Pharmacology Lecture Slides on Antimicrobials intro by Sanjaya Mani Dixit Assistant Professor of Pharmacology at Kathmandu Medical College

1. Introduction to
Antimicrobials
Sanjaya Mani Dixit
Assistant Prof of Pharmacology

2. Contents
• Introduction and history
• Terminologies
• Bacteriostatic Vs Bactericidal
• Emperical, Directed and Prophylactic use
• Narrow Vs Broad Spectrum of coverage
• General Principles of Antibiotics
1. Mechanisms of actions
2. Combination therapy
3. Resistance to antibiotics.

3. Antimicrobials
• Antimicrobials are the drugs that destroy
microbes, prevent their multiplication or
growth, or prevent their pathogenic action.
• They, however:
– Differ in physical, chemical, and pharmacological properties
– Differ in antibacterial spectrum of activity
– Differ in their mechanism of action

4. Classification of antimicrobial drugs
 Antibacterial drugs
 Antiviral drugs
 Antifungal drugs

5. Terminologies
Chemotherapy
• The term chemotherapy refers to the treatment of systemic
infections with specific drugs that selectively suppress the
infecting microorganisms without significantly affecting the host.
• Also due to resemblance between the malignant cancer cells
and microbes, the treatment of neoplastic diseases is included in
chemotherapy.
Chemotherapeutic agent
• The term chemotherapeutic agent was restricted to synthetic
compounds earlier but now many antibiotics and their
analogues have been synthesized and therefore both synthetic
and microbiologically produced drugs are included together.

6. Terminologies
Antimicrobial agents
• Antimicrobial agents are used to designate synthetic as well
as naturally obtained drugs that attenuate micro-organisms.
Antibiotics
• These are the substances produced by microbes, which
suppress the growth of or kill other microorganisms at very
low concentrations.
Antibacterial drugs
• These are the substances produced by synthetic manner
which suppress the growth of or kill other microorganisms at
very low concentrations.

7. Zone of Inhibition
• Around the fungal
colony is a clear zone
where no bacteria are
growing
• Zone of inhibition due
to the diffusion of a
substance with
antibiotic properties
from the fungus

8. BS Vs BC
Bacteriostatic drugs
• Inhibit the growth of microorganisms.
• Depend on natural host immune system to kill the remaining
bacteria.
• Chloramphenicol, Clindamycin, Tetracyclines
Bactericidal drugs
• Kill the microorganisms on their own and therefore do not
need any assistance from host immune system.
• B-lactams, Aminoglycosides, Rifampicin

11. How are antibiotics used?
• Empirical therapy
• Directed therapy
• Prophylactic use
Empirical therapy
• Empiric antibiotic therapy is antibiotic therapy commenced
before the identification of the causative micro-organism.
Typically, full identification and susceptibility testing of
bacteria from clinical specimens is not available for 48-72
hours after collection of the specimen from the patient.

12. Empirical therapy

13. Directed therapy
• Definitive therapy is defined as all antibiotic therapy
administered after receiving the final culture result.
• Antimicrobial therapy directed at specific organisms
should include the most effective, least toxic,
narrowest spectrum agent available. This practice
reduces the problems associated with broad-
spectrum therapy, viz. selection of resistant micro-
organisms and super-infection, and will usually be
the most cost-effective.

14. Prophylactic Use
• Use for prophylaxis or prevention
• Often before surgery, prophylactic use of
antibiotics is done
• Also before and following tooth extraction
prophylactic antibiotics are prescribed

15. Antimicrobial spectrum
Antimicrobial spectrum of a drug means the species
of microorganisms that the drug can inhibit or
kill.
Broad spectrum
Narrow spectrum
Using broad spectrum antibiotics interfere the
nature of the normal bacterial flora and can
precipitate a superinfection of microbes.

17. Antibiotic Spectrum (Broad Vs Narrow)
• Broad Spectrum antibiotic covers many potential pathogens
• Example: Carbapenem which has Gram positive, Gram
negative, and anaerobic coverage
• An antibiotic active against a single or limited group of
microbes, which has a more targeted spectrum of activity—
k/a Narrow spectrum antibiotic.
• Example: Clindamycin which only has Gram positive and
anaerobic coverage— no Gram negative coverage
• Isoniazid is active against Mycobacteria only.

18. Post Antibiotic Effect (PAE)
A period of time after complete removal of an antibiotic
during which there is no growth of the target organism.
The PAE appears to be a feature of most antimicrobial
agents and has been documented with a variety of common
bacterial pathogens.
Several factors influence the presence or duration of the PAE:
• type of organism,
• type of antimicrobial,
• concentration of antimicrobial,
• duration of antimicrobial exposure, and
• antimicrobial combinations.

19. Superinfection
A new or secondary infection that occurs during
an antimicrobial therapy of a primary
infection.
Clostridium difficile associated diarrhoea
• Superinfection by fungus

20. General Principles of Antibiotics
1. Mechanisms of actions of
different groups of antibiotics.
2. Combination therapy (use of
two or more drugs
concomitantly).
3. Mechanisms by which
pathogens acquire and express
resistance to antibiotics.

21. 1. Mechanisms of Axn of Antibiotics

22. 2. Combination Therapy
• Clinical interest in antimicrobial combination was triggered in the early
1950s. The high frequency of relapse in enterococcal endocarditis treated
with penicillin G alone was reduced by addition of streptomycin to the
treatment.
Effects of combination
• Synergism
• Antagonism
• Indifference

23. Synergistic Effect
• When two bactericidal antibiotics are used
in combination. One of the two drugs must
show at least 4-fold increase in
antibacterial activities (or a decrease in
MIC to ¼) for a synergism to exist
between the two drugs.
• (e.g. penicillin + streptomycin).

24. Antagonism
• Usually bacteriostatic antibiotics are
antagonistic to bactericidal agents.
• E.g. Chloramphenicol has been shown to
antagonize the bactericidal activities of
penicillin in the treatment of
Pneumococcal meningitis.

25. Justification for combination therapy
(1) Broad-spectrum coverage for the initial therapy of severely
infected patients;
(2) Poly-microbial infections;
(3) Prevention of selection of resistant microorganisms when a
high mutation rate of the causal organism exists to the
antibiotic indicated;
(4) Reduction of dose-related toxicity – (Rare now- Sulfonamide
drugs)
(5) Antimicrobial synergistic activity.

26. Pathogens Notorious for Resistance

27. Rise of Staph aureus as Superbugs
VISA-
Vancomycin
Intermediate
SA
CA-MRSA-
Community
Acquired
MRSA
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2871281/

28. Mechanisms of resistance

29. Susceptibility Vs. Resistance
• Success of therapeutic outcome depends on:
– Achieving concentration of AB at the site of infection
that is sufficient to inhibit bacterial growth.
– Host defenses maximally effective –MI effect is
sufficient – bacteriostatic agents (slow protein
synthesis, prevent bacterial division)
– Host defenses impaired- bactericidal agents
– Complete AB-mediated killing is necessary

30. Susceptibility vs. Resistance
• Dose of drug has to be sufficient to produce intended
effect inhibit/kill microorganism:
• However concentration of the drug must remain
below those that are toxic to human cells –
1. If can be achieved – microorganism susceptible to
the antibiotic
2. If effective concentration is higher than toxic-
microorganism is resistant

31. Prevention of Resistance
• Do not use AMA for a prolonged time unless necessary. For acute
localized infections in otherwise healthy patients, symptom
determined shorter courses recommended.
• Prefer rapidly acting and selective (narrow-spectrum) AMAs
whenever possible; broad-spectrum drugs should be used only
when a specific one cannot be determined or is not suitable.
• Use combination of AMAs whenever prolonged therapy is
undertaken, e.g. tuberculosis, SABE.
• Infection by organisms notorious for developing resistance, e.g.
Staph. aureus, E. coli, M. tuberculosis, Proteus, etc. must be
treated intensively.

38. Why has the pharmaceutical industry reduced
its production of new antibiotics?
• Resistance emerges too quickly and reduces the
effective life of an antibiotic
• Too little profit
• Big Biology has failed to produce new antibiotics
• Increased costs due to more regulation
• Litigation (Law suit) fears
• Government restrictions on use (Keep in
reserve)

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