Polypeptide antibiotics disrupt bacterial cell walls.
is a polypeptide antibiotic that inhibits cell wall synthesis and is active against gram-positive bacteria.
Colistin are cationic polypeptide antibiotics that disrupt the outer membrane of gram-negative bacteria by binding to the anionic lipopolysaccharide (endotoxin) 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
Resistance to colistin and polymyxin B 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 [mobilized 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).
is used mainly as a topical treatment for
Superficial skin infections caused by Staphylococcus aureus
demonstrate rapid exposure-dependent bactericidal activity in vitro (area under the concentration-time curve/minimum inhibitory concentration [AUC/MIC] ratio best predicts killing) against
Most facultative and aerobic gram-negative bacilli, including Pseudomonas aeruginosa and Acinetobacter species (1, 2)
These antibiotics are not active against Proteus, Providencia, Burkholderia, and Serratia species and some obligate anaerobes, including Bacteroides fragilis and gram-positive bacteria.
Some Clinical Uses of Polypeptides
Preparation | Uses | Comments |
|---|---|---|
Combination treatments | ||
Ointment containing bacitracin plus neomycin, polymyxin B | Wound infection | May cause contact dermatitis |
Prevention of postoperative wound infections | May cause contact dermatitis | |
Polymyxin B | 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 May cause contact dermatitis |
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 Not first-line therapy |
Solutions | Genitourinary irrigation | — |
Parenteral | Severe infections due to multidrug-resistant gram-negative bacilli such as P. aeruginosa or Acinetobacter species | — |
Indications references
1. Tamma PD, Aitken SL, Bonomo RA, Mathers AJ, van Duin D, Clancy CJ. Infectious Diseases Society of America 2023 Guidance on the Treatment of Antimicrobial Resistant Gram-Negative Infections. Clin Infect Dis. Published online July 18, 2023. doi:10.1093/cid/ciad428
2. Tsuji BT, Pogue JM, Zavascki AP, et al. International Consensus Guidelines for the Optimal Use of the Polymyxins: Endorsed by the American College of Clinical Pharmacy (ACCP), European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Infectious Diseases Society of America (IDSA), International Society for Anti-infective Pharmacology (ISAP), Society of Critical Care Medicine (SCCM), and Society of Infectious Diseases Pharmacists (SIDP). Pharmacotherapy. 2019;39(1):10-39. doi:10.1002/phar.2209
Contraindications to Polypeptide Antibiotics
All polypeptides are contraindicated in patients who have had an allergic reaction to them.
Use of Polypeptides During Pregnancy and Breastfeeding
may pose minimal risk during pregnancy and breastfeeding because systemic absorption is minimal; however, safety has not been established.
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
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, 2). However, nephrotoxicity is dose-dependent and becomes a greater concern with higher doses (1, 2). Dosing should be discussed with an expert.
Dosing considerations references
1. Tamma PD, Aitken SL, Bonomo RA, Mathers AJ, van Duin D, Clancy CJ. Infectious Diseases Society of America 2023 Guidance on the Treatment of Antimicrobial Resistant Gram-Negative Infections. Clin Infect Dis. Published online July 18, 2023. doi:10.1093/cid/ciad428
2. Tsuji BT, Pogue JM, Zavascki AP, et al. International Consensus Guidelines for the Optimal Use of the Polymyxins: Endorsed by the American College of Clinical Pharmacy (ACCP), European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Infectious Diseases Society of America (IDSA), International Society for Anti-infective Pharmacology (ISAP), Society of Critical Care Medicine (SCCM), and Society of Infectious Diseases Pharmacists (SIDP). Pharmacotherapy. 2019;39(1):10-39. doi:10.1002/phar.2209
