BIO 120 Lecture Exam 3

Goal of Antimicrobial Chemotherapy

administer a drug to an infected person that destroys the infective agent without harming the host’s cells

Characteristics of Ideal Antimicrobial Drug

• Toxic to the microbe, but nontoxic to the host

• Does not lead to development of antimicrobial resistance

• Microbiocidal rather than microbiostatic

• Complements or assists the activities of the host’s defenses

• Reasonably priced

• Relatively soluble; functions even when highly diluted in body fluids

• Remains active in tissues and body fluids

• Does not disrupt the host’s health by causing allergies or predisposing the host to other infections

• Remains potent long enough to act and is not broken down or excreted prematurely

• Readily delivered to the site of infection

Prophylaxis

use of a drug to prevent imminent infection of a person at risk

Antimicrobial Chemotherapy

the use of drugs to control infection

Antimicrobials

all-inclusive term for any antimicrobial drug, regardless of what type of microorganism it targets

Antibiotics

substances produced by the natural metabolic processes of some microorganisms - or created by scientists - that can inhibit or destroy microorganisms; generally, the term is used for drugs targeting bacteria and not other types of microbes.

Semisynthetic Drugs

drugs that are chemically modified in the lab after being isolated from natural sources

Synthetic Drugs

drugs produced entirely by chemical reactions within a lab setting

Narrow-Spectrum (limited spectrum)

antimicrobials effective against a limited array of microbial types

Broad-Spectrum (extended spectrum)

antimicrobials effective against a wide variety of microbial types

Origins of Antimicrobial Drugs

• Antibiotics are common metabolic products of bacteria and fungi

• Inhibiting the growth of other microorganisms in the same habitat, reduces competition for nutrients and space

• Selective advantage has allowed the genes for antibiotics production to be preserved in evolution

3 Factors to Know Before Starting Antimicrobial Therapy

• Identity of the microorganism causing the infection

• Degree of the microorganism’s susceptibility (sensitivity) to various drugs

• The overall medical condition of the patient

Identifying the Agent

• Should be attempted as soon as possible

  • Before any antimicrobial drug is given

• Direct examination of body fluids, sputum, or stool

Kirby-Bauer Technique

• Technique for testing for drug susceptibility

  • The surface of a plate of special medium is spread with the test bacterium

  • Small discs containing premeasured amounts of antibiotics are dispensed on the bacterial lawn

• A zone of inhibition (agar is uncolonized) formed during incubation is measured and compared with a standard for each drug

Etest

• An alternative test for drug susceptibility

• A strip with different concentrations of a specific antibiotic is placed on a colonized agar plate

• Can identify the lowest possible concentration of the antibiotic that the bacteria are susceptible to (MIC)

Minimum Inhibitory Concentration (MIC)

the smallest (highest dilution) of the drug that visibly inhibits growth

• Useful in determining the smallest effective dosage of a drug

• Provides a comparative index against other antimicrobials

• Performed by automated machinery in clinical laboratories

Tube Dilution Test

• Used to determine the MIC

MIC and Therapeutic Index

results of antimicrobial sensitivity tests guide the physician’s choice of a suitable drug

Why antimicrobial treatments fail?

• Inability of the drug to diffuse into that body compartment (brain, joints, skin, etc)

• Resistant microbes in the infection that did not make it into the sample collected for testing

• An infection caused by more than one pathogen (mixed), some of which are resistant to the drug

Therapeutic Index (TI)

• Ratio of the dose of the drug that is toxic to humans to its minimum effective (therapeutic) dose

  • The closer these two figures are to one another, the greater the potential for toxic drug reactions

If drugs have similar MICs…

the drug with the highest TI has the widest margin of safety

Patient History

• Must be considered, including

  • Preexisting medical conditions that will influence the activity of the drug or the response of the patient

  • History of allergy to a certain class of drugs

  • Underlying liver or kidney disease

  • Infants, the elderly, and pregnant women require special precautions

Selective Toxicity

Antimicrobial drugs should kill or inhibit microbial cells without simultaneously damaging host tissues

• The best drugs in current use block the actions or synthesis of molecules in microorganisms, but not vertebrate cells

• Central concept in antibiotic treatment

• Difficult to achieve, the more similar the characteristics of the infectious agent become to those of the host

Penicllins

drug that blocks the synthesis of the cell wall found only in bacteria. Exhibits excellent selective toxicity

Drugs that are most toxic to human cells

Act upon a structure common to both the infective agent and the host cell

Metabolic Targets of Chemotherapeutic Agents

• Inhibition of cell wall synthesis

• Inhibition of nucleic acid (DNA and RNA) structure and function

• Inhibition of protein synthesis

• Interference with cell membrane structure or function

• Inhibition of folic acid synthesis