Polypeptide Antibiotics: Bacitracin, Colistin, Polymyxin B
Polypeptide antibiotics disrupt bacterial cell walls (see Table: Polypeptides).
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
Polymyxin B and colistin have rapid concentration-dependent bactericidal activity (see Effectiveness) against
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
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 include
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.
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, 1many 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.
1Garonzik 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.