Brand name: BACiiM
Drug class: Bacitracins
VA class: AM900
Molecular formula: C₆₆H₁₀₃N₁₇O₁₆S
CAS number: 1405-87-4

Introduction

Antibacterial; polypeptide antibiotic.^{100 104}

Uses for Bacitracin

Staphylococcal Pneumonia and Empyema in Infants

Has been used IM in infants for treatment of pneumonia and empyema caused by susceptible staphylococci.^{100 104}

Not considered a preferred or alternative agent for treatment of staphylococcal infections; other anti-infectives are used for treatment of staphylococcal respiratory tract infections.^{137 138 139}

Manufacturers state use bacitracin only when adequate laboratory facilities are available and constant supervision of the patient is possible.^{100 104}

Clostridium difficile-associated Diarrhea and Colitis (CDAD)

Has been used orally† for treatment of CDAD† (also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis).^{101 102 103 110 111 112 113 117 140 143} Designated an orphan drug by FDA for use in this condition.¹¹⁴

Oral bacitracin not recommended as a preferred or alternative agent for treatment of C. difficile infection (CDI) or CDAD.^{110 111 112 113} Bacitracin-resistant C. difficile reported,^{111 113} and the drug generally has been less effective that other anti-infectives used in management of CDAD.^{110 111 112 113} In addition, bacitracin oral preparations not commercially available in US.

Related/similar drugs

amoxicillin, doxycycline, ciprofloxacin, azithromycin, metronidazole, clindamycin

Bacitracin Dosage and Administration

Administration

Administer IM.^{100 104}

Has been administered orally†,^{101 102 103 112 113 117 140 143} but oral preparations not commercially available in US.

IM Injection

Inject into upper outer quadrant of the buttocks.^{100 104} Alternate injection sites between right and left side.^{100 104} Avoid making multiple injections in same region because of transient pain following injection.^{100 104}

Reconstitution

Reconstitute lyophilized powder for injection by dissolving in 0.9% sodium chloride injection containing 2% procaine hydrochloride.^{100 104} If 9.8 mL of this diluent is used to reconstitute a vial containing 50,000 units of bacitracin, resultant solution contains 5000 units/mL.^{100 104}

Do not use bacitracin solutions containing <5000 units/mL or >10,000 units/mL.^{100 104}

Do not use diluents containing parabens;^{100 104} cloudy solutions and precipitate formation may occur.^{100 104}

Dosage

Pediatric Patients

Staphylococcal Pneumonia and Empyema in Infants

IM

Infants <2.5 kg: Manufacturers recommend 900 units/kg daily given in 2 or 3 divided doses.^{100 104}

Infants >2.5 kg: Manufacturers recommend 1000 units/kg daily in 2 or 3 divided doses.^{100 104}

Prescribing Limits

Pediatric Patients

Staphylococcal Pneumonia and Empyema in Infants

Do not exceed recommended dosage;^{100 104} duration >12 days not recommended.^a

Special Populations

No special population dosage recommendations.^{100 104}

Cautions for Bacitracin

Contraindications

• History of hypersensitivity or toxic reactions to bacitracin.^{100 104}

Warnings/Precautions

Warnings

Nephrotoxicity

IM bacitracin may cause renal failure due to tubular and glomerular necrosis.^{100 104} Albuminuria,^{100 104} hematuria,^a cylindruria,^{100 104} and rising blood concentrations of the drug^{100 104} may occur initially followed eventually by oliguria,^a azotemia,^{100 104} and renal failure.^{100 104}

Infants less prone to bacitracin nephrotoxicity than older children and adults.^a Toxicity is related to total daily dosage and duration of therapy.^a

Assess renal function prior to and daily during therapy.^{100 104} Discontinue drug if renal toxicity occurs.^{100 104}

Keep patient well hydrated using oral or, if necessary, parenteral fluids.^{100 104} Maintain urine output at proper levels to avoid renal toxicity.^{100 104} Some suggest using sodium bicarbonate or another alkali to keep urine at pH 6 or greater to avoid renal irritation.^a

Avoid concomitant use with other nephrotoxic drugs.^{100 104} (See Specific Drugs under Interactions.)

Because of the risk of nephrotoxicity, manufacturers state restrict use of IM bacitracin only to the treatment of staphylococcal pneumonia and empyema in infants when the causative organism has been shown to be susceptible to the drug.^{100 104} In addition, use the drug only if adequate laboratory facilities are available and constant supervision of the patient is possible.^{100 104}

Sensitivity Reactions

Hypersensitivity

Anaphylaxis and/or allergic contact dermatitis reported when bacitracin used for non-FDA-labeled indications.^{100 104}

Rash^{100 104} and pruritus^a also reported.

General Precautions

Superinfection/Clostridium difficile-associated Diarrhea and Colitis (CDAD)

Possible emergence and overgrowth of nonsusceptible bacteria or fungi may occur.^{100 104} Institute appropriate therapy if superinfection occurs.^{100 104}

Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridium difficile.^{100 104 110 111 112} C. difficile infection (CDI) and CDAD (also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) reported with nearly all anti-infectives and may range in severity from mild diarrhea to fatal colitis.^{100 104 110 111 112} C. difficile produces toxins A and B which contribute to development of CDAD;^{100 104 110} hypertoxin-producing strains of C. difficile are associated with increased morbidity and mortality since they may be refractory to anti-infectives and colectomy may be required.^{100 104}

Consider CDAD if diarrhea develops during or after therapy and manage accordingly.^{100 104 110 111 112} Obtain careful medical history since CDAD may occur as late as ≥2 months after anti-infective therapy is discontinued.^{100 104}

If CDAD suspected or confirmed, discontinue anti-infectives not directed against C. difficile whenever possible.^{100 104 110} Initiate appropriate supportive therapy (e.g., fluid and electrolyte management, protein supplementation), anti-infective therapy directed against C. difficile (e.g., metronidazole, vancomycin), and surgical evaluation as clinically indicated.^{100 104 110 111 112}

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of bacitracin and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.^{100 104}

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.^{100 104} In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.^{100 104}

Specific Populations

Pregnancy

Category C.¹⁴⁵

Not labeled for use in adults, including pregnant women.^{100 104}

Lactation

Not known whether bacitracin is distributed into milk.¹⁴⁵

Not labeled for use in adults, including nursing women.^{100 104}

Common Adverse Effects

Nephrotoxicity (albuminuria, cylindruria, azotemia, rising blood concentrations of the drug);^{100 104} GI effects (nausea, vomiting);^{100 104} pain at injection site;^{100 104} hypersensitivity reactions (rash).^{100 104}

Interactions for Bacitracin

Specific Drugs

Bacitracin Pharmacokinetics

Absorption

Bioavailability

Not appreciably absorbed from GI tract.¹⁴

Completely and rapidly absorbed following IM injection.^{100 104}

Following IM dosage of 200–300 units/kg every 6 hours in individuals with normal renal function, serum concentrations are 0.2–2 mcg/mL.^{100 104}

Following single IM dose of 10,000–20,000 units in adults with normal renal function, peak serum concentrations occur after 1–2 hours and the drug is detectable in serum for 6–8 hours after the dose.^a

Distribution

Extent

Widely distributed into all body organs;^{100 104} readily diffuses into ascitic and pleural fluids following IM injection.^{100 104}

Only low concentrations distributed into CSF.¹⁴

Plasma Protein Binding

Only slightly protein bound.^a

Elimination

Elimination Route

IM: 10–40% of a dose excreted slowly by glomerular filtration and appears in urine within 24 hours.¹⁴

Oral: Excreted in feces.^a

Stability

Storage

Parenteral

Powder for Injection

2–8°C.^{100 104}

Following reconstitution with 0.9% sodium chloride injection containing 2% procaine hydrochloride as directed by manufacturer, stable at 2–8°C for 1 week.^{100 104}

Actions and Spectrum

• Polypeptide antibiotic produced by B. subtilis or B. licheniformis;^{7 14 100 104} bacitracin commercially available in US is derived from cultures of B. subtilis (Tracey).^{100 104}

• Mixture of polypeptides (bacitracin A, B1, B2, B3);^{7 100 104} major component is bacitracin A.^{100 104}

• Commercially available bacitracin for injection has a potency of not less than 50 units of bacitracin activity per mg.^{7 100 104}

• May be bactericidal or bacteriostatic, depending on drug concentration at site of infection.^a

• Inhibits bacterial cell wall synthesis.^a

• Active in vitro against some gram-positive bacteria, including staphylococci (e.g., Staphylococcus aureus) and Streptococcus pyogenes (group A β-hemolytic streptococci, GAS).¹⁴⁴ Also active in vitro against some gram-negative bacteria, including Haemophilus influenzae and Neisseria, but not active against most gram-negative bacilli.^{14 144}

• Although some strains of Clostridium difficile are susceptible to bacitracin in vitro,¹⁴² strains with high-level resistance to the drug reported.^{113 141 142 144}

• S. aureus resistant to bacitracin have been reported.^{14 144}

• Does not exhibit cross-resistance with other antibiotics.^a

Advice to Patients

• Advise patients that antibacterials (including bacitracin) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).^{100 104}

• Advise patients that it is common to begin feeling better after a few days, but that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with bacitracin or other antibacterials in the future.^{100 104}

• Advise patients that diarrhea is a common problem caused by anti-infectives and usually ends when the drug is discontinued.^{100 104} Importance of contacting a clinician if watery and bloody stools (with or without stomach cramps and fever) occur during or as late as 2 months or longer after the last dose.^{100 104}

• Importance of informing clinicians of existing concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.^{100 104}

• Importance of informing patients of other important precautionary information.^{100 104} (See Cautions.)

Preparations

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.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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