The polypeptide antibacterials have little in common other than their basic structural elements -- amino acids. Vancomycin can be used to treat both systemic and gastrointestinal infections whereas because of serious systemic toxicities the others, polymyxin B and bacitracin, are limited to topical applications nowadays. They have been replaced by the anti-Pseudomonas penicillins, cephalosporins, and aminoglycosides.
Vancomycin, isolated from Streptomyces orientalis (India) is a glycopeptide of molecular weight 1500. It is highly water soluble.
Vancomycin inhibits bacterial cell wall synthesis by inhibiting peptidoglycan synthase, apparently by binding to D-alanyl-D-alanine, a component of the cross-link between chains. This action inhibits peptidoglycan chain elongation, and as might be expected, the effect is cidal for most organisms if they are rapidly dividing. Note that because the target enzyme is different, vancomycin is not cross-resistant with the beta-lactams. Thus, it may be effective in "methicillin-resistant" strains and serve as a replacement for beta-lactams in these cases. There is also an effect on RNA synthesis so that vancomycin is also effective against L-forms in contrast to the beta-lactams.
Vancomycin is considered to be a narrow spectrum drug that affects primarily gram-positive bacteria. Staphylococcus aureus are sensitive in the range of 0.1 to 2 ug/ml, much the same as when the drug was first marketed. It is apparently synergistic with streptomycin in the treatment of Streptococcus faecalis infections, against which the combination is cidal. It is also useful for treating Staphylococcal enteritis and enterocolitis. Vancomycin is the drug-of-choice for treatment of Antibiotic-Associated Pseudomembranous Enterocolits (AAPEC) where it is used by oral administration. For its systemic uses, e.g., to treat septicemias and bone infections caused by Staphylococci and endocarditis prophylaxis or therapy in penicillin-hypersensitive patients, it should be used only when less toxic drugs are not available.
Vancomycin is poorly absorbed from the gastrointestinal tract, producing less than 1 mcg/mL in plasma via this route. Because of this, its effects are usually not a problem when it is given orally.
For systemic infections it must be given intravenously, preferrably via infusion, because it is highly irritating and causes abscessation and pain after extravasation or IM injection. Slow infusion helps avoid rarely occurring cardiac arrest and more common "red-neck syndrome" and hypotension.
Vancomycin is widely distributed to the tissues and even crosses the placental barrier in humans. Intraperitoneally administered drug has a bioavailability of 0.6. Its volume of distribution is 0.43 to 1.25 L/kg.
Vancomycin is eliminated by glomerular filtration and has an elimination half-life of approximately 6 hours. With oliguria or anuria, the half-life may increase to 6 to 10 DAYS! The drug is not appreciably removed by hemodialysis or peritoneal dialysis.
Bacitracin is a narrow spectrum antibiotic derived from a bacterum, Bacillus subtilis, Tracy-I strain. Its spectrum includes primarily gram-positive cocci and bacilli. It inhibits cell wall biosynthesis by inhibiting lipid pyrophatase which is involved in transmembrane transport of peptidoglycan precursors. It is NOT used systemically nowadays because there are equally or more effective drugs with less toxicity. It produces nephrotoxicity. It is primarily used topically where it has very low toxicity.
Polymyxin B is a narrow spectrum antibiotic derived from a bacterium Bacillus polymyxa, an aerobic spore-forming rod. It is a basic peptide with a molecular weight of approximately 1000. Prior to the development of superior drugs with less toxicity, it was used to treat systemic infections caused by gram-negative bacteria, e.g., Pseudomonas aeruginosa, Salmonella, and Campylobacter.
It acts by being a cationic surface active agent, due to its lipophilic and lipophobic ends, that disturbs the integrity of the cell membrane. Specificity is apparently related to the phospholipid content of the membrane, but its toxicity indicates that there is not enough difference between bacterium and patient! Effective concentrations are cidal regardless of the growth phase of the organism.
Because of its severe systemic toxicity which includes nephrotoxicity, neuromuscular blockade, and severe pain upon injection, it is used only topically. In this application it is very safe.