**Pharmacology: Lesson 14: Peptide Antibiotics**

1. Introduction

Peptide antibiotics are a group of antibiotics whose structure consists of polypeptide or glycopeptide chains that act on bacteria by inhibiting cell wall synthesis. This group includes two main subgroups:

• Polypeptide group: Includes Bacitracin and Polymyxins.

• Glycopeptide group: Includes Vancomycin and Teicoplanin.

2. Structure and mechanism of action

a. Polypeptide group

• Structure: The peptide molecules in this group often have a fatty acid moiety that helps them bind to the bacterial cell membrane.

• Mechanism of action: Polypeptides inhibit bacterial cell wall synthesis by:

• Bacitracin: inhibits peptidoglycan biosynthesis at the dephosphorylation stage, disrupting the permeability function of the bacterial cell membrane.

• Polymyxin: combines with the phospholipid layer of the cytoplasmic membrane, disrupting the lipoprotein layer arrangement, changing the selective permeability of the membrane, leading to the outflow of cell components, causing bacteria to be destroyed.

b. Glycopeptide group

• Structure:

• Glycopeptide antibiotics have a polycyclic structure, composed of amino acids linked together by peptide bonds.

• Glycopeptides are hydrophilic, can be acidic or alkaline, and are poorly absorbed orally.

• Mechanism of action:

• Vancomycin and Teicoplanin: inhibit the synthesis of the cell wall of gram-positive bacteria during the replication stage, by tightly binding to the acyl-D-alanyl-D-alanine molecule, increasing membrane permeability and inhibiting ribonucleic acid synthesis.

3. Typical antibiotics

a. Polypeptide group

• Bacitracin:

• Good activity against gram-positive cocci.

• Used topically due to high toxicity to the kidneys and nerves, poorly absorbed through the skin, intestines, pleura, and synovial membrane, not absorbed orally.

• Polymyxin:

• Includes Polymyxin B (B1 and B2), and Polymyxin E2 (Colistin).

• Polymyxin B is the molecule with the best antibacterial activity.

• All polymyxins have the same gram-negative antibacterial spectrum.

• Excreted through the kidneys in active form.

• Indications: treatment of meningitis, bacteremia, severe urinary tract infections caused by P. aeruginosa.

• Oral colistin is used in the treatment of gastrointestinal infections. Polymycin B is more toxic than colistin and is used topically.

b. Glycopeptide group

• Vancomycin:

• Is a glycopeptide consisting of 3 rings, combined with 1 disaccharide molecule.

• The main activity is in the aglycol peptide portion.

• Vancosamine sugar plays a role in drug binding to the receptor.

• Narrow antibacterial spectrum, limited to Gram (+) bacteria.

• Used orally in the treatment of pseudomembranous colitis caused by Clostridium difficile and enteritis caused by Staphylococcus aureus (however, it is not absorbed orally so topical treatment is used).

• Renal toxicity is significantly increased when combined with aminosides.

• Indications:

• Methicillin-resistant S. aureus or S. coagulase negative.

• Severe Streptococcus in patients allergic to beta lactams.

• Other multi-drug resistant gram-positive pathogens.

• Teicoplanin:

• Is a complex of many lipoglycopeptide molecules, consisting of 5 main molecules.

• Chlorine attached to aglycol determines antibacterial activity, the diphenyl ether group contributes to antibacterial activity.

• Combined with aminosides, imipenem, and fosfomycin, teicoplanin shows synergistic effects in vitro on G+ cocci.

4. Note

• Vancomycin and teicoplanin are very effective against methicillin-resistant gram-positive bacterial strains, especially Staphylococcus aureus.

• Impurities in the manufacturing process (co-fermentation sp) have a significant impact on the poor tolerance and toxicity of Vancomycin.

• Peptide antibiotics can cause adverse effects such as:

• Renal side effects: cause renal toxicity, especially when combined with aminosides.

• Neurological side effects: cause dizziness, nausea, vomiting, seizures.

• Hematological side effects: cause leukopenia, thrombocytopenia.

• Skin side effects: cause rash, itching, urticaria.

5. Conclusion

Peptide antibiotics are an important group of antibiotics in the treatment of bacterial infections, especially those caused by methicillin-resistant gram-positive bacteria. However, it is necessary to be aware of the toxicity of this group of antibiotics and use them according to the doctor’s prescription.