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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
 Synthetic analogues
ANTIMICROBIAL AGENTS :
 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/Carbapene
ms
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. 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
 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.  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.  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.