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Polypeptide Antibiotics: Bacitracin, Colistin, Polymyxin B

by Hans P. Schlecht, MD, MSc, Christopher Bruno, MD

Polypeptide antibiotics disrupt bacterial cell walls (see Table: Polypeptides).




Polymyxin B

Bacitracin is a polypeptide antibiotic that inhibits cell wall synthesis and is active against gram-positive bacteria.

Colistin (polymyxin E) and polymyxin B are cationic polypeptide antibiotics that disrupt the outer bacterial cell membrane by binding to the anionic outer membrane and thereby neutralizing the bacteria’s toxicity and causing bacterial cell death.

Colistin methane sulfonate (colistimethate sodium [CMS]) is a parenteral preparation of a prodrug that is transformed in blood and urine to colistin. CMS is less toxic than colistin.

Polypeptides other than colistin are usually used topically; systemic absorption is negligible.


Polypeptides are used for several types of infections (see Table: Some Clinical Uses of Polypeptides).

Bacitracin is used mainly as a topical treatment for

  • Superficial skin infections caused by Staphylococcus aureus

Polymyxin B and colistin have rapid concentration-dependent bactericidal activity (see Bacteria and Antibacterial Drugs:Effectiveness) against

  • Most facultative and aerobic gram-negative bacilli, including Pseudomonas aeruginosa and Acinetobacter sp

These drugs are not active against Proteus, Providencia, Burkholderia, and Serratia spp and some obligate anaerobes, including Bacteroides fragilis and gram-positive bacteria. Development of resistance is uncommon.

The increasing prevalence of extensively drug-resistant gram-negative bacilli in hospitals has led to a resurgence of the use of IV colistin for serious systemic infections (eg, ventilator-associated pneumonia, bacteremia). However, IV polymyxin B and colistin should typically be used only when there are no less toxic options.

Some Clinical Uses of Polypeptides




Combination treatments

Ointment containing bacitracin plus neomycin, polymyxin B, or both

Wound infection

No confirmation of clinical efficacy

Spray containing neomycin, bacitracin, and polymyxin

Prevention of postoperative wound infections

Appears to help

Polymyxin B ophthalmic ointments and solutions with other antimicrobials (eg, bacitracin, neomycin, trimethoprim/sulfamethoxazole) and corticosteroids

Ophthalmic use

Significantly improved rates of early clinical remission (although acute bacterial conjunctivitis is frequently self-limited)

Otic suspension with polymyxin B, neomycin, and hydrocortisone or with colistin, neomycin, and hydrocortisone

Otitis externa (commonly due to Pseudomonas aeruginosa)

Clinically effective, but may be no more effective than 2% acetic acid with hydrocortisone

In patients with a tympanostomy tube or known perforation of the tympanic membrane, must use a nonototoxic topical preparation (no aminoglycoside or alcohol)



Eradication of Staphylococcus aureus nasal carriage


Less effective than other treatments


Clostridium difficile–induced diarrhea (pseudomembranous colitis)

Less effective and less palatable than oral vancomycin or metronidazole


Aerosolized colistin methane sulfonate (colistimethate sodium [CMS])

Cystic fibrosis

Occasionally hospital-acquired pneumonia caused by multidrug-resistant gram-negative bacilli

Associated with fewer adverse effects (eg, chest tightness, throat irritation, cough) than colistin sulfate

Aerosolized colistin sulfate

Same as for aerosolized colistin methane sulfonate

May be beneficial for patients with cystic fibrosis or nosocomial pneumonia (ventilator-associated or not) due to multidrug-resistant gram-negative bacteria

Parenteral CMS

Severe infections due to multidrug-resistant gram-negative bacilli such as P. aeruginosa or Acinetobacter sp

Reduced dose in patients with renal insufficiency

Polymyxin B


GU irrigation


All polypeptides are contraindicated in patients who have had an allergic reaction to them.

CMS and polymyxin B should not be given simultaneously with drugs that block neuromuscular transmission or are nephrotoxic (eg, aminoglycosides, curare-like drugs).

Use During Pregnancy and Breastfeeding

Bacitracin may pose minimal risk during pregnancy and breastfeeding because systemic absorption is minimal; however, safety has not been established.

Polymyxin B is in pregnancy category B (animal studies show no risk and human evidence is incomplete, or animal studies show risk but human studies do not).

Colistin is in pregnancy category C (animal studies show some risk, evidence in human studies is inadequate, but clinical benefit sometimes outweighs risk); this drug crosses the placenta. Whether use during breastfeeding is safe is unknown.

Adverse Effects

Adverse effects include

  • Nephrotoxicity

  • Central and peripheral neurotoxicity

Polymyxins are nephrotoxic. CMS and polymyxin B may cause circumoral and extremity paresthesias, vertigo, slurred speech, and muscle weakness and respiratory difficulty due to neuromuscular blockade, especially in patients with renal insufficiency.

Dosing Considerations

Because colistin was released before the advent of modern pharmacokinetic/pharmacodynamic analysis, appropriate dosing has not been studied as rigorously as for many modern antibiotics. In addition, manufacturers do not use a uniform method of describing drug amount; some use international units, and others use mg of colistin base activity or mg of actual colistimethate.

Whatever units are used, 1 many experts believe that the manufacturer-recommended dose of 2.5 to 5 mg/kg of colistin base activity per day divided into 2 to 4 doses is too low and recommend higher dosing regimens, including the use of a loading dose. However, nephrotoxicity is dose-dependent and becomes a greater concern with higher doses. Dosing should be discussed with an expert.

  • 1 Garonzik SM, et al: Population pharmacokinetics of colistin methanesulfonate and formed colistin in critically ill patients from a multicenter study provide dosing suggestions for various categories of patients. Antimicrob Agents Chemother 55(7): 3284–3294, 2011.

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