This monograph discusses the use of the bacitracin, hydrocortisone, neomycin, and polymyxin B in combination for inflammatory and infectious conditions of the eyes or skin. Clinicians may wish to consult the individual monographs for more information.
Bacitracin, hydrocortisone, neomycin, and polymyxin B are used together in ophthalmic preparations or in a topical ointment to treat corticosteroid-responsive dermatoses with secondary infection. Hydrocortisone is a corticosteroid that exhibits both mineralocorticoid and glucocorticoid activity; it is used in these preparations for its antiinflammatory properties. Bacitracin is a mixture of cyclic polypeptides produced by Bacillus subtilis. Neomycin is a aminoglycoside antibiotic derived from cultures of Streptomyces fradiae. Polymyxin B is a polypeptide antibiotic derived from a strain of Bacillus polymyxa. Neomycin and polymyxin B affect primarily gram-negative, aerobic bacteria, while bacitracin is effective against gram-positive organisms. The FDA approved bacitracin, hydrocortisone, neomycin, and polymyxin B ophthalmic and topical preparations prior to 1982.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Topical Administration
-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 open tube per individual patient.
Cream/Ointment/Lotion Formulations
-Do not apply topical skin ointment to eyes or ears.
Ophthalmic Administration
-For topical ophthalmic administration only.
-Instruct patient on proper instillation of eye ointment.
-Patients should not wear contact lenses if they have an ocular infection.
-Do not to touch the tip of the applicator to the eye, eyelid, fingertips, 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.
-Keep tightly closed when not in use.
-To avoid risk of infection, use one open tube per individual patient.
This monograph discusses the use of the bacitracin, hydrocortisone, neomycin, and polymyxin B in combination for inflammatory and infectious conditions of the eyes or skin. Clinicians may wish to consult the individual monographs for more information about the specific adverse reactions of each agent.
Neomycin topical use has been rarely associated with nephrotoxicity and ototoxicity, which may result in permanent sensorineural hearing loss due to cochlear damage. The risk of ototoxicity is increased with prolonged use; therefore, the recommended duration of bacitracin; hydrocortisone; neomycin; polymyxin B therapy should not be exceeded.
Superinfection may occur after use of combinations containing corticosteroids and antimicrobials, such as bacitracin; hydrocortisone; neomycin; polymyxin B preparations. Fungal infection and viral infection of the cornea are particularly prone to develop with long-term applications of a corticosteroid to the eye. The possibility of fungal invasion must be considered in any persistent corneal ulceration when corticosteroid treatment is being used.
Neomycin has been associated with skin sensitization, including rash (unspecified). Sensitivity is more common with chronic use on inflamed skin. About 1% of patients have reported allergic contact hypersensitivity. The manifestation of the sensitization to neomycin is usually low-grade erythema with swelling, dry scaling, and pruritus, or it may manifest as a failure to heal. Neomycin may also cause mast cell degranulation and histamine release. Local adverse reactions have been reported with topical corticosteroids, especially when the preparation is covered by occlusive dressings: burning, pruritus, skin irritation, xerosis, folliculitis, hypertrichosis, acneiform eruptions (acneiform rash), skin hypopigmentation, perioral dermatitis, allergic contact dermatitis, maceration of the skin, skin atrophy, striae, and miliaria. The use of corticosteroids topically may also lead to impaired wound healing.
Adverse reactions to the ocular preparations of bacitracin, hydrocortisone, neomycin, and polymyxin B include ocular irritation including swelling, ocular pruritus, and conjunctival erythema due to allergic reactions to the antibiotic components. Reactions due to the corticosteroid component in decreasing order of frequency are elevation of intraocular pressure (IOP) with possible development of glaucoma or ocular hypertension, infrequent optic nerve damage; formation of posterior subcapsular cataracts; and as with use of topical skin corticosteroids, potential for impaired wound healing.
This monograph discusses the use of the bacitracin, hydrocortisone, neomycin, and polymyxin B in combination for inflammatory and infectious conditions of the eyes or skin. Clinicians may wish to consult the individual monographs for more information about the specific contraindications and precautions of each agent.
Bacitracin; hydrocortisone; neomycin; polymyxin B products are contraindicated in patients who are allergic to any of the components including those patients with aminoglycoside hypersensitivity, polymyxin hypersensitivity, or neomycin hypersensitivity. Patients should be monitored for the development of neomycin hypersensitivity, and the patient should discontinue treatment if symptoms are observed. Long-term use of neomycin products may place the patient at risk to develop neomycin hypersensitivity. Patients should avoid neomycin-containing products after the development of such reactions. Use with caution in patients with a stated corticosteroid hypersensitivity.
Use of bacitracin; hydrocortisone; neomycin; polymyxin B products is contraindicated in the treatment of fungal infection or viral infection including varicella-zoster or other herpes infection (e.g., herpes simplex or vaccinia). Specifically, the ophthalmic preparations are contraindicated in fungal infections of ocular structures, most viral infections of the cornea and conjunctiva, including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella, and mycobacterial infection of the eye. Further, the topical ointment is contraindicated in cutaneous tuberculosis lesions. Secondary infections, especially of fungi, may occur with prolonged use of bacitracin-hydrocortisone-neomycin-polymyxin B products. In acute purulent conditions of the eye, corticosteroids may mask infection or enhance existing infection. It is recommended that the topical ointment not be used for longer than 7 days and the ophthalmic preparations should not be used for longer than 10 days to avoid development of secondary infections.
Hearing loss is associated with the use of neomycin-containing products, particularly with prolonged use. Systemic absorption of bacitracin and neomycin may occur following topical application to denuded or damaged epithelium. Following systemic absorption of these agents in patients with renal impairment or renal failure, there is a risk of developing ototoxicity (hearing impairment) that is irreversible and progressive even after the therapy is stopped.
Bacitracin; hydrocortisone; neomycin; polymyxin B topical skin ointment is contraindicated for all ocular exposure and is contraindicated for external ear canal application if the eardrum is perforated (tympanic membrane perforation).
Ocular corticosteroids should be used with caution in patients with glaucoma. If bacitracin; hydrocortisone; neomycin; polymyxin B ophthalmic products are used for 10 days or longer, intraocular pressure should be routinely monitored due to the risk development of glaucoma. Prolonged use of corticosteroids may result in ocular hypertension with damage to the optic nerve, defects in visual acuity and fields of vision, and in posterior subcapsular cataracts formation. The initial prescription and renewal of the medication order beyond 8 g should be made only after ophthalmic examination of the patient with aid of magnification such as slit lamp biomicroscopy, and where appropriate, fluorescein staining. If signs and symptoms fail to improve after 2 days, the patient should be re-evaluated. Use of these ophthalmic products after ocular surgery for cataracts or other corneal procedures may retard wound healing and increase the incidence of filtering blebs. The ophthalmic ointment should never be directly introduced into the anterior chamber of the eye.
Patients who wear contact lenses should avoid wearing them while being treated with bacitracin; hydrocortisone; neomycin; polymyxin B ophthalmic products for an ocular infection.
Bacitracin; hydrocortisone; neomycin; polymyxin B ophthalmic and topical products are classified as FDA pregnancy risk category C. Although systemic exposures of all 4 components are expected to be minimal, use of topical corticosteroids, such as hydrocortisone, have been shown to be teratogenic in animals. No adequate and well-controlled studies have been conducted in pregnant women, therefore this medication should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus.
It is unknown if bacitracin, neomycin, or polymyxin B are excreted in breast milk; however, hydrocortisone does appear in human milk following oral administration. Therefore, bacitracin; hydrocortisone; neomycin; polymyxin B products should be used cautiously in nursing mothers even though systemic absorption following topical and ophthalmic application is negligible. To minimize potential infant exposure, instruct mothers not to apply the topical products directly to the breast during times of breast-feeding. If using the ophthalmic products, instruct patients to apply pressure over the tear duct by the corner of the eye for 1 minute after each administration. 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.
Use of topical corticosteroids may result in signs and symptoms of exogenous hyperadrenocorticism; use with caution in patients with pre-existing hypothalamic-pituitary-adrenal (HPA) suppression. Systemic absorption of topical corticosteroids will be increased if an extensive body surface area is treated or if an occlusive dressing is used. In children, sufficient absorption of hydrocortisone may occur during prolonged topical use to cause inhibition of growth, as well as other signs and symptoms of hyperadrenocorticism. The safety and efficacy of bacitracin; hydrocortisone; neomycin; polymyxin B topical and ophthalmic formulations have not been established in neonates, infants, or children.
Clinical studies have not identified a difference in response to bacitracin; hydrocortisone; neomycin; polymyxin B products among patients 65 years and older as compared to younger patients. However, geriatric patients are more likely to have damaged skin through aging, and this may increase the risk of side effects following topical use. No age-based precautions are associated with ophthalmic formulations of this medication.
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 corticosteroid-responsive inflammatory ocular conditions where a bacterial ophthalmic infection or a risk of bacterial ophthalmic infection exists (e.g., inflammation of palpebral and bulbar conjunctiva, cornea and anterior segment of the globe where the inherent risk of corticosteroid use in bacterial conjunctivitis is accepted to obtain a decrease in edema and inflammation; also in chronic anterior uveitis and corneal injury from chemical, radiation, or thermal burns, or penetration of foreign objects):
Ophthalmic dosage (ophthalmic ointment):
Adults: Apply a thin strip into the affected eye(s) every 3 to 4 hours, depending upon the severity of the infection. Use not more than 8 g or for longer than 10 days initially; the prescription should not be refilled without further evaluation.
For the treatment of corticosteroid-responsive dermatoses with secondary infection:
Topical dosage (topical ointment):
Adults: Apply as a thin film topically to the affected area(s) 2 to 4 times per day. Therapy should be limited to 7 days.
Maximum Dosage Limits:
-Adults
8 g or 10 days for ophthalmic ointment then reevaluate before further therapy; 4 applications/day for up to 7 days topically.
-Elderly
8 g or 10 days for ophthalmic ointment then reevaluate before further therapy; 4 applications/day for up to 7 days topically.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
No dosage adjustment is needed.
Patients with Renal Impairment Dosing
No dosage adjustment is needed; use caution with prolonged therapy under conditions where systemic exposure is possible.
*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.
-Bacitracin: Bacitracin is primarily bacteriostatic, but may have bacteriocidal activity depending upon the antibiotic concentration and the susceptibility of the organism. Bacitracin inhibits bacterial cell wall formation. Bacitracin inhibits the final dephosphorylation step in the phospholipid carrier cycle, which inhibits mucopeptide transfer to the growing cell wall. Bacitracin is active against many gram-positive organisms and some gram-negative organisms.
-Hydrocortisone: The antiinflammatory activity of hydrocortisone is thought to involve phospholipase A2 inhibitory proteins, collectively called lipocortins. Lipocortins control the biosynthesis of potent mediators of inflammation, such as prostaglandins and leukotrienes, by inhibiting the release of the precursor molecule arachidonic acid.
-Neomycin: Neomycin is bacteriocidal. It inhibits bacterial protein synthesis through irreversible binding to the 30S ribosomal subunit of susceptible bacteria. Neomycin is actively transported into the bacterial cell where it binds 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 gram-negative bacterial cell membrane phospholipids. This binding destroys bacterial membranes with a surface detergent-like mechanism and increases the permeability of the cell membrane, which results in loss of metabolites essential to bacterial existence. 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 organisms.
Bacitracin, polymyxin B sulfate, and neomycin sulfate in combination are considered active against the following microorganisms: Enterobacter sp., Escherichia coli, Haemophilus influenzae, Klebsiella sp., Neisseria sp., Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus sp., including Streptococcus pneumoniae. These agents do not provide adequate coverage against Serratia marcescens.
Bacitracin; hydrocortisone; neomycin; polymyxin B combination products are applied topically to the eye or skin.
-Route-Specific Pharmacokinetics
Topical Route
Except when applied to large areas or for an extended period of time, systemic absorption of these agents is negligible after topical administration. Percutaneous penetration of hydrocortisone varies among individual patients and can be increased by the use of occlusive dressings, by increasing the concentration of the hydrocortisone, and by using different formulation vehicles. Topical preparations of hydrocortisone are primarily metabolized in the skin; systemic exposure is increased when there is breakdown of the skin barrier. 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 denuded or damaged epithelium. Any systemically absorbed bacitracin, polymyxin B, and neomycin are primarily excreted by the kidneys.
-Special Populations
Renal Impairment
Patients with renal dysfunction may develop ototoxicity or worsening nephrotoxicity following prolonged systemic exposure to bacitracin; hydrocortisone; neomycin, polymyxin B.