Antimicrobial therapy

Terminology

§  Chemotherapy - use of chemical agents to treat disease

§  Chemotherapeutic agents - chemical agents used for treatment

§  Antimicrobial agent - chemical agent used to treat diseases caused by microbes

Three groups of antimicrobial agents:

v  Synthetic agents - produced in laboratory

v  Natural agents - metabolic products (secondary metabolites) produced by certain groups of fungi and fungal-like bacteria that are antibacterial in action; commonly called antibiotics.

v  Semi-synthetic agents - derivatives of natural agents altered in laboratory by adding chemical groups (to improve effectiveness, etc.)

Criteria that determines the effectiveness of antimicrobial agents used in the treatment of infectious diseases:

ü  Selective toxicity - destroys or inhibits microbe without affecting host cells

ü  Broad spectrum - effective against a wide variety of organisms

ü  Non-mutagenic - does not induce development of resistant strains

ü  Soluble in body fluids - distributed through body (in bloodstream)

ü  Stable in body fluids - not easily broken down or excreted, to maintain constant and effective levels

ü  Absorbed by tissues - to reach site of infection

ü  Non-allergenic to host - should not cause adverse reactions in host

ü  Should not disturb host’s normal flora (organisms normally living in body) causing secondary (super) infections produced by opportunists

Modes of action

ž  Interfere with microbe’s vital metabolic process that does not occur in host cells (inhibit microbial enzymes) Act by: a.Competitive inhibition – competes with essential substrate to act with microbial enzyme.  b. Non-competitive inhibition – reacts directly with enzyme

ž  Targets structural/ metabolic differences between eukaryotic, prokaryotic cells.

ž  Action of antimicrobial agents - interfere with:

o   Metabolic pathways – production of an essential metabolite (By competitive inhibition)

o   The cell wall (murein) synthesis.

o   Protein synthesis (enzymes)

o   Nucleic acid replication/transcription.

o   Cause damage to cell membrane

Examples of antimicrobial agents and their actions 

Ø  Sulfonamides - Metabolic Pathway - Inhibits synthesis folic acid by competitive inhibition.

Ø   Penicillin - inhibits Cell Wall Synthesis

Ø  Erythromycin – Stops Protein Synthesis

Ø  Tetracyclines  -  Stops protein synthesis

Ø   Chloramphenicol  -  Stops protein synthesis

Ø  Streptomycin -  Stops protein synthesis

Ø  Quinolones  -  Inhibits DNA  Synthesis 

Ø  Rifampin  - Inhibits RNA Synthesis

Ø  AZT  -  Inhibits reverse transcriptase ad DNA Synthesis

Ø  Acyclovir, Ribavirin  - Prevents viral replication and  DNA, RNA Synthesis

Ø  Griseofulvin  -  affects RNA Synthesis

Ø  Polymixins  -  Damage Cytoplasmic Membrane

Disadvantages of Antimicrobial Therapy:

·         Allergic reactions

·         Toxic effects on normal tissues

·         Disturbs host normal flora ® secondary infections

·         Development of resistant strains – spontaneous mutations, DNA transfer