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ANTIBACTERIAL CHEMOTHERAPY

ANTIBACTERIAL CHEMOTHERAPY. The most important concept underlying antimicrobial therapy is selective toxicity Broad-spectrum antibiotics : active against several types of microorganisms Tetracyclines are active against Gram-negative rods, Chlamydiae, Mycoplasmas, Rickettsiae

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ANTIBACTERIAL CHEMOTHERAPY

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  1. ANTIBACTERIAL CHEMOTHERAPY The most important concept underlying antimicrobial therapy is selective toxicity Broad-spectrum antibiotics: active against several types of microorganisms Tetracyclines are active against Gram-negative rods, Chlamydiae, Mycoplasmas, Rickettsiae Narrow-spectrum antibiotics: active against one or very few types of microorganisms Vancomycin is active against Staphylococci & Enterococci

  2. ANTIBACTERIAL CHEMOTHERAPY Bactericidal drugs kill bacteria: e.g. Penicillin Use indicated in: Life-threatening infections Endocarditis PMN < 500/microliter Bacteriostatic drugs inhibit bacterial growth Immune response is necessary to kill the bacteria

  3. MECHANISMS AND SITES OF ANTIBIOTIC ACTIVITY Ampicillin Penicillin Gentamicin Streptomycin

  4. ANTIBACTERIAL CHEMOTHERAPY Antibiotic susceptibility testing

  5. ANTIBACTERIAL CHEMOTHERAPY MIC (Minimum Inhibitory Concentration) MBC (Minimum Bactericidal Concentration)

  6. INHIBITORS OF CELL WALL SYNTHESIS

  7. INHIBITORS OF CELL WALL SYNTHESIS The peptides in adjacent glycan chains are cross- linked to each other by membrane bound transpeptidases. Transpeptidases are also penicillin-binding proteins. Penicillins bind to a variety of penicillin-binding proteins.

  8. The beta-lactam family Common ring structure must be intact Bactericidal to growing cells Murein hydrolases (autolytic enzymes) are activated Inactivated by beta-lactamases

  9. INHIBITORS OF CELL WALL SYNTHESIS

  10. INHIBITORS OF CELL WALL SYNTHESIS Clavulanic acid inhibits beta-lactamase

  11. INHIBITORS OF CELL WALL SYNTHESIS Augmentin

  12. Made by the Actinomycete Streptomyces Effective against G+ cocci G- cocci (Neisseria) G- rods ( Pseudomonas, Haemophilus) Effective against Enterobacteriaceae & Pseudomonas

  13. INHIBITORS OF CELL WALL SYNTHESIS Vancomycin Binds to the D-alanyl-D-alanine portion of the peptidoglycan pentapeptide, and blocks transpeptidase from binding

  14. INHIBITORS OF PROTEIN SYNTHESIS

  15. Prototype structure of aminoglycosides Resistant bacteria can phosphorylate, adenylate or acetylate the antibiotic Used against Gram-negative infections (P. aeruginosa) Nephrotoxicity, ototoxicity Poorly absorbed orally Ineffective vs anaerobes

  16. INHIBITORS OF PROTEIN SYNTHESIS

  17. INHIBITORS OF PROTEIN SYNTHESIS Tetracyclines Broad spectrum Block aminoacyl-tRNA from entering acceptor site on the 30S ribosome Their selectivity for bacteria is based on greatly increased uptake in susceptible bacterial cells

  18. INHIBITORS OF PROTEIN SYNTHESIS Tetracyclines Resistance is common Used against Mycoplasmas Chlamydiae Rickettsiae Periodontal bacteria Side effects: Suppression of normal flora of GI tract Deposition in teeth due to calcium chelation

  19. INHIBITORS OF PROTEIN SYNTHESIS

  20. INHIBITORS OF PROTEIN SYNTHESIS Macrolides Large ring structure Bind to the 50S subunit Blocks the release of the uncharged tRNA after the peptide bond has formed Bacteriostatic 2 sugars

  21. INHIBITORS OF PROTEIN SYNTHESIS Macrolides Bacteriostatic Used against pneumonia caused by Legionella and Mycoplasma And against G+ cocci in penicillin-allergic patients

  22. INHIBITORS OF PROTEIN SYNTHESIS

  23. INHIBITORS OF PROTEIN SYNTHESIS Clindamycin is used against anaerobic G+ bacteria (Clostridium perfringens) anaerobic G- bacteria (Bacteroides fragilis) Oral or iv Oral administration can cause pseudomembranous colitis due to overgrowth of a drug-resistant strain of Clostridium difficile

  24. INHIBITORS OF PROTEIN SYNTHESIS Novel antibiotics Linezolid (Zyvox) Used in treatment of vancomycin-resistant Enterococcus faecalis (skin and blood infections, and pneumonia) Administered orally Synercid Vs. vancomycin-resistant Enterococcus faecium Administered iv

  25. ANTIBACTERIAL CHEMOTHERAPY

  26. ANTIBACTERIAL CHEMOTHERAPY Sulfonamides

  27. ANTIBACTERIAL CHEMOTHERAPY Trimethoprim Resembles folic acid Inhibits dihydrofolate reductase

  28. Prevalence of penicillin-nonsusceptible S. pneumoniae vs total antibiotic use in the outpatient setting Albrich et al. 2004 Emerging Infectious Diseases 10, 514

  29. Important bacteria that exhibit significant drug resistance Type of bacteria Resistance to Gram-positive cocci Staphylococcus aureus Penicillin G, nafcillin Streptococcus pneumoniae Penicillin G Enterococcus faecalis Penicillin G, aminoglycosides, vancomycin Gram-negative cocci Neisseria gonorrhoeae Penicillin G

  30. Important bacteria that exhibit significant drug resistance Type of bacteria Resistance to Gram-negative rods Haemophilus influenzae Ampicillin Pseudomonas aeruginosa ß-lactams, aminoglycosides Enterobacteriaceae ß-lactams, aminoglycosides E. coli Klebsiella pneumoniae Mycobacteria M. tuberculosis isoniazid, rifampin M. avium complex isoniazid, rifampin and others

  31. A new antibiotic Which molecular class does it belong to? How does it work?

  32. Tygacil (Tigecycline) A glycylcycline antibiotic Administered IV Use during tooth development may cause discoloration Binds to the ribosome with 5 times higher affinity than tetracycline Against Gram-positive pathogens including MRSA, MRSE and VRE

  33. Indicated for the treatment of complicated intra-abdominal infections (cIAI) and complicated skin and skin structure infections (cSSSI) in adults MRSA Methicillin-resistant Staphylococcus aureus MRSE Methicillin-resistant Staphylococcus epidermidis VRE vancomycin-resistant enterococci (Enterococcus faecalis & Enterococcus faecium)

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