Ch 10: Antimicrobials Flashcards
Who was Paul Ehrlich?
searched for the “magic bullet,” a chemical that could kill a pathogen without harming the host
On his 606th attempt, he made salvarsan for the treatment of syphilis
Who was Alexander Fleming?
physician during WWI. Began studying Staphylococcus aureus b/c so many soldiers died of wound infections.
found a contaminating mold (Penicillium notatum) growing on a plate that inhibited the growth of staph.
- couldn’t isolate inhibitory compound mold was produced
Who was Howard Florey & Ernst Chain?
read about Fleming’s work and asked for his mold sample. They were the first to isolate enough of this inhibitory compound (penicillin) to treat patients.
What important historical event is going to be impacted by the production of penicillin?
1942-1944
Penicillin used exclusively for military (3 million doses made in preparation for D-Day)
1944
Penicillin became available to pharmacists for retail sale
What is the Magic Bullet when developing antimicrobials?
selective toxicity for pathogen
non-toxic to host
What is antibiotic prophylaxis?
using antibiotics as a preventative measure
Is antibiotic prophylaxis a good idea?
Prophylaxis for general antibiotic usage not a good idea b/c of bacterial mutation
What is subacute endocarditis?
heart valve condition
- Dental patients w/ this condition at risk for developing a valve infection.
- instance where antibiotics prophylaxis taken before a dental procedure to control bacteria entering the bloodstream from the oral cavity.
How are antibiotics tested to determine which one works best for the type of bacteria and how much should be given?
Which one works best?
disk diffusion susceptibility testing
What dosage should be given?
minimum inhibitory concentration (MIC)
What is disk diffusion susceptibility testing?
testing antibiotics against specific bacteria
- cover petri dish w/ bacteria of interest
- place pieces of filter paper containing antibiotic on dish
and see if it affects bacteria
- zone of inhibition: zone of no growth of bacteria around
the antibiotic
- the antibiotics that don’t work have an R-factor
(resistance)
What is minimum inhibitory concentration (MIC)?
Used to determine how much of the antibiotic should be given to the patient
- Take a plate w/ many wells and make numerous
dilutions - add bacteria to the wells
- At what concentrations do we still kill bacteria?
- When you start seeing color change in wells you know
the antibiotic is killing the bacteria
What are the properties of an antibiotic we’re concerned with?
Activity and Spectrum
What is antibiotic activity?
bactericidal vs. bacteriostatic
bactericidal: kills bacteria
bacteriostatic: inhibits bacteria
by slowing the bacteria down, your immune system will take care of the rest
Why do we have to be concerned about endotoxin when using a bactericidal antibiotic on a gram-negative infection?
As the bacteria die they are lysed and the endotoxin will be released
What is antibiotic spectrum?
Narrow vs Broad
Narrow: Work on small group of related bacteria
Broad: More general, able to use against large range of bacteria
eg. protein synthesis inhibitors that work against 70S ribosomes (bacteria only)
What is the risk of using broad spectrum antibiotics?
Superinfection
- kill good gut flora but leaves a few types remain
could lead to superinfection
- decrease in competition leads to overgrowth of 1-2 types of bacteria
What types of bacteria take over during superinfection resulting from long term broad spectrum antibiotic usage?
Candida albicans
- cause yeast infections (oral thrush + vaginal yeast
infections)
Clostridium difficile (C. diff) - makes pseudomembranous colitis leading to diarrhea
Candida albicans + Clostridium difficile are opportunists
under normal conditions they are not a problem
if good flora amount decreases the opportunists will take over
Why do these microbes survive broad-spectrum therapy?
Candida albicans is not a bacteria it’s a yeast. C. diff is a bacteria but forms endospores
How did Alexander Fleming discover the first antibiotic, penicillin?
A. He gave some to a wounded soldier with a staph
infection and the patient recovered
B. He gave some to a sick cow and it got better
C. He noticed a mold inhibiting staph on a petri dish
D. He used it prophylactically on himself in place of hand
washing
E. He made it from chemicals he had available in his lab
C. He noticed a mold inhibiting staph on a petri dish
Penicillin causes lysis of gram-positive bacteria, but does not affect gram-negative bacteria because it cannot penetrate the porins in the outer membrane. Which is the best description of penicillin’s activity?
Narrow spectrum, bactericidal
What are the potential antibiotic targets?
Antibiotics that affect bacteria:
- Cell Wall synthesis
- peptidoglycan
- Cell membrane integrity
- DNA/RNA synthesis
- Folic Acid Synthesis in cytoplasm
- Protein synthesis
Usually targets the enzymes that perform these actions
Why is peptidoglycan cell-wall synthesis in bacteria an important antibiotic target?
Peptidoglycan synthesis builds glycan chains (NAG & NAM) and peptide crosslinks hold them together.
Without crosslinks, peptidoglycan is unstable.
