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4  introduction to antimicrobials
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4 introduction to antimicrobials




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4  introduction to antimicrobials 4 introduction to antimicrobials Presentation Transcript

  • Introduction to Antimicrobials
  • Definitions CHEMOTHERAPY : • Treatment of infection/cancer with drugs that selectively kill the micro-organisms or cancer cells • Anti-microbials: Drugs/substances to kill micro-organisms (viruses, bacteria, fungi & protozoa, etc) • Antibiotics – Antimicrobials obtained from microorganisms, such as fungus, etc. – Bactericidal – kill the bacteria – (Beta lactam antibiotics, Cotrimoxazole, Aminoglycosides, etc.) – Bacteriostatic – prevent the multiplication of bacteria – (Macrolides, Tetracyclines, Sulfonamides, Trimethoprim, etc.) CHEMOPROPHYLAXIS: • Prevention of infection by chemicals/drugs
  • Mechanism of Action of Antibacterial drugs • Inhibition of bacterial cell wall synthesis: – Penicillins, Cephalosporins, Vancomycin, etc • Inhibition of cell membrane: – Polymixins, Amphotericin B & Nystatin • Inhibition of protein synthesis : – Tetracyclines, Aminoglycosides, Macrolides, • Inhibition of DNA synthesis : – Flouroquinolones, Rifampicin, Metronidazole • Anti-metabolites: – Sulphonamides (inhibit folic acid synthesis), – Trimethoprim (inhibits conversion of folic acid to folinic acid)
  • Mechanism of action (overview) 50S & 30S Inhibitors of cell wall synthesis Inhibitors of DNA & cell division Inhibitors of cell membrane synthesis Inhibitors of protein synthesis PABA Pteridine Folic acidFolinic acid Purines Pyrimidines DNA Ribosome mRNA
  • Resistance to Antibiotics Unresponsiveness of microorganisms to an antimicrobial agent Mechanisms of Resistance: • Inactivation of the drug by bacterial enzymes – beta-lactamases inactivate some Penicillins & Cephalosporins • ↓↓bacterial permeability to drug: Tetracyclines • ↑↑elimination of the drug from the cell: Fluoroquinolones • Change in ribosomal binding site: Erythromycin • Genetic methods - Mutation, Plasmid mediated, Cross resistance: Resistance to one drug usually leads to resistance against other drugs in the same group
  • Prophylactic Antibiotics Certain clinical situations require the use of antibiotics for the prevention of infections. • 1. Prevention of streptococcal infections in patients with a history of rheumatic heart disease. – Patients may require years of treatment • 2. Bacterial endocarditis following dental extractions • 3. Tuberculosis in close contacts of an infective TB patient • 4. Surgical procedures (bowel surgery, joint replacement & some gynecological operations) to prevent infections • 5. Neonatal HIV infection (Vertical transmission) Zidovudine to HIV infected pregnant mother • 6. Prevention of epidemics: Meningitis, Influenza, Cholera, Typhoid
  • Antimicrobial drug combinations • Broad-spectrum empiric therapy in seriously ill pts • To treat mixed (polymicrobials) infections – Intra-abdominal abscesses due to a combination of anaerobic & aerobic gram-negative organism, and enterococci) • To enhance (synergism) anti-microbial activity • To decrease the emergence of resistance
  • Antimicrobial drug combinations • Synergism: When the inhibitory or killing effects of two or more antimicrobials used together are greater than expected from their effects when used individually. • Penicillin or Ampicillin in combination with Gentamicin or Streptomycin is superior to monotherapy with penicillin – Enterococcal endocarditis – Febrile neutropenic patients – Infections caused by Pseudomonas aeruginosa Trimethoprim-sulfamethoxazole –treatment of bacterial infections and Pneumocystis jiroveci (carinii) infection Beta lactamase inhibitors – prevent the hydrolysis of Beta lactams by inhibiting beta lactamases produced by the bacteria
  • Antimicrobial drug combinations • Mechanisms of synergism a. Inhibition of enzymatic inactivation Beta-lactam antibiotics (penicillins & ceophalosporins) combined with beta-lactamase inhibitors (clavulanic acid) b. Increased uptake: Penicillins increase uptake of aminoglycosides c. Blockade of sequential steps in metabolic pathway Sulphonamides folic acid synth. & Trimethoprim conversion of folic acid to folinic acid Mechanisms of antagonism a. Inhibition of -cidal activity by -static agents Tetracyclines decrease action of penicillins & cephalosporins b. Enzyme induction: Imipenem & ampicillin formation of beta- lactamase by some bacteria, will action of effective antibiotics
  • SULFONAMIDES • Bacteriostatic • Folate antagonists Mechanism of Action : Inhibition of bacterial folic acid synthesis • Sulfonamides inhibit the enzyme Dihdropteroate synthetase which is responsible for the incorporation of PABA into the precursor of folic acid. – PABA - essential metabolite of bacterial cells required for the synthesis of folic acid.
  • Uses: • Sulfacetamide: Bacterial conjunctivitis • Sulmethoxazole: Urinary tract infection • Sulfadiazine + Pyrimethamine: Acute toxoplamosis • Sulfadoxin + Pyrimethamine (FANSIDAR) – Chloroquine resistant Malaria. Sulmethoxazole + Trimethoprim (COTRIMOXAZOLE) SULFONAMIDES
  • SULFONAMIDES Adv effects: • Crystalluria • Allergy, Skin rash, Stevens-Johnson Syndrome- skin & mm eruptions • Kernicterus ( Displace bilirubin from serum albumin, the free bilirubin can cross the immature blood brain barrier in new born babies ). • Hemolytic anaemia in G6PD deficiency • Megaloblastic anemia Contraindications: • Pregnancy at term, • New born & infants < 2 months of age. • Hypersensitivity
  • COTRIMOXAZOLE • Trimethoprim/Sulmethoxazole ratio (1:5) • Synergistic action Mech of action : Sequential blockade in the synthesis of Folic acid. Sulfamethoxazole inhibits the incorporation of PABA into dihydrofolic acid precursors, and trimethoprim prevents reduction of dihydrofolate to tetrahydrofolate. – Tetrahydrofolate is required for purine, pyrimidine, & amino acid synthesis. Adv effects: Skin rash, Megaloblastic anaemia, Hemolytic anemia in patients with G6PD deficiency Uses: Lower UTI, Chronic bronchitis, Pneumocystis carinii pneumonia, Shigellosis, Salmonellosis,