Intro to Antibiotics Flashcards
Define antibiotic
Natural compound produced by bacteria or fungi to suppress growth of other microorganisms
Define antimicrobial
Synthetic agents to suppress growth of microorganisms
Define bactericidal
Kills organism directly
Define bacteriostatic
Prevents reproduction
How long does it take for a bacteria to reproduce?
20 minutes
Penicillins are _________; Sulfonamides are _________
Penicillins are antibiotics/bactericidal
Sulfonamides are antibicrobials/bacteriostatic
Which drugs inhibit cell wall synthesis?
Bacitracin
B-lactams
Vancomycin
Cycloserin
Which drugs inhibit DNA replication?
Quinolones
Nitroimidazoles
Which drugs inhibit DNA-Dependent RNA polymerase?
Rifampin
Rifabutin
Which drugs inhibit protein synthesis?
Aminoglycosides Macrolides Ketolides Lincosamides Streptogramins Tetracyclines Glycyclines Chloramphenicol Oxazolidinones
Which drugs inhibit Cell membranes?
Polymyxins
Daptomycin
Which drugs affect folic acid metabolism?
Trimethoprim
Sulfonamides
Sulfones
What are the factors influencing selection of an antimicrobial agent?
Identify the organism Resistance Microbial susceptibility Bactericidal vs bacteriostatic Knowledge of the patient Pharmacokinetics/Metabolism Other factors (allergies, prior adverse drug reactions, contraindications)
Describe “indiscriminant use” in terms of resistance
Increased exposure to antibiotics due to things like using antibiotics for viral infections and increasing use of antibiotics in animals for eating
Which examples of bugs are resistant to all known drugs?
Enterococci
Enterobactor
Pseudomonas
Where in the US is MRSA most prevalent?
Southeast
59% prevalence average in the US
How does the US compare globally for MRSA?
US has 55% prevalence
Canada has 2.3% and Netherlands has
What examples are there of sensitivity testing?
Disk diffusion
Microdilution
E-test
Describe the disk diffusion test
Used to detect antimicrobial/antibiotic sensitivity
An agar plate is spread with bacteria, when filter papers soaked with different antimicrobials/antibiotics are placed on the plate with different doses
The bacteria are allowed to grow at 37 degrees for 18-24 hours, an the agents to which the bacteria are most susceptible have a large ring around them where the bacteria did not grow
Describe the test for MIC
Minimum inhibitory concentration
A lot of test tubes are filled with growth medium
Then you have one control (no antibiotic) and slowly add more to increasing concentrations
The first test tube that has no growth in it is the MIC, which is the least amount of antibiotic needed to prevent replication (usually pick 2-3x the MIC for the dose)
Describe the test for MBC
Minimum bactericidal concentration
Take the test tube from MIC and the ones beyond it (with higher concentrations) and plate them
The plate that has no growth is the lowest concentration at which you’ll kill ALL of the bacteria
Why would you consider host immune defenses when selecting an antibiotic?
Bacteriostatic would not be ideal for someone that is immunocompromised because the drug can only stop replication, to get rid of the infection we depend on the host’s immune system to kill off what is left
Why do we care about the status of the immune system for selecting an antimicrobial agent?
We care about white cell function (T cells and B cells)
He didn’t go into too much detail about this
Why do we care about age when selecting an antimicrobial agent?
Avoid tetracyclines in children. Tetracyclines bind calcium and stain your teeth, do not use in children under 14 because their teeth are still growing
Also do not use chloramphenicol in babies - grey baby children
Chloramphenicol has to be glucuronidated, and the enzymes that do this aren’t developed until 6 months to 1 year, and that can lead to toxicity.
Which drug causes teeth staining?
Tetracyclines
Which drug causes gray baby syndrome? Why?
Chloramphenicol
Babies don’t have enzymes for glucuronidation, chloramphenicol use can cause toxicity
Why do we care about diabetes when selecting an agent?
High blood sugar enhances bacterial growth, uncontrolled diabetic patients have poor wound healing
Why do we care about pregnancy when selecting an agent?
Some antibiotics can cross the placenta. We do not want the baby to get the same dose of antibiotic as the mother.
Also be aware of breast feeding bc some agents pass through the breast milk. Passing antibiotics onto the baby may also increase resistance development.
When do we use combination therapy? (multiple agents at once)
Treatment of life-threatening infections in which causative organism is unknown
Treatment of polymicrobial infections (esp abdominal contamination)
Enhanced antimicrobial activity (can use two agents to have synergistic effect, ie Penicillins and Aminoglycosides have synergistic effect in treating pseudomonas aeruginosa infection)
Treatment of resistant strains
Permits lower doses of each (lower toxicity)
Possibly reduces emergence of resistant strains (NEVER BEEN PROVEN CLINICALLY)
Why do penicillins and aminoglycosides have a synergistic effect?
Penicillin affects the cell wall and makes it easier for aminoglycosides to get into the bacteria and have its effects
What is the main mechanism by which ALL bacteria develop resistance?
Selection
As bacteria replicate, various small mistakes are made in DNA replication, these can lead to resistance
Can make bacteria more OR less sensitive!
What role do enzymes play in resistance?
Penicillinase
Carbepenemases
Cephalosporinases
These can be developed in bacteria that will destroy the beta lactam structure of the antibiotics, which are essential for antibiotic activity
How can bacteria change their permeability to drugs?
Through porins
(Beta lactamase activity)
Can decrease permeability of agents into the cell
Which drugs have resistance developed against them bc of changes in efflux pathways?
Tetracyclines
Chloramphenicol
Macrolides
Transporters bind them and immediately send them back outside of the cell
Which drugs are especially sensitive to resistance to changes in affinity of site of active drug?
Protein synthesis inhibitors bc there is a loss or alteration of binding proteins
Which drugs are sensitive to resistance developed due to altered metabolic pathways?
Sulfonamides
Increased production of PABA in the cell makes sulfonamides useless bc there is less competition (more PABA = less binding of sulfonamides)
What role do spores play in resistance?
Microorganisms can go into a dormant state (spores - anthrax). When conditions aren’t favorable for growth, they stop metabolic activity and form protective proteins around the DNA. After many years the spores can regenerate active bacteria
What genetic changes contribute to resistance?
Mutational resistant (chromosomal)
Conjugation (Plasmid transfers - common among gram negative, vancomycin)
Transduction (bacterial DNA transferred through phages, important in S Aureus)
Transformation (free DNA is absorbed from the environment - can alter penicillin binding proteins)
When is it appropriate to treat prophylactically with antibiotics?
Heart valves
Surgery