Antimicrobial agents

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

15.

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

32.

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.