Antibiotics Lecture Notes

Introduction

• Topic: Antibiotics
• Recommendation: Download illustrations from website for effective learning
• Study Tip: Regularly review and try to recall the information independently

Mechanism of Action of Antibiotics

• Antibiotics target different bacterial structures and processes:
  • Cell wall synthesis inhibitors:
    • Peptidoglycan synthesis: Vancomycin, Phosphomycin
    • Cross-linking inhibition: Penicillins, Cephalosporins, Carbapenems, Monobactams
  • Cell membrane alteration: Daptomycin, Polymixins
  • **Protein synthesis inhibitors: **
    • 50s subunit: Macrolides, Clindamycin, Chloramphenicol, Linezolid
    • 30s subunit: Aminoglycosides, Tetracyclines
  • DNA/RNA synthesis inhibitors:
    • Folic Acid Pathway: Trimethoprim, Sulfamethoxazole
    • DNA integrity: Metronidazole, Nitrofurantoin
    • Other mechanisms: Rifampin (RNA polymerase)
  • Topoisomerase/DNA gyrase inhibitors: Fluoroquinolones
• Bactericidal vs. Bacteriostatic:
  • Bactericidal agents: Kill bacteria (e.g., Cell wall/membrane disruptors)
  • Bacteriostatic agents: Inhibit bacterial growth (e.g., Protein synthesis inhibitors)
• Beta-lactamase inhibitors: Clavulanate, Sulbactam, Tazobactam, Avibactam

Bacterial Coverage

• Gram-Positive Bacteria:
  • MSSA: Anti-staphylococcal penicillins, 1st Gen Cephalosporins, Fluoroquinolones
  • MRSA: 5th Gen Cephalosporin (Ceftaroline), Vancomycin, TMP-SMX, Clindamycin, Linezolid, Daptomycin
• Gram-Negative Bacteria:
  • HENs, PEK: Aminopenicillins, Anti-Pseudomonal penicillins, Cephalosporins (2nd-4th Gen), Carbapenems, Monobactams, Fluoroquinolones, Aminoglycosides
  • Pseudomonas & Acinetobacter: Piperacillin-Tazobactam, Ceftazidime, Cefepime, Carbapenems, Monobactams
  • ESBLs: Carbapenems, Aminoglycosides, Polymyxins, Ceftazidime-Avibactam
• Anaerobes:
  • Above Diaphragm: Clindamycin
  • Below Diaphragm: Metronidazole
  • Both: Carbapenems, Piperacillin-Tazobactam
• Atypicals:
  • Pathogens: Mycoplasma, Chlamydia, Legionella
  • Treatment: Fluoroquinolones, Macrolides, Doxycycline

Empiric Antibiotic Therapy for Common Infections

• Community-Acquired Pneumonia (CAP):
  • Mono: Fluoroquinolones
  • Combo: Beta-lactam (Ceftriaxone) + Macrolide/Doxycycline
• Hospital-Acquired Pneumonia (HAP):
  • MRSA: Vancomycin, Linezolid
  • Pseudomonas: Piperacillin-Tazobactam, Cefepime, Ceftazidime, Aminoglycosides
• Gastrointestinal Infections:
  • Gram-negative + Anaerobes: Carbapenems, Piperacillin-Tazobactam
  • Combo: Metronidazole + Fluoroquinolone/Ceftriaxone/Cefepime
• Skin and Soft Tissue Infections:
  • MSSA: Dicloxacillin, Cephalexin
  • MRSA (PO): TMP-SMX/Bactrim, Doxycycline, Clindamycin
  • MRSA (IV): Vancomycin, Linezolid
• Urinary Tract Infections (UTIs):
  • Pyelonephritis: Ceftriaxone, Fluoroquinolones
  • Acute Cystitis: TMP-SMX, Nitrofurantoin, Fosfomycin
  • Complicated UTIs: Piperacillin-Tazobactam, Cefepime, Vancomycin
• Bone & Joint Infections:
  • MRSA: Vancomycin
  • N. gonorrhoeae: Ceftriaxone
  • Pseudomonas: Cefepime, Ceftazidime
• Central Nervous System Infections (Meningitis):
  • Community-Acquired: Vancomycin + Ceftriaxone +/- Ampicillin
  • Hospital-Acquired (post-neurosurgery): Vancomycin + Cefepime
• Bloodstream Infections (Sepsis):
  • Empiric: Vancomycin + Piperacillin-Tazobactam/Carbapenem

Adverse Effects and Contraindications

• Neurotoxicity: Penicillins, Cephalosporins, Carbapenems, Polymyxins, Linezolid
• Pancytopenia: Penicillins, Cephalosporins, Bactrim, Chloramphenicol, Linezolid
• Respiratory Failure: Polymyxins, Nitrofurantoin (pulmonary fibrosis)
• Nephrotoxicity and Ototoxicity: Aminoglycosides, Vancomycin
• Myasthenia Gravis: Fluoroquinolones, Aminoglycosides, Macrolides, Clindamycin
• QT Prolongation: Fluoroquinolones, Macrolides
• Teratogenicity: Bactrim, Fluoroquinolones, Tetracyclines (Doxycycline)
• Disulfiram Reaction: Metronidazole, Ceftriaxone
• CYP450 Inhibitors: Fluoroquinolones, Macrolides, Bactrim
• Hemolytic Anemia: Penicillins, Cephalosporins (Coombs+), Bactrim, Nitrofurantoin (G6PDH), Fluoroquinolones
• Phototoxicity: Doxycycline, Bactrim

Specific Drug Adverse Effects

• Penicillins: Anaphylactic shock
• Cephalosporins: Vitamin K deficiency, biliary sludge (especially Ceftriaxone)
• Vancomycin: Phlebitis, Red Man Syndrome, DRESS
• Daptomycin: Rhabdomyolysis
• Doxycycline: Pill-induced esophagitis, teeth discoloration
• Macrolides: Motility dysfunction, Arrhythmias, Cholestasis, Rash, Eosinophilia (MACRO mnemonic)
• Clindamycin: C. difficile risk
• Linezolid: Lactic acidosis
• Fluoroquinolones: Hyper/hypoglycemia, Arthropathy (children), Tendon rupture
• Bactrim: Hyperkalemia

Antibiotic Resistance Mechanisms

• Reduced Permeability: Vancomycin, Aminoglycosides, Tetracyclines, Beta-lactams
• Efflux Pumps: Fluoroquinolones, Aminoglycosides, Tetracyclines, Macrolides
• Altered Target Sites: Fluoroquinolones, Aminoglycosides, Tetracyclines, Beta-lactams, Macrolides, Linezolid, TMP-SMX
• Enzymatic Inactivation: Beta-lactams, Aminoglycosides, Macrolides

Transmission of Antibiotic Resistance

• Horizontal Gene Transfer:
  • Transformation
  • Conjugation
  • Transduction
• Vertical Gene Transfer:
  • Binary Fission

Antibiotic Susceptibility Testing

• Methods: Broth microdilution/macro dilution, Kirby-Bauer method
• Measurement: Minimum Inhibitory Concentration (MIC)
• Judgment: Susceptible, Intermediate, Resistant

Case Studies

• Detailed case studies with diagnosis, pathogen identification, appropriate antibiotic choices, and considerations of adverse effects and resistance mechanisms.