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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?


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


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


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?


What are adverse effects?

Hypersensitivity

Toxic effects

aminoglycosides; chloramphenicol

Suppression of normal flora

Efficacy

Cost


p. 511 How do these drugs work?


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


p. 515


Inhibition of protein synthesis

p. 516


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)


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


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)


p. 519


Kirby-Bauer is quicker and easier

p. 519; tests have been modified


It doesn’t take long for

microbes to become

drug-resistant!

p. 521


Mechanisms of drug resistance, p. 522

Mutation or gene transfer?


p. 522 many resistance genes are on plasmids


Important resistant organisms

Vancomycin-resistant enterococci

MRSA (methicillin-resistant S. aureus)

Penicillin-resistant S. pneumoniae

Multiple-drug-resistant M. tuberculosis


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?


Not all infections are caused by bacteria.

What are appropriate treatments for

viruses

fungi

protozoans

helminths


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


p. 525


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


Treating protozoan and helminthic diseases

Inhibit cell division or metabolism

Neurotoxins for helminths (see p. 529)


New strategies

New targets for antimicrobials?

Interfere with resistance mechanisms?

Enhance host defenses?

New vaccine concepts?


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