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Antimicrobial medications history mechanisms risks and benefits How do you test effectiveness? How is resistance spread? PowerPoint PPT Presentation


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Antimicrobial medications history mechanisms risks and benefits How do you test effectiveness? How is resistance spread?. First steps: chemotherapeutics drugs that killed the microbe but not the patient! Salvarsan (Ehrlich; arsenic; syphilis)

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Antimicrobial medications history mechanisms risks and benefits How do you test effectiveness? How is resistance spread?

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Antimicrobial medications

history

mechanisms

risks and benefits

How do you test effectiveness?

How is resistance spread?


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First steps: chemotherapeutics

drugs that killed the microbe but not the

patient!

Salvarsan (Ehrlich; arsenic; syphilis)

Pronotsil (Domagk; sulfa drugs; streptococcus)

Antibiotics: produced by microorganisms

Fleming: penicillin

Waksman: streptomycin

More recently, compounds have been altered


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Features of antimicrobials

(why do most come from soil microbes?)

Selective toxicity

Type of action

bactericidal

bacteriostatic

Depends of stage of growth of microbe; sensi-

tivity to immune mechanisms

Spectrum- broad or narrow

broad can be prescribed quickly but kill

normal flora, too


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Metabolism; distribution; stability

Must drug be injected?

How long does drug persist in system?

Can drug cross blood-brain barrier?

Does patient have normal liver and kidney

function?


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What are adverse effects?

Hypersensitivity

Toxic effects

aminoglycosides; chloramphenicol

Suppression of normal flora

Efficacy

Cost


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p. 511 How do these drugs work?


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Inhibitors of cell-wall synthesis

Penicillins

Cephalosporins

(what types of organisms make them?)

Enzyme inhibitors (-lactam rings)

Prevent formation of peptidoglycan (vancomycin)

Interfere with precursor transport (bacitracin)

See table 21.2, pp. 513-514


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p. 515


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Inhibition of protein synthesis

p. 516


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These are pretty toxic

Aminoglycosides- kidney damage, deafness

Neomycin can’t be taken internally

Tetracyclines can discolor teeth in children

Chloramphenicol- aplastic anemia

Newer drugs are less toxic

Tend to be broad spectrum (not always)


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Other targets

nucleic acid synthesis (fluoroquinolones,

rifamycins)

metabolic pathways, etc. folic acid

(humans lack this pathway, therefore

these enzymes)

trimethoprim, sulfanolamides

cell membranes (polymixin B)

specialty drugs- antituberculars

slow growth; waxy coat; intracellular


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How do you know if a particular drug will be

effective?

Minimum inhibitory concentration (MIC)

Minimum bactericidal concentration (MBC)

(giving combinations is risky for toxicity,

hypersensitivity, drug resistance)


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p. 519


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Kirby-Bauer is quicker and easier

p. 519; tests have been modified


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It doesn’t take long for

microbes to become

drug-resistant!

p. 521


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Mechanisms of drug resistance, p. 522

Mutation or gene transfer?


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p. 522 many resistance genes are on plasmids


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Important resistant organisms

Vancomycin-resistant enterococci

MRSA (methicillin-resistant S. aureus)

Penicillin-resistant S. pneumoniae

Multiple-drug-resistant M. tuberculosis


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How can we prevent the formation of drug-

resistant microbes?

Health workers: prescribe appropriately!

Patients: take drugs as prescribed!

Don’t take antibacterials for viral infections!

Should antibacterials be easily available?

Should we use them in animal feed?


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Not all infections are caused by bacteria.

What are appropriate treatments for

viruses

fungi

protozoans

helminths


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Viruses are challenging because many have no

unique target structure

If immune system doesn’t control infection:

Prevent viral replication

Prevent viral polymerase activity

Prevent assembly and release of new virions


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p. 525


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Fungal cells are similar in structure to animal

cells: drugs toxic to fungi are generally

toxic

Exception: ergosterol (found in plasma

membrane). Drugs are usually safe topically

but not systemically


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Treating protozoan and helminthic diseases

Inhibit cell division or metabolism

Neurotoxins for helminths (see p. 529)


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New strategies

New targets for antimicrobials?

Interfere with resistance mechanisms?

Enhance host defenses?

New vaccine concepts?


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