Merck Manual

Please confirm that you are a health care professional

honeypot link

Polypeptide Antibiotics: Bacitracin, Colistin, Polymyxin B


Brian J. Werth

, PharmD, University of Washington School of Pharmacy

Last full review/revision May 2020| Content last modified May 2020
Click here for Patient Education
Topic Resources

Polypeptide antibiotics disrupt bacterial cell walls.

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.


Resistance is typically acquired via modifications to the lipid A moiety of the lipopolysaccharide outer membrane; these modifications lead to a more positively charged cell surface, which lacks affinity for the positively charged polymyxins. Acquired resistance can be carried on mobile genetic elements (eg, mcr-1, 2, 3 [plasmid-mediated colistin resistance] plasmid), increasing the risk of horizontal transfer. Cross-resistance between colistin and polymyxin B is nearly 100%.

Indications for Polypeptide Antibiotics

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

Bacitracin is used mainly as a topical treatment for

Polymyxin B and colistin have rapid concentration-dependent bactericidal activity against

These drugs are not active against Proteus, Providencia, Burkholderia, and Serratia species and some obligate anaerobes, including Bacteroides fragilis and gram-positive bacteria (1).

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. When polymyxins are used, they should be used in combination with other drugs such as meropenem, not as monotherapy. Colistin is often combined with other antibiotics to treat infections caused by multidrug-resistant bacteria; effectiveness of these combinations has not yet been rigorously assessed in clinical trials. Some of the newer combination beta-lactam plus inhibitor drugs are preferable to polymyxin-based therapy whenever possible.


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

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


Aerosolized colistin methane sulfonate (colistimethate sodium [CMS])

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 species

Reduced dose in patients with renal insufficiency

Polymyxin B


Genitourinary irrigation


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

Indications reference

Contraindications to Polypeptide Antibiotics

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

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

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 has not been adequately evaluated in animal reproduction studies. No well-controlled studies have been done in pregnant women. Safety of polymyxin B in pregnant women has not been determined.

Colistin methane sulfonate (CMS) showed some risk in animal reproduction studies. Data related to pregnancy in humans are inadequate. Whether it is safe to use colistin or CMS during breastfeeding is unknown.

Adverse Effects of Polypeptide Antibiotics

Adverse effects of polypeptides 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 for Polypeptide Antibiotics

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 milligrams of colistin base activity or milligrams of actual colistimethate.

Whatever units are used, 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 (1). However, nephrotoxicity is dose-dependent and becomes a greater concern with higher doses. Dosing should be discussed with an expert.

Dosing considerations reference

Click here for Patient Education
NOTE: This is the Professional Version. CONSUMERS: Click here for the Consumer Version

Test your knowledge

Toxoplasmosis is infection with Toxoplasma gondii. The only known hosts of this organism are domestic cats and their relatives. Infection with T. gondii in humans can occur in various ways. Which of the following is the most common mode of infection in humans? 
Download the Manuals App iOS ANDROID
Download the Manuals App iOS ANDROID
Download the Manuals App iOS ANDROID
Download the Manuals App iOS ANDROID
Download the Manuals App iOS ANDROID
Download the Manuals App iOS ANDROID

Also of Interest

Download the Manuals App iOS ANDROID
Download the Manuals App iOS ANDROID
Download the Manuals App iOS ANDROID