Antibiotics and Antibacterial Therapy

1. Mode of Action

• Bacteriostatic antibiotics:
  Inhibit bacterial growth.
  Require a functioning immune system to clear the infection.
  Some may act bactericidal at higher doses or against specific bacteria.

  Examples:

  • Tetracyclines (e.g. doxycycline, minocycline)

  • Macrolides (e.g. erythromycin, azithromycin)

  • Sulphonamides (e.g. sulphadimidine)

  • Chloramphenicol

• Bactericidal antibiotics:
  Kill bacteria directly.
  Preferred in severe infections and immunocompromised patients.
  Do not depend on immune system action.

  Examples:

  • Penicillins (e.g. amoxicillin, benzylpenicillin)

  • Cephalosporins (e.g. cephalexin, ceftriaxone)

  • Aminoglycosides (e.g. gentamycin, amikacin)

  • Quinolones (e.g. ciprofloxacin, levofloxacin)

2. Antibiotic Resistance

• Definition: Reduced effectiveness of antibiotics against certain bacteria.

• Types:

  • Natural resistance: Exists without prior antibiotic exposure.
    ▸ Examples:

    • Streptococcus pneumoniae is naturally resistant to ciprofloxacin

    • Pseudomonas aeruginosa is resistant to penicillin G

  • Acquired resistance: Develops after exposure to antibiotics that were previously effective.
    ▸ Examples:

    • N. gonorrhoeae became resistant to ciprofloxacin

    • Staphylococcus aureus became resistant to penicillin G

• Mechanisms of resistance:

  • Enzyme production that destroys antibiotic structure

  • Altered cell wall or membrane permeability

  • Modified target sites for antibiotics

  • Development of alternative metabolic pathways

• Prevention:

  • Avoid unnecessary antibiotic use

  • Use full, appropriate dosages

  • Avoid prolonged topical antibiotic use

  • Prefer narrow-spectrum antibiotics

  • Use combination therapy or alternate regimens when necessary

3. Indications for Antibiotic Use

• Definitive Therapy:

  • Based on culture and sensitivity testing

  • Pathogen is known

  • Narrow-spectrum antibiotics preferred

• Empirical Therapy:

  • Based on best clinical judgment (before lab results)

  • Broad-spectrum or combination therapy used

  • Common in resource-limited settings (e.g. Uganda)

• Surgical Prophylaxis:

  • Given before surgery to prevent infection

  • Single effective dose preferred

  • Common antibiotics: cefazolin, ceftriaxone, clindamycin

4. Antibiotic Combinations

• Definition: Use of two or more antibiotics simultaneously

• Uses:

  • Prevent resistance (e.g., in TB)

  • Treat mixed infections (e.g., PID, sepsis)

  • Lower toxicity by reducing doses

  • Enhance effectiveness (e.g., gentamycin + benzylpenicillin for sepsis)

• Disadvantages:

  • Increased risk of side effects

  • Higher chance of superinfections (e.g., candidiasis)

  • Increased cost

  • Risk of drug antagonism

5. Factors to Consider in Antibiotic Selection

• Spectrum of activity: Ensure coverage of suspected pathogens

• Tissue penetration: Ability to reach infection site
  ▸ Considerations:

  • Blood supply (e.g., diabetic foot)

  • Abscesses (may require drainage)

  • Chronic infections (e.g., prostatitis)

• Antibiotic resistance: Use local resistance patterns when possible
  ▸ Example: 96% resistance of N. gonorrhoeae to ciprofloxacin

• Safety profile: Prefer drugs with mild side effects

• Patient factors:

  • Pregnancy, age, allergies

  • Some antibiotics are contraindicated during pregnancy, breastfeeding, or childhood

• Organ function:

  • Check liver and kidney status

  • Adjust dose or avoid certain drugs in renal or hepatic impairment

• Cost:

  • Select cost-effective options to improve access

• Compliance:

  • Recommend antibiotics with fewer daily doses if adherence is a concern

• Route of administration:

  • Injectables for severe infections

  • Oral switch after ~72 hours if clinical improvement occurs

  • Oral route preferred for mild/moderate infections

6. Causes of Antibiotic Failure

• Resistance

• Incorrect diagnosis

• Wrong dose or duration

• Poor tissue penetration (e.g., due to pus)

• Substandard antibiotics

• Non-compliance

• Incomplete pathogen coverage

• Drug interactions

7. Common Antibiotic Classes

• Penicillins

• Cephalosporins

• Macrolides

• Quinolones

• Tetracyclines

• Aminoglycosides

• Sulphonamides