Principles of Antimicrobial therapy

1. Principles of Antimicrobial therapy
PHRM306
PHARMACOLOGY II

2. Principles of Antimicrobial Therapy
I. Overview:
 Antimicrobial therapy takes advantage of the
biochemical differences that exist between
microorganisms are human beings.
 Antimicrobial drugs are effective in the
treatment of infections because of their selective
toxicity.
 That is, they have the ability to injure kill an
invading microorganism without harming the
cells of the host.

3. II. Selection of Antimicrobial Agents
1. The organism’s identity
2. Its susceptibility to a particular agent
3. The site of the infection
4. Patient factors
5. The safety of the agent
6. The cost of the therapy

4. A. Identification of the infecting organism
• Characterization of the organism is central to selection
of the proper drug.
• A rapid assessment of the nature of the pathogen can
sometimes be made on the basis of the Gram stain,
which is particularly useful in identifying the presence
and morphologic features of microorganisms in body
fluids that are normally sterile.

5. B. Empiric therapy prior to identification of
the organism
1. The acutely ill patient with
infections of unknown origin
2. Selection a Drug

6. C. Determination of antimicrobial
susceptibility of infective organisms
1. Bacteriostatic drugs: Which arrest the growth
& replication of bacteria at serum levels
achievable in the patient.
Bactericidal agents: Which kills bacteria at
serum levels achievable in patients.
• Cholarmphenicol is static against gram
negative rods and is cidal against other
organisms such as S. pneumoniae

7. • 2. Minimum inhibitory concentration: Minimum
Inhibitory Concentration (MIC) is the lowest
concentration of antibiotics that inhibits bacterial
growth.
• To provide effective antimicrobial therapy, the
clinically obtainable antibiotic concentration in body
fluid should be greater then the MIC.
• 3. Minimum Bactericidal concentration: the
minimum bactericidal concentration (MBC) is the
lowest concentration of antimicrobial agent that
results in a 99.9 percent decline in colony count
after overnight broth dilution incubations.

8. D. Effect of the site of injection on
therapy
• The blood Brain Barrier: this barrier is formed by
the single layer of tail-like endothelial cells fused
by tight junctions that impede entry from the blood
to the brain of virtually all molecules, except those
that are small and lipophilic.
• The penetration and concentration of an
antibacterial agent in the CSF is particularly
influenced by the following:

9. 1. Lipid soluble drug, such as quinolones and
metronidazole, have significant penetration into
the CNS.
• In contrast, β-lactum antibiotics, such as
penicillin, are ionized at physiologic PH and have
low solubility in lipids.
• They therefore have limited penetration through
the intact blood brain barrier under normal
circumstances.
2. Molecular Weight of the drug
3. Protein binding of the drug

10. E. Patient factors
1. Immune System
2. Renal Dysfunction: serum creatinine levels
are frequently used as an index of renal
function for adjustment of drug regimens.
3. Hepatic dysfunction
4. Poor perfusion
5. Age
6. Pregnancy
7. Lactation
F. Safety of the agent
G. Cost of the therapy

11. III. Route of Administration
• Some antibiotics, such as Vancomycin, the
aminoglycosides and amphotericin are so poorly
absorbed from gastrointestinal tract that adequate
serum levels can not be obtained by oral
administration.
• Parenteral administration is used for drugs that
are poorly absorbed from the gastrointestinal tract
and for the treatment of the patients with serious
infections.

12. IV. Determinants of Rational Dosing
• Two important pharmacodynamic
properties that have a significant influence
on the frequency dosing are:
1.Concentration-depending Killing
2.Post-antibiotic effect

13. V. Agents used bacterial infections
• Penicillin
• Cephalosporin's
• Tetracycline's
• Aminoglycosides
• Macrolides
• Fluoroquinolones
• Others

14. VI. Chemotherapeutic Spectra
A. Narrow-Spectrum antibiotics: Isoniazid is
active only against mycobacteria
B. Extended-Spectrum: Ampicillin acts against
gram positive and some gram negative
bacteria
C. Broad-Spectrum Antibiotics: Tetracycline and
chloramphenicol affect a wide variety of
microbial species

15. VII. Combinations of antimicrobial
drugs
• Treatment of tuberculosis
• Advantages of drug combinations: When
infection is of unknown origin. Beta lactums and
aminoglycosides show synergism
• Disadvatages of drug combinations: A number of
antibotics act only when organisms are
multiplying. Thus co administration of an agent
that causes bacteriostasis plus a second agent
that is bactericidal may result in the first drug
interferring with the action of second.

16. VIII. Drug Resistance
A. Genetic alterations leading to drug resistance
1. Spontaneous mutations of DNA: Emergence of
rifampin-resistant Mycobacterial tuberculosis
when rifampin is used as a single antibitotic.
2. DNA transfer of drug resistance
B. Altered expression of proteins in drug-resistant
organisms
1. Modification of target site
2. Decreased accumulation
3. Enzymic Inactivation

17. IX. Prophylactic Antibiotics
X. Complications of Antibiotics Therapy
1.Hypersensitivity
2.Direct toxicity
3.Superinfections
XI. Sites of Antimicrobial Actions