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Bacitracin

Bacitracin is a polypeptide antibiotic.

Uses

Staphylococcal Infections

IM bacitracin has been used in infants with pneumonia and empyema caused by staphylococci that are susceptible to the drug; however, use of bacitracin has, in most cases, been replaced by penicillinase-resistant penicillins or cephalosporins for infections caused by penicillinase-producing staphylococci and by vancomycin for resistant strains. Penicillin is the drug of choice in infections caused by susceptible strains of nonpenicillinase-producing staphylococci. If bacitracin is used, the patient should be closely observed, and adequate laboratory facilities should be available.

Bacitracin

Clostridium difficile-associated

Diarrhea and Colitis Bacitracin has been used orally in a limited number of patients for the treatment of Clostridium difficile-associated diarrhea and colitis (also known as antibiotic-associated diarrhea and colitis), including pseudomembranous colitis. Bacitracin is designated an orphan drug by the US Food and Drug Administration (FDA) for use in this condition. Limited data suggest that oral bacitracin may be as effective as oral vancomycin hydrochloride in resolving C. difficile-induced diarrhea, but substantially less effective in eradicating the organism and its toxin from the stools, at least at the dosages employed to date.

Although additional data are needed, some clinicians have suggested that oral bacitracin may be an alternative to metronidazole or vancomycin and may also be useful in patients who are allergic to vancomycin or whose diarrhea and/or colitis does not respond to vancomycin.

Because of cost considerations and concerns about increasing enterococcal resistance to vancomycin and the risk of selection of such strains secondary to widespread and/or injudicious use of the drug, most clinicians and experts state that oral metronidazole therapy generally is the preferred agent when anti-infective therapy is indicated for mild to moderate cases of C. difficile-associated colitis and diarrhea, unless a resistant strain of C. difficile is suspected or therapy with the drug is contraindicated or not tolerated.

The relative efficacy of oral metronidazole for severe, potentially life-threatening cases of pseudomembranous colitis remains unclear, and some clinicians continue to consider vancomycin the drug of choice when anti-infective therapy is indicated for such cases (e.g., in critically ill patients).

Most clinicians currently recommend that oral vancomycin only be used for the treatment of C. difficile-associated colitis in seriously ill patients (i.e., with severe or potentially life-threatening colitis) or those who cannot tolerate or do not respond to oral metronidazole. Further studies are needed to determine the optimum dosage of oral bacitracin and the relative value of the drug compared with other anti-infectives in the treatment of C. difficile-induced diarrhea and colitis.

Other Uses

Bacitracin solutions have been injected intrathecally for the treatment of meningeal infections, intraperitoneally for the treatment of infections of the peritoneal cavity, intrapleurally for the treatment of staphylococcal empyema, and intrasynovially to prevent infection after surgical treatment of chronic osteomyelitis. Substantial evidence of effectiveness by these routes of administration is lacking.

Dosage and Administration

Reconstitution and Administration

Bacitracin is administered by IM injection into the upper outer quadrant of the buttocks. Injection sites should be alternated and multiple injections in the same region should be avoided because of the transient pain following injection. Bacitracin should not be administered IV because severe thrombophlebitis occurs.

The drug has also been administered orally, intrapleurally, intrathecally, intraperitoneally, intrasynovially, and orally. For IM administration, bacitracin powder for injection should be dissolved in 0.9% sodium chloride injection containing 2% procaine hydrochloride. Addition of 9.8 mL of this diluent to a vial labeled as containing 50,000 units will provide a solution containing 5000 units of bacitracin per mL. Alternatively, 50 mL of 0.9% sodium chloride injection may be added to a vial labeled as containing 50,000 units to provide a solution containing 1000 units/mL; this solution may be further diluted with an equal volume of 2% procaine hydrochloride injection to provide a solution containing 500 units/mL.

One manufacturer states that bacitracin solutions containing less than 5000 units/mL and those containing more than 10,000 units/mL should not be used. Diluents containing parabens should not be used.

Dosage

Staphylococcal Infections

The usual IM dosage of bacitracin for infants weighing less than 2.5 kg is 900 units/kg daily given in 2 or 3 divided doses. Infants weighing more than 2.5 kg may receive 1000 units/kg daily given in 2 or 3 divided doses. These dosages should not be exceeded. It has been recommended that bacitracin not be administered for longer than 12 days. For adults, IM bacitracin doses of 10,000-25,000 units every 6 hours have been used. The total daily dose for an adult should not exceed 100,000 units and the amount per dose should not exceed 25,000 units.

Clostricium-difficile-associated Diarrhea and Colitis

For the treatment of Clostridium difficile-associated diarrhea and colitis in adults, oral bacitracin dosages of 20,000-25,000 units every 6 hours for 7-10 days have been used. Further studies are needed to determine the optimum dosage.

Cautions

Renal Effects

The most important toxic effect of IM bacitracin therapy is renal tubular and glomerular necrosis manifested initially by albuminuria, hematuria, cylindruria, and rising blood concentrations of the drug, and followed eventually by oliguria, azotemia, and renal failure. Infants are much less prone to this toxicity than are older children and adults, and significant renal toxicity usually does not occur in infants. Renal toxicity of bacitracin is related to the total daily dose and the duration of administration.

Bacitracin

The total daily dose should not exceed 900 units/kg daily for infants weighing less than 2.5 kg and 1000 units/kg daily for infants weighing more than 2.5 kg. It has been recommended that bacitracin not be administered for longer than 12 days.

Other Adverse Effects

Anorexia, nausea, vomiting, diarrhea, rectal itching and burning, and rash may occur following IM administration of bacitracin. Pain, sometimes accompanied by induration, may occur at the site of injection. Urticaria, fever, bone marrow toxicities, blood dyscrasias, eosinophilia, and anaphylactoid reactions have also occurred. In addition, respiratory paralysis may occur as a result of neuromuscular blockade, especially in patients with a neuromuscular disease such as myasthenia gravis.

Severe neuromuscular blockade resulting in respiratory depression unresponsive to calcium or neostigmine has occurred in several patients treated with bacitracin and neomycin sulfate instilled intrapleurally or into a pancreatic pseudocyst.

Precautions and Contraindications

Renal function should be determined prior to and daily during bacitracin therapy. Microscopic urinalysis should be performed frequently in patients receiving bacitracin. If there is evidence of renal dysfunction prior to therapy, the drug is contraindicated. If renal toxicity occurs during treatment, the drug should be discontinued.

Patients receiving IM bacitracin should be well hydrated by oral or parenteral administration of fluids, and their urine should be kept at pH 6 or greater by the administration of sodium bicarbonate or another alkali in order to decrease renal irritation. Urine output should be maintained at proper levels to avoid renal toxicity.

As with other anti-infectives, use of bacitracin may result in overgrowth of nonsusceptible organisms including fungi, particularly Candida; appropriate therapy should be instituted if superinfection occurs. Bacitracin is contraindicated in patients with renal disease or impairment, in patients with a history of previous hypersensitivity or toxic reactions to the drug, or in patients who, during bacitracin therapy, experience oliguria while maintaining normal fluid intake, or who experience progressive azotemia.

Pregnancy

Bacitracin should not be used during pregnancy.

Drug Interactions

Nephrotoxic Drugs

Since nephrotoxic effects may be additive, concurrent and/or sequential use of systemic bacitracin and other drugs (administered systemically, orally, or topically) with similar nephrotoxic potential (e.g., aminoglycosides, polymyxin antibiotics) should be avoided.

Neuromuscular Blocking

Agents and Anesthetics Bacitracin is believed to inhibit neuromuscular transmission. Parenterally administered bacitracin may increase or prolong skeletal muscle relaxation produced by neuromuscular blocking agents and/or anesthetics if the antibiotic is administered during surgery, or may reinstate neuromuscular blockade if administered parenterally postoperatively. Mechanism of Action 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 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. Spectrum Bacitracin is active against many gram-positive organisms, such as staphylococci (including some penicillin G-resistant strains), streptococci, anaerobic cocci, corynebacteria, and clostridia. In vitro, bacitracin concentrations of 0.05-5 mcg/mL inhibit most susceptible strains of Staphylococcus aureus.

The drug is active against gonococci, meningococci, and fusobacteria, but not against most other gram-negative organisms. Bacitracin is also active against Actinomyces israelii, Treponema pallidum, and T. vincenti. Resistance In susceptible bacteria, the development of resistance to bacitracin seldom occurs; if it does occur, it emerges slowly. An increasing number of staphylococci, including penicillin G-resistant staphylococci, are resistant to bacitracin. Bacitracin does not exhibit cross-resistance with any other antibiotic.

Pharmacokinetics

Absorption

Bacitracin is not absorbed from the GI tract, pleura, or synovia. The drug is rapidly and completely absorbed following IM injection. A bacitracin dosage of 200-300 units/kg administered IM every 6 hours gives sustained serum concentrations of 0.2-2 mcg/mL in adult patients with normal renal function. After a single IM dose of 10,000-20,000 units, the maximum serum concentration occurs after 1-2 hours, and detectable amounts of bacitracin are present in the serum 6-8 hours after injection in adult patients with normal renal function. There are no data on serum concentrations of bacitracin in infants.

Distribution

Bacitracin is widely distributed in all body organs and is present in ascitic and pleural fluids following IM injection. The drug is only slightly protein bound. Only trace amounts of bacitracin cross the blood-brain barrier into the CSF, unless the meninges are inflamed.

Elimination

Bacitracin is excreted in the feces following oral administration. After IM administration, 10-40% of the dose is excreted slowly by glomerular filtration and appears in the urine within 24 hours. A considerable amount of bacitracin has not been accounted for and is thought to be either retained or destroyed in the body.

Chemistry and Stability

Chemistry

Bacitracin is a polypeptide antibiotic produced by Bacillus subtilis. The antibiotic consists of 3 separate compounds, bacitracin A, B, and C; bacitracin A is the chief constituent. Bacitracin has a potency of not less than 40 units of bacitracin activity per mg; when intended for parenteral use, it has a potency of not less than 50 units of bacitracin activity per mg. Bacitracin occurs as a white to pale buff, hygroscopic powder that is odorless or has a slight odor, and has a bitter taste. The drug is freely soluble in water and soluble in alcohol. Aqueous solutions of bacitracin have a pH of 5-7.5.

Stability

Prior to reconstitution, bacitracin for injection should be stored at 2-8°C104 and protected from direct sunlight. The commercially available powder for injection has an expiration date of 2 years following the date of manufacture. Following reconstitution, bacitracin solutions are stable for one week when stored at 2-8°C; aqueous solutions of the drug deteriorate rapidly by oxidation at room temperature. In one study, aqueous solutions of bacitracin 5000 units/mL were stable for up to 5 months in glass vials or plastic syringes when frozen at -15°C. Diluents containing parabens should not be used to reconstitute bacitracin powder for injection, since cloudy solutions and formation of a precipitate may result. Bacitracin is rapidly inactivated in solutions having a pH less than 4 or greater than 9. Bacitracin is precipitated from solutions by many heavy metal salts and is inactivated by benzoates, salicylates, tannates, cetylpyridinium chloride, benzalkonium chloride, and sodium lauryl sulfate.

Preparations

Bacitracin Parenteral For injection, for 50,000 units Baci-IM®, Pharma-IM use Tek Bacitracin for injection,Schein Pfizer

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