this is a presentation for undergraduate theory class

1. CLASSIFICATION OF ANTIMICROBIALS
and
PROBLEMS ARISING FROM ANTIMICROBIALS
Dr. Anupam Das

2. ANTI-MICROBIALS?
HOW CAN WE CLASSIFY
ANTIMICROBIAL AGENTS?

3.  Structure
Mechanism of Action
Type of organism it acts against
Spectrum of Activity
Type of Action
Sources

4. CHEMICAL STRUCTURE
• 1.SULFONAMIDES and related drugs
• 2.DIAMINOPYRIMIDINES
• 3.QUINOLONES
• 4.Beta- LACTAM ANTIBIOTICS
• 5.NITROBENZENE derivatives
• 6.MACROLIDES
• 7.AMINOGLYCOSIDES
• 8.LINCOSAMIDES

5. CHEMICAL STRUCTURE…
• 9.TETRACYCLINES
• 10.GLYCOPEPTIDES
• 11.OXAZOLIDINONE
• 12.POLYPEPTIDES
• 13.NITROFURAN derivatives
• 14.NITROIMIDAZOLES
• 15.NICOTINIC ACID derivatives
• 16.POLYENE antibiotics
• 17.AZOLE derivatives
• 18. Others

6. MECHANISM OF ACTION
• Drugs inhibiting cell wall synthesis.
DRUG STEP INHIBITED IN CELL WALL
SYNTHESIS
Firmly FOSFOMYCIN Enolpyruvate transferase
Bind to Beta-LACTAMS Transpeptidase
Bacterial BACITRACIN Dephosphorylation of bactoprenol
Cell CYCLOSERINE Alanine racemase, Alanine ligase
Wall VANCOMYCIN Transglycosylase

8. DRUGS INHIBITING
TRANSLATION(PROTEIN SYNTHESIS)

9. DRUG BINDS TO MOA
AMINOGLYCOSIDES 30S mainly FREEZING OF INITIATION
MISREADING OF mRNA code
TETRACYCLINES 30S Inhibit aminoacyl tRNA attachment
to A site.
CHLORAMPHENICOL 50S Inhibits peptidyl transferase that
results in the inhibition of peptide
bond formation and transfer of
peptide chain from P to A site.
MACROLIDES
LINCOSAMIDES
TETRACYCLINES
50S Inhibit translocation of peptide chain
from A to P site
LINEZOLID 50S Inhibit initiation

10. • Buy AT 30 and SELL at 50.
• AT : Aminoglycosides and Tetracyclines-
30S
• SELL:
Streptogramins,Erythromycin,Lincosamide
,Linezolid.-50S

11. DRUGS AFFECTING CELL
MEMBRANE
• These drugs act by causing disruption of cell
membrane and leakage of ions and molecules
from the cell. These drugs include:
• POLYPEPTIDE ANTIBIOTICS: Polymyxin B,
Colistin,
• POLYENE ANTIBIOTICS: Amphotericin B,
nystatin, Natamycin.
• AZOLES: Ketoconazole, fluconazole,
Itraconazole.

12. DRUGS AFFECTING NUCLEIC
ACIDS (DNA and RNA)
• DNA GYRASE INHIBITORS
• RNA POLYMERASE INHIBITORS
• DRUGS DESTROYING DNA
• NUCLEOTIDE/NUCLEOSIDE
ANALOUGES

13. DRUGS ACTING BY
INTERMEDIARY METABOLISM
• DRUGS INHIBITING FOLIC ACID
SYNTHESIS
• Dihydrofolate reductase inhibitors
• Arabinogalactan synthesis inhibitors

14. TYPES OF ORGANISMS
AGAINST WHICH PRIMARILY
ACTIVE
• ANTIBACTERIAL
• ANTIFUNGAL
• ANTIVIRAL
• ANTIPROTOZOAL
• ANTIHELMINTIC

15. SPECTRUM OF ACTIVITY
• NARROW SPECTRUM:
Penicillin G, Streptomycin, Erythromycin
• BROAD SPECTRUM:
Tetracyclines, Chloramphenicol

16. TYPES OF ACTION
• BACTERIOSTATIC:
Sulfonamides, Erythromycin,
Tetracyclines,
Linezolid, Ethambutol.
• BACTERICIDAL:
Penicillins, Aminoglycosides,
Cephalosporins, Vancomycin, Isoniazid,
Ciprofloxacin

17. SOURCES
• Fungi: Penicillin, Cephalosporin,
Griseofulvin
• Bacteria: Polymyxin B, Colistin, Bacitracin
• Actinomycetes: Polyenes,
Chloramphenicol, Aminoglycosides,
Macrolides

18. PROBLEMS FROM AMAs.
TOXICITY : Local / Systemic.
HYPERSENSITIVITY REACTIONS.
DRUG RESISTANCE
SUPERINFECTION
NUTRITIONAL DEFICIENCIES
MASKING OF AN INFECTION

19. DRUG RESISTANCE
• Refers to unresponsiveness of a
microorganism to an AMA, similar to the
phenomenon of tolerance seen in higher
organisms.
NATURAL
AQUIRED

20. NATURAL RESISTANCE
Lack of metabolic process or target site
which is affected by the particular drug.
This is characteristic of the group or
species.
 Gm-ve bacilli unaffected by penicillin G.
Aerobic organisms unaffected by
metronidazole.

21. ACQUIRED RESISTANCE
Development of resistance due to the use
of an AMA over a period of time.
 This is a major clinical problem.
Rapid acquisition of resistance:
Staphylococci,Tubercle Bacilli, Coliforms.
This type of resistance develops either by:
MUTATION
GENE TRANSFER

22. MUTATION
 aka : VERTICAL RESISTANCE.
Relatively slow and of low grade.

23. MUTATION

24. MUTATION
.

25. GENE TRANSFER
• The resistance causing gene is passed from
one organism to the other.
• aka HORIZONTAL TRANSFER.
• Rapid and can cause multidrug resistance.
• Occurs via:
# CONJUGATION
# TRANSDUCTION
#TRANSFORMATION

26. THREE TYPES OF
RESISTANT ORGANISMS
 DRUG TOLERANT : loss of affinity of the
target biomolecule of the microorganism
for a particular AMA.
DRUG DESTROYING: The resistant
microbe elaborates an enzyme which
inactivates the drug.
DRUG IMPERMEABLE: Loss of certain
specific channels / porins via which AMA
enters into the microorganism.

27. CROSS RESISTANCE
• Aquistion of resistance to one AMA
conferring resistance to another AMA, to
which the organism has not been
exposed.
• Usually occurs between chemically related
drugs.

28. How do we prevent resistance?
Avoid unnecessary use and prolongation
of AMAs.
Prefer rapidly acting and selective (narrow
spectrum ) drugs whenever possible.
Use combined therapy whenever there is
need of prolonged therapy. Eg. TB, SABE.
Intensive treatment of infections which
develop resistance rapidly.

29. SUPERINFECTION
• Refers to the appearance of a new
infection as a result of AMA therapy.
• Mainly due to supression of normal flora of
the body.
• Frequently involved organisms:
 Candida Albicans
Resistant staphylococci
Clostridium difficle
Proteus
Pseudomonas

30. Conditions predisposing to
superinfection…
 Corticosteroid therapy.
 Leukemias and other malignancies.
AIDS.
Agranulocytosis.
Diabetes.
Disseminated lupus erythomatosus(DLE)

31. Choosing an AMA
• PATIENT FACTORS
• ORGANISM RELATED CONSIDERATIONS
• DRUG FACTORS

32. PATIENT FACTORS
Age
Renal and Hepatic function
Local factors like the presence of pus
decreases efficacy;the presence of
necrotic matter or foreign body decreases
penetration of drug.
Drug allergy
Pregnancy
Genetic factors

33. Organism related factors
 Clinical diagnosis itself directs choice of
AMA.
Choice based on bacteriological
examinations

34. Drug factors
Spectrum of activity.
Type of activity.
Sensitivity to organism.
Relative toxicity.
Pharmacokinetics of the drug.
Route of administration.
Cost.

35. Combined use of AMA
To achieve synergism
To reduce severity or incidence of adverse
effects.
To prevent emergence of resistance.
To broaden the spectrum of antimicrobial
action
 Treat mixed infection.
Initial treatment of severe infections.
Topical application.

36. PROPHYLACTIC USE OF
AMAs.
• Refers to the use of AMAs for preventing
the setting in of an infection, or supressing
contacted infection before it manifests
clinically.
• Difference b/w treating and preventing
infections?

37.  treatment is directed against a specific
organism infecting an individual.
Prophylaxis is against all organisms
capable of causing infection.
 Prophylaxis against specific organisms.
Prevention of infection in high risk
situations
Prevention of infection in general

38.  Rheumatic fever- penicillinG
 TB – given to children & HIV +ve : INH+Rmp
 MAC – in HIV+ve : azithro/clarithro.
 HIV – zidovudine+ lamivudine +/- indinavir
 Meningococcal Meningitis : Rmp/
Ceftriaxone/ Suphazidine.
 Malaria : travel prophylaxis : chloroquine
 Cholera : tetracycline.

39. • Influenza A : amantadine
• Plague : doxycycline

40. High risk situations
• Dental extraction, tonsillectomy : there is
ed risk of endocarditis – amoxy / clinda
• Catheterization / instrumentation of urinary
tract : cotrimox / norflox ; In patients with
valvular heart dz: ampi / genta.
• COPD/ Chr. Bronchitis : ampi / doxy/ cipro
• Immunocompromised : penicillin/ cephalo

41. Prevention in general
• Neonates
• Viral URTI : to prevent 2nd ry bacterial
infection.
• Prevent respiratory infections in patients
on ventilators.

42. Surgical prophylaxis
• Oral:
 Amoxy
Cephalexin
Cephadroxil
Clinda
Azithro
Clarithro

43. Surgical prophylaxis
• Parenteral :
 Ampicillin
Cefazolin
Vanco
Clinda

44. • DOC for MRSA : vancomycin
• DOC for VRSA : linezolid