Polypeptide antibiotics disrupt bacterial cell walls.
is a polypeptide antibiotic that inhibits cell wall synthesis and is active against gram-positive bacteria.
Colistin (polymyxin E) and 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
mcr-1, 2, 3
Indications for Polypeptide Antibiotics
Polypeptides are used for several types of infections (see table Some Clinical Uses of Polypeptides).
is used mainly as a topical treatment for
Superficial skin infections caused by Staphylococcus aureus
have rapid concentration-dependent bactericidal activity against
Most facultative and aerobic gram-negative bacilli, including Pseudomonas aeruginosa and Acinetobacter species
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
Some Clinical Uses of Polypeptides
Preparation | Uses | Comments |
|---|---|---|
Combination treatments | ||
Wound infection | — | |
Prevention of postoperative wound infections | Appears to help | |
Ophthalmic use | Significantly improved rates of early clinical remission (although acute bacterial conjunctivitis is frequently self-limited) | |
Otitis externa (commonly due to Pseudomonas aeruginosa) | In patients with a tympanostomy tube or known perforation of the tympanic membrane, must use a nonototoxic topical preparation (no aminoglycoside or alcohol) | |
Topical | Eradication of Staphylococcus aureus nasal carriage | Less effective than other treatments |
Colistin | ||
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 |
Solutions | Genitourinary irrigation | — |
Parenteral | Severe infections due to multidrug-resistant gram-negative bacilli such as P. aeruginosa or Acinetobacter species | — |
Indications reference
1. Lenhard JR, Bulman ZP, Tsuji BT, Kaye KS: Shifting gears: The future of polymyxin antibiotics. Antibiotics (Basel) 8(2):42, 2019. doi: 10.3390/antibiotics8020042
Contraindications to Polypeptide Antibiotics
All polypeptides are contraindicated in patients who have had an allergic reaction to them.
Use During Pregnancy and Breastfeeding
may pose minimal risk during pregnancy and breastfeeding because systemic absorption is minimal; however, safety has not been established.
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
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
1. Nation RL, Garonzik SM, Thamlikitkul V, et al: Dosing guidance for intravenous colistin in critically-ill patients. Clin Infect Dis 64:565–571, 2017. doi: 10.1093/cid/ciw839
