1. ANTIMICROBIAL AGENTS

2. ANTIBIOTICS
ANTIMICROBIAL AGENTS
CHEMOTHERAPEUTIC AGENTS

3. ANTIBIOTICS
Natural substances produced by various species of microorganisms
bacteria
fungi
actinomycetes
suppress growth / kill other microorganisms

4. ANTIMICROBIAL AGENTS ANTIMICROBIAL AGENTS : Synthetic analogues
includes synthetic as well as naturally obtained drugs that attenuate microorganisms

5. CHEMOTHERAPEUTIC AGENTS
Drugs in this class differ from all others in that they are
Designed to inhibit/kill the infecting organism and have no/minimal effect on the recipient.

6. Classification
Of AMA’s

7. Microorganisms of medical impotance fall into four categories
Bacteria
Viruses
Fungi
Parasites

8. Anti-bacterial
Anti-viral
Anti-fungal
Anti-parasitic agents

9. Mechanism of Action
Agents that inhibit synthesis of bacterial cell walls
Penicillins & cephalosporins
Cycloserine,
Vancomycin
Bacitracin
Azole antifungal agents (clotrimazole, fluconazole, itraconazole)

10. Agents that act directly on the cell membranes of the microorganisms
Polymixin
Polyene antifungal agents
(Nystatin, Amphotericin B)
Alter cell memb. Permeability,
leakage of intracellular comp.

11. Agents that affect the function of 30S or 50S ribosomal subunits to cause a reversible inhibition of protein synthesis
Bacteriostatic drugs
Chloramphenicol, Tetracyclines, Erythromycin, Clindamycin, Pristinamycins

12. Agents that bind to 30S ribosomal subunit & alter protein synthesis, which eventually leads to cell death
Aminoglycosides

13. Agents that affect bacterial nucleic acid metabolism.
Rifamycins which inhibit RNA polymerase
Quinolones which inhibit topoisomerases

14. Anti-metabolites
including trimethoprim & sulphonamides
Antiviral agents
Nucleic acid analogues,
Non-nucleoside reverse transcriptase inhibitors,
Inhibitors of viral enzymes

16. TYPE OF ACTION
Bacteriostatic Agents
Bactericidal Agents

17. Bacteriostatic Agents
Sulphonamides
Tetracyclines
Chloramphenicol
Erythromycin
Ethambutol

18. Bactericidal Agents Penicillins/Cephalosporins/Carbapenems
Aminoglycosides
Rifampin
Isoniazid
Pyrazinamide

19. Cephalosporins Vancomycin Nalidixic acid Ciprofloxacin Metronidazole & Cotrimoxazole

20. Some primarily static drugs may become cidal at higher concentrations (as attained in the urinary tract) & vice-versa.

21. SPECTRUM Of ACTIVITY
Narrow spectrum
Broad spectrum

22. Narrow spectrum Penicillin G Streptomycin
SPECTRUM Of ACTIVITY
Narrow spectrum Penicillin G Streptomycin
Broad spectrum
Tetracyclines
Chloramphenicol

23. Successful Antimicrobial Therapy
Concentration: site of infection
Concentration should inhibit microorganisms
simultaneously it should be below the level toxic to human beings.
Host Defences
Immunity intact - Bacteriostatic Agents
Impaired immunity - Bactericidal Agents

24. Source of antibiotics
Fungi
Bacteria
Actinomycetes.

25. Source of antibiotics Fungi Bacteria Actinomycetes.
Penicillin, Griseofulvin, Cephalosporin
Bacteria
Polymyxin B, Colistin, Bacitracin, Aztreonam.
Actinomycetes.
Aminoglycosides, Macrolides, Tetracyclines, Polyenes, Chloramphenicol

26. Resistance

27. Bacterial resistance to ANTIMICROBIAL AGENTS
3 general categories
Drug does not reach its target
Drug is not active
Target is altered

28. Drug does not reach its target
Porins
Absence/mutation
Reduce drug entry
Reduced effective drug concentration at the target site.
Efflux pumps
Transport drugs out of the cell
Resistance to tetracyclines & β-lactam antib

29. Inactivation of Drug Second general mechanism of drug resistance
β-lactam antibiotics - β-lactamase
Aminoglycosides - Aminoglycoside modifying enzymes
Variant: failure of bacterial cell to convert an inactive drug to its active metabolite. Resistance to INH in mycobacterium TB

30. Alteration of the Target
Mutation of natural target
Target modification
The new target does not bind the drug for native target
Resulting in resistance to antibiotic.

31. Components mediating resistance to β –lactam antibiotics in psuedomonas aeruginosa

33. β –lactam antibiotics hydrophilic
Must cross outer membrane barrier of the cell via outer membrane protein (Omp) channel or porins
Mutation/missing/deleted
Drug entry slow or prevented.

34. β - lactamase concentrated between the inner & outer membrane in the periplasmic space
constitutes an enzymatic barrier
Drug destroyed
Effective concentration not achieved

35. Target: PBP penicillin binding protein
Low affinity for drug
Altered

36. RESISTANCE Efflux transporter Mex A, Mex B & Opr F
Pumps the antibiotic across the outer membrane
Reduced intracellular concentration of active drug
RESISTANCE

37. Mutations May occur in Target protein Drug transport protein
Protein important for drug activation
Random events
Survival advantage upon re-exposure to the drug

38. Transduction Transformation Conjugation
Resistance is acquired by horizontal transfer of resistance determinants from a donor cell, often of another bacterial species by
Transduction
Transformation
Conjugation

39. Insatiable need for new antibiotics

40. Emergence of antibiotic resistance in bacterial pathogens both nosocomially & in the community setting is a very serious development that threatens the end of antibiotic era.

41. Responsible approach to the use of antibiotics
That are now available & new agents that might be developed in future
Is essential
If the end of antibiotic era is to be averted.

42. CROSS RESISTANCE

43. CROSS RESISTANCE
Acquisition of resistance to one AMA conferring resistance to another antimicrobial agent to which the organism has not been exposed,is called cross resistance
Seen b/w chemically or mechanistically related drugs.

44. Resistance to one sulphonamide means resistance to all others
Resistance to one tetracyclines means insenstivity to all others
Complete cross resistance

45. Resistance to one aminoglycoside may not extend to others, Gentamycin resistant strains may respond to amikacin.
partial cross resistance

46. Sometimes unrelated drugs show partial cross resistance,
e.g. Tetracyclines
& Chloramphenicol

47. Prevention DRUG RESISTANCE

48. Prevention DRUG RESISTANCE
Use of AMAs should not be:
indiscriminate
inadequate
unduly prolonged
Use rapidly acting & narrow spectrum (Selective) AMA whenever possible.

49. Prevention DRUG RESISTANCE
Combination AMA
whenever prolonged therapy is undertaken. Tuberculosis, SABE
Infection by organism notorious for developing resistance Staph, E. Coli, M. Tuberculosis must be treated intensively.