians should promptly stabilize the patient.

Bacitracin should be used with caution in patients with pre-existing renal impairment or renal failure. To ensure patient safety, an interprofessional team approach involving physicians, nurses, and pharmacists is essential to monitor patients' fluid intake, urinary output, and renal function. Due to the significant risk of nephrotoxicity, pharmacists should suggest alternative medication options when available. Effective communication among clinicians (MDs, DOs, NPs, PAs), pharmacists, nurses, and specialists is crucial to optimizing patient outcomes with topical bacitracin treatment.

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Disclosure: Rosalee Nguyen declares no relevant financial relationships with ineligible companies.

Disclosure: Niloufar Khanna declares no relevant financial relationships with ineligible companies.

Disclosure: Anthony Safadi declares no relevant financial relationships with ineligible companies.

Disclosure: Preeti Patel declares no relevant financial relationships with ineligible companies.

Disclosure: Yan Sun declares no relevant financial relationships with ineligible companies.