Antibiotic Therapy and Metabolism Quiz

Introduction to Antibiotics

• Antibiotics are medications used to treat bacterial infections.
• The choice of antibiotic depends on several criteria.

How to Choose the Most Suitable Antibiotic for Bacterial Infections?

• Patient factors: safety, cost, and limiting conditions (e.g., liver or kidney disease).
• Antibiotic factors: spectrum (range of bacteria it targets) and pharmacokinetics (ability to reach the site of infection).
• Bacterial factors: resistance to the antibiotic.

Safety of the Antibiotic

• Aminoglycosides: nephrotoxicity, neurotoxicity, ototoxicity.
• Penicillins, beta-lactams, quinolones: neurotoxicity (seizures, confusion/encephalopathy).
• Quinolones: arrhythmia, tendon rupture (especially when combined with corticosteroids).

Safety of the Antibiotic (cont.)

• Linezolid: myelosuppression, serotonin syndrome. Note: Linezolid is a monoamine oxidase inhibitor.
• Isoniazide: seizures, hepatotoxicity.
• Rifampicin: hepatotoxicity, renal toxicity, hematological toxicity.

Antibiotic Spectrum

• Broad-spectrum antibiotics: kill Gram-positive and Gram-negative bacteria.
• Narrow-spectrum antibiotics: kill only Gram-positive or Gram-negative bacteria.

Antibiotic Spectrum (cont.)

• GLAM: Mnemonic to remember examples of narrow-spectrum antibiotics.
  • G: Glycopeptides (Gram-positive).
  • L: Lincosamides (Gram-positive).
  • A: Aminoglycosides (Gram-negative).
  • M: Macrolides (Gram-positive).

Antibiotic Spectrum (cont.)

• Glycopeptides (vancomycin, teicoplanin): hydrophilic and large, cannot pass through the outer membrane of Gram-negative bacteria.

Gram-Negative vs. Gram-Positive Bacteria

(Diagram showing structural differences)

Antibiotic Spectrum (cont.)

• Lincosamides (clindamycin, lincomycin): bacteriostatic; hydrophilic and large, cannot pass inside Gram-negative bacterial cells. Effective against anaerobes, used for dental and vaginal infections.

Antibiotic Spectrum (cont.)

• Macrolides (erythromycin, clarithromycin, azithromycin, roxithromycin): bacteriostatic; active against some Gram-negative bacteria but mainly effective against Gram-positive bacteria.

Antibiotic Spectrum (cont.)

• Aminoglycosides (gentamicin, amikacin, tobramycin, neomycin, streptomycin): active against Gram-negative bacteria. To kill Gram-positive bacteria, often combined with another cell-wall-acting drug (e.g., penicillin).

Bacteriostatic vs. Bactericidal

• For most infections, bacteriostatic and bactericidal antibiotics have similar effectiveness in inhibiting/killing organisms; difference is not a major factor in selection.
• Some antibiotics are cidal for certain bacteria but static for others (e.g., linezolid is static against Staphylococcus aureus but cidal against Streptococcus pneumoniae).
• Bactericidal antibiotics often preferred in severe infections (e.g., endocarditis, meningitis, febrile neutropenia).

Antibiotics Prescribing During Renal or Hepatic Insufficiency

• Renal impairment: Use alternative antibiotics that are hepatically eliminated. (List of specific antibiotics given).
• Hepatic impairment: Use alternative antibiotics that are renally eliminated. (List of specific antibiotics given).

Antibiotics Prescribing During Renal or Hepatic Insufficiency (cont.)

• Co-existing renal and hepatic insufficiency: if renal function is worse, use a hepatically cleared alternative and vice versa

Interesting Information (Examples)

• Certain antibiotics are eliminated by the kidney despite the main side effect not on the kidney.
• Example: Oxacillin (kidney elimination but hepatitis side effect).
• Example: Nafcillin (liver elimination but interstitial nephritis side effect).

Empiric vs. Definitive Antibiotic Therapy

• Empiric therapy: based on clinician's experience and knowledge of possible causative microorganisms.
• Definitive therapy: based on sample culture results.

Invitro Susceptibility Testing

• Sample culture results do not always predict effective treatment in vivo.
• Differences in antibiotic concentration in vitro vs. in vivo.
• Example of antibiotic that is effective in vitro but not in vivo due to the inability to reach target site.

Pharmacokinetics of the Antibiotic

• Bioavailability: Important factor with oral therapy.
• (list of examples of antibiotics with poor bioavailability given)
• Ability to penetrate tissues: Important factor in reaching the site of infection. (Examples)
• Antibiotic penetration limitations: include abscesses, foreign bodies, protected areas (e.g., cerebrospinal fluid), hypoperfusion.

Duration of Antibiotic Therapy

• Most bacterial infections: 1-2 weeks sufficient.
• Longer treatment durations may be necessary for certain conditions like immunocompromised patients, chronic infections.
• Avoid excessive antibiotic use to prevent bacterial resistance.

Mechanism of Action of Antibiotics

• Inhibition of metabolism: (e.g., folate synthesis).
• Inhibition of DNA replication/synthesis: (e.g., Fluoroquinolones).
• Inhibition of protein synthesis: (e.g., Macrolides, aminoglycosides, lincosamides, tetracyclines).
• Inhibition of cell wall synthesis: (e.g., penicillins, cephalosporins, carbapenems, glycopeptides)

Classification of Antimicrobial Agents (Diagram)

Test your knowledge on antibiotic therapy and the factors influencing their elimination from the body, particularly focusing on hepatic metabolism. This quiz covers key concepts such as empiric vs. definitive therapy, and the significance of identifying causative microorganisms involved in antibiotic treatment.