MOBILE VIEW  | 

BACITRACIN

Classification   |    Detailed evidence-based information

Therapeutic Toxic Class

    A) Bacitracin is polypeptide antibiotic, produced by a strain of Bacillus subtilis. It has a bactericidal activity in vitro against a variety of gram-positive organisms and a few gram-negative organisms. However, only staphylococcal infections may be treated with bacitracin.

Specific Substances

    1) Bacitracinum
    2) Bacitracin zinc
    3) Bacitracins zinc complex
    4) Zinc bacitracin
    5) CAS 1405-87-4
    6) CAS 1405-89-6 (bacitracin zinc)

Available Forms Sources

    A) FORMS
    1) There are three main bacitracins, A, B, and C. The commercial mix is primarily bacitracin A (Kanof, 1970).
    2) Bacitracin is available in the following formulations:
    a) Intramuscular powder for solution: 50,000 Units (Prod Info bacitracin IM injection, 2010)
    b) Ophthalmic ointment: 500 Units/g (Prod Info bacitracin topical ointment, 2006; Prod Info bacitracin ophthalmic ointment, 1998)
    c) Topical ointment: 500 Units/g (Prod Info bacitracin topical ointment, 2006)
    3) Bacitracin zinc is also available in combination with a variety of agents such as polymyxin B, neomycin (SEE AMINOGLYCOSIDES), and hydrocortisone (SEE CORTICOSTEROIDS) (Katz & Fisher, 1987).
    4) BACITRACIN ZINC: Contains about 7% zinc. It is more stable than bacitracin at elevated temperatures, is less water soluble, and has a shelf-life of more than twice that of bacitracin at 5 years (Katz & Fisher, 1987).
    B) SOURCES
    1) Bacitracin is an antibiotic first isolated in 1943 by Johnson, Anker, and Melenev from the Tracey I strain of the Bacillus subtilis.
    2) It was isolated from the damaged tissue and street contamination of a compound fracture of a young girl named Tracey; thus, the name baci-tracin (Meleney & Johnson, 1949).
    3) Commercial bacitracin comes from B. subtilis var. lichenformis. It is a mixture of polypeptides with an approximate molecular weight of 1460. It has a potency of approximately 40 to 50 units/mg. It is stable as the zinc salt.
    C) USES
    1) Topical bacitracin is mainly used to treat bacterial infection of skin and eyes. Intramuscular bacitracin is available to treat infants with pneumonia and empyema caused by susceptible staphylococci (Prod Info bacitracin IM injection, 2010; Prod Info bacitracin topical ointment, 2006; Prod Info bacitracin ophthalmic ointment, 1998).

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Topical bacitracin is mainly used to treat bacterial infection of skin and eyes. Intramuscular bacitracin is available to treat infants with pneumonia and empyema caused by susceptible staphylococci. Bacitracin zinc is also available in combination with a variety of agents such as polymyxin B, neomycin (SEE AMINOGLYCOSIDES), and hydrocortisone (SEE CORTICOSTEROIDS).
    B) PHARMACOLOGY: Bacitracin is polypeptide antibiotic, produced by a strain of Bacillus subtilis. It has a bactericidal activity in vitro against a variety of gram-positive organisms and a few gram-negative organisms. However, only staphylococcal infections may be treated with bacitracin.
    C) EPIDEMIOLOGY: Overdose is rare.
    D) WITH THERAPEUTIC USE
    1) Bacitracin is used primarily topically, where it is poorly absorbed. Oral doses of up to 240,000 units per day did not produce significant gastrointestinal side effects. Transient epigastric distress, including nausea, vomiting, diarrhea, or anal itching or burning may occur. Nausea and vomiting have also been reported with bacitracin IM injection. Although ototoxicity and nephrotoxicity are possible, they are unlikely unless bacitracin is administered parenterally or as a surgical irrigating solution. Nephrotoxicity has been seen when 200,000 units has been given parenterally to humans for several days, or when the agent has been used as an irrigation solution. Bacitracin has a low sensitizing potential, but has still caused allergic contact dermatitis, eczema, and histamine wheal and flare. Several cases of anaphylaxis have been reported after the use of bacitracin ointment. Skin rash and pain at the injection site may occur with IM bacitracin.
    E) WITH POISONING/EXPOSURE
    1) Overdose data are limited. Overdose effects are anticipated to be an extension of adverse effects observed following therapeutic doses, and severe toxicity is not expected.
    0.2.20) REPRODUCTIVE
    A) Bacitracin-containing ophthalmic ointments are rated FDA Pregnancy Category C. Teratogenic effects have been observed with topical use in animal studies.

Laboratory Monitoring

    A) No laboratory monitoring is needed in most patients after acute overdose.
    B) Monitor serum electrolytes in patients with severe vomiting and/or diarrhea.
    C) If bacitracin is being used parenterally, or as a surgical irrigating solution, the patient should be monitored for nephrotoxicity and ototoxicity. Early stages of albuminuria and proteinuria appear to be reversible.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Treatment is symptomatic and supportive. Most cases of bacitracin toxicity occur through parenteral administration, or the use of bacitracin in surgical irrigating solutions. There is little absorption through intact skin, or GI tract. Ingestions of bacitracin are rarely a problem, causing only nausea, vomiting, and other minor GI upset. Correct any significant fluid and/or electrolyte abnormalities in patients with vomiting or diarrhea.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Treatment is symptomatic and supportive. Severe toxicity is not expected after ingestion of bacitracin. In patients with acute allergic reaction, oxygen therapy, bronchodilators, diphenhydramine, corticosteroids, vasopressors, and epinephrine may be required.
    C) DECONTAMINATION
    1) PREHOSPITAL: Prehospital gastrointestinal decontamination is generally not necessary.
    2) HOSPITAL: Gastrointestinal decontamination is generally not necessary.
    D) AIRWAY MANAGEMENT
    1) Endotracheal intubation and mechanical ventilation may be required in patients with severe allergic reaction.
    E) ANTIDOTE
    1) None.
    F) HYPERSENSITIVITY REACTIONS
    1) Bacitracin ointments applied to broken skin may be absorbed systemically, and result in anaphylactic reactions. Surgical wounds irrigated with bacitracin have also resulted anaphylaxis in rare cases. MILD/MODERATE: Monitor airway. Administer antihistamines with or without inhaled beta agonists, corticosteroids, or epinephrine. SEVERE: Oxygen, aggressive airway management, antihistamines, epinephrine, corticosteroids, ECG monitoring, and IV fluids.
    G) ENHANCED ELIMINATION
    1) Hemodialysis is not recommended given the low toxicity of topical bacitracin. The effectiveness of hemodialysis following IM bacitracin overdose is unknown.
    H) PATIENT DISPOSITION
    1) HOME CRITERIA: A patient with an inadvertent ingestion, that remains asymptomatic can be managed at home.
    2) OBSERVATION CRITERIA: All patients with deliberate self-harm ingestions should be evaluated in a healthcare facility and monitored until symptoms resolve.
    3) ADMISSION CRITERIA: Hospital admission is rarely necessary. Patients should be admitted for severe vomiting, profuse diarrhea, severe abdominal pain, dehydration, and electrolyte abnormalities.
    4) CONSULT CRITERIA: Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    I) PITFALLS
    1) When managing a suspected bacitracin overdose, the possibility of multi-drug involvement should be considered.
    J) PHARMACOKINETICS
    1) Intramuscular injection of 200 to 300 units every 6 hours produces blood levels about 0.2 to 2 units/mL. Absorption: dermal: negligible. IM: rapid and complete. Vd: (intramuscular) widely distributed. Excretion: renal: 10% to 40% within 24 hours. Elimination half-life: 1.5 hours.
    K) DIFFERENTIAL DIAGNOSIS
    1) Includes other agents that cause nephrotoxicity or ototoxicity.
    0.4.4) EYE EXPOSURE
    A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
    0.4.6) PARENTERAL EXPOSURE
    A) Refer to ORAL OVERVIEW for treatment information.
    B) If bacitracin is being used parenterally or as a surgical irrigating solution, the patient should be monitored for nephrotoxicity and ototoxicity.

Range Of Toxicity

    A) TOXICITY: PARENTERAL: Bacitracin 200,000 units given parenterally for several days has caused nephrotoxicity in humans. Minor symptoms have been noted on total daily doses of less than 80,000 units per day intramuscularly. ORAL: Oral bacitracin 80,000 to 100,000 units in 4 divided doses for 7 to 10 days has been used to treat antibiotic-associated pseudomembranous colitis. Oral doses of up to 240,000 units caused virtually no side effects or absorption.
    B) THERAPEUTIC DOSES: INTRAMUSCULAR: CHILDREN: Infants under 2500 grams: 900 units/kilogram/day IM in 2 or 3 divided doses. Infants over 2500 grams: 1000 units/kilogram/day IM in 2 or 3 divided doses. ADULTS AND CHILDREN: OCULAR: A thin ribbon of ophthalmic ointment every 3 to 4 hr for 7 to 10 days. TOPICAL: Apply topically 2 to 5 times/day.

Summary Of Exposure

    A) USES: Topical bacitracin is mainly used to treat bacterial infection of skin and eyes. Intramuscular bacitracin is available to treat infants with pneumonia and empyema caused by susceptible staphylococci. Bacitracin zinc is also available in combination with a variety of agents such as polymyxin B, neomycin (SEE AMINOGLYCOSIDES), and hydrocortisone (SEE CORTICOSTEROIDS).
    B) PHARMACOLOGY: Bacitracin is polypeptide antibiotic, produced by a strain of Bacillus subtilis. It has a bactericidal activity in vitro against a variety of gram-positive organisms and a few gram-negative organisms. However, only staphylococcal infections may be treated with bacitracin.
    C) EPIDEMIOLOGY: Overdose is rare.
    D) WITH THERAPEUTIC USE
    1) Bacitracin is used primarily topically, where it is poorly absorbed. Oral doses of up to 240,000 units per day did not produce significant gastrointestinal side effects. Transient epigastric distress, including nausea, vomiting, diarrhea, or anal itching or burning may occur. Nausea and vomiting have also been reported with bacitracin IM injection. Although ototoxicity and nephrotoxicity are possible, they are unlikely unless bacitracin is administered parenterally or as a surgical irrigating solution. Nephrotoxicity has been seen when 200,000 units has been given parenterally to humans for several days, or when the agent has been used as an irrigation solution. Bacitracin has a low sensitizing potential, but has still caused allergic contact dermatitis, eczema, and histamine wheal and flare. Several cases of anaphylaxis have been reported after the use of bacitracin ointment. Skin rash and pain at the injection site may occur with IM bacitracin.
    E) WITH POISONING/EXPOSURE
    1) Overdose data are limited. Overdose effects are anticipated to be an extension of adverse effects observed following therapeutic doses, and severe toxicity is not expected.

Heent

    3.4.4) EARS
    A) WITH THERAPEUTIC USE
    1) Bacitracin is ototoxic by an unknown mechanism. Ringing of the ears is an infrequent symptom, but was reported in one case (Zintel et al, 1949).
    2) Bacitracin was tested with various other agents to determine if it would cause sensory hearing loss and inflammation which might lead to deafness. It caused no sensory hearing loss but did cause moderate inflammation when given by intra-tympanic administration in animals (Parker & James, 1978).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) GASTRITIS
    1) WITH THERAPEUTIC USE
    a) Oral doses of up to 240,000 units per day did NOT produce significant gastrointestinal side effects (Anon, 1977). Transient epigastric distress, including nausea, vomiting, diarrhea, or anal itching or burning may occur with therapeutic use (Gurney, 1968).
    B) NAUSEA AND VOMITING
    1) WITH THERAPEUTIC USE
    a) Nausea and vomiting have been reported with bacitracin IM injection (Prod Info bacitracin IM injection, 2010).

Genitourinary

    3.10.2) CLINICAL EFFECTS
    A) ABNORMAL RENAL FUNCTION
    1) WITH THERAPEUTIC USE
    a) Possible renal adverse effects with bacitracin IM injection include tubular necrosis and glomerular necrosis, albuminuria, cylindruria, azotemia, severe renal failure, and nephrotoxicity. Concomitant use with other nephrotoxic agents may increase the risk of nephrotoxicity (Prod Info bacitracin IM injection, 2010).
    b) Bacitracin 200,000 units given parenterally for several days has caused nephrotoxicity in humans (Zintel et al, 1949).
    c) The kidney damage appears to be done to the proximal tubules (Kjarheim & Hansson, 1969).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) CONTACT DERMATITIS
    1) WITH THERAPEUTIC USE
    a) Bacitracin has a low sensitizing potential, but has still been reported to cause allergic contact dermatitis, eczema, and a histamine wheal and flare (Bjorkner & Moller, 1973; Held et al, 1987; Pirila & Rouhunkowsky, 1959).
    b) INCIDENCE: Of 198 patients who had undergone surgery and were treated with topical bacitracin therapy (either used alone or in combination with other antibiotic therapies {i.e., neomycin, polymyxin B}), 9 developed allergic contact dermatitis. Seven of the 9 patients agreed to patch testing, and the frequency of sensitivity to bacitracin was 2% (Gette et al, 1992).
    c) CASE REPORTS: Two patients experienced bacitracin-induced allergic reactions described as acute vesicular dermatitis, with pruritus, swelling, blisters and weepiness (Held et al, 1987).
    B) INJECTION SITE PAIN
    1) WITH THERAPEUTIC USE
    a) Pain at the injection site was a frequent complaint in patients given the drug intramuscularly (Prod Info bacitracin IM injection, 2010; Zintel et al, 1949).
    C) ERUPTION
    1) WITH THERAPEUTIC USE
    a) Skin rash has been reported with the use of bacitracin for IM injection (Prod Info bacitracin IM injection, 2010).

Immunologic

    3.19.2) CLINICAL EFFECTS
    A) ANAPHYLACTOID REACTION
    1) WITH THERAPEUTIC USE
    a) SUMMARY: Anaphylaxis has been reported following various routes of exposure (ie, irrigation, topical) to bacitracin (Gall et al, 1999; Knowles & Shear, 1995; Lin et al, 1998; Saryan et al, 1998; Roupe & Strannegard, 1969).
    b) SYMPTOMS have included generalized erythema, severe pruritus, swelling of the feet, hands, lips, a choking sensation, dyspnea, hypotension, pulselessness, abdominal pain, and vomiting.
    c) SYSTEMIC ABSORPTION: In most case reports, bacitracin appears to have been systemically absorbed via a compromised skin barrier (ie, stasis ulcers, stasis dermatitis, burns, deep abrasions, surgical irrigation) (Netland et al, 1987; Knowles & Shear, 1995; Lin et al, 1998; Saryan et al, 1998; Blas et al, 2000), and in conditions which predispose to hypersensitivity (Schechter et al, 1984; Vale et al, 1978)
    1) In one case, systemic absorption occurred following tattooing in which bacitracin ointment was applied to the site (Dyck & Vadas, 1997).
    d) CASE REPORTS
    1) TOPICAL: A 45-year-old man developed pruritus within minutes of applying bacitracin ointment to an excoriated area on his foot. Despite attempts to wash off the ointment the patient developed generalized flushing, swelling of the tongue and face, and loss of consciousness. The patient was found pulseless by emergency medical personnel, and cardiopulmonary resuscitation was performed. The patient was resuscitated and recovered with no residual symptoms. Skin testing was not performed (Lin et al, 1998).
    2) TOPICAL: A 48-year-old man developed intraoperative anaphylaxis following the use of bacitracin ointment to insert nasal packing after a septorhinoplasty procedure. Effects were observed within seconds (i.e., increased oxygen demand followed by pulselessness), which resolved with intensive supportive care. The patient recovered completely, and remained neurologically intact. Skin testing was positive for bacitracin (Gall et al, 1999).
    3) TOPICAL/TATTOO: Anaphylaxis (severe generalized pruritus, hives, tongue swelling, hypotension and lightheadedness) developed in a 21-year-old man following a tattooing process (the twelfth tattoo in 3 years using the same dyes and needles), which was covered with methyl alcohol and bacitracin ointment upon completion. Although there was a small amount of bleeding at the site, no pruritis or swelling was present when the procedure was finished. Symptoms developed within 20 minutes, and resolved with supportive care. Skin testing two weeks after the episode was positive for hypersensitivity to bacitracin (Dyck & Vadas, 1997).
    4) TOPICAL: An elderly woman developed anaphylaxis following topical administration of bacitracin ointment (Polysporin(R)) to a cut on her leg, despite previous use for skin abrasions and a negative allergy history. Signs/symptoms improved following diphenhydramine and corticosteroid administration (Fox, 1994).
    5) IRRIGATION: Intraoperative anaphylaxis was reported in an adult undergoing surgical debridement following irrigation with bacitracin (approximately 25 U/mL). Postoperatively, the patient reported an earlier reaction (rash) to bacitracin after using an over-the-counter ointment (Blas et al, 2000).
    e) SKIN SENSITIZATION: Skin-sensitizing antibodies against bacitracin have been found in the sera of susceptible patients (Roupe & Strannegard, 1969).
    B) ACUTE ALLERGIC REACTION
    1) WITH THERAPEUTIC USE
    a) NEOMYCIN CO-SENSITIZATION: There is evidence that bacitracin will cross react with neomycin sensitive patients (Anon, 1977; Pirila & Rouhunkowsky, 1959).

Reproductive

    3.20.1) SUMMARY
    A) Bacitracin-containing ophthalmic ointments are rated FDA Pregnancy Category C. Teratogenic effects have been observed with topical use in animal studies.
    3.20.2) TERATOGENICITY
    A) LACK OF EFFECT
    1) Heinonen et al (1977) reported 18 patients with first trimester exposure (route unknown) who did not develop associated malformations.
    B) ANIMAL STUDIES
    1) MICE: Teratogenic effects were observed in mice administered topical corticosteroids 15% on days 10 to 13 of gestation (Prod Info CORTISPORIN(R) topical ointment, 2003; Prod Info neomycin sulfate polymyxin B sulfate bacitracin zinc hydrocortisone ophthalmic ointment, 2011).
    2) RABBITS: Teratogenic effects were observed in rabbits administered topical corticosteroids 0.5% on days 6 to 18 of gestation (Prod Info CORTISPORIN(R) topical ointment, 2003; Prod Info neomycin sulfate polymyxin B sulfate bacitracin zinc hydrocortisone ophthalmic ointment, 2011).
    3.20.3) EFFECTS IN PREGNANCY
    A) PREGNANCY CATEGORY
    1) Bacitracin-containing ophthalmic ointments are rated FDA pregnancy category C (Prod Info CORTISPORIN(R) topical ointment, 2003; Prod Info neomycin sulfate polymyxin B sulfate bacitracin zinc hydrocortisone ophthalmic ointment, 2011; Prod Info neomycin sulfate polymyxin B sulfate bacitracin zinc ophthalmic ointment, 2011).
    2) This ointment should only be used during pregnancy if the potential maternal benefit outweighs the fetal risk (Prod Info CORTISPORIN(R) topical ointment, 2003; Prod Info neomycin sulfate polymyxin B sulfate bacitracin zinc hydrocortisone ophthalmic ointment, 2011) and if clearly needed (Prod Info neomycin sulfate polymyxin B sulfate bacitracin zinc ophthalmic ointment, 2011).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) BREAST MILK
    1) Exercise caution when administered this drug to a woman who is breastfeeding (Prod Info neomycin sulfate polymyxin B sulfate bacitracin zinc ophthalmic ointment, 2011) and a decision should be made to either discontinue the drug or nursing, taking into the account the importance of the drug to the mother (Prod Info CORTISPORIN(R) topical ointment, 2003; Prod Info neomycin sulfate polymyxin B sulfate bacitracin zinc hydrocortisone ophthalmic ointment, 2011).
    3.20.5) FERTILITY
    A) ANIMAL STUDIES
    1) RABBITS: No adverse effects on fertility, litter size, or survival were observed in male or female rabbits administered bacitracin zinc 100 gm/ton of diet (Prod Info neomycin sulfate polymyxin B sulfate bacitracin zinc hydrocortisone ophthalmic ointment, 2011; Prod Info neomycin sulfate polymyxin B sulfate bacitracin zinc ophthalmic ointment, 2011).

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) No laboratory monitoring is needed in most patients after acute overdose.
    B) Monitor serum electrolytes in patients with severe vomiting and/or diarrhea.
    C) If bacitracin is being used parenterally, or as a surgical irrigating solution, the patient should be monitored for nephrotoxicity and ototoxicity. Early stages of albuminuria and proteinuria appear to be reversible.
    4.1.2) SERUM/BLOOD
    A) OTHER
    1) PATCH TESTING FOR SENSITIVITY REACTIONS: Standard patch testing at 48 hours may miss bacitracin allergy since about one half of cases in one study did not react for 96 hours (Katz & Fisher, 1987).

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Hospital admission is rarely necessary. Patients should be admitted for severe vomiting, profuse diarrhea, severe abdominal pain, dehydration, and electrolyte abnormalities.
    6.3.1.2) HOME CRITERIA/ORAL
    A) A patient with an inadvertent ingestion, that remains asymptomatic can be managed at home.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) All patients with deliberate self-harm ingestions should be evaluated in a healthcare facility and monitored until symptoms resolve.

Monitoring

    A) No laboratory monitoring is needed in most patients after acute overdose.
    B) Monitor serum electrolytes in patients with severe vomiting and/or diarrhea.
    C) If bacitracin is being used parenterally, or as a surgical irrigating solution, the patient should be monitored for nephrotoxicity and ototoxicity. Early stages of albuminuria and proteinuria appear to be reversible.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) Prehospital gastrointestinal decontamination is generally not necessary.
    6.5.2) PREVENTION OF ABSORPTION
    A) SUMMARY: Gastrointestinal decontamination is generally not necessary.
    6.5.3) TREATMENT
    A) MONITORING OF PATIENT
    1) Monitor serum electrolytes in patients with severe vomiting and/or diarrhea.
    2) If bacitracin is being used parenterally, or as a surgical irrigating solution, the patient should be monitored for nephrotoxicity and ototoxicity. Early stages of albuminuria and proteinuria appear to be reversible.
    B) SKIN ABSORPTION
    1) Bacitracin ointments applied to broken skin may be absorbed systemically, and result in anaphylactic reactions. Surgical wounds irrigated with bacitracin have also resulted anaphylaxis in rare cases.
    C) ACUTE ALLERGIC REACTION
    1) Anaphylaxis has been reported infrequently following cases of dermal exposure to bacitracin which appears to have been systemically absorbed via stasis ulcers, stasis dermatitis, surgical irrigation, or deep abrasions (Netland et al, 1987; Knowles & Shear, 1995; Lin et al, 1998; Saryan et al, 1998; Gall et al, 1999), but was also reported in one case following a tattooing process in a young male (Dyck & Vadas, 1997). Subcutaneous epinephrine, nasal oxygen and intravenous hydrocortisone has been a successful treatment for bacitracin anaphylaxis (Vale et al, 1978).
    2) SUMMARY
    a) Mild to moderate allergic reactions may be treated with antihistamines with or without inhaled beta adrenergic agonists, corticosteroids or epinephrine. Treatment of severe anaphylaxis also includes oxygen supplementation, aggressive airway management, epinephrine, ECG monitoring, and IV fluids.
    3) BRONCHOSPASM
    a) ALBUTEROL
    1) ADULT: 2.5 to 5 milligrams in 2 to 4.5 milliliters of normal saline delivered per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 2.5 to 10 mg every 1 to 4 hours as needed, or 10 to 15 mg/hr by continuous nebulization as needed (National Heart,Lung,and Blood Institute, 2007). CHILD: 0.15 milligram/kilogram (minimum 2.5 milligrams) per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 0.15 to 0.3 mg/kg (up to 10 mg) every 1 to 4 hours as needed, or 0.5 mg/kg/hr by continuous nebulization (National Heart,Lung,and Blood Institute, 2007).
    4) CORTICOSTEROIDS
    a) Consider systemic corticosteroids in patients with significant bronchospasm.
    b) PREDNISONE: ADULT: 40 to 80 milligrams/day. CHILD: 1 to 2 milligrams/kilogram/day (maximum 60 mg) in 1 to 2 divided doses divided twice daily (National Heart,Lung,and Blood Institute, 2007).
    5) MILD CASES
    a) DIPHENHYDRAMINE
    1) SUMMARY: Oral diphenhydramine, as well as other H1 antihistamines can be used as indicated (Lieberman et al, 2010).
    2) ADULT: 50 milligrams orally, or 10 to 50 mg intravenously at a rate not to exceed 25 mg/min or may be given by deep intramuscular injection. A total of 100 mg may be administered if needed. Maximum daily dosage is 400 mg (Prod Info diphenhydramine HCl intravenous injection solution, intramuscular injection solution, 2013).
    3) CHILD: 5 mg/kg/24 hours or 150 mg/m(2)/24 hours. Divided into 4 doses, administered intravenously at a rate not exceeding 25 mg/min or by deep intramuscular injection. Maximum daily dosage is 300 mg (Prod Info diphenhydramine HCl intravenous injection solution, intramuscular injection solution, 2013).
    6) MODERATE CASES
    a) EPINEPHRINE: INJECTABLE SOLUTION: It should be administered early in patients by IM injection. Using a 1:1000 (1 mg/mL) solution of epinephrine. Initial Dose: 0.01 mg/kg intramuscularly with a maximum dose of 0.5 mg in adults and 0.3 mg in children. The dose may be repeated every 5 to 15 minutes, if no clinical improvement. Most patients respond to 1 or 2 doses (Nowak & Macias, 2014).
    7) SEVERE CASES
    a) EPINEPHRINE
    1) INTRAVENOUS BOLUS: ADULT: 1 mg intravenously as a 1:10,000 (0.1 mg/mL) solution; CHILD: 0.01 mL/kg intravenously to a maximum single dose of 1 mg given as a 1:10,000 (0.1 mg/mL) solution. It can be repeated every 3 to 5 minutes as needed. The dose can also be given by the intraosseous route if IV access cannot be established (Lieberman et al, 2015). ALTERNATIVE ROUTE: ENDOTRACHEAL ADMINISTRATION: If IV/IO access is unavailable. DOSE: ADULT: Administer 2 to 2.5 mg of 1:1000 (1 mg/mL) solution diluted in 5 to 10 mL of sterile water via endotracheal tube. CHILD: DOSE: 0.1 mg/kg to a maximum of 2.5 mg administered as a 1:1000 (1 mg/mL) solution diluted in 5 to 10 mL of sterile water via endotracheal tube (Lieberman et al, 2015).
    2) INTRAVENOUS INFUSION: Intravenous administration may be considered in patients poorly responsive to IM or SubQ epinephrine. An epinephrine infusion may be prepared by adding 1 mg (1 mL of 1:1000 (1 mg/mL) solution) to 250 mL D5W, yielding a concentration of 4 mcg/mL, and infuse this solution IV at a rate of 1 mcg/min to 10 mcg/min (maximum rate). CHILD: A dosage of 0.01 mg/kg (0.1 mL/kg of a 1:10,000 (0.1 mg/mL) solution up to 10 mcg/min (maximum dose 0.3 mg) is recommended for children (Lieberman et al, 2010). Careful titration of a continuous infusion of IV epinephrine, based on the severity of the reaction, along with a crystalloid infusion can be considered in the treatment of anaphylactic shock. It appears to be a reasonable alternative to IV boluses, if the patient is not in cardiac arrest (Vanden Hoek,TL,et al).
    8) AIRWAY MANAGEMENT
    a) OXYGEN: 5 to 10 liters/minute via high flow mask.
    b) INTUBATION: Perform early if any stridor or signs of airway obstruction.
    c) CRICOTHYROTOMY: Use if unable to intubate with complete airway obstruction (Vanden Hoek,TL,et al).
    d) BRONCHODILATORS are recommended for mild to severe bronchospasm.
    e) ALBUTEROL: ADULT: 2.5 to 5 milligrams in 2 to 4.5 milliliters of normal saline delivered per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 2.5 to 10 mg every 1 to 4 hours as needed, or 10 to 15 mg/hr by continuous nebulization as needed (National Heart,Lung,and Blood Institute, 2007).
    f) ALBUTEROL: CHILD: 0.15 milligram/kilogram (minimum 2.5 milligrams) per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 0.15 to 0.3 milligram/kilogram (maximum 10 milligrams) every 1 to 4 hours as needed OR administer 0.5 mg/kg/hr by continuous nebulization (National Heart,Lung,and Blood Institute, 2007).
    9) MONITORING
    a) CARDIAC MONITOR: All complicated cases.
    b) IV ACCESS: Routine in all complicated cases.
    10) HYPOTENSION
    a) If hypotensive give 500 to 2000 milliliters crystalloid initially (20 milliliters/kilogram in children) and titrate to desired effect (stabilization of vital signs, mentation, urine output); adults may require up to 6 to 10 L/24 hours. Central venous or pulmonary artery pressure monitoring is recommended in patients with persistent hypotension.
    1) VASOPRESSORS: Should be used in refractory cases unresponsive to repeated doses of epinephrine and after vigorous intravenous crystalloid rehydration (Lieberman et al, 2010).
    2) DOPAMINE: Initial Dose: 2 to 20 micrograms/kilogram/minute intravenously; titrate to maintain systolic blood pressure greater than 90 mm Hg (Lieberman et al, 2010).
    11) H1 and H2 ANTIHISTAMINES
    a) SUMMARY: Antihistamines are second-line therapy and are used as supportive therapy and should not be used in place of epinephrine (Lieberman et al, 2010).
    1) DIPHENHYDRAMINE: ADULT: 25 to 50 milligrams via a slow intravenous infusion or IM. PEDIATRIC: 1 milligram/kilogram via slow intravenous infusion or IM up to 50 mg in children (Lieberman et al, 2010).
    b) RANITIDINE: ADULT: 1 mg/kg parenterally; CHILD: 12.5 to 50 mg parenterally. If the intravenous route is used, ranitidine should be infused over 10 to 15 minutes or diluted in 5% dextrose to a volume of 20 mL and injected over 5 minutes (Lieberman et al, 2010).
    c) Oral diphenhydramine, as well as other H1 antihistamines, can also be used as indicated (Lieberman et al, 2010).
    12) DYSRHYTHMIAS
    a) Dysrhythmias and cardiac dysfunction may occur primarily or iatrogenically as a result of pharmacologic treatment (epinephrine) (Vanden Hoek,TL,et al). Monitor and correct serum electrolytes, oxygenation and tissue perfusion. Treat with antiarrhythmic agents as indicated.
    13) OTHER THERAPIES
    a) There have been a few reports of patients with anaphylaxis, with or without cardiac arrest, that have responded to vasopressin therapy that did not respond to standard therapy. Although there are no randomized controlled trials, other alternative vasoactive therapies (ie, vasopressin, norepinephrine, methoxamine, and metaraminol) may be considered in patients in cardiac arrest secondary to anaphylaxis that do not respond to epinephrine (Vanden Hoek,TL,et al).

Eye Exposure

    6.8.1) DECONTAMINATION
    A) Exposed eyes should be irrigated with copious amounts of tepid (room temperature) water for at least 15 minutes. If irritation, pain, swelling, lacrimation or photophobia persist after 15 minutes of irrigation, an ophthalmic examination should be considered.

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DERMAL DECONTAMINATION
    1) Chronic application to skin lesions may cause oto- or nephrotoxicity. Wash exposed area twice with soap and water. A physician may need to examine the area if irritation or pain persists after washing.
    6.9.2) TREATMENT
    A) SKIN ABSORPTION
    1) Bacitracin ointments applied to broken skin may be absorbed systemically, and result in anaphylactic reactions. Surgical wounds irrigated with bacitracin have also resulted anaphylaxis in rare cases.
    B) ANAPHYLAXIS
    1) Anaphylaxis has been reported infrequently following cases of dermal exposure to bacitracin which appears to have been systemically absorbed via stasis ulcers, stasis dermatitis, surgical irrigation, or deep abrasions (Netland et al, 1987; Knowles & Shear, 1995; Lin et al, 1998; Saryan et al, 1998; Gall et al, 1999), but was also reported in one case following a tattooing process in a young male (Dyck & Vadas, 1997). Subcutaneous epinephrine, nasal oxygen and intravenous hydrocortisone has been a successful treatment for bacitracin anaphylaxis (Vale et al, 1978).
    2) SUMMARY
    a) Mild to moderate allergic reactions may be treated with antihistamines with or without inhaled beta adrenergic agonists, corticosteroids or epinephrine. Treatment of severe anaphylaxis also includes oxygen supplementation, aggressive airway management, epinephrine, ECG monitoring, and IV fluids.
    3) BRONCHOSPASM
    a) ALBUTEROL
    1) ADULT: 2.5 to 5 milligrams in 2 to 4.5 milliliters of normal saline delivered per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 2.5 to 10 mg every 1 to 4 hours as needed, or 10 to 15 mg/hr by continuous nebulization as needed (National Heart,Lung,and Blood Institute, 2007). CHILD: 0.15 milligram/kilogram (minimum 2.5 milligrams) per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 0.15 to 0.3 mg/kg (up to 10 mg) every 1 to 4 hours as needed, or 0.5 mg/kg/hr by continuous nebulization (National Heart,Lung,and Blood Institute, 2007).
    4) CORTICOSTEROIDS
    a) Consider systemic corticosteroids in patients with significant bronchospasm.
    b) PREDNISONE: ADULT: 40 to 80 milligrams/day. CHILD: 1 to 2 milligrams/kilogram/day (maximum 60 mg) in 1 to 2 divided doses divided twice daily (National Heart,Lung,and Blood Institute, 2007).
    5) MILD CASES
    a) DIPHENHYDRAMINE
    1) SUMMARY: Oral diphenhydramine, as well as other H1 antihistamines can be used as indicated (Lieberman et al, 2010).
    2) ADULT: 50 milligrams orally, or 10 to 50 mg intravenously at a rate not to exceed 25 mg/min or may be given by deep intramuscular injection. A total of 100 mg may be administered if needed. Maximum daily dosage is 400 mg (Prod Info diphenhydramine HCl intravenous injection solution, intramuscular injection solution, 2013).
    3) CHILD: 5 mg/kg/24 hours or 150 mg/m(2)/24 hours. Divided into 4 doses, administered intravenously at a rate not exceeding 25 mg/min or by deep intramuscular injection. Maximum daily dosage is 300 mg (Prod Info diphenhydramine HCl intravenous injection solution, intramuscular injection solution, 2013).
    6) MODERATE CASES
    a) EPINEPHRINE: INJECTABLE SOLUTION: It should be administered early in patients by IM injection. Using a 1:1000 (1 mg/mL) solution of epinephrine. Initial Dose: 0.01 mg/kg intramuscularly with a maximum dose of 0.5 mg in adults and 0.3 mg in children. The dose may be repeated every 5 to 15 minutes, if no clinical improvement. Most patients respond to 1 or 2 doses (Nowak & Macias, 2014).
    7) SEVERE CASES
    a) EPINEPHRINE
    1) INTRAVENOUS BOLUS: ADULT: 1 mg intravenously as a 1:10,000 (0.1 mg/mL) solution; CHILD: 0.01 mL/kg intravenously to a maximum single dose of 1 mg given as a 1:10,000 (0.1 mg/mL) solution. It can be repeated every 3 to 5 minutes as needed. The dose can also be given by the intraosseous route if IV access cannot be established (Lieberman et al, 2015). ALTERNATIVE ROUTE: ENDOTRACHEAL ADMINISTRATION: If IV/IO access is unavailable. DOSE: ADULT: Administer 2 to 2.5 mg of 1:1000 (1 mg/mL) solution diluted in 5 to 10 mL of sterile water via endotracheal tube. CHILD: DOSE: 0.1 mg/kg to a maximum of 2.5 mg administered as a 1:1000 (1 mg/mL) solution diluted in 5 to 10 mL of sterile water via endotracheal tube (Lieberman et al, 2015).
    2) INTRAVENOUS INFUSION: Intravenous administration may be considered in patients poorly responsive to IM or SubQ epinephrine. An epinephrine infusion may be prepared by adding 1 mg (1 mL of 1:1000 (1 mg/mL) solution) to 250 mL D5W, yielding a concentration of 4 mcg/mL, and infuse this solution IV at a rate of 1 mcg/min to 10 mcg/min (maximum rate). CHILD: A dosage of 0.01 mg/kg (0.1 mL/kg of a 1:10,000 (0.1 mg/mL) solution up to 10 mcg/min (maximum dose 0.3 mg) is recommended for children (Lieberman et al, 2010). Careful titration of a continuous infusion of IV epinephrine, based on the severity of the reaction, along with a crystalloid infusion can be considered in the treatment of anaphylactic shock. It appears to be a reasonable alternative to IV boluses, if the patient is not in cardiac arrest (Vanden Hoek,TL,et al).
    8) AIRWAY MANAGEMENT
    a) OXYGEN: 5 to 10 liters/minute via high flow mask.
    b) INTUBATION: Perform early if any stridor or signs of airway obstruction.
    c) CRICOTHYROTOMY: Use if unable to intubate with complete airway obstruction (Vanden Hoek,TL,et al).
    d) BRONCHODILATORS are recommended for mild to severe bronchospasm.
    e) ALBUTEROL: ADULT: 2.5 to 5 milligrams in 2 to 4.5 milliliters of normal saline delivered per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 2.5 to 10 mg every 1 to 4 hours as needed, or 10 to 15 mg/hr by continuous nebulization as needed (National Heart,Lung,and Blood Institute, 2007).
    f) ALBUTEROL: CHILD: 0.15 milligram/kilogram (minimum 2.5 milligrams) per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 0.15 to 0.3 milligram/kilogram (maximum 10 milligrams) every 1 to 4 hours as needed OR administer 0.5 mg/kg/hr by continuous nebulization (National Heart,Lung,and Blood Institute, 2007).
    9) MONITORING
    a) CARDIAC MONITOR: All complicated cases.
    b) IV ACCESS: Routine in all complicated cases.
    10) HYPOTENSION
    a) If hypotensive give 500 to 2000 milliliters crystalloid initially (20 milliliters/kilogram in children) and titrate to desired effect (stabilization of vital signs, mentation, urine output); adults may require up to 6 to 10 L/24 hours. Central venous or pulmonary artery pressure monitoring is recommended in patients with persistent hypotension.
    1) VASOPRESSORS: Should be used in refractory cases unresponsive to repeated doses of epinephrine and after vigorous intravenous crystalloid rehydration (Lieberman et al, 2010).
    2) DOPAMINE: Initial Dose: 2 to 20 micrograms/kilogram/minute intravenously; titrate to maintain systolic blood pressure greater than 90 mm Hg (Lieberman et al, 2010).
    11) H1 and H2 ANTIHISTAMINES
    a) SUMMARY: Antihistamines are second-line therapy and are used as supportive therapy and should not be used in place of epinephrine (Lieberman et al, 2010).
    1) DIPHENHYDRAMINE: ADULT: 25 to 50 milligrams via a slow intravenous infusion or IM. PEDIATRIC: 1 milligram/kilogram via slow intravenous infusion or IM up to 50 mg in children (Lieberman et al, 2010).
    b) RANITIDINE: ADULT: 1 mg/kg parenterally; CHILD: 12.5 to 50 mg parenterally. If the intravenous route is used, ranitidine should be infused over 10 to 15 minutes or diluted in 5% dextrose to a volume of 20 mL and injected over 5 minutes (Lieberman et al, 2010).
    c) Oral diphenhydramine, as well as other H1 antihistamines, can also be used as indicated (Lieberman et al, 2010).
    12) DYSRHYTHMIAS
    a) Dysrhythmias and cardiac dysfunction may occur primarily or iatrogenically as a result of pharmacologic treatment (epinephrine) (Vanden Hoek,TL,et al). Monitor and correct serum electrolytes, oxygenation and tissue perfusion. Treat with antiarrhythmic agents as indicated.
    13) OTHER THERAPIES
    a) There have been a few reports of patients with anaphylaxis, with or without cardiac arrest, that have responded to vasopressin therapy that did not respond to standard therapy. Although there are no randomized controlled trials, other alternative vasoactive therapies (ie, vasopressin, norepinephrine, methoxamine, and metaraminol) may be considered in patients in cardiac arrest secondary to anaphylaxis that do not respond to epinephrine (Vanden Hoek,TL,et al).
    C) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Enhanced Elimination

    A) HEMODIALYSIS
    1) Hemodialysis is not recommended given the low toxicity of topical bacitracin. The effectiveness of hemodialysis following IM bacitracin overdose is unknown.

Summary

    A) TOXICITY: PARENTERAL: Bacitracin 200,000 units given parenterally for several days has caused nephrotoxicity in humans. Minor symptoms have been noted on total daily doses of less than 80,000 units per day intramuscularly. ORAL: Oral bacitracin 80,000 to 100,000 units in 4 divided doses for 7 to 10 days has been used to treat antibiotic-associated pseudomembranous colitis. Oral doses of up to 240,000 units caused virtually no side effects or absorption.
    B) THERAPEUTIC DOSES: INTRAMUSCULAR: CHILDREN: Infants under 2500 grams: 900 units/kilogram/day IM in 2 or 3 divided doses. Infants over 2500 grams: 1000 units/kilogram/day IM in 2 or 3 divided doses. ADULTS AND CHILDREN: OCULAR: A thin ribbon of ophthalmic ointment every 3 to 4 hr for 7 to 10 days. TOPICAL: Apply topically 2 to 5 times/day.

Therapeutic Dose

    7.2.1) ADULT
    A) OCULAR
    1) Apply to conjunctival sac 1 to 3 times daily or apply evenly over lid margins (Prod Info bacitracin ophthalmic ointment, 2013).
    B) TOPICAL
    1) Apply topically 1 to 3 times daily for one week, unless directed by doctor (OTC Product Information, as posted to the DailyMed site 02/2013).
    C) ORAL
    1) Oral bacitracin 80,000 to 100,000 units in 4 divided doses for 7 to 10 days has been used to treat antibiotic-associated pseudomembranous colitis (Chang et al, 1980; Tedesco, 1980; Young et al, 1985).
    D) UNIT EQUIVALENCE
    1) One unit of bacitracin is equivalent to 0.026 mg (Gilman et al, 1985).
    7.2.2) PEDIATRIC
    A) INTRAMUSCULAR
    1) Infants under 2500 grams: 900 units/kilogram/day IM in 2 or 3 divided doses (Prod Info bacitracin IM injection, 2010).
    2) Infants over 2500 grams: 1000 units/kilogram/day IM in 2 or 3 divided doses (Prod Info bacitracin IM injection, 2010).

Maximum Tolerated Exposure

    A) ROUTE OF EXPOSURE
    1) Bacitracin 200,000 units given parenterally for several days has caused nephrotoxicity in humans (Zintel et al, 1949).
    2) Oral doses of up to 240,000 units caused virtually no side effects or absorption (Anon, 1977). Minor symptoms have been noted on total daily doses of less than 80,000 units per day intramuscularly (Zintel et al, 1949).
    3) Some authors estimate the maximum tolerated dose of bacitracin as being 50 Units/kg or 3,500 units per average adult (Anon, 1979). Others state that as much as 100,000 units per day may be administered, but current thinking is that this is too high (Gurney, 1968).

Serum Plasma Blood Concentrations

    7.5.2) TOXIC CONCENTRATIONS
    A) TOXIC CONCENTRATION LEVELS
    1) GENERAL
    a) DERMAL: When 30 grams of ointment with zinc bacitracin (400 units per gram) was applied to patients with widespread lesions of atopic dermatitis or psoriasis for 7 days, no antibiotic could be detected (test sensitivity 0.01 units per mL of blood) (Anon, 1976).
    b) INTRAMUSCULAR: An intramuscular dose of 50,000 units should give peak concentration of 0.3 units/mL and increase to 1 to 3 units/mL if injections are repeated (Zintel et al, 1949).
    c) When bacitracin (50,000 units per 200 mL of 0.9 sodium chloride) was used as a peritoneal lavage, bacitracin was absorbed to achieve an average serum concentration of 3.8 units per mL. Most patients developed peak levels at 15 minutes but some delayed up to 75 minutes. None of these serum levels, for the short time experienced, resulted in changes in renal function (Ericsson et al, 1979).
    d) Westerman (1983) reported a serum level of 10.7 units/mL after a three day infusion of a solution of 50,000 units/L at 100 ml/hour for mediastinal irrigation. The level increased BUN from 16 to 30 mg/dL. Creatinine and urine output remain normal (Westerman, 1983).

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) ANIMAL DATA
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) 300 mg/kg (RTECS , 2001)
    2) LD50- (ORAL)MOUSE:
    a) >3750 mg/kg (RTECS , 2001)
    3) LD50- (SUBCUTANEOUS)MOUSE:
    a) 1300 mg/kg (RTECS , 2001)
    4) LD50- (INTRAPERITONEAL)RAT:
    a) 190 mg/kg (RTECS , 2001)

Pharmacologic Mechanism

    A) Bacitracin interferes with bacterial cell wall synthesis by prevention of mucopeptide linkage. Susceptible organisms include gram-positive cocci, bacilli, and corynebacteria as well as the beta-hemolytic group A strep and penicillin resistant staph. It is not useful for treatment of gram-negative rod infections (Toscano & Storm, 1982; Anon, 1977).

Physical Characteristics

    A) a white to pale buff, hyroscopic powder, with a slight odor or odorless (S Sweetman , 2002).
    1) solid, produced by a mixture of polypeptides (S Sweetman , 2002)

Ph

    A) 5.5-7.5 (For an aqueous solution of bacitracin containing 10,000 units/mL) (S Sweetman , 2002)
    B) 6.0 to 7.0 in a 1% solution in water (S Sweetman , 2002)

Molecular Weight

    A) approximately 1460

General Bibliography

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