antimicrobial drug resistance (AMR) EXAM II

what is kirby bauer test?

a way that AMR is measure qualitatively: disc diffusion assay.

• filter paper disks saturated with the antimicrobial drug of interest are placed on a plate spread with bacteria isolated from a clinical sample. antibiotic then diffuses from the disk into the media and if the organism is sensitive to it, a clear zone will appear where the bacteria fail to grow (inhibited or killed by drug)

what is etest?

a way that AMR is measure quantitatively: measure the minimum inhibitory concentration (MIC)

• has an antibiotic on it, but measures many different concentrations

• looks at the concentration it will take for an antibiotic to kill bacteria. under specific conditions

Why is it important clinically to measure MIC?  How does MIC relate to the “therapeutic window” for antimicrobial drugs?

MIC is important to know because we want to know if the drug is going to work on the patient. for clinical use, MIC needs to be in the therapeutic window, which is the concentration of drug that inhibits the microbe without harming the host.

• most drugs exhibit adverse effects at high concentrations

How does taking an antibacterial drug lead to drug resistance?

resistant bacteria pass along traits that make it resistant (natural selection)

Describe 4 basic mechanisms of AMR caused by genetic change.  What type of genetic change is happening in each one? 

drugs can enter the cell: eg. gram negative produces porins that alter permeability… instead of having big proteins they produce small porins

drugs are pumped out of the cell: eg. efflux pump… gets bigger and pumps our more antibiotic

enzymes inactive drugs: eg. beta lactamases degrade beta lactam drugs

host target isn’t attached: changes shape so drug can’t bind (eg. ribosomal mutans to streptomycine and RNA polyermase mutans to rifampin)

How do bacteria gain spontaneous mutations?  How does this contrast with horizontal gene transfer?

1. spontaneous mutations video: when genes hit a boundary with higher antibiotics, they have to mutate to be able to survive that antibiotic… through the process of accumulating mutations, bacteria can evolve resistance to extremely high concentrations of antibiotic in a short period of time

   1. taking two drugs that cover different targets make resistance less likely

2. Spontaneous mutation alters existing internal DNA sequences during replication, whereas 3.1: Horizontal Gene Transfer in Bacteria transfers whole genes or blocks of DNA from an external donor cell.

Given that the mutation rate is low, why does mutation still play an important role in the development of antibiotic resistance?

populations are large and reproduce fast

How does co-selection for antimicrobial drugs work?

one bacteria has several different resistance factors that sit closely together on. one piece of DNA, such as plasmid, transposon or integron. when a bacterium is exposed to one selective pressure, it preserves the entire genetic package. as a result, the bacterium automatically gains or keeps resistance to unrelated antibiotcs

On average, approximately how long does it take for AMR to develop after a new drug has been introduced?

no super long, penicillium came out in 1943 and resistance was seen in 1946

What are the top 5 AMR urgent threats listed by the CDC?

acinetobacter: hospital acquired

candida auris: fungus, highly drug resistant, infect and kill elderly in assisted living

clostridioides difficle: can be drug resistant, and also caused by antiobiotics

enterobacteriaceae (CREs): transfered in hospitals

neisseria gonorrhoeae: highly drug resistant, getting harder to treat

how can the use of broad spectrum antibiotics result in the overgrowth of c. diff?

kill of good bacteria, allowing c. diff to grow uncontrolled

What are two reasons why new antimicrobial drugs have not been developed?

1. drug companies aren’t investing money this because it is super expensive and they already aren’t getting anything in return.

2. commonly occurring antibiotics that are medically useful have been found.

How does AMR develop in hospitals, in the community and in agriculture?  What are some ways in which it spreads?

hospitals: heavy use of antibiotic

community: poor use of antibiotic/hygiene

agriculture: use of antibiotics on live stuck and antifungals on crops

What are some ways we can slow the spread of AMR? (Why is it important not to prescribe antibacterial drugs for viral infections, just in case.)

1. global surveillance and cooperation

2. responsibilities of healthcare workers

   1. increase efforts to identify cause of infection

   2. only prescribe antibiotics when absolutely necessary

   3. antimicrobial stewardships programs to monitor

3. prescribing antibiotics for viral infections is not useful, kills beneficial bactera, increases resistance

Are antimicrobial resistance genes new (since 1928)?  Why do they exist in nature?

They are not new. They exist in nature so that they can survive. They are changing to be the best fit for their environment. 

Can your microbiota become resistant to drugs?  Why might that be a problem?

yes, can make infections hard to treat, can kill of good bacteria causes overgrowth of bad bacteria, reduced drug effectiveness