VA Class:AM900
Staphylococcal Pneumonia and Empyema in Infants
Bacitracin has been used IM in infants for the treatment of pneumonia and empyema caused by staphylococci susceptible to the drug.100, 104 However, other anti-infectives are used for the treatment of staphylococcal respiratory tract infections, and bacitracin is not considered a preferred or alternative agent for treatment of these infections.137, 138, 139 The manufacturers state that bacitracin should be used only when adequate laboratory facilities are available and when constant supervision of the patient is possible.100, 104 (See Cautions.)
Clostridium difficile-associated Diarrhea and Colitis
Bacitracin has been used orally† for the treatment of Clostridium difficile -associated diarrhea and colitis† (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis),101, 102, 103, 110, 111, 112, 113, 117, 140, 143 and is designated an orphan drug by FDA for use in this condition.114 Oral bacitracin is not recommended as a preferred or alternative agent for the treatment of C. difficile infection (CDI) or CDAD. 110, 111, 112, 113 Bacitracin-resistant C. difficile have been reported (see Resistance), 111, 113 and the drug generally has been less effective that other anti-infectives used in the management of CDAD.110, 111, 112, 113 In addition, oral preparations of bacitracin are not commercially available in the US.
For topical uses of bacitracin, see 52:04.04 and 84:04.04.
Reconstitution and Administration
Bacitracin is administered by IM injection.100, 104
Although bacitracin has been administered orally†, 101, 102, 103, 112, 113, 117, 140, 143 an oral dosage form is not commercially available in the US.
IM injections of bacitracin should be made into the upper outer quadrant of the buttocks.100, 104 Injection sites should be alternated between the right and left side.100, 104 Multiple injections in the same region should be avoided because of transient pain following injection.100, 104
For IM administration, bacitracin lyophilized powder for injection should be reconstituted by dissolving the drug 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 labeled as containing 50,000 units of bacitracin, the resultant bacitracin solution contains 5000 units/mL.100, 104
Bacitracin solutions containing less than 5000 units/mL or more than 10,000 units/mL should not be used.100, 104
Diluents containing parabens should not be used to prepare bacitracin solutions for IM injection.100, 104 (See Chemistry and Stability: Stability.)
Staphylococcal Pneumonia or Empyema in Infants
If bacitracin is used for the treatment of staphylococcal pneumonia or empyema in infants weighing less than 2.5 kg, the manufacturers recommend a dosage of 900 units/kg daily given in 2 or 3 divided doses.100, 104 Infants weighing more than 2.5 kg may receive 1000 units/kg daily given in 2 or 3 divided doses.100, 104
Recommended dosages should not be exceeded.100, 104 It also has been recommended that bacitracin not be administered for longer than 12 days.
IM bacitracin is nephrotoxic and may cause renal failure due to renal tubular and glomerular necrosis.100, 104 Albuminuria,100, 104 hematuria, cylindruria,100, 104 and rising blood concentrations of the drug100, 104 may occur initially, followed eventually by oliguria, azotemia,100, 104 and renal failure.100, 104 Infants are less prone to bacitracin nephrotoxicity than are older children and adults.
Bacitracin renal toxicity is related to the total daily dosage and duration of therapy. The manufacturers state that the total daily dosage should not exceed 900 units/kg daily in infants weighing less than 2.5 kg and should not exceed 1000 units/kg daily in infants weighing more than 2.5 kg.100, 104
Anaphylaxis and/or allergic contact dermatitis have been reported in patients receiving bacitracin for indications that were not FDA-labeled uses.100, 104 Rash100, 104 and pruritus also have been reported in patients receiving bacitracin.
Adverse GI effects, including nausea and vomiting, have been reported in patients receiving IM bacitracin.100, 104
Pain has occurred at bacitracin IM injection sites;100, 104 induration also has been reported.
Fever, bone marrow toxicities, blood dyscrasias, and eosinophilia have occurred in patients receiving bacitracin.
Precautions and Contraindications
Bacitracin is contraindicated in patients with a history of previous hypersensitivity or toxic reactions to the drug.100, 104
Precautions Related to Nephrotoxicity
Because IM bacitracin may cause renal failure due to tubular and glomerular necrosis (see Cautions: Renal Effects), the manufacturers state that use of the drug should be restricted only to the treatment of staphylococcal pneumonia and empyema in infants when the causative organism has been shown to be susceptible to bacitracin.100, 104 In addition, IM bacitracin should be used only if adequate laboratory facilities are available and constant supervision of the patient is possible.100, 104
Renal function should be determined prior to and daily during IM bacitracin therapy.100, 104 The recommended dosage should not be exceeded.100, 104 (See Dosage and Administration: Dosage.) If renal toxicity occurs, the drug should be discontinued.100, 104
Fluid intake and urinary output should be maintained at proper levels to avoid renal toxicity.100, 104 Patients receiving IM bacitracin should be well hydrated using oral or, if necessary, parenteral fluids.100, 104 It has been suggested that urine should be kept at pH 6 or greater by the administration of sodium bicarbonate or another alkali to avoid renal irritation.
Concurrent use of other nephrotoxic drugs should be avoided.100, 104 (See Drug Interactions: Nephrotoxic Drugs.)
Superinfection/Clostridium difficile-associated Diarrhea and Colitis
As with other anti-infectives, use of bacitracin may result in overgrowth of nonsusceptible organisms, including fungi.100, 104 Appropriate therapy should be instituted 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 C. difficile -associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) have been 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
CDAD should be considered in the differential diagnosis of patients who develop diarrhea during or after anti-infective therapy.100, 104, 110, 111, 112 Careful medical history is necessary since CDAD has been reported to occur as late as 2 months or longer after anti-infective therapy is discontinued.100, 104 Patients should be advised that diarrhea is a common problem caused by anti-infectives and usually ends when the drug is discontinued; however, they should contact 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
If CDAD is suspected or confirmed, anti-infective therapy not directed against C. difficile should be discontinued whenever possible.100, 104, 110 Patients should be managed with 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, the drug should be used only for the treatment of infections proven or strongly suspected to be caused by susceptible bacteria.100, 104 When selecting or modifying anti-infective therapy, results of culture and in vitro susceptibility testing should be used.100, 104 In the absence of such data, local epidemiology and susceptibility patterns should be considered when selecting anti-infectives for empiric therapy.100, 104
Patients should be advised 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 Patients also should be advised about the importance of completing the full course of therapy, even if feeling better after a few days, and that skipping doses or not completing 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
IM bacitracin is not labeled by FDA for use in adults, including pregnant or lactating adults.100, 104 It is not known whether bacitracin is distributed into milk.145
Since nephrotoxic effects may be additive,14 concomitant use of bacitracin and other nephrotoxic drugs, particularly aminoglycosides (kanamycin, neomycin, streptomycin), polymyxin B, colistin (commercially available in the US as colistimethate sodium), and vancomycin, should be avoided.14, 100, 104
Neuromuscular Blocking Agents and Anesthetics
Bacitracin may enhance the neuromuscular blocking action of certain drugs, including neuromuscular blocking agents and/or anesthetics, if the antibiotic is administered during surgery or postoperatively.14
Bacitracin may be bactericidal or bacteriostatic in action, depending on the concentration of the drug attained at the site of infection and the susceptibility of the infecting organism. Bacitracin inhibits bacterial cell wall synthesis by preventing the incorporation of amino acids and nucleotides into the cell wall. The drug probably interferes with the final dephosphorylation step in the phospholipid carrier cycle, and in this manner bacitracin prevents the transfer of the mucopeptide to the growing cell wall. Bacitracin also damages the bacterial plasma membrane and, in contrast to penicillins, is active against protoplasts.144
Bacitracin is active in vitro against some gram-positive bacteria, including staphylococci (e.g., Staphylococcus aureus ) and Streptococcus pyogenes (group A β-hemolytic streptococci, GAS).144 In vitro, susceptible S. aureus generally are inhibited by bacitracin concentrations of 0.05-5 mcg/mL. The drug also is active in vitro against some gram-negative bacteria, including Haemophilus influenzae and Neisseria , but is not active against most gram-negative bacilli.14, 144
Although some strains of Clostridium difficile are susceptible in vitro to bacitracin,142 other strains are resistant to the drug.113, 141, 142, 144 (See Resistance.)
Staphylococcus aureus resistant to bacitracin have been reported.14, 144
Clostridium difficile resistant to bacitracin, including some with high-level resistance, have been reported.113, 141, 142, 144
Bacitracin does not exhibit cross-resistance with other antibiotics.
Bacitracin is not appreciably absorbed from the GI tract.14
The drug is rapidly and completely absorbed following IM injection.100, 104
IM bacitracin given in a dosage of 200-300 units/kg every 6 hours in individuals with normal renal function results in serum concentrations of 0.2-2 mcg/mL.100, 104 After a single IM dose of 10,000-20,000 units in adults with normal renal function, the maximum serum concentration occurs after 1-2 hours and detectable amounts of bacitracin are present in serum 6-8 hours after the dose.
Bacitracin is widely distributed in all body organs and readily diffuses into ascitic and pleural fluids following IM injection.100, 104 Only low concentrations of bacitracin are distributed into CSF.14
Bacitracin is only slightly protein bound.
After IM administration of bacitracin, 10-40% of the dose is excreted slowly by glomerular filtration and appears in the urine within 24 hours.14 A considerable amount of bacitracin is not accounted for and is thought to be retained or destroyed in the body.
Bacitracin is excreted in feces following oral administration.
Bacitracin is a polypeptide antibiotic produced by Bacillus subtilis or B. licheniformis .7, 14, 100, 104 Bacitracin commercially available in the US is derived from cultures of B. subtilis (Tracey).100, 104 The antibiotic is a mixture of polypeptides (bacitracin A, B1, B2, B3);7, 100, 104 the 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
Bacitracin occurs as a white to pale buff, hygroscopic powder that is odorless or has a slight odor.7, 100, 104 The drug is freely soluble in water and soluble in alcohol.7, 100, 104
Prior to reconstitution, bacitracin lyophilized powder for injection should be stored at 2-8°C.100, 104
Following reconstitution with 0.9% sodium chloride injection containing 2% procaine hydrochloride as directed by the manufacturer, bacitracin solutions are stable for 1 week when stored at 2-8°C.100, 104 Bacitracin solutions (e.g., aqueous solutions) deteriorate rapidly at room temperature.7, 106 In one study, aqueous solutions of bacitracin containing 5000 units/mL in sterile water for injection were stable for up to 5 months in glass vials or plastic syringes when frozen at <15°C.115
Diluents containing parabens should not be used to reconstitute bacitracin powder for injection since cloudy solutions and formation of a precipitate may result.100, 104
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, for IM use | 50,000 units* | ||
Bacitracin for Injection |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
7. Bacitracin. In: U.S. pharmacopeia, 38th rev, and The national formulary, 33rd ed. Rockville, MD: The United States Pharmacopeial Convention. From UPS-NF online. Accessed 2015 Nov 12.
14. Bacitracin. In: Martindale: The complete drug reference. London: Pharmaceutical Press; 2015. From MedicinesComplete website. Accessed 2015 Nov 11. [Web]
100. X-gen Pharmaceuticals, Inc. BACiiM® (bacitracin) lyophilized powder for injection for IM use prescribing information. Big Flatts, NY. 2012 Jun.
101. Chang TW, Gorbach SL, Bartlett JG et al. Bacitracin treatment of antibiotic-associated colitis and diarrhea caused by Clostridium difficile toxin. Gastroenterology . 1980; 78:1584-6. [PubMed 7372074]
102. Young GP, Ward PB, Bayley N et al. Antibiotic-associated colitis due to Clostridium difficile : double-blind comparison of vancomycin with bacitracin. Gastroenterology . 1985; 89:1038-45. [PubMed 4043661]
103. Dudley MN, McLaughlin JC, Carrington G et al. Oral bacitracin vs vancomycin therapy for Clostridium difficile -induced diarrhea: a randomized double-blind trial. Arch Intern Med . 1986; 146:1101-4. [PubMed 3521518]
104. Pharmacia & Upjohn Company division of Pfizer. Bacitracin lyophilized powder for injection, USP, for IM use prescribing information. New York, NY. 2013 Oct.
106. Bond GC, Himelick RE, Macdonald LH. The stability of bacitracin. J Am Pharm Assoc . 1949; 38:30-4.
110. Cohen SH, Gerding DN, Johnson S et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infect Control Hosp Epidemiol . 2010; 31:431-55. [PubMed 20307191]
111. Fekety R for the American College of Gastroenterology Practice Parameters Committee. Guidelines for the diagnosis and management of Clostridium difficile - associated diarrhea and colitis. Am J Gastroenterol . 1997; 92:739-50. [PubMed 9149180]
112. American Society of Health-System Pharmacists Commission on Therapeutics. ASHP therapeutic position statement on the preferential use of metronidazole for the treatment of Clostridium difficile -associated disease. Am J Health-Syst Pharm . 1998; 55:1407-11. [PubMed 9659970]
113. Venugopal AA, Johnson S. Current state of Clostridium difficile treatment options. Clin Infect Dis . 2012; 55 Suppl 2:S71-6.
114. Food and Drug Administration. List of orphan designations and approvals. From FDA website. Accessed 2015 Nov 2. [Web]
115. Souney PF, Braun L, Steele L et al. Stability of bacitracin solution frozen in glass vials or plastic syringes. Am J Hosp Pharm . 1987; 44:1125-6. [PubMed 3605124]
117. Kelly CP, Pothoulakis C, LaMont JT. Clostridium difficile colitis. N Engl J Med . 1994; 330:257-62. [PubMed 8043060]
137. Bradley JS, Byington CL, Shah SS et al. The management of community-acquired pneumonia in infants and children older than 3 months of age: clinical practice guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. Clin Infect Dis . 2011; 53:e25-76. [PubMedCentral]
138. Mandell LA, Wunderink RG, Anzueto A et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis . 2007; 44 Suppl 2:S27-72. [PubMed 17278083]
139. Anon. Choice of antibacterial drugs. Med Lett Treat Guid . 2007; 5:33-50.
140. Nelson R. Antibiotic treatment for Clostridium difficile-associated diarrhea in adults. Cochrane Database Syst Rev . 2007; :CD004610.
141. Bourgault AM, Lamothe F, Loo VG et al. In vitro susceptibility of Clostridium difficile clinical isolates from a multi-institutional outbreak in Southern Québec, Canada. Antimicrob Agents Chemother . 2006; 50:3473-5. [PubMed 17005836][PubMedCentral]
142. Bacon AE, McGrath S, Fekety R et al. In vitro synergy studies with Clostridium difficile. Antimicrob Agents Chemother . 1991; 35:582-3. [PubMed 2039211][PubMedCentral]
143. McMaster-Baxter NL, Musher DM. Clostridium difficile: recent epidemiologic findings and advances in therapy. Pharmacotherapy . 2007; 27:1029-39. [PubMed 17594209]
144. Kucers A, Crowe S, Grayson ML et al, eds. The use of antibiotics. A clinical review of antibacterial, antifungal, and antiviral drugs. 5th ed. Jordan Hill, Oxford: Butterworth-Heinemann; 1997: 542-3.
145. Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation. 8th ed. Baltimore, MD: Williams & Wilkins; 2008:162-3.