Pharmaceutical Microbiology - Antibiotic Chemotherapy III

  • Field of Pharmacy Pharm D Program Lecture: Focus on Antibiotic Chemotherapy III

    • Date: March 18, 2024

    • Lecturer: Dr. Amro Hanora

  • Learning Objectives:

    • Familiarity with the following classes of antibiotics and their uses:

      • Aminoglycosides

      • Tetracyclines

      • Chloramphenicol

      • Macrolides

      • Antifungals

      • Anti-tubercular agents

      • Antivirals

  • Fusidic Acid:

    • Source: Derived from the fungus Fusidium coccineum

    • Structure: Steroid-like structure

    • Administration: Oral

    • Target: Effective against Staphylococcus aureus, including β-lactamase producers

    • Resistance: Reduced effectiveness if used in combination with cloxacillin or flucloxacillin

  • Macrolides:

    • Mechanism: Binds to the 50S subunit of the prokaryotic ribosome

    • Members:

      • Erythromycin

      • Oleandomycin

      • Spiramycin

      • Clarithromycin

      • Azithromycin

    • Source: Streptomyces erythreus

    • Administration: Oral (as estolate or stearate)

    • Applications:

      • Low toxicity makes it suitable for pediatric use

      • Recommended for prophylaxis in whooping cough

      • Choice drug for Campylobacter and Legionella infections

      • Erythromycin considered equivalent to Penicillin G for those allergic to penicillin

  • Lincosamines:

    • Members: Lincomycin, Clindamycin

    • Mechanism: Inhibits peptide bond formation by binding to the 50S ribosomal subunit

    • Characteristics:

      • Semi-synthetic variants enhance effectiveness and absorption

      • Effective against Gram-positive cocci, anaerobes, and Streptococcus pyogenes

      • Particularly penetrates bone, useful for osteomyelitis

  • Aminoglycosides:

    • Mechanism: Interferes with protein synthesis by altering the shape of the 30S ribosomal subunit, causing improper mRNA translation

    • Origin: Mostly derived from Streptomyces species

    • Characteristics:

      • Bactericidal against aerobic Gram-negative bacteria and Staphylococcus aureus

      • Ineffective against anaerobes and Gram-positive bacteria

      • Administered parentally, with risk of nephrotoxicity and ototoxicity (irreversible)

    • Members:

      • Streptomycin

      • Gentamycin

      • Kanamycin

      • Tobramycin

      • Amikacin

      • Neomycin

      • Spectinomycin

  • Rifamycins:

    • Type: Semi-synthetic derivatives of Rifamycin

    • Administration: Oral with good absorption

    • Properties: Bactericidal against Gram-positive bacteria, some Gram-negative, and T.B.

    • Use: Effective in tuberculous meningitis

    • Adverse Effects:

      • Jaundice

      • Gastrointestinal disturbances

  • Chloramphenicol:

    • Mechanism: Inhibits protein synthesis by interfering with peptide bond formation

    • Source: Streptomyces venezuelae (produced synthetically)

    • Characteristics:

      • Broad-spectrum, bacteriostatic

      • Penetrates the CNS, useful for meningitis and typhoid fever

      • Topical formulations also available

    • Adverse Effects: Fatal bone marrow suppression (aplastic anemia)

  • Tetracyclines:

    • Mechanism: Inhibits protein synthesis by binding to the 30S ribosomal subunit

    • Structure: Composed of a four-ring structure, either natural or synthetic

    • Spectrum: Broad-spectrum, with activity against Gram-positive and Gram-negative bacteria, Rickettsiae, Chlamydiae, etc.

    • Members:

      • Chlortetracycline

      • Oxytetracycline

      • Tetracycline

      • Doxycycline (new generation)

    • Adverse Effects:

      • Nausea, vomiting, diarrhea

      • Reduced absorption with certain foods and supplements

      • Risk of yellow staining of teeth in children and pregnant women

  • Polymyxins:

    • Mechanism: Disrupts cell membrane integrity

    • Origin: Derived from Bacillus species

    • Indications: Effective against Gram-negative bacteria like Pseudomonas aeruginosa

    • Administration: Can be used orally for localized effects or topically

    • Adverse Effects: Generally nephrotoxic

  • Sulfonamides:

    • Mechanism: Inhibit folic acid synthesis via PABA analogues

    • Classification: Grouped based on absorption and excretion characteristics

    • Rapidly absorbed and excreted members:

      • Sulfadiazine (for UTI)

      • Sulfaisoxazole (acid-stable)

    • Rapidly absorbed, slowly excreted: Sulfamethoxazole (often used in combination with trimethoprim)

    • Non-absorbed members: Used for bowel flora suppression preoperatively

  • Trimethoprim:

    • Mechanism: Blocks conversion of DHF to tetrahydrofolic acid

    • Combination with sulfamethoxazole is synergistic

  • Quinolones:

    • Mechanism: Inhibits DNA gyrase

    • Members: Nalidixic acid, Ciprofloxacin, Ofloxacin

    • Indications: Effective against Gram-positive, Gram-negative bacteria

    • Adverse Effects: Nausea, vomiting, rash, hypersensitivity

  • Nitrofurans:

    • Mechanism: Cause DNA strand breaks through chemical action

    • Members: Nitrofurazone (topical), Nitrofurantoin (for UTIs)

    • Nitroimidazoles: Metronidazole (antianaerobic)

  • Antifungal Agents:

    • Topical Treatments: Polyenes (e.g., Amphotericin, Nystatin) and Imidazoles (e.g., Clotrimazole, Miconazole)

    • Systemic Treatments: Amphotericin B and Ketoconazole

  • Anti-tuberculosis Drugs:

    • First-Line Drugs: Rifampicin, Isoniazid, Ethambutol

    • Second-Line Drugs: Streptomycin, Pyrazinamide

    • Management: At least two drugs in combination for treatment

  • Antiviral Agents:

    • Mechanism: Block viral entry, replication & release

    • Types: Anti-Herpes agents (Acyclovir, Ganciclovir)

    • Resistance: Occurs via mutation in thymidine kinase or DNA polymerase

  • Key Concepts Related to Viral Mechanisms:

    • Herpes viruses require their own thymidine kinase for growth

    • Activation of drugs occurs primarily in infected cells, enhancing selectivity

  • Antiviral Drug Activation:

    • Focus on improved selectivity for infected cells

    • Nucleotide analogs and their modifications increase efficiency against viral polymerases