The document provides definitions and mechanisms of action for various antimicrobial agents, including antibiotics, antivirals, antifungals, and antihelminthics, highlighting their selective toxicity and therapeutic strategies. It explains the selection process for antimicrobial agents based on factors such as organism identity, site of infection, and patient considerations, while also addressing issues of drug resistance and prophylactic use. Additionally, it details complications associated with antimicrobial therapy, like hypersensitivity and superinfections.

1. Definitions
1. Chemotherapy
treatment of a disease by a chemical compound selectively directed against
invading microbes or abnormal cells.
Or
 use of drugs to treat infections and malignancy. (Antimicrobials and
Antineoplastic agents).
2. Antimicrobial
any agent that kills or inhibits growth of a susceptible organism.
3. Antibiotic
a microbial product or its derivative that kills or inhibits growth of a
susceptible organism.
All antibiotics are antimicrobials but all antimicrobials are not antibiotics

2. Antimicrobial Drugs
• Antimicrobial therapy takes advantage of the biochemical differences
between microorganisms and humans.
• Antimicrobial drugs should have selective toxicity towards the invading
microorganism without harming the cells of the host.
• This selective toxicity is usually relative rather than absolute, requiring
careful control of the drug concentration.

3. Antimicrobial Drugs
Antibiotic producing microbes include:
• Gram-Positive Rods:
- Bacillus subtilis: Bacitracin
- Bacillus polymyxa: Polymyxin
• Fungi:
- Penicillium notatum: Penicillin
- Cephalosporium spp.: Cephalothin
• Actinomycetes:
- Streptomyces venezuelae: Chloramphenicol
- Streptomyces griseus: Streptomycin
- Streptomyces nodosus: Amphotericin B
- Micromonospora purpurea: Gentamycin

4. • Antibacterials: Relatively easy to develop and find with low toxicity
because procaryotic cells are very different from host cells.
• Antihelminthic, antiprotozoan, and antifungal drugs: More difficult to
develop because eucaryotic cells resemble human cells.
• Antivirals: Most difficult to develop because virus reproduces using host
cell enzymes and machinery.

5. Spectrum of Antibiotic Activity
• Narrow Spectrum Antibiotics: Effective against a subset of bacteria
(either gram positive and negative). Examples: Penicillin, Isoniazid
(Mycobacteria only).
• Broad Spectrum Antibiotics : Effective against many different types
of bacteria (e.g.: both gram positive and negative). Examples:
Tetracyclin.

6. The Action of Antibiotic Drugs
• Bactericidal
Kill microbes directly.
• Bacteriostatic
Prevent microbes from growing.

7. Mechanisms of Antimicrobial Action
• Bacteria have their own enzymes for:
1. Cell wall formation
2. Protein synthesis
3. DNA replication
4. RNA synthesis
5. Synthesis of essential metabolites.
• Viruses use host enzymes inside host cells.
• Fungi and protozoa have own eukaryotic enzymes.
• The more similar the pathogen and host enzymes, the more side effects the
antimicrobials will have.

8. The Action of Antimicrobial Drugs
Antimicrobial mechanisms of action include:
1. Inhibition of Cell Wall Synthesis: Interfere with peptidoglycan synthesis. E.g.:
Penicillin and vancomycin.
2. Inhibition of Protein Synthesis: Interfere with procaryotic (70S) ribosomes. E.g.:
Tetracyclin and erythromycin.
3. Injury to the Plasma Membrane: Cause changes in membrane permeability.
Result in loss of metabolites and/or cell lysis. E.g.: Polymyxin B (antibacterial) or
miconazole (antifungal).
4. Inhibition of Nucleic Acid (DNA/RNA) Synthesis: Interfere with DNA replication
and transcription. May be toxic to human cells. E.g.: Rifampin and quinolones.
5. Inhibition of Synthesis of Essential Metabolites: Involve competitive inhibition
of key enzymes. Closely resemble substrate of enzyme. E.g.: Sulfa drugs inhibit the
synthesis of folic acid which is necessary for DNA and RNA synthesis.

10. Selection of antimicrobial agents
Selection of the most appropriate antimicrobial agent requires knowing:
1) the organism’s identity
2) the organism’s susceptibility to antimicrobial agent
3) the site of the infection
4) patient factors
5) the safety of the antimicrobial agent.
6) the cost of therapy.

11. Selection of antimicrobial agents
Patient factors taken into consideration when selecting an antimicrobial
agent
• Immune system
• Renal dysfunction
• Hepatic dysfunction
• Poor perfusion
• Age
• Pregnancy
• Lactation

12. Routes of administration
• Oral route is chosen for mild infections, and is favorable for
outpatients.
• Parenteral route is used for more serious infections, or when the anti-
microbial agent of choice has poor GI absorption such as vancomycin,
amphotericin B and aminoglycosides.

13. Determination of rational dosing
Pharmacodynamics of the drug (the relationship of drug concentrations to
antimicrobial effects):
1. Concentration dependent killing
Rate of microbial killing increases as the concentration increases e.g.
aminoglycosides like tobramycin.
2. Time dependent (concentration-independent) killing
Increasing concentration does not increase the rate of killing e.g. β-lactams,
glycopeptides, macrolides, clindamycin.

14. Drug resistance
• Bacteria is resistant to an antibiotic if the maximal level of the antibiotic does not stop
their growth.
• Some organisms are inherently resistant to antibiotics Ex. Gram negative bacteria are
inherently resistant to vancomycin. Or maybe due to absent of mechanism to transport
the drug into the cell or do not contain antibiotic’s target process or protein
• Microbial species that are normally responsive to a particular drug may develop more
virulent or resistant strains through spontaneous mutation or acquired resistance by
genes passing from resistant to non-resistant strain or by gene transfer mechanisms:
• Conjugation.
• Transduction.
• Transformation.
• Some organisms may become resistant to more than one antibiotic.

15. Mechanisms of Antimicrobial Resistance
1. Modification of target sites: Alteration of an antibiotic's target site
through mutation can confer organismal resistance to one or more
related antibiotics. For example, S. pneumoniae .
2. Decreased uptake or increased efflux: of an antibiotic can confer
resistance, because the drug is unable to attain access to the site of its
action in sufficient concentrations to injure or kill the organism
3. Enzymic inactivation: The ability to destroy or inactivate the
antimicrobial agent can also confer resistance on microorganisms.

17. Factors Promote Antimicrobial Resistance
1. If a patient taking a course of antibiotic treatment does not complete it
2. Or forgets to take the doses regularly.
3. Exposure to microbes carrying resistance genes.
4. The use of antibiotics also promotes antibiotic resistance in non-
pathogens ,These non-pathogens may later pass their resistance genes into
pathogens.
5. Use of antibiotics in foods.
6. Antibiotics for viral infections
7. Spread of resistant microbes in hospitals due to lack of hygiene and using it
extensively.

18. Prophylactic antibiotics
Antibiotics use for prevention is restricted to situations where the
benefit outweighs the risks of bacterial resistance and superinfections
such as:
• Prevention of tuberculosis or meningitis among individuals who are in
close contact with infected patients.
• Treatment prior to most surgical procedures to decrease the incidence
of infection afterwards.

19. Complications of antimicrobial therapy
1.Hypersensitivity : Penicillins can cause serious hypersensitivity
problems ranging from urticaria (hives) to anaphylactic shock
2. Direct toxicity : Aminoglycosides can cause ototoxicity by interfering
with membrane function in the cells.
3. Superinfections :Drug therapy especially broad spectrum
antimicrobials can lead to alterations to the normal flora of the upper
respiratory, intestinal and genitourinary tracts permitting overgrowth of
opportunistic organisms like fungi or resistant bacteria.

20. Antiviral drugs
• Because viruses are obligate intracellular parasites, antiviral agents must be
capable of inhibiting viral function without damaging the host.
• In general antiviral agents are very limited because of their toxicity.
• Antiviral chemotherapy should be chosen in such a way that they
affect on the steps of replication of the virus either they inhibit entry of
the virus in to the host cells or they prevent replication of the virus by
inhibiting certain peptides which are responsible for viral replication.

21. Antiviral drugs
Mechanisms of action include:
• inhibition of virus adsorption
• inhibition of virus-cell fusion
• inhibition of the HIV integrase (HIV)
• inhibition of viral DNA or RNA synthesis
• viral protease inhibition
• viral neuraminidase inhibition (influenza)

23. Antifungal drugs
• Also called antimycotic drugs
• Used to treat two types of fungal infections:
1. superficial fungal infections
skin or mucus membrane
2. Systemic fungal infections
Lungs or central nervous system

24. Antifungal drugs
Groups :
• Polyenes :amphotericin B, Nystatin.
• Antimetabolic antifungal: Flucytosine
• Imidazoles: ketoconazole, miconazole, clotrimazole.
• Griseofulvin
Antifungals generally kill fungi by disrupting the synthesis or function of
fungal cellular membranes or by interference with intracellular functions .

25. Antihelmentic drugs
According the mechanism of action Anthelmintics are divided into:
1) Cellular poisons – Tetrachloroethylene.
2) Disturbing the function of the neuromuscular apparatus in nematodes –
Piperazine adipinate and Ditrazin.
3) Paralyzing neuromuscular system predominantly of flatworms
(cestodes) and damaging their coating tissues –Praziquantel
andNiclosamide.
4) Affecting predominantly the energy processes – Mebendazole and
Levamisole.

26. Antihelmentic drugs
• Anthelmintics must be selectively toxic to the parasite.
• This is usually achieved by inhibiting metabolic processes that are vital to
the parasite but not vital to or absent in the host.
• While the precise mode of action of many anthelmintics is not fully
understood, the sites of action and biochemical mechanisms of many of them
are generally known.
• The pharmacologic basis of the treatment for helminths generally lead to
starvation, paralysis, and expulsion or digestion of the parasite.