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)
risks and benefits
How do you test effectiveness?
How is resistance spread?
First steps: chemotherapeutics
drugs that killed the microbe but not the
Salvarsan (Ehrlich; arsenic; syphilis)
Pronotsil (Domagk; sulfa drugs; streptococcus)
Antibiotics: produced by microorganisms
More recently, compounds have been altered
Features of antimicrobials
(why do most come from soil microbes?)
Type of action
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
What are adverse effects?
Suppression of normal flora
p. 511 How do these drugs work?
Inhibitors of cell-wall synthesis
(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
Inhibition of protein synthesis
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)
nucleic acid synthesis (fluoroquinolones,
metabolic pathways, etc. folic acid
(humans lack this pathway, therefore
cell membranes (polymixin B)
specialty drugs- antituberculars
slow growth; waxy coat; intracellular
How do you know if a particular drug will be
Minimum inhibitory concentration (MIC)
Minimum bactericidal concentration (MBC)
(giving combinations is risky for toxicity,
hypersensitivity, drug resistance)
Kirby-Bauer is quicker and easier
p. 519; tests have been modified
It doesn’t take long for
microbes to become
Mechanisms of drug resistance, p. 522
Mutation or gene transfer?
p. 522 many resistance genes are on plasmids
Important resistant organisms
MRSA (methicillin-resistant S. aureus)
Penicillin-resistant S. pneumoniae
Multiple-drug-resistant M. tuberculosis
How can we prevent the formation of drug-
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 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
Fungal cells are similar in structure to animal
cells: drugs toxic to fungi are generally
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 targets for antimicrobials?
Interfere with resistance mechanisms?
Enhance host defenses?
New vaccine concepts?