Polymyxin B is a polymyxin antibiotic.102, 103, 105, 106, 125, 126, 127, 128
Bacterial Ophthalmic Infections
Polymyxin B sulfate is used in fixed combination with other anti-infectives (i.e., bacitracin zinc; bacitracin zinc and neomycin sulfate; neomycin sulfate and gramicidin; trimethoprim sulfate) for the topical treatment of superficial infections of the eye (e.g., conjunctivitis, keratitis, keratoconjunctivitis, blepharitis, blepharoconjunctivitis) caused by susceptible bacteria.102, 103, 105, 106, 125, 126, 127, 128
Fixed-combination topical ophthalmic preparations containing polymyxin B sulfate and bacitracin zinc with or without neomycin sulfate are considered active against Staphylococcus aureus , streptococci (including Streptococcus pneumoniae ), Escherichia coli , Haemophilus influenzae , Enterobacter , Klebsiella , Neisseria , and Pseudomonas aeruginosa , but do not provide adequate coverage against Serratia marcescens .103, 105, 106
Fixed-combination topical ophthalmic preparations containing polymyxin B sulfate, neomycin sulfate, and gramicidin are considered active against S. pneumoniae , E. coli , H. influenzae , Enterobacter , Klebsiella , Neisseria , and Ps. aeruginosa , but do not provide adequate coverage against S. marcescens .125, 126
Fixed-combination topical ophthalmic preparations containing polymyxin B and trimethoprim sulfate are active against S. aureus , S. epidermidis , S. pneumoniae , viridans streptococci, H. influenzae , and Ps. aeruginosa .127, 128
Polymyxin B sulfate also has been given subconjunctivally in the treatment of infections of the eye caused by susceptible Ps. aeruginosa .104
Although mild, acute bacterial conjunctivitis often resolves spontaneously without anti-infective treatment,135, 136, 137, 141 topical ophthalmic anti-infectives may shorten the time to resolution and reduce severity and risk of complications.135, 136, 137, 141 Treatment of acute bacterial conjunctivitis generally is empiric and use of a broad-spectrum topical ophthalmic antibacterial usually is recommended;135, 136, 141 however, indiscriminate use of topical anti-infectives should be avoided.135, 141 In vitro staining and/or cultures of conjunctival material may be indicated in the management of recurrent, severe, or chronic purulent conjunctivitis or when acute conjunctivitis does not respond to initial empiric topical treatment.135, 136, 141
Because many forms of bacterial keratitis are associated with subsequent loss of vision as the result of corneal scarring or topographic irregularities and because untreated or severe bacterial keratitis may result in perforation of the cornea with the potential for endophthalmitis and possible loss of the eye, optimal management involves rapid evaluation and diagnosis, timely initiation of treatment, and appropriate follow-up.138 Treatment of community-acquired bacterial keratitis generally is empiric and use of a broad-spectrum topical ophthalmic antibacterial usually is recommended.138 Subconjunctival therapy with an appropriate anti-infective may be necessary if scleral spread or perforation is imminent.138 In vitro staining and/or cultures are indicated in the management of keratitis involving corneal infiltrates that are central, large, and extending to the middle to deep stroma; when keratitis is chronic or unresponsive to broad-spectrum topical anti-infective treatment; or when atypical features are present suggesting fungal, amebic, or mycobacterial infection.138
Polymyxin B sulfate is used in fixed combination with neomycin sulfate and a corticosteroid (i.e., hydrocortisone) for the topical treatment of superficial infections of the external auditory canal (otitis externa) caused by susceptible bacteria.121, 122, 123, 124, 139 These fixed-combination otic preparations also are used for topical treatment of infections of mastoidectomy and fenestration cavities caused by susceptible bacteria.121, 124
Diffuse, uncomplicated acute otitis externa in otherwise healthy patients usually should be treated initially with topical therapy (e.g., otic anti-infective or antiseptic with or without an otic corticosteroid).139, 143 Topical therapy should be supplemented with systemic anti-infective therapy if the patient has a medical condition that could impair host defenses (e.g., diabetes mellitus, human immunodeficiency virus [HIV] infection) or if the infection has spread into the pinna, skin of the neck or face, or into deeper tissues such as occurs with malignant otitis externa.139 Malignant otitis externa is an invasive, potentially life-threatening infection, especially in immunocompromised patients, and requires prompt diagnosis and treatment with systemic anti-infectives.139
Topical ophthalmic preparations containing polymyxin B sulfate in fixed combination with neomycin sulfate and a corticosteroid (i.e., dexamethasone)119, 120 or polymyxin B sulfate in fixed combination with neomycin sulfate, bacitracin zinc, and a corticosteroid (i.e., hydrocortisone or hydrocortisone acetate)107, 108 are used for the treatment of corticosteroid-responsive ocular conditions when a corticosteroid is indicated and superficial bacterial ocular infection or risk of such infection exists.107, 108, 119, 120
Ophthalmic corticosteroids may be indicated in inflammatory conditions of the palpebral and bulbar conjunctiva, cornea, and anterior segment of the globe where the inherent risk of corticosteroid use in certain infective conjunctivitides is accepted to obtain diminution in edema and inflammation.107, 108, 119, 120 Ophthalmic corticosteroids also may be indicated in the treatment of chronic anterior uveitis and corneal injury from chemical, radiation, or thermal burns or penetration of foreign bodies.107, 108, 119, 120
Although the manufacturers state that use of fixed-combination ophthalmic preparations containing anti-infectives and a corticosteroid may be indicated in ocular inflammatory conditions when the risk of superficial ocular infection is high or when there is an expectation that potentially dangerous numbers of bacteria will be present in the eye,107, 108, 119, 120 experts state that such preparations should be avoided in patients with bacterial conjunctivitis because of the risk of potentiating the infection.136
Clinicians should consider that use of fixed-combination ophthalmic preparations containing anti-infectives and a corticosteroid may mask the clinical signs of bacterial, fungal, or viral infections; prevent recognition of ineffectiveness of the anti-infectives; and/or increase intraocular pressure.107, 108, 119, 120
Ophthalmic Administration (Topical)
Polymyxin B sulfate in fixed combination with bacitracin zinc with or without neomycin sulfate is applied topically to the eye as an ophthalmic ointment.102, 103, 105, 106
Polymyxin B sulfate in fixed combination with neomycin sulfate and gramicidin is applied topically to the eye as an ophthalmic solution.125, 126
Polymyxin B sulfate in fixed combination with trimethoprim sulfate is applied topically to the eye as an ophthalmic solution.127, 128
Polymyxin B sulfate also is commercially available in fixed combination with neomycin sulfate and a corticosteroid (i.e., dexamethasone)119, 120 or in fixed combination with neomycin sulfate, bacitracin zinc, and a corticosteroid (i.e., hydrocortisone or hydrocortisone acetate) for topical application to the eye as ophthalmic ointments or suspensions.107, 108
Ophthalmic preparations containing polymyxin B sulfate and other anti-infectives with or without a corticosteroid are for topical ophthalmic use only ;103, 105, 106, 107, 108, 119, 120, 125, 126, 127, 128 these preparations are not for subconjunctival injection and should not be introduced directly into the anterior chamber of the eye.103, 105, 106, 107, 108, 119, 120, 125, 126, 127, 128
Care should be taken to avoid contaminating the container tip with material from the eye, eyelids, fingers, or other source.103, 105, 106, 107, 108, 119, 120, 125, 126, 127, 128
Ophthalmic Administration (Subconjunctival)
Polymyxin B sulfate has been administered by subconjunctival injection.104
For subconjunctival administration, a vial labeled as containing 500,000 units of polymyxin B sterile powder for injection should be reconstituted by adding 20-50 mL of sterile water for injection or 0.9% sodium chloride injection to provide a solution containing 10,000-25,000 units per mL.104 The appropriate dose of reconstituted solution should then be administered by subconjunctival injection.104
Polymyxin B sulfate in fixed combination with neomycin sulfate and a corticosteroid (i.e., hydrocortisone) is instilled topically into the ear canal as an otic solution or suspension.121, 122, 123, 124
Otic solutions and suspensions containing polymyxin B are for topical otic use only ;121, 122, 123, 124 these preparations should not be used in the eyes.122, 123, 124
Prior to topical otic instillation, the ear canal should be thoroughly cleaned and dried.121, 122, 123, 124
Otic suspensions should be shaken well prior to each use.121, 124
The patient should lie with the affected ear upward.121, 122, 123, 124 The appropriate amount of otic solution or suspension should be instilled into the ear;121, 122, 123, 124 this position should be maintained for 5 minutes to facilitate penetration into the ear canal.121, 122, 123, 124 The procedure should be repeated for the opposite ear if necessary.121, 122, 123, 124
If the ear canal is narrow or edematous and there are concerns that this might impede drug delivery,139 consideration can be given to inserting a cotton wick into the ear canal and saturating the wick with the otic preparation.121, 122, 123, 124 The manufacturers state that the wick should be kept moist by adding additional otic solution or suspension every 4 hours and should be replaced once every 24 hours.121, 122, 123, 124 Experts state that a wick is unnecessary after ear canal edema subsides, which may occur within 24 hours or a few days after topical otic treatment is initiated.139
Care should be taken to avoid contaminating the tip of the container with material from the ear, fingers, or other source.121, 122, 123, 124
Potency and dosage of polymyxin B sulfate are expressed in terms of polymyxin B activity (units of polymyxin B).102, 103, 104, 105, 106, 107, 108, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128
Bacterial Ophthalmic Infections
When a fixed-combination ophthalmic ointment containing polymyxin B sulfate and bacitracin zinc with or without neomycin sulfate is used for the topical treatment of superficial bacterial infections of the eye in adults, the ophthalmic ointment should be applied to the affected eye(s) every 3 or 4 hours for 7-10 days, depending on the severity of the infection.102, 103, 105, 106
When a fixed-combination ophthalmic solution containing polymyxin B sulfate, neomycin sulfate, and gramicidin is used for the topical treatment of superficial bacterial infections of the eye in adults, 1 or 2 drops of the solution should be instilled in the affected eye(s) every 4 hours for 7-10 days.125, 126 For severe infections, up to 2 drops may be instilled every hour.125, 126
When a fixed-combination ophthalmic solution containing polymyxin B sulfate and trimethoprim is used for the topical treatment of mild to moderate superficial bacterial infections of the eye in adults and pediatric patients 2 months of age or older, 1 drop of the solution should be instilled in the affected eye(s) every 3 hours (maximum of 6 doses daily) for 7-10 days.127, 128
The usual duration of topical anti-infective treatment for bacterial conjunctivitis is 5-10 days;135, 136, 141 some experts state that 5-7 days of such treatment usually is adequate for mild bacterial conjunctivitis.135
If subconjunctival injection of polymyxin B is indicated for the treatment of infections of the eye caused by susceptible Pseudomonas aeruginosa , up to 100,000 units of the reconstituted solution containing 10,000-25,000 units/mL may be administered daily.104
If polymyxin B is administered subconjunctivally in conjunction with topical administration of the drug, total polymyxin B dosage should not exceed 25,000 units/kg daily.104
When fixed-combination otic solutions or suspensions containing polymyxin B sulfate, neomycin sulfate, and hydrocortisone are used for the topical treatment of superficial bacterial infections of the external auditory canal (otitis externa) in adults, 4 drops should be instilled into the canal of the affected ear(s) 3 or 4 times daily.121, 122, 123, 124 When used in children 2 years of age or older, 3 drops of the otic solution or suspension should be instilled into the canal of the affected ear(s) 3 or 4 times daily.121, 122, 123, 124 One manufacturer does not include an age restriction for use of the otic suspension in pediatric patients.121
Topical otic therapy should be continued for a maximum of 10 consecutive days.121, 122, 123, 124 The optimal duration of topical therapy for the treatment of acute otitis externa has not been determined, but 7-10 days is usually recommended.139 Some experts state that appropriate treatment of acute otitis externa should result in improvement in symptoms (otalgia, pruritus, fullness) within 48-72 hours, although resolution of symptoms may take up to 2 weeks.139
When a fixed-combination ophthalmic ointment containing polymyxin B sulfate, neomycin sulfate, and dexamethasone is used in adults, approximately 1.25 cm (½ inch) of the ointment should be applied in the conjunctival sac of the affected eye(s) up to 3 or 4 times daily.119
When a fixed-combination ophthalmic suspension containing polymyxin B sulfate, neomycin sulfate, and dexamethasone is used in adults and pediatric patients 2 years of age or older with mild disease, 1 or 2 drops of the suspension should be instilled in the conjunctival sac of the affected eye(s) up to 4-6 times daily.120 In severe disease, 1 or 2 drops of the suspension may be instilled every hour initially and dosage tapered by decreasing the frequency of administration as inflammation subsides.120
When a fixed-combination ophthalmic ointment containing polymyxin B sulfate, neomycin sulfate, bacitracin zinc, and hydrocortisone or hydrocortisone acetate is used in adults, the ointment should be applied to the affected eye(s) every 3 or 4 hours, depending on the severity of the condition.107, 108
If there is no improvement after 48 hours of treatment with a fixed-combination preparation containing anti-infectives and a corticosteroid, the patient should be reevaluated.107, 108, 119, 120
Polymyxin B sulfate has a low order of toxicity when applied topically to the eyes or ears; however, local irritation and allergic reactions may occur when fixed-combination topical preparations containing polymyxin B are used.103, 105, 106, 107, 108, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128 More serious hypersensitivity reactions, including anaphylaxis, have been reported rarely.103, 105, 106, 107, 108, 119, 120, 125, 126, 127, 128
Topical anti-infectives, particularly neomycin sulfate, may cause cutaneous sensitization.103, 105, 106, 107, 108, 119, 120, 121, 122, 123, 124, 125, 126 A precise incidence of hypersensitivity reactions (primarily skin rash) due to topical anti-infectives is not known.105, 106, 107, 108, 125, 126
Local irritation and allergic reactions reported in patients receiving topical ophthalmic preparations containing polymyxin B and other anti-infectives include pruritus, edema of the conjunctiva and eyelid, and conjunctival erythema.103, 105, 106, 107, 108, 119, 120, 125, 126, 127, 128
There have been reports of bacterial keratitis developing in patients using topical ophthalmic preparations.103, 105, 106, 107, 108, 125, 126 These infections occurred because the patients inadvertently contaminated the multiple-dose container of the ophthalmic preparation; in most reported cases, the patient had concurrent corneal disease or disruption of the ocular epithelial surface.103, 105, 106, 107, 108, 125, 126
Precautions and Contraindications
Polymyxin B sulfate is contraindicated in patients hypersensitive to polymyxins.104
Fixed-combination ophthalmic preparations containing polymyxin B sulfate and other anti-infectives (i.e., bacitracin zinc; bacitracin zinc and neomycin sulfate; neomycin sulfate and gramicidin; trimethoprim sulfate) are contraindicated in patients hypersensitive to any ingredient in the formulation.102, 103, 105, 106, 125, 126, 127, 128
Fixed-combination ophthalmic preparations containing polymyxin B sulfate, other anti-infectives (i.e., neomycin sulfate; neomycin sulfate and bacitracin zinc), and a corticosteroid (i.e., dexamethasone, hydrocortisone, or hydrocortisone acetate) are contraindicated in patients hypersensitive to any ingredient in the formulation.107, 108, 119, 120 In addition, these fixed-combination preparations are contraindicated in patients with viral diseases of the cornea and conjunctiva (e.g., epithelial herpes simplex keratitis [dendritic keratitis], vaccinia, varicella) and in patients with mycobacterial infections of the eye or fungal diseases of ocular structures.107, 108, 119, 120
Fixed-combination otic preparations containing polymyxin B sulfate, neomycin sulfate, and hydrocortisone are contraindicated in patients hypersensitive to any ingredient in the formulation.121, 122, 123, 124 In addition, these fixed combinations are contraindicated in patients with viral infections of the external ear canal (e.g., herpes simplex, vaccinia, varicella zoster).121, 122, 123, 124
Prolonged use of ophthalmic or otic preparations containing polymyxin B and other anti-infectives may result in overgrowth of nonsusceptible organisms, including fungi.102, 103, 104, 105, 106, 121, 122, 123, 124, 125, 126, 127, 128 Appropriate therapy should be initiated if superinfection occurs.102, 103, 105, 106, 125, 126, 127, 128 Resistance to polymyxin B or other anti-infectives in fixed-combination preparations may develop.103, 105, 106, 125, 126
Serious adverse reactions, including nephrotoxicity and neurotoxicity, have occurred in patients receiving systemic polymyxin B therapy.104 If polymyxin B is administered topically in conjunction with systemic polymyxin B therapy, the possibility of cumulative toxicity should be considered.
Precautions Related to Sensitivity Reactions
During long-term use of topical ophthalmic or otic anti-infectives, patients should be examined periodically for signs of sensitization.103, 105, 106, 107, 108, 121, 122, 123, 124, 125, 126
In patients receiving ophthalmic preparations, sensitization may manifest as rash, pruritus, edema of the conjunctiva and eyelid, or conjunctival erythema;103, 105, 106, 107, 108, 125, 126, 127, 128 in patients receiving otic preparations, sensitization may manifest as swelling, dry scaling, and pruritus.121, 122, 123, 124 Sensitization to topical ophthalmic or otic preparations may manifest as failure to heal in some patients.103, 105, 106, 107, 108, 121, 122, 123, 124, 125, 126
Patients should be advised to discontinue ophthalmic or otic preparations if any signs of sensitivity or allergic reactions occur.103, 105, 106, 107, 108, 121, 122, 123, 124, 125, 126, 127, 128 Symptoms usually subside quickly after the preparation is discontinued.103, 105, 106, 107, 108, 121, 122, 123, 124, 125, 126
Patients allergic to one of the fixed-combination preparations should avoid preparations containing any of the component drugs.103, 105, 106, 107, 108, 121, 122, 123, 124, 125, 126 Cross-allergenicity occurs among the aminoglycosides,119, 120 and patients allergic to fixed-combination preparations containing neomycin may also be allergic to other aminoglycosides (e.g., gentamicin, paromomycin, streptomycin).103, 105, 106, 107, 108, 121, 122, 123, 124, 125, 126
Precautions Related to Ophthalmic Administration
Patients should be informed that ophthalmic preparations, if handled improperly, can become contaminated by common bacteria known to cause ocular infections and that serious damage to the eye and subsequent loss of vision may occur if contaminated ophthalmic preparations are used.103, 105, 106, 107, 125, 126 Patients should be advised to avoid allowing the tip of the dispensing container to contact the eye, eyelid, fingers, or any other surface103, 105, 106, 107, 108, 119, 120, 125, 126, 127, 128 and to not share ophthalmic preparations with others.103, 105, 106, 107, 108, 119, 120, 125, 126
Patients should be advised that their vision may be temporarily blurred after administration of topical ophthalmic preparations.119, 120 Care should be taken in operating machinery or driving a motor vehicle.119, 120
Contact lenses should not be worn if any signs or symptoms of ocular infection are present.127, 128
Some manufacturers caution that ophthalmic ointments may delay corneal healing.102, 103, 105, 106, 107, 108
Precautions Related to Otic Administration
Fixed-combination otic preparations containing polymyxin B sulfate, neomycin sulfate, and hydrocortisone should not be used in patients with a perforated tympanic membrane.121, 122, 123, 124
Neomycin, especially with prolonged use, can induce permanent sensorineural hearing loss due to cochlear damage, mainly destruction of hair cells in the organ of Corti.121, 122, 123, 124
Patients being treated with otic preparations containing neomycin should be under close clinical observation and such preparations should not be used for longer than 10 consecutive days.121, 122, 123, 124
If otic infections have not improved after 1 week of topical otic treatment, cultures should be obtained to guide further treatment.121, 122, 123, 124
When using fixed-combination otic preparations containing polymyxin B sulfate, neomycin sulfate, and hydrocortisone to control secondary infection in chronic otitis externa, clinicians should consider that skin in this condition is more liable than normal skin to become sensitized to many substances, including neomycin.121, 122, 123, 124 Sensitization to topical neomycin usually manifests as a low-grade reddening with swelling, dry scaling, and pruritus; it may manifest simply as failure to heal.121, 122, 123, 124
Commercially available fixed-combination otic solutions containing polymyxin B sulfate, neomycin sulfate, and hydrocortisone contain potassium metabisulfite,122, 123 a sulfite that can cause allergic-type reactions, including anaphylaxis and life-threatening or less severe asthmatic episodes, in certain susceptible individuals.111, 112, 113, 114, 115, 116, 117, 118, 122, 123 The overall prevalence of sulfite sensitivity in the general population is unknown but probably low; such sensitivity appears to occur more frequently in asthmatic than in nonasthmatic individuals.117, 122, 123
Precautions Related to Use of Fixed Combinations Containing Corticosteroids
When ophthalmic or otic preparations containing polymyxin B in fixed combination with other anti-infectives and a corticosteroid (i.e., dexamethasone, hydrocortisone, or hydrocortisone acetate) are used, the usual cautions, precautions, and contraindications associated with the corticosteroid also must be considered.107, 108, 119, 120, 121, 122, 123, 124
Initial prescriptions for fixed-combination ophthalmic preparations containing a corticosteroid or renewal prescriptions (beyond 8 g of ophthalmic ointment or beyond 20 mL of ophthalmic suspension) should be made only after examining the patient with slit lamp microscopy and, when appropriate, fluorescein staining.107, 108, 119, 120
Patients should be advised to discontinue the fixed-combination ophthalmic preparation and contact a clinician if inflammation or pain persists for more than 48 hours or becomes aggravated.108, 119, 120
Prolonged use of fixed-combination ophthalmic preparations containing a corticosteroid may result in glaucoma, with damage to the optic nerve, defects in visual acuity and fields of vision, and posterior subcapsular cataract formation.107, 108, 119, 120 If an ophthalmic preparation containing a corticosteroid is used for 10 days or longer, intraocular pressure should be routinely monitored, even though this may be difficult in children and uncooperative patients.107, 108, 119, 120 Such preparations should be used with caution in patients with glaucoma and intraocular pressure should be checked frequently in such patients.107, 108, 119, 120
Use of fixed-combination ophthalmic preparations containing a corticosteroid after cataract surgery may delay healing and increase the incidence of bleb formation.107, 108, 119, 120
Various ocular diseases and long-term use of topical ophthalmic corticosteroids have caused corneal and scleral thinning.108, 120 Use of topical ophthalmic corticosteroids in patients with thin corneal and scleral tissue may result in perforation.107, 108, 119, 120
Prolonged use of fixed-combination ophthalmic preparations containing a corticosteroid may suppress host responses and increase the risk of secondary ocular infections.107, 108, 119, 120 Use of such preparations in patients with acute purulent or parasitic infections of the eye may mask infection or enhance existing infection.107, 108, 119, 120
Use of ophthalmic preparations containing a corticosteroid may prolong the course and exacerbate severity of many viral infections of the eye (including herpes simplex).107, 108, 119, 120 Such preparations should be used with great caution in patients with herpes simplex107, 108, 119, 120 and frequent slit lamp microscopy is recommended.108, 119, 120
The possibility of fungal infections of the cornea should be considered after prolonged use of ophthalmic preparations containing a corticosteroid,107, 108, 119, 120 especially in patients with persistent corneal ulceration.119, 120 Fungal cultures should be taken when appropriate.107, 108, 119, 120
Fixed combinations of polymyxin B sulfate and bacitracin zinc with or without neomycin sulfate (ophthalmic): Safety and efficacy have not been established in pediatric patients.103, 105, 106
Fixed combinations of polymyxin B sulfate, neomycin sulfate, and gramicidin (ophthalmic): Safety and efficacy have not been established in pediatric patients.125, 126
Fixed combinations of polymyxin B sulfate and trimethoprim sulfate (ophthalmic): Safety and efficacy have not been established in infants younger than 2 months of age.127, 128
Fixed combinations of polymyxin B sulfate, neomycin sulfate, and dexamethasone (ophthalmic): Safety and efficacy of the suspension have not been established in children younger than 2 years of a 120 safety and efficacy of the ointment have not been established in pediatric patients.119
Fixed combinations of polymyxin B sulfate, neomycin sulfate, bacitracin zinc, and either hydrocortisone or hydrocortisone acetate (ophthalmic): Safety and efficacy have not been established in pediatric patients.107, 108
Fixed combinations of polymyxin B sulfate, neomycin sulfate, and hydrocortisone (otic): Most manufacturers state that safety and efficacy have not been established for the treatment of otitis external in children younger than 2 years of age because of insufficient data in this age group.122, 123, 124 One manufacturer states that safety and efficacy have been established in pediatric patients and does not specify an age range.121
Fixed combinations of polymyxin B sulfate, neomycin sulfate, and gramicidin (ophthalmic): Clinical studies did not include sufficient numbers of patients 65 years of age or older to determine whether they respond differently than younger adults.125 Other reported clinical experience has not identified differences in responses between geriatric and younger patients.125
Fixed combinations of polymyxin B sulfate and trimethoprim sulfate (ophthalmic): No overall differences in safety or efficacy have been observed between geriatric and younger adults.127, 128
Fixed combinations of polymyxin B sulfate, neomycin sulfate, and dexamethasone (ophthalmic): No overall differences in safety or efficacy have been observed between geriatric and younger patients.119, 120
Fixed combinations of polymyxin B sulfate, neomycin sulfate, bacitracin zinc, and hydrocortisone acetate (ophthalmic): No overall differences in safety or efficacy have been observed between geriatric and younger adults.108
Fixed combinations of polymyxin B sulfate, neomycin sulfate, and hydrocortisone (otic): Clinical studies did not include sufficient numbers of patients 65 years of age or older to determine whether they respond differently than younger adults.121, 122, 123, 124 Other reported clinical experience has not identified differences in responses between geriatric and younger patients.121, 122, 123, 124
Animal reproduction studies have not been performed with polymyxin B sulfate.103, 105, 106, 125, 126 It is not known whether ophthalmic preparations containing polymyxin B sulfate can cause fetal harm when administered to pregnant women.103, 105, 106, 125, 126
Fixed-combination ophthalmic preparations of polymyxin B sulfate and bacitracin zinc or polymyxin B sulfate, neomycin sulfate, and either bacitracin zinc or gramicidin should be used during pregnancy only if clearly needed.103, 105, 106, 125, 126
Because trimethoprim may interfere with folic acid metabolism, fixed-combination ophthalmic preparations containing polymyxin B sulfate and trimethoprim sulfate should be used during pregnancy only if potential benefits justify potential risks to the fetus.127, 128
Fixed-combination ophthalmic preparations containing polymyxin B sulfate, other anti-infectives (i.e., neomycin sulfate, bacitracin zinc), and a corticosteroid (i.e., dexamethasone, hydrocortisone, hydrocortisone acetate) should be used during pregnancy only if potential benefits justify potential risks to the fetus.107, 108, 119, 120
Fixed-combination otic preparations containing polymyxin B sulfate, neomycin sulfate, and hydrocortisone should be used during pregnancy only if potential benefits justify potential risks to the fetus.121, 122, 123, 124
Fixed-combination ophthalmic preparations containing polymyxin B sulfate and other anti-infectives (i.e., bacitracin zinc, gramicidin, neomycin sulfate, trimethoprim sulfate) should be used with caution in nursing women.103, 105, 106, 125, 126, 127, 128
Fixed-combination ophthalmic preparations containing polymyxin B sulfate, neomycin sulfate, and dexamethasone should be used with caution in nursing women.119, 120
The manufacturers of fixed-combination ophthalmic preparations containing polymyxin B sulfate, neomycin sulfate, bacitracin zinc, and hydrocortisone or hydrocortisone acetate state that a decision should be made whether to discontinue nursing or the ophthalmic preparation, taking into account the importance of the drug to the woman.107, 108
Fixed-combination otic preparations containing polymyxin B sulfate, neomycin sulfate, and hydrocortisone should be used with caution in nursing women.121, 122, 123, 124
Polymyxin B sulfate usually is bactericidal in action. The drug binds to phosphate groups in the lipids of the bacterial cytoplasmic membrane of susceptible bacteria and acts as a cationic detergent, thereby altering the osmotic barrier of the membrane and causing leakage of essential metabolites.
Polymyxin B is active in vitro against many gram-negative aerobic bacteria; however, most species of Proteus and Neisseria are resistant to the drug. Polymyxin B is inactive against gram-positive bacteria, fungi, and viruses.
Polymyxin B sulfate in fixed combination with neomycin sulfate is considered active against Staphylococcus aureus , Escherichia coli , Haemophilus influenzae , Enterobacter , Klebsiella , Neisseria , and Pseudomonas aeruginosa ,119, 120, 121, 122, 123, 124 but does not provide adequate coverage against streptococci (including Streptococcus pneumoniae ) or Serratia marcescens .119, 120, 121, 122, 123, 124
Polymyxin B sulfate in fixed combination with bacitracin zinc with or without neomycin sulfate is considered active against S. aureus , streptococci (including S. pneumoniae ), E. coli , H. influenzae , Enterobacter , Klebsiella , Neisseria , and Ps. aeruginosa ,105, 106, 107, 108 but does not provide adequate coverage against S. marcescens .105, 106, 107, 108
Polymyxin B sulfate in fixed combination with neomycin sulfate and gramicidin is considered active against S. pneumoniae , E. coli , H. influenzae , Enterobacter , Klebsiella , Neisseria , and Ps. aeruginosa , but does not provide adequate coverage against S. marcescens .125, 126
Polymyxin B sulfate in fixed combination with trimethoprim sulfate is considered active against S. aureus , S. epidermidis , S. pneumoniae , viridans streptococci, H. influenzae , and Ps. aeruginosa .127, 128
Resistance to polymyxin B has been reported rarely in Pseudomonas aeruginosa .
Bacteria resistant to polymyxin B may emerge in patients receiving topical ophthalmic preparations containing the drug.103, 105, 106, 125, 126
There is complete cross-resistance between polymyxin B and colistin, but there is no evidence to date of cross-resistance between these polymyxins and other anti-infectives.
There is some evidence suggesting that polymyxin B is not absorbed from the conjunctival sac. Systemically administered polymyxin B does not penetrate into the aqueous humor of the eye, even in the presence of inflammation.
Polymyxin B does not appear to be absorbed to any appreciable extent from mucous membranes or intact or denuded skin.
Polymyxin B is a polymyxin antibiotic derived from Bacillus polymyxa . Polymyxin B is structurally and pharmacologically related to colistin. Commercially available polymyxin B sulfate is a mixture of the sulfate salts of polymyxins B1 and B2.104
Polymyxin B sulfate occurs as a white to buff-colored, hygroscopic powder that is odorless or has a faint odor. The drug is freely soluble in water and in 0.9% sodium chloride injection and is slightly soluble in alcohol. Polymyxin B sulfate contains not less than 6000 units of polymyxin B activity per mg, calculated on the dried basis, and each mg of pure polymyxin B base is equivalent to 10,000 units of polymyxin B activity.
Polymyxin B sulfate is commercially available for topical ophthalmic use only in fixed combination with other anti-infectives.102, 103, 105, 106, 125, 126, 127, 128 This includes fixed-combination ophthalmic ointments containing polymyxin B sulfate and bacitracin zinc with or without neomycin sulfate;102, 103, 105, 106 fixed-combination ophthalmic solutions containing polymyxin B sulfate, neomycin sulfate, and gramicidin;125, 126 and fixed-combination ophthalmic solutions containing polymyxin B sulfate and trimethoprim sulfate.127, 128 The ophthalmic solutions containing polymyxin B sulfate, neomycin sulfate, and gramicidin contain thimerosal as a preservative;125, 126 the ophthalmic solutions containing polymyxin B sulfate and trimethoprim sulfate contain benzalkonium chloride as a preservative.127, 128
Polymyxin B sulfate also is commercially available for topical ophthalmic use as fixed-combination ophthalmic ointments or suspensions containing other anti-infectives and a corticosteroid.107, 108, 119, 120 This includes fixed-combination ointments or suspensions containing polymyxin B sulfate, neomycin sulfate, and dexamethasone119, 120 and fixed-combination ointments containing polymyxin B sulfate, neomycin sulfate, bacitracin zinc, and either hydrocortisone or hydrocortisone acetate.107, 108 The ophthalmic ointments containing polymyxin B sulfate, neomycin sulfate, and dexamethasone contain methylparaben and propylparaben as preservatives;119 the ophthalmic suspension of these drugs contains benzalkonium chloride as a preservative.120
For topical otic use, polymyxin B sulfate is commercially available in fixed-combination otic solutions or suspensions containing polymyxin B sulfate, neomycin sulfate, and a corticosteroid (i.e., hydrocortisone).121, 122, 123, 124 The otic solutions containing polymyxin B sulfate, neomycin sulfate, and hydrocortisone contain potassium metabisulfite as a preservative;122, 123 the otic suspensions of these drugs contain thimerosal as a preservative.121, 124
Commercially available vials containing polymyxin B sulfate sterile powder for injection (500,000 units of polymyxin B) should be stored at 20-25°C and protected from light.104 After reconstitution with sterile water for injection or 0.9% sodium chloride injection, solutions of the drug containing 10,000-25,000 units per mL should be stored at 2-8°C and unused portions should be discarded after 72 hours.104
Fixed-combination ophthalmic ointments containing polymyxin B sulfate and bacitracin zinc with or without neomycin sulfate should be stored at 15-25°C.102, 103, 105, 106
Fixed-combination ophthalmic solutions containing polymyxin B sulfate, neomycin sulfate, and gramicidin should be stored at 15-25°C125, 126 and protected from light.125
Fixed-combination ophthalmic solutions containing polymyxin B sulfate and trimethoprim sulfate should be stored at 15-25°C and protected from light.127, 128
Fixed-combination ophthalmic ointments containing polymyxin B sulfate, neomycin sulfate, and dexamethasone should be stored at 2-25°C.119 Fixed-combination ophthalmic suspensions containing these drugs should be stored upright at 8-25°C.120
Fixed-combination ophthalmic ointments containing polymyxin B sulfate, neomycin sulfate, bacitracin zinc, and either hydrocortisone or hydrocortisone acetate should be stored at 15-25°C.107, 108
Fixed-combination otic solutions or suspensions containing polymyxin B sulfate, neomycin sulfate, and hydrocortisone should be stored at 15-25°C.121, 122, 123, 124
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | For injection | 500,000 units (of polymyxin B)* | Polymyxin B Sulfate for Injection |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Ophthalmic | Ointment | Bacitracin Zinc 500 units (of bacitracin) per g and Polymyxin B Sulfate 10,000 units (of polymyxin B) per g* | Bacitracin Zinc and Polymyxin B Sulfate Ophthalmic Ointment |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Ophthalmic | Ointment | Neomycin Sulfate 3.5 mg (of neomycin) per g, Polymyxin B Sulfate 10,000 units (of polymyxin B) per g, and Bacitracin Zinc 400 units (of bacitracin) per g* | Neomycin and Polymyxin B Sulfates and Bacitracin Zinc Ophthalmic Ointment | |
Neosporin® Ophthalmic Ointment | Burroughs Wellcome |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Ophthalmic | Ointment | Neomycin Sulfate 3.5 mg (of neomycin) per g, Polymyxin B Sulfate 10,000 units (of polymyxin B) per g, Bacitracin Zinc 400 units (of bacitracin) per g, and Hydrocortisone 1%* | Neomycin and Polymyxin B Sulfates, Bacitracin Zinc, and Hydrocortisone Ophthalmic Ointment |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Ophthalmic | Ointment | Neomycin Sulfate 3.5 mg (of neomycin) per g, Polymyxin B Sulfate 10,000 units (of polymyxin B) per g, Bacitracin Zinc 400 units (of bacitracin) per g, and Hydrocortisone Acetate 1%* | Neomycin and Polymyxin B Sulfates, Bacitracin Zinc, and Hydrocortisone Acetate Ophthalmic Ointment |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Ophthalmic | Ointment | Neomycin Sulfate 3.5 mg (of neomycin) per g, Polymyxin B Sulfate 10,000 units (of polymyxin B) per g, and Dexamethasone 0.1%* | Maxitrol® | Alcon |
Neomycin and Polymyxin B Sulfates and Dexamethasone Ophthalmic Ointment | ||||
Suspension | Neomycin Sulfate 3.5 mg (of neomycin) per mL, Polymyxin B Sulfate 10,000 units (of polymyxin B) per mL, and Dexamethasone 0.1%* | Maxitrol® | Alcon | |
Neomycin and Polymyxin B Sulfates and Dexamethasone Ophthalmic Suspension |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Ophthalmic | Solution | Neomycin Sulfate 1.75 mg (of neomycin) per mL, Polymyxin B Sulfate 10,000 units (of polymyxin B) per mL, and Gramicidin 0.025 mg per mL* | Neomycin and Polymyxin B Sulfates and Gramicidin Ophthalmic Solution | |
Neosporin® Ophthalmic Solution | Pfizer |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Ophthalmic | Suspension | Neomycin Sulfate 3.5 mg (of neomycin) per mL, Polymyxin B Sulfate 10,000 units (of polymyxin B) per mL, and Hydrocortisone 1%* | Neomycin and Polymyxin B Sulfates and Hydrocortisone Ophthalmic Suspension | |
Otic | Solution | Neomycin Sulfate 3.5 mg (of neomycin) per mL, Polymyxin B Sulfate 10,000 units (of polymyxin B) per mL, and Hydrocortisone 1%* | Cortisporin® Otic Solution | Pfizer |
Neomycin and Polymyxin B Sulfates and Hydrocortisone Otic Solution | ||||
Suspension | Neomycin Sulfate 3.5 mg (of neomycin) per mL, Polymyxin B Sulfate 10,000 units (of polymyxin B) per mL, and Hydrocortisone 1%* | Casporyn® HC | Casper | |
Neomycin and Polymyxin B Sulfates and Hydrocortisone Otic Suspension |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Ophthalmic | Solution | Polymyxin B Sulfate 10,000 units (of polymyxin B) per mL and Trimethoprim Sulfate 1 mg (of trimethoprim) per mL* | Polymyxin B Sulfate and Trimethoprim Sulfate Ophthalmic Solution | |
Polytrim® | Allergan |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
AHFS® Drug Information. © Copyright, 1959-2025, Selected Revisions October 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
Only references cited for selected revisions after 1984 are available electronically.
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