Bacteriology lecture-------------------------------------------------------------------------------------- - Dr.Zina AL-Shami
Antibiotics and chemotherapeutic agents
Antibiotics are drugs that are used in the treatment or prevention of bacterial infections.
Antibiotics are natural substances produced by micro-organisms as opposed to semisynthetic or synthetic antibiotics, which are either natural substances artificially modified or
totally human created respectively. Antibiotics form part of a wider range of antimicrobial
agents, a group which also includes antifungal, antiviral, antiprotozoals and disinfectants.
This group is also known as chemotherapeutic agents.
Blind therapy Initial or Blind or Umbrella or Empirical therapy refers to the treatment
of an infection without knowing the causative pathogen.
Mechanism of Action
The ideal antimicrobial agent exhibit selective toxicity this mean that the drug must be toxic
to pathogens rather than the host. Variation in site of action can indicate why certain
antibiotics operate against certain bacteria, but not others. The principle sites of action are:
1. Inhibition of Cell wall synthesis (e.g.) cephalosporins
2. Inhibition of Cell membrane function(e.g.) polymyxins
3. Inhibition of Protein synthesis(e.g.) aminoglycosides and tetracyclines
4. Inhibition of Nucleic acid synthesis(e.g.) rifampin and trimethoprim
Classification :
Antibiotics can be classified according to:
1- Action /
Bacteriostatic
A drug that inhibits growth or development of a bacterium, rather than directly killing it.
Bacteriostatic drugs depend upon the immune system of the patient for activity, and so make
poor choices where the immune system is compromised, for example patients with AIDS.
Bacteriology lecture-------------------------------------------------------------------------------------- - Dr.Zina AL-Shami
The MIC (minimum inhibitory concentration) is the minimum concentration of drug which
can inhibit the growth of the microorganism.
Bactericidal
A drug that directly kills a bacterium. The MBC (minimum bactericidal concentration) is the
minimum concentration of drug which can kill the microorganism.
2- Chemotherapeutic Spectrum / Antimicrobial Spectrum
The range of bacteria that an antibiotic affects, divided into Narrow Spectrum and Broad
Spectrum.

Narrow spectrum antibiotics act against a limited group of bacteria, for example
sodium fusidate only acts against staphylococcal bacteria.

Broad spectrum—antibiotics act against a larger group of bacteria, for example
amoxicillin.
Causes of anti-microbial failure—
1. Development of drug resistance
2. Improper diagnosis
3. Improper selection of antimicrobials
4. Improper dose and dosing schedule
5. If the combination therapy is not used where necessary
Antimicrobial resistance
Bacteria are said to be resistant if their growth is not inhibited by the maximal level of an
antibiotic. Development of antimicrobial resistance is one of the important causes of failure
of anti-microbial therapy. Resistance develops as a result of the followings—
Bacteriology lecture-------------------------------------------------------------------------------------- - Dr.Zina AL-Shami
1. Production of enzyme that can modify the drug or inactivate the drug (e.g.) Staphylococci
produce β-lactamase enzyme and inhibit β-lactam containing drugs
2. ↓ the passage of anti-microbial into the cells
3. ↑ the influx of anti-microbial out of the cell
4. Modification of the target site of the drug
5. M.o. develop an altered enzyme that can still perform its metabolic function but not
affected by the drug
Origin of drug resistance:
Development of Bacterial Resistance may be non-
genetic or -genetic
A-Non-genetic:1. organisms inherently resistant to an antibiotic. (Vancomycin—gm -ve)
2. metabolically inactive Microorganisms. (Mycobacterium—non multiplying)
3. Microorganisms may loss their specific target structure for a drug of several generations.
(Mycoplasma, Chlamydia, Rickettsia all of these are devoid of cell wall, Tetracycline is
given in these cases)
B-Genetic—may be of 2 types—
1. Chromosomal—
This develops due to spontaneous mutation of DNA.
· Alteration of PBP (Penicillin binding protein
· Alteration of PBP
· Alteration of amino acids in ribosomes
Bacteriology lecture-------------------------------------------------------------------------------------- - Dr.Zina AL-Shami
· Alteration of DNA gyrase (it is inhibited by Quinolones)
· Alteration of protein of ribosomes
· Alteration of pathway of synthesis of folate
2. Extrachromosomal / Plasmid mediated—
Plasmid—plasmids are extra-chromosomal DNA molecule which may exist free in the
bacterial cytoplasm. As they are extra-chromosomal the genetic information is readily
transformed among the bacteria of same species and sometimes among the bacteria of other
species. This transfer is encoded in the R-factor.
Combination therapy
The use of two or more agents simultaneously.
Reasons of antibiotic combination include:
1. To avoid the development of resistance, particularly in bacteria
2. To provide broad coverage in polymicrobial infection
3. Severe infections where the cause is unknown, or in empirical therapy.
4. Synergy in specific infections
5. Where the pathogen cannot be easily killed and prevention of emergence of resistance.
(Tuberculosis, Leprosy)
This combination can produce:
1. An additive effect
2. Synergistic effect, where the effect of using both agents together is greater than the
sum of the effects of the drugs. This can be seen in Co-amoxiclav, and Penicillin and
an Aminoglycoside for endocarditis
3. Antagonism, where the combination reduces the activity of each antibiotic. This is
seen where a bacteriostatic and a bactericidal drug are used in combination.
4. indifference
Bacteriology lecture-------------------------------------------------------------------------------------- - Dr.Zina AL-Shami
disadvantage of combination:
Reasons why combination therapy might not be preferred include:
1. Increased toxicity
2. Antagonism - the two agents interact resulting in reduced antibiotic effect
3. Increased cost
4. Superinfection
Proper selection of drug—
§ Specificity
§ Routes of administration and Safe drug
§ Cost effectiveness and Easy availability
§ Proper combination
Time and dose
1. Right dose—usually we give initially loaded dose followed by maintenance dose.
2. Right duration—at least 3-5 days antibiotic should be continued.
3. Right time schedule—to maintain MIC and MBC.
4. Status of the patient— Age of the patient
5. Hepatic and renal function
6. Pregnancy and Lactating mother
7. Immune system of the patient 8. Site of infection
Chemoprophylaxis—
It is the use of drug to prevent infection by one organism virtually uniform susceptibility.
e.g. after surgery