Mechanisms and Classes of Antimicrobial Agents

Exam Tip: Beta-lactams only kill bacteria that are actively growing and synthesizing a cell wall. They are ineffective against non-growing or dormant bacteria.

Classification of Beta-Lactams

The beta-lactam family is divided into several major groups:

• Penicillins: These include original penicillins like Penicillin G. They are often narrow-spectrum, showing high activity against Gram-positive bacteria and Gram-positive anaerobes, but they struggle to penetrate the outer membrane of most Gram-negative bacteria. They are also highly susceptible to beta-lactamases—enzymes produced by bacteria to destroy the beta-lactam ring.
• Cephalosporins: These are also beta-lactams but offer improved penetration and greater resistance to beta-lactamases. They are categorized into four generations; generally, as you move from the 1st to the 4th generation, the Gram-negative antibacterial activity increases.
• Carbapenems and Monobactams: These represent further specialized groups within the beta-lactam family.

Note on Mycoplasma: Because Mycoplasma species lack a cell wall entirely, they are inherently resistant to all beta-lactam antibiotics.

Other Antimicrobial Classes

Protein Synthesis Inhibitors

These drugs target the bacterial ribosome to stop the production of essential proteins. Because bacterial ribosomes (70S) differ from eukaryotic ribosomes (80S), these drugs can achieve selective toxicity.

• 30S Subunit Targets:
  • Tetracyclines: Bacteriostatic drugs that block peptide elongation. They are lipid-soluble and can penetrate host cells, making them effective against intracellular bacteria.
  • Aminoglycosides: Bactericidal drugs that cause the production of truncated or non-sense proteins. They are primarily effective against Gram-negative aerobes; they are ineffective against anaerobes because their uptake requires oxygen.
• 50S Subunit Targets:
  • Macrolides (e.g., Erythromycin) and Lincosamides (e.g., Clindamycin): Usually bacteriostatic, these are highly lipid-soluble and penetrate mammalian cells well.
  • Chloramphenicol: A broad-spectrum drug that can cause serious side effects like aplastic anemia in humans.

Clinical Warning: Clindamycin can significantly disrupt normal gastrointestinal flora. In certain species like horses and rabbits, this can lead to fatal Clostridium difficile colitis.

Nucleic Acid Synthesis Inhibitors

• Quinolones/Fluoroquinolones: Bactericidal drugs that inhibit DNA gyrase, preventing the supercoiling of the bacterial chromosome.
• Sulfonamides and Trimethoprim: These interfere with the synthesis of folic acid. While sulfonamides are bacteriostatic, combining them with trimethoprim results in a bactericidal effect.
• Rifampicin: Inhibits RNA polymerase, thereby blocking the synthesis of mRNA.

Cell Membrane Disruptors

• Polymyxins: These act like detergents, binding to phospholipids in the bacterial cell membrane to cause distortion or pore formation.

Summary Table of Mechanisms

Determining Susceptibility

To ensure the correct antibiotic is chosen, susceptibility testing is performed to identify if a pathogen is susceptible or resistant. Common methods include:

• Disk Diffusion (Kirby-Bauer): Measuring zones of inhibition around antibiotic disks on agar.
• Broth Dilution: Determining the Minimum Inhibitory Concentration (MIC).
• E-test: Using a gradient strip to determine susceptibility.