This monograph discusses the use of neomycin, polymyxin B, and bacitracin in combination for infectious conditions of the eyes and skin. Clinicians may wish to consult the individual monographs for more information.
Neomycin; polymyxin B; bacitracin are used together in ophthalmic and topical preparations. The ophthalmic preparations are indicated for the treatment of ocular bacterial infections such as conjunctivitis, keratitis, keratoconjunctivitis, blepharitis, and blepharoconjunctivitis. The topical preparations are used to prevent superficial skin infections on minor cuts, abrasions, and burn wounds. Bacitracin is a mixture of cyclic polypeptides produced by Bacillus subtilis. Neomycin is an aminoglycoside antibiotic derived from cultures of Streptomyces fradiae. Polymyxin B is a polypeptide antibiotic derived from a strain of Bacillus polymyxa. The combined use of neomycin; polymyxin B; bacitracin provides a wide antibacterial spectrum. Neomycin and polymyxin B are primarily active against gram-negative, aerobic bacteria, while bacitracin is effective against gram-positive bacteria. The FDA approved bacitracin, neomycin, and polymyxin B ophthalmic preparations prior to 1982 and the first topical product in November 1987.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Topical Administration
-Clean affected area of any debris prior to treatment.
-Apply sparingly in a thin film to the affected area.
-Do not cover with an occlusive dressing. A light gauze dressing may be used if required.
-To avoid risk of infection, use one tube per individual patient.
Cream/Ointment/Lotion Formulations
-Do not apply topical ointment to eyes or ears.
Ophthalmic Administration
-For topical ophthalmic administration only.
-Inspect product prior to use. Do not use if cap and neck-ring are not intact.
-Instruct patient on proper instillation of eye ointment.
-Do not touch applicator tip to the eye, eyelid, fingers, or other surface.
-Apply directly into the conjunctival sac. In blepharitis all scales and crusts should be carefully removed and the ointment then spread uniformly over the lid margins.
-Instruct patient to avoid wearing contact lenses during treatment.
-To avoid risk of infection, use one tube per individual patient.
This monograph discusses the use of neomycin; polymyxin B; bacitracin in combination for infectious conditions of the eyes and skin. Clinicians may wish to consult the individual monographs for more information about specific adverse reactions of each agent.
Hypersensitivity and anaphylactoid reactions have occurred following administration of neomycin; polymyxin B; bacitracin containing products. The exact incidence is unknown; however, serious anaphylactic reactions have been rarely reported. Neomycin hypersensitivity has been reported following the administration of topical products. Topical neomycin hypersensitivity reactions can be manifested as eczematous exacerbation with reddening, scaling, swelling, and pruritus, or it may manifest as a failure to heal. Periodic examinations for these symptoms are advised; instruct patients to discontinue treatment if allergic reactions are observed. These symptoms regress quickly upon withdrawing the medication. Allergic reactions associated with the ophthalmic preparations include edema of the conjunctiva and eyelid, ocular pruritus, and conjunctival erythema. Other adverse effects of topically applied products include pain, erythema, edema, and exacerbations of underlying skin conditions.
While not common with topical therapy, systemic absorption of neomycin has been associated with ototoxicity; symptoms of ototoxicity include tinnitus, vertigo, and permanent hearing loss. Exercise caution when administering neomycin containing products to patients with damaged endothelium as this may increase absorption and the risk of ototoxicity. In addition, prolonged use of neomycin containing products, such as neomycin; polymyxin B; bacitracin may increase the risk of developing ototoxicity; therefore, avoid exceeding the recommended duration of therapy.
Microbial overgrowth and superinfection can occur with antibiotic use. C. difficile-associated diarrhea (CDAD) or pseudomembranous colitis has been reported with neomycin; polymyxin B; bacitracin. If pseudomembranous colitis is suspected or confirmed, ongoing antibacterial therapy not directed against C. difficile may need to be discontinued. Institute appropriate fluid and electrolyte management, protein supplementation, C. difficile-directed antibacterial therapy, and surgical evaluation as clinically appropriate. Discontinue therapy and instruct patient to consult a health care provider if a purulent discharge, inflammation, or pain occurs during treatment.
This monograph discusses the use of neomycin; polymyxin B; bacitracin in combination for infectious conditions of the eyes and skin. Clinicians may wish to consult the individual monographs for more information about specific contraindications and precautions of each agent.
Neomycin; polymyxin B; bacitracin products are contraindicated in patients who are allergic to any of the components including those patients with aminoglycoside hypersensitivity, neomycin hypersensitivity, or polymyxin hypersensitivity. Monitor patients for the development of hypersensitivity reactions and discontinue treatment if symptoms are observed. Long-term use of neomycin products may place patients at risk of developing neomycin hypersensitivity. Avoid further use of neomycin-containing products in those patients who develop this reaction.
Neomycin; polymyxin B; bacitracin products are approved for the treatment and prevention of infections caused by susceptible bacteria and should not be used in patients with viral infection, fungal infection, or mycobacterial infection. Avoid use of the ophthalmic preparations for fungal infections of ocular structures, viral infections of the cornea and conjunctiva (including herpes infection [dendritic keratitis], vaccinia, varicella), and for mycobacterial infections of the eye. In addition, the topical ointment is not recommended for use in patients with cutaneous tuberculosis. According to the manufacturer, prolonged use of neomycin; polymyxin B; bacitracin products may result in secondary infections from non-susceptible organisms; therefore, it is recommended not to use the topical ointment longer than 7 days nor the ophthalmic preparations longer than 10 days.
Systemic exposure to bacitracin and neomycin may be increased in patients with damaged epithelium, renal impairment, or renal failure. As a result, these patients are at an increased risk of developing side effects such as bacitracin or neomycin-induced nephrotoxicity and neomycin-induced irreversible ototoxicity (hearing impairment). Consider the possibility of increased systemic exposure prior to administering topical neomycin; polymyxin B; bacitracin products to patients with damaged skin or preexisting renal disease.
Geriatric patients are more likely to have damaged skin and preexisting renal impairment placing them at risk of developing side effects from systemically absorbed bacitracin and neomycin with topical product use. Monitor elderly patients closely while on neomycin; polymyxin B; bacitracin products. No particular precautions exist for the use of ophthalmic products in geriatric patients.
The safety and efficacy of neomycin; polymyxin B; bacitracin ophthalmic products have not been established in neonates, infants, children, or adolescents. Patients with immature skin, including children younger than 2 years of age, infants, and neonates, may be at increased risk of side effects from systemically absorbed bacitracin and neomycin when applied topically to the skin. Avoid use of these topical products in patients younger than 2 years of age.
Consider pseudomembranous colitis in patients presenting with diarrhea after antibacterial use. Careful medical history is necessary as pseudomembranous colitis has been reported to occur over 2 months after the administration of antibacterial agents. Almost all antibacterial agents, including neomycin; polymyxin B; bacitracin, have been associated with pseudomembranous colitis or C. difficile-associated diarrhea (CDAD) which may range in severity from mild to life-threatening. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
Patients should avoid wearing contact lenses while being treated with neomycin; polymyxin B; bacitracin ophthalmic preparations for an ocular infection.
Apply neomycin; polymyxin B; bacitracin topical ointment only to the skin; avoid ophthalmic administration of the topical ointment. The ophthalmic preparations should never be directly administered into the anterior chamber of the eye. Ophthalmic ointments may retard corneal wound healing.
Neomycin; polymyxin B; bacitracin products have not been studied in pregnant women and animal reproduction studies have not been conducted. It is not known if they can cause fetal harm when administered to a pregnant woman or if they can affect reproduction capacity. There is little information to demonstrate the possible effect of topically applied neomycin in pregnancy; however, neomycin present in maternal blood can cross the placenta. Neomycin; polymyxin B; bacitracin ophthalmic ointment should be used during pregnancy only if clearly needed. Neomycin; polymyxin B; bacitracin topical ointment is not recommended in pregnancy.
It is not known whether neomycin; polymyxin B; bacitracin products are excreted in human milk. Topical and ophthalmic use would result in minimal absorption. To minimize the amount of drug that reaches the systemic circulation and breast milk, apply pressure over the tear duct by the corner of the eye for 1 minute after ophthalmic administration. Oral ingestion by the nursing infant would also result in minimal absorption. Only water-miscible cream or gel products should be applied to the breast because ointments may expose the infant to high levels of mineral paraffins. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.
Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: Enterobacter sp., Escherichia coli, Haemophilus influenzae (beta-lactamase negative), Haemophilus influenzae (beta-lactamase positive), Klebsiella sp., Neisseria sp., Pseudomonas aeruginosa, Staphylococcus aureus (MSSA), Streptococcus pneumoniae, Streptococcus sp.
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.
For the treatment of superficial ophthalmic infection (e.g., bacterial conjunctivitis, keratitis, keratoconjunctivitis, blepharitis, and blepharoconjunctivitis) caused by susceptible bacteria:
Ophthalmic dosage (ophthalmic ointment):
Adults: Apply a thin strip (approximately 1/2 inch) of ointment to the affected eye(s) every 3 to 4 hours for 7 to 10 days, depending upon the severity of the infection.
For the prevention of skin and skin structure infections, including wound management for skin abrasion and minor burn wound infection:
Topical dosage (topical skin ointment):
Adults, Adolescents, and Children >= 2 years: Apply a thin film (amount equal to the surface area of the fingertip) to the affected area 1 to 3 times daily. Continue for full course of treatment; therapy should be limited to 7 days.
Maximum Dosage Limits:
-Adults
8 applications/day for up to 10 days for ophthalmic ointment; 3 applications/day for up to 7 days topically.
-Elderly
8 applications/day for up to 10 days for ophthalmic ointment; 3 applications/day for up to 7 days topically.
-Adolescents
Safety and efficacy have not been established for ophthalmic ointment; 3 applications/day for up to 7 days topically.
-Children
>= 2 years: Safety and efficacy have not been established for ophthalmic ointment; 3 applications/day for up to 7 days topically.
< 2 years: Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
No dosage adjustment needed.
Patients with Renal Impairment Dosing
No dosage adjustment needed; use topically with caution in situations where systemic exposure may occur.
*non-FDA-approved indication
Amphotericin B lipid complex (ABLC): (Minor) Additive nephrotoxicity may occur with concurrent use of systemic bacitracin and other nephrotoxic agents, such as amphoteracin B; when possible, avoid concomitant administration. Topical administration of any preparation containing bacitracin, especially when applied to large surface areas, should not be given with other drugs that have a nephrotoxic potential.
Amphotericin B liposomal (LAmB): (Minor) Additive nephrotoxicity may occur with concurrent use of systemic bacitracin and other nephrotoxic agents, such as amphoteracin B; when possible, avoid concomitant administration. Topical administration of any preparation containing bacitracin, especially when applied to large surface areas, should not be given with other drugs that have a nephrotoxic potential.
Amphotericin B: (Minor) Additive nephrotoxicity may occur with concurrent use of systemic bacitracin and other nephrotoxic agents, such as amphoteracin B; when possible, avoid concomitant administration. Topical administration of any preparation containing bacitracin, especially when applied to large surface areas, should not be given with other drugs that have a nephrotoxic potential.
Bumetanide: (Minor) Additive nephrotoxicity may occur with concurrent use of systemic bacitracin and other nephrotoxic agents. When possible, avoid concomitant administration of systemic bacitracin and other nephrotoxic drugs such as loop diuretics. Topical administration of any preparation containing bacitracin, especially when applied to large surface areas, also should not be given with other drugs that have a nephrotoxic potential.
Ethacrynic Acid: (Minor) Additive nephrotoxicity may occur with concurrent use of systemic bacitracin and other nephrotoxic agents. When possible, avoid concomitant administration of systemic bacitracin and other nephrotoxic drugs such as loop diuretics. Topical administration of any preparation containing bacitracin, especially when applied to large surface areas, also should not be given with other drugs that have a nephrotoxic potential.
Furosemide: (Minor) Additive nephrotoxicity may occur with concurrent use of systemic bacitracin and other nephrotoxic agents. When possible, avoid concomitant administration of systemic bacitracin and other nephrotoxic drugs such as loop diuretics. Topical administration of any preparation containing bacitracin, especially when applied to large surface areas, also should not be given with other drugs that have a nephrotoxic potential.
Loop diuretics: (Minor) Additive nephrotoxicity may occur with concurrent use of systemic bacitracin and other nephrotoxic agents. When possible, avoid concomitant administration of systemic bacitracin and other nephrotoxic drugs such as loop diuretics. Topical administration of any preparation containing bacitracin, especially when applied to large surface areas, also should not be given with other drugs that have a nephrotoxic potential.
Torsemide: (Minor) Additive nephrotoxicity may occur with concurrent use of systemic bacitracin and other nephrotoxic agents. When possible, avoid concomitant administration of systemic bacitracin and other nephrotoxic drugs such as loop diuretics. Topical administration of any preparation containing bacitracin, especially when applied to large surface areas, also should not be given with other drugs that have a nephrotoxic potential.
Mechanism of Action:-Neomycin: Neomycin is an aminoglycoside antibiotic with bactericidal activity against many gram-positive and gram-negative bacteria. In susceptible bacteria, neomycin prevents the formation of functional proteins. This is accomplished through active transport into the bacterial cell and subsequent irreversible binding to receptors present on the 30S ribosomal subunit. This binding interferes with the initiation complex between the messenger RNA (mRNA) and the subunit. As a result, abnormal, nonfunctional proteins are formed due to misreading of the bacterial DNA. Eventually, susceptible bacteria die because of the lack of functional proteins. Neomycin may also inhibit DNA polymerase.
-Polymyxin B: Polymyxin B binds to phospholipids on cell membranes of gram-negative bacteria. This binding destroys bacterial membranes with a surface detergent-like mechanism resulting in increased cell membrane permeability and loss of essential metabolites. Polymyxin B is bactericidal against most gram-negative bacilli; however, some Proteus and Serratia species may be resistant. Polymyxin B has no in vitro activity against gram-positive bacteria.
-Bacitracin: Bacitracin is primarily bacteriostatic, but may have bactericidal activity depending upon the antibiotic concentration and the susceptibility of the bacteria. Bacitracin inhibits bacterial cell wall synthesis. This is achieved by preventing the final dephosphorylation step in the phospholipid carrier cycle, which interferes with the mucopeptide transfer to the growing cell wall. Bacitracin is active against many gram-positive and some gram-negative bacteria.
Neomycin; polymyxin B; bacitracin combination products are applied topically to the eyes or skin. If any systemic absorption occurs, bacitracin and neomycin are excreted renally.
-Route-Specific Pharmacokinetics
Topical Route
Except when applied to large areas or for an extended period of time, systemic absorption of neomycin; polymyxin B; bacitracin is negligible. Polymyxin B has a high affinity for cell membranes so there is little systemic absorption even when applied to open wounds. Bacitracin and neomycin may be absorbed systemically if applied to damaged epithelium.
-Special Populations
Renal Impairment
Patients with renal dysfunction may develop ototoxicity or worsening nephrotoxicity following prolonged systemic exposure to neomycin; polymyxin B; bacitracin.
Pediatrics
The bacitracin and neomycin components of neomycin; polymyxin B; bacitracin may be absorbed systemically if applied to patients with immature skin such as children younger than 2 years.