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Monday, October 25, 2004

Mechanisms and Retardation of Antibiotic Resistance

I The three main categories of side effects of antimicrobial drugs are:
1.) Toxicity- this means that the body has identified the agent as a poison and can damage normal cells.
2.) Allergies - Some of us are sensitive to certain ingredients in antibiotics, and although rare, anaphylactic shock (shock resulting from ingesting or contacting any agent that triggers the body's allergic immune response) may be immediate and life- threatening.
3.) Disruption of Normal Flora - Normal flora may be affected by some antimicrobials, allowing pathogenic activity to cause a secondary infection.

In nature, we have certain "wild type" populations of organisms. Infection plus antibiotics cause susceptible organisms to die, while resistant organisms still flourish. The resistant organisms are named Mutants. Resistance to antimicrobials was first noticed in the 1940's. This resistance is hastened by three main groups of activity.
1.) Mis-prescribed antibiotics- an increasing problem that has gotten the attention of the CDC.
2.) Medical noncompliance- unmonitored dosage or early cessation of the antimicrobial(s).
3.) The same antibiotics are being used for both livestock and humans.

II) Resistance by Bacteria to Antimicrobial Drugs- there are five mechanisms possible. 1.) Natural Mutation- (vertical gene transfer)
2.) Plasmid Transfer- (horizontal gene transfer)
3.) Conjugation- transfer of plasmids from one organism to another via sex pillus.
4.) Transformation- taking up a plasmid or gene fragment from environment and incorporating it into the genome.
5.) Transduction- A (phage) has a gene from a previous host that it takes into the next host cell.

III) Multiple and Cross Resistance to Antimicrobial Drugs - there are three basic types included.
1.) The pathogen itself can acquire resistance to more that one drug at a time.
2.) Cross-resistance occurs when antimicrobial drugs given are similar in their structure.
3.) Pathogens resistant to most antimicrobial strains are called superbugs.

IV) Retarding Resistance - The development of pathogen resistant populations can possibly be averted in at least six different ways.
1.) Giving high concentrations for a short time.
2.) Using antimicrobial combinations. (synergism)
3.) Limit usage in necessary cases.
4.) Develop new variations of existing drugs.
5.) Second-generation drugs. (adding side chains to the original molecule)
6.) Third-generation drugs. (adding side chains . . . )

V) Notes on Certain Antimicrobial Drugs
_A) The Beta-lactams - inhibit cell wall synthesis and are the penicillins.
__1) They have limited action against most Gram negative bacteria
___a) resistance to Gram negatives is due to the peptinoglycan layer of the bacterial cell.
Chloramphenicol - is an antibacterial that inhibits protein synthesis. It is prescribed for Typhoid Fever and is rarely used due to its dangerous adverse effects, including death.
_B) Antivirals
__1) inhibit viral protein synthesis.
__2) Protease inhibitors are used for HIV.
_C) Antifungals
__1) active against fungi
__2) no resistance is known
__3) are especially effective against Gram positive pathogens. (topical drugs are examples)
_D) Antiprotozoans
__1) include heavy metals
__2) little or no resistance is known
__3) their spectrum of action has a better chance to cause allergic reactions than other antimicrobials.

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