1. PRINCIPLES OF ANTIBIOTIC THERAPY
DR FATAI OLUYADI
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2. OVERVIEW
Antimicrobial medications are drugs used in the treatment of microbial infections
ANTIBACTERIAL
ANTIFUNGAL
ANTI-PROTOZOAL
ANTIVIRUSES
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3. SELECTION OF ANTIMICROBIAL AGENTS
Identification of the infecting organism
Empiric therapy prior to identification of the organism
Determining antimicrobial susceptibility of infective organism – Minimum Inhibitory concentration
Effect of the site of infecton on therapy e.g Lipid solubility
Patient factors – Immune system (Higher dose and longer course recommended), Renal Dysfunction (Aminoglycoside toxicity), Hepatic dysfunction, Poor perfusion, Age (Gray baby syndrome, Neonatal Jaundice, Bone toxicity), Pregnancy, lactation.
Safety of the agent, Cost of therapy
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4. ROUTE OF ADMINISTERATION
Oral – For most infections
Parenteral – for drugs that are poorly absorbed in the GI(Vancomycin, Aminoglycosides, Amphotericin B), and for treatment of Serious/Systemic infections(Amphotericin B, Vancomycin).
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5. CHEMOTHERAPEUTIC SPECTRA
Narrow Spectrum Antibiotics -
Extended Spectrum Antibiotics
Broad Spectrum Antibiotics
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6. COMBINATION OF ANTIMICROBIALS
Advantage of combination
Synergistic: Synergism between B-Lactams and Aminoglycoside. Cell wall inhibiton by B-lactams to allow easy penetration of Aminoglycosides. Aminoglycosides, normally inactive against gram- positive organisms but combined penicillin or cephalosporin. (1+1=3)
Additive: Ciprofloxacin and metronidazole are usually combined to treat aerobic and anaerobic gut flora (1+1=2)
Disadvantage of combination – Antagonistic: Tetracyclines and penicillin cannot be administered concurrently because tetracyclines decrease the synthesis of penicillin-binding proteins. Combination of bactericidal and bacteriostatic drugs are not very effective (1+1=0)
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8. DRUG RESISTANCE
Genetic alterations – Spontaneous mutation(Rifampin resistant mycobacterium tuberculosi, DNA transfer of drug resistance usually Plasmid mediated
Altered expression of proteins in drug resistant organisms (Staph aureus and strep pneumonia alteration of penicillin binding proteins)
Modification of target sites
Decreased accumulation (presence of Efflux pump) (Porin channels alteration in pseudomonas auruginosa)
Enzymatic inactivation – Presence of B-lactamase enzyme causes resistance to B-lactam Drugs
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9. ADVERSE EFFECTS OF ANTIMICROBIALS
Hypersensitivity – Penicillin induced allergic reaction, Sulfonamides (Steven Johnson syndrome)
Direct toxicity – Aminoglycoside induced Ototoxicity
Superinfection – Pseudomembranous colitis due to Broad Spectrum Antibiotics
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10. ANTIBACTERIAL PRINCIPLES
Antibacterial drugs either kill bacteria directly (Bactericidal) or prevent the proliferation of the bacteria (Bacteriostatic)
Bactericidal antibiotics disrupt cellular structures compromising cellular integrity ultimately leading to bacterial cell death
Bacteriostatic antibiotics inhibits various Molecular biology processes involved in proliferation of the bacteria
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11. ANTIBACTERIAL DRUG CLASSES
CELL WALL INHIBITORS
PROTEIN SYNTHESIS INHIBITORS
NUCLEIC ACID SYNTHESIS INHIBITORS
ANTIMYCOBACETERIAL DRUGS
MISCELLANOUS
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13. A. Amoxicillin and Ampicillin B. Nafcillin and Methicillin
Which of the following is an example of a clinically relevant synergism between Antibiotics?
A. Amoxicillin and Ampicillin
B. Nafcillin and Methicillin
C. Ampicillin and Gentamicin
D. Tetracycline and Doxycycline
E. Piperacillin and Carbenicillin
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14. When choosing antibiotics for infectious diseases, many factors are considered. The patient’s immune system competence, safety of drug and cost of drug are some of the factors considered. The mechanism of antimicrobial effects are also considered for example whether they are bactericidal or bacteriostatic. Which of the following best describes bactericidal activity of antibacterial agents?
A. Prevention of bacterial proliferation B. Direct damage to cellular structures leading to cell death C. Inhibition of Bacterial penetration of human tissue D. Prevention of bacterial release of toxins E. Prevention of bacterial DNA synthesis
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