Principles of Antimicrobials Therapy

Antimicrobial agents Dr.
lnssaf Al-Shemmary
Principles of Antimicrobials Therapy
Lec.1
Definition and Characterization: Antimicrobial drugs or antibiotics are
the substances produced by various species of microorganisms (bacteria,
fungi, viruses, parasites and others) that suppress the growth or kill of other
microorganisms. Antibiotics differ markedly in physical, chemical,
pharmacological properties, antimicrobial spectra and mechanisms of action.
Selection of Antimicrobial Agents

Selection of antimicrobial drugs require knowledge of the followings:
1. 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 by
A. Gram stain (if bacteria or not, bacteria ve + or bacteria ve -).
B. Culture the infective organism for diagnosis and to determine the
susceptibility of the bacteria to antibiotics.
2. Empiric therapy prior to identification of the organism
A. Timing: Acutely ill patients with infections of unknown origin e.g. a
patient with severe headache, a rigid neck, and sensitivity to bright lights
(symptoms characteristic of meningitis) require immediate treatment. Then
give a specific antibiotics after results of investigations.
B. Selecting a drug: The choice of drug in the absence of susceptibility data

is influenced by the site of infection and the patient's history. Broad-
spectrum therapy may be needed initially for serious infections.
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Antimicrobial agents Dr.lnssaf Al-Shemmary
3. Determination of antimicrobial susceptibility of infective

organisms
After a pathogen is cultured, its susceptibility to specific antibiotics as a
guide in choosing antimicrobial therapy. The susceptibility tests are:
1. Kirby-Bauer method to determine if the bacteria are sensitive or resistant
to antibiotics
2. Minimum inhibitory concentration (MIC) is a minimum inhibitory
concentration of drug or the lowest concentration of drug that inhibits
bacterial growth. Also determine if the antimicrobial drugs is bacteriostatic
or bactericidal
Bacteriostatic drug: is the drug that inhibits growth and replication of

bacteria.
Bactericidal drug: is the drug that kills bacteria.
Effect of bactericidal and bacteriostatic drugs on the growth of bacteria in vitro.
4. Effect of the site of infection on therapy

The endothelial cells comprising the walls of capillaries of many tissues have
fenestrations (openings that act like windows) that allow most drugs to
penetrate. However, natural barriers of the capillaries in some tissues to drug
delivery such as the prostate, the vitreous body of the eye, and the central
nervous system (CNS). capillaries in the brain, which help to create and
maintain the blood-brain barrier (BBB). This barrier is formed by the single
layer of tile-like endothelial cells fused by tight junctions that entry from the
blood to the brain
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The penetration and concentration of an antibacterial agent in the CSF is

particularly influenced by the following:
A. Lipid solubility of the drug: The lipid solubility of a drug is a major

determinant of its ability to penetrate into the brain. E. g: lipid-soluble drugs
such as the quinolones.
B. Molecular weight of the drug: A compound with a low molecular

weight has an enhanced ability to cross the blood-brain barrier, but the high
molecular weight (vancomycin) is poorly penetrated.
C. Protein binding of the drug: A high degree of protein binding of a drug

in the serum reduce its entry into the CSF.
5. Patient factors: In selecting an antibiotic, attention to the condition of

the patient such as
A. Immune system: Elimination of infecting organisms depends on immune

system. Alcoholism, diabetes, infections can affect the immunity of patients.
Thus higher doses of bactericidal agents or longer courses of treatment are
required to eliminate organisms.
B. Renal dysfunction: Poor kidney function causes accumulation of

antibiotics in the body that ordinarily are eliminated by kidney. This may
lead to serious adverse effects unless drug accumulation is controlled by
adjusting the dose of the antibiotic. Serum creatinine levels are used as an
index of renal function for adjustment of drug regimens.
C. Hepatic dysfunction: Antibiotics that are concentrated or eliminated by

the liver e.g. erythromycin are contraindicated in treating patients with liver
disease or liver dysfunction.
D. Poor perfusion: Decreased circulation to an anatomic area, such as the

infection in the lower limbs of a diabetic patient lead to reduce the amount of
antibiotic that reaches to area of infection, result in difficult to treat.
E. Age: Renal or hepatic elimination processes are poorly developed in

newborns, neonates lead to toxic effects, e.g: chloramphenicol.l
F. Pregnancy: All antibiotics cross the placenta but the adverse effects to
the fetus are rare, except some antibiotics , e.g tetracyclines can cause
dysplasia and inhibition of bone growth.
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G. Lactation: Drugs administered to a lactating mother may enter to infant

by the breast milk.
6. Safety of the agent: Many of the antibiotics, such as the penicillins are
among the least toxic of all drugs because they interfere with a site unique to
the growth of microorganisms.
7. Cost of therapy: Often several drugs may show similar efficacy in

treating an infection but vary widely in cost.
Classification of Antimicrobial agents

Antimicrobial drugs can be classified in a number of ways, one of these is
classified according to the mechanism of action as:
1. Cell Wall Inhibitor antimicrobial drugs.

2. Protein Synthesis Inhibitors.
3. Fluoroquinolones (DNA Gyrase Inhibitors).
4. Folic Acid Antagonists (sulfonamides, trimethoprim).

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Antimicrobial agents Dr.

Principles of Antimicrobials Therapy

Selection of Antimicrobial Agents

1. Identification of the infecting organism :Characterization of the

B. Selecting a drug: The choice of drug in the absence of susceptibility data

3. Determination of antimicrobial susceptibility of infective

Bacteriostatic drug: is the drug that inhibits growth and replication of

Bactericidal drug: is the drug that kills bacteria.

Effect of bactericidal and bacteriostatic drugs on the growth of bacteria in vitro.

4. Effect of the site of infection on therapy

The penetration and concentration of an antibacterial agent in the CSF is

A. Lipid solubility of the drug: The lipid solubility of a drug is a major

B. Molecular weight of the drug: A compound with a low molecular

C. Protein binding of the drug: A high degree of protein binding of a drug

5. Patient factors: In selecting an antibiotic, attention to the condition of

A. Immune system: Elimination of infecting organisms depends on immune

B. Renal dysfunction: Poor kidney function causes accumulation of

C. Hepatic dysfunction: Antibiotics that are concentrated or eliminated by

D. Poor perfusion: Decreased circulation to an anatomic area, such as the

E. Age: Renal or hepatic elimination processes are poorly developed in

G. Lactation: Drugs administered to a lactating mother may enter to infant

7. Cost of therapy: Often several drugs may show similar efficacy in

Classification of Antimicrobial agents

1. Cell Wall Inhibitor antimicrobial drugs.

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