Ch 20: Antimicrobial Drugs Flashcards
Define antibiotic (according to the textbook).
An antimicrobial agent, usually produced naturally by a bacterium or fungus
Why have pharmaceutical companies put very little investment in the development of new antibiotics?
- Difficult to identify new mechanisms to kill pathogens
- Generate small revenue
What genus produces more than half of our antibiotics?
Streptomyces
Are all antibiotics produced by aerobic or anaerobic organisms?
Aerobic
What characteristics do almost all antibiotic producing microbes have in common?
- Gram+ rods
- Live in soil
- Produce spores
What is the advantage and disadvantage of treating a bacterial infection with a broad spectrum antibiotic?
- Adv: can treat without knowing specific infection
- Dis: kill off normal microbiota
What organisms are common causes of superinfections? (Cause a second infection during the course of treatment for an existing infection)
- Clostridium difficile
- Candida albicans (yeast)
What is the difference between bacteriocidal and bacteriostatic?
- Bacteriocidal - kills microbes directly
- Bacteriostatic - prevents microbes from grown
Why is it more difficult to find or develop antimicrobials effective against fungi compared to bacteria?
- More targets for selective toxicity in bacteria
- Fungi more closely related to humans, so drugs could harm humans
There is concern that antibiotics that target ribosomes could adversely affect host cells. Why?
Mitochondria have the same ribosomes as bacteria (70s)
What is a common antimicrobial target in fungal plasma membranes?
Ergosterol (equivalent to cholesterol in humans)
Why does penicillin only affect actively growing cells?
Stops synthesis of new peptidoglycan
Antimicrobials that target replication and transcription generally have limited medical usefulness. Why?
Most interfere with mammalian DNA/RNA
Aside from penicillin, what other antibiotics inhibit peptidoglycan synthesis by inhibiting transpeptidase? (3)
- Carbapenem
- Monobactam
- Cephalosporin
What are the similarities and differences between penicillin G vs penicillin V?
- Penicillin G - injection; “gold standard”; most active
- Penicillin V - oral; less active; rapidly excreted
- Both - common core; rxn occurs with PBP within β-lactam ring
How do Procaine or Benzathine extend the duration of action of penicillin?
- Distribute into storage tissue to be released slowly into the blood-stream
What are some disadvantages of natural penicillins?
- Limited to gram-positive bacteria
- Susceptible to penicillinases
What advantages do the semisynthetic penicillins oxacillin and ampicillin have over natural penicillin?
- Oxacillin - resistant to penicillinase
- Ampicillin - extended-spectrum to gram-negative
What is the function of potassium clavulanate when combined with a penicillin?
Suicide inhibitor of β-lactamase to prevent degredation of penicllin
Staphylococcal infections rapidly became resistant to penicillin due to a plasmid-borne _____ gene
β-lactamase
_____ are a class of β-lactam antibiotics that swaps a “S” in penicillin for a “C”.
Carbapenems
Why do carbapenems have the broadest spectrum of activity of β-lactam antibiotics?
They selectively get taken up by porins
True or false. Carbapenems are resistant to penicillinases.
True
Monobactams are a class of monocyclic β-lactam antibiotics with activity limited to gram-negative bacteria. Why is this?
Poorly binds the penicillin-binding proteins of gram-positive and anaerobic bacteria
Activity and β-lactam ring structure of ______ matches penicillin.
Cephalosporins
Cephalosporins were developed from cephalosporin C, a natural product of ______.
Cephalosporin acreminium
______ is a mixture of related cyclic polypeptides from Bacillus subtilus that interferes with the transport of peptidoglycan precursors NAG and NAM across the plasma membrane, therefore inhibiting cell wall synthesis.
Bacitracin
Is bacitracin limited to gram-positive or gram-negative bacteria?
Gram-positive
How is bacitracin administered?
- Strictly topically
- Toxic orally
_____ is a polypeptide inhibitor of cell wall synthesis by binding NAG and NAM subunits to prevent their incorporation into the peptidoglycan matrix.
Vancomycin
Is vancomycin limited to gram-positive or gram-negative bacteria?
Gram-positive
Vancomycin is derived from what genus of bacteria?
Streptomyces
Isoniazid inhibits mycolic acid synthesis and is used to treat _____
Active turberculosis
What drugs are often given with Isoniazid to prevent tuberculosis from developing resistance?
Rifampin or ethambutol
What is the function of ethambutol (on its own)?
- Inhibits incorporation of mycolic acid into cell walls
- Comparatively weak on its own