<< Chapter < Page | Chapter >> Page > |
A small group of antibacterials target the bacterial membrane as their mode of action ( [link] ). The polymyxins are natural polypeptide antibiotics that were first discovered in 1947 as products of Bacillus polymyxa ; only polymyxin B and polymyxin E ( colistin ) have been used clinically. They are lipophilic with detergent-like properties and interact with the lipopolysaccharide component of the outer membrane of gram-negative bacteria, ultimately disrupting both their outer and inner membranes and killing the bacterial cells. Unfortunately, the membrane-targeting mechanism is not a selective toxicity , and these drugs also target and damage the membrane of cells in the kidney and nervous system when administered systemically. Because of these serious side effects and their poor absorption from the digestive tract, polymyxin B is used in over-the-counter topical antibiotic ointments (e.g., Neosporin ), and oral colistin was historically used only for bowel decontamination to prevent infections originating from bowel microbes in immunocompromised patients or for those undergoing certain abdominal surgeries. However, the emergence and spread of multidrug-resistant pathogens has led to increased use of intravenous colistin in hospitals, often as a drug of last resort to treat serious infections. The antibacterial daptomycin is a cyclic lipopeptide produced by Streptomyces roseosporus that seems to work like the polymyxins, inserting in the bacterial cell membrane and disrupting it. However, in contrast to polymyxin B and colistin, which target only gram-negative bacteria, daptomycin specifically targets gram-positive bacteria. It is typically administered intravenously and seems to be well tolerated, showing reversible toxicity in skeletal muscles.
Drugs That Inhibit Bacterial Membrane Function | ||||
---|---|---|---|---|
Mechanism of Action | Drug Class | Specific Drugs | Spectrum of Activity | Clinical Use |
Interacts with lipopolysaccharide in the outer membrane of gram-negative bacteria, killing the cell through the eventual disruption of the outer membrane and cytoplasmic membrane | Polymyxins | Polymyxin B | Narrow spectrum against gram-negative bacteria, including multidrug-resistant strains | Topical preparations to prevent infections in wounds |
Polymyxin E (colistin) | Narrow spectrum against gram-negative bacteria, including multidrug-resistant strains | Oral dosing to decontaminate bowels to prevent infections in immunocompromised patients or patients undergoing invasive surgery/procedures. | ||
Intravenous dosing to treat serious systemic infections caused by multidrug-resistant pathogens | ||||
Inserts into the cytoplasmic membrane of gram-positive bacteria, disrupting the membrane and killing the cell | Lipopeptide | Daptomycin | Narrow spectrum against gram-positive bacteria, including multidrug-resistant strains | Complicated skin and skin-structure infections and bacteremia caused by gram-positive pathogens, including MRSA |
Notification Switch
Would you like to follow the 'Microbiology' conversation and receive update notifications?