Introduction to Antibiotics & Beta-Lactam Antibiotics

Key Concepts

• Pharmacokinetics: Movement and elimination of drugs, determining drug administration routes.
• Pharmacodynamics: Connection between drug concentration and clinical effect. Three requirements for effective antibiotics:
  • Bind to the bacteria’s target site.
  • Occupy sufficient binding sites.
  • Remain at sites long enough to inhibit bacteria.

Antibiotic Classification

• Cell Wall Synthesis Inhibitors: Penicillins, cephalosporins, imidazole antifungals.
• Cell Membrane Disruptors: Detergents, polyene antifungals.
• Protein Synthesis Inhibitors: Tetracyclines, aminoglycosides.
• DNA Synthesis Inhibitors: Rifamycins, TMP, acyclovir.
• Folic Acid Metabolism: Requires a bacterial cell wall to be effective.

Treatment Considerations

• Factors: Bacterial, drug, and host characteristics.
• Bactericidal vs Bacteriostatic: Killing bacteria vs inhibiting growth.

Antibiotic Resistance

• Mechanisms:
  • Target modification, efflux, immunity & bypass, enzyme-catalyzed destruction.
  • Resistance acquired via mutation or horizontal gene transfer.
• Resistance Management: Avoid broad-spectrum unless necessary; use narrow, specific antibiotics.

Antibiotic Selection

• Empirical Treatment: Based on educated guess before culture results.
• Definitive Treatment: Tailored based on culture/sensitivity tests.

Sensitivity Testing

• Disc Diffusion & Agar/Broth Dilution: Determines bacterial sensitivity to antibiotics.
• MIC/MBC: Lowest concentration to inhibit growth/kill bacteria.

Patient & Drug Considerations

• Patient Factors: Renal/liver function, age, allergies.
• Drug Factors: Access to infection site, dosing schedules, renal excretion.
• Special Populations: Immunocompromised, pregnancy, combination therapy requirements.

Penicillins & Beta-Lactam Compounds

• Mechanism of Action: Interferes with bacterial cell wall synthesis, mainly bactericidal.
• Classification:
  • First Group: Penicillins (PenG, PenVK) for gram-positive.
  • Second Group: Anti-staphylococcal penicillins (nafcillin) for resistant staph/strep.
  • Third Group: Extended-spectrum penicillins (amoxicillin, ampicillin) for broader activity.
• Resistance: Inactivation by beta-lactamase, modification of PBPs, efflux.

Cephalosporins

• Generations:
  • First Gen: Cephalexin for gm+ cocci.
  • Second Gen: Cefaclor for extended gram-negative coverage.
  • Third Gen: Ceftriaxone for serious infections, crosses BBB.
  • Fourth Gen: Cefepime for resistant strains.
• Adverse Effects: Cross-allergenicity mainly with early generations.

Other Beta-Lactam Drugs

• Monobactams (Aztreonam): Safe for penicillin-allergic patients.
• Carbapenems: Broad spectrum, resistant to most beta-lactamases.

Vancomycin

• Use: Effective against MRSA/MRSE, no beta-lactam ring.
• Adverse Reactions: Red man syndrome, ototoxicity, nephrotoxicity.

Bacitracin

• Application: Topical use only due to nephrotoxicity.

Bibliography

• Beauduy CE, Winston LG. Chapter 43 in Basic & Clinical Pharmacology, 15th edition. McGraw Hill; 2021.