Polypeptide antibiotics disrupt bacterial cell walls (see Table 15: Bacteria and Antibacterial Drugs: Polypeptides).

Table 15
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Polypeptides Bacitracin Colistin 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, which contains lipopolysaccharide (endotoxin), and thereby neutralizing the bacteria's toxicity.

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 are usually used topically; systemic absorption is negligible.

Indications

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

Polypeptides are used for several types of infections (see Table 16: Bacteria and Antibacterial Drugs: Some Clinical Uses of Polypeptides).

Table 16
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Some Clinical Uses of Polypeptides Preparation Uses Comments 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) Bacitracin Topical Eradication of Staphylococcus aureus nasal carriage Impetigo Less effective than other treatments Oral Clostridium difficile–induced diarrhea (pseudomembranous colitis) Less effective and less palatable than oral vancomycin or metronidazole Colistin 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 Solutions GU irrigation — Some Clinical Uses of Polypeptides Preparation Uses Comments 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) Bacitracin Topical Eradication of Staphylococcus aureus nasal carriage Impetigo Less effective than other treatments Oral Clostridium difficile–induced diarrhea (pseudomembranous colitis) Less effective and less palatable than oral vancomycin or metronidazole Colistin 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 Solutions GU irrigation —

Contraindications

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.

Last full review/revision July 2009 by Matthew E. Levison, MD