Principles of Antimicrobial Action and Resistance

Study Notes

Antibiotics are chemical compounds that kill or inhibit the growth of infectious microorganisms.
Antibiotics must be in an active form, and the route of administration and intended site of action must be considered.

The bacterial cell wall, composed of peptidoglycan, confers structural rigidity and shape.
Beta-lactam antibiotics interrupt cell wall synthesis by binding to transpeptidases.
Bacteria have developed resistance to beta-lactam antibiotics by producing beta-lactamases.
Three beta-lactamase inhibitors (clavulanic acid, sulbactam, and tazobactam) can bind beta-lactamase.
Glycopeptides (e.g., vancomycin and teicoplanin) bind to precursors of cell wall synthesis, blocking access to transpeptidases.

The cytoplasmic membrane surrounds the bacterial cell, functioning in enzyme synthesis and secretion, energy gradient formation, and metabolite retention.
Polymyxins (e.g., polymyxin B and colistin) act on the cell membrane, causing intracellular material leakage.
Daptomycin is a lipopeptide that binds and disrupts the cell membrane of gram-positive bacteria.

Protein synthesis can be disrupted at the ribosomal level by antibiotic binding to the 50s or 30s subunit.
Aminoglycosides (e.g., gentamicin, tobramycin, amikacin, and streptomycin) bind the 30s ribosomal subunit, interfering with translation.
Macrolide-lincosamide-streptogramin (MLS) group (e.g., erythromycin, azithromycin, and clindamycin) binds receptors on the 50s ribosomal subunit, disrupting peptide chain growth.
Ketolides (e.g., telithromycin) are derivatives of macrolides, inhibiting protein synthesis.
Oxazolidinones (e.g., linezolid) inhibit protein synthesis by a unique mechanism.
Tetracyclines halt peptide chain elongation, having a broad range of activity against intracellular pathogens.
Chloramphenicol inhibits the addition of new amino acids, effective against a wide range of bacteria.

Bacterial strategies that mediate resistance to beta-lactam antibiotics include enzymatic destruction of the drug, altered targets for the antibiotic, and decreased cellular uptake of the drug.