Antibiotics Flashcards
Difference between bacteriostatic and bactericidal antibiotics?
Bacteriostatic = prevent growth and allow immune system to kill Bactericidal = kill bacteria directly
When should you start a broad range antibiotic? What are the side effects?
If the microbe is unknown and treatment needs to be started immediately. Causes disruption of natural flora and Gi distress.
What does an antibiogram consist of?
Susceptibility profile including Minimum inhibitory concentrations (MIC). Identifying effective therapies to exceed MIC and MBC levels.
What are common side effects of antibiotics?
Tetracycline = discoloration of teeth
Streptomycin = auditory damage
Chloramphenicol = anemia
- alters flora, diarrhea, prophylaxis, Abx Resistance
What is the problem with treating C. Difficle?
The antibiotics used to treat C.Diff can also prevent the natural flora from recolonizing allowing C.Diff to continue to populate without competition.
How can bacteria develop resistance?
Horizontal gene transfer and spontaneous mutations.
- modify abx or target
- reduction in abx concentration by pumps/permeability
What are the key differences in Gram Positive vs Negative?
Gram Positive = Significant amount of peptidoglycan layer and no outer membrane
Gram Negative = small amount of peptidoglycan with an outer membrane and porins
What are the three main steps in synthesis of peptidoglycan?
- Synthesis of the precursors that have the terminal D-Ala + D-Ala
- Transport across the membrane to the extracellular space
- Polymerization and cross-linking of L-Ala+L-Ala to Lys and D-Ala
Where do beta-lactams work and how?
Beta-Lactams bind Penicillin Binding Proteins (PBPs) inhibiting them from cross-linking the peptides to make peptidoglycan. Beta-Lactams mimic the natural substrate in the active site.
What are the two types of resistance from penicillin?
Encoding Beta-Lactamases and extended spectrum that degrade more than one B-lactams
Mutations of PBP
What organism has B-lactamase encoded in their genome?
Pseudomonas. (E. Coli is frequently resistant as well)
What type of organisms usually have Beta-Lactamase compared to mutations in PBP?
Beta-Lactamase = Gram Negative
PBP Mutations = Gram Positive
How can you overcome an organism with B-lactamase?
Clavulanic Acid inhibits the B-lactamase and use a B-lactam at the same time.
What are the most common organisms that are gram positive to become resistant to B-lactams?
Streptococcus and Staph (MRSA)
How can you overcome gram positive cocci that is resistant to B-lactams?
There is not a remedy other than using a different type of antibiotic such as Vancomycin.
What is a common Glycopeptide and how does it work?
Vancomycin. Binds the D-Ala-D-Ala end of the precursor peptide to prevent synthesis of peptidoglycan.
When is Vancomycin primarily used?
Gram Positive organisms when resistant to B-lactams.
Can’t fit well through outer membrane of gram negative
What organism is typically associated with vancomycin resistance?
enterococci in hospital settings. Vancomycin-Resistant Enterocci. (VRE) Be aware it can transfer the resistance to Staph if in the same wound or area.
Where does cycloserine act in peptidoglycan synthesis?
Structurally similar to D-Ala, prevents the D-Ala-D-Ala synthesis due to having higher affinity than endogenous substrate and preventing cross-linking.
-inhibits Alanine Racemase and Synthase
When is cycloserine usually used?
Used as a second-line therapy for TB treatment.
How does Bacitracin work and where is it used?
Binds to Bactoprenol-PP preventing the recycling of lipid carriers moving peptidoglycan.
– TOPICAL ONLY – Used for both Gram +/-
What are the two lipopeptides in the class and how do they work?
Daptomycin - Gram Positive Only - binds cytoplasmic membrane, narrow spectrum.
Polymyxins - Gram Negative - binds LPS on outer membrane. Toxic, limited use.
What are the difference between bacterial ribosomes and human?
Bacterial - 30S and 50S = 70S
Human - 40S and 60S
What do the tetracyclines target and what are in the class?
Tetracyclins target - 30S subunit to inhibit protein synthesis. Broad spectrum/bacteriostatic
Include: Doxycyline, Tetracycline, and Minocycline
How can an organism become resistant to Tetracyclines?
Efflux Pumps and Ribosome mutations.
- Much more common/wide spread due to overuse
What can be used on hard to kill Gram Negatives such as Pseudomonas Aeruginosa?
Aminoglycosides. Irreversibly bind 30S causing misreading and inhibition of protein synthesis.
How are aminoglycosides typically resisted by bacteria?
Modifying the antibiotic with transferases inactivating it.
How do Macrolids work and who do they work on?
Gram Positive. Bacteriostatic. Binds 50S and blocks elongation. Useful when allergic to B-lactams.
Included: Erythromycin and Azithromycin
How can bacteria become resistant to Macrolids?
Methylating the binding site on the 50S blocking the abx
What kind of infections is Chloramphenicol typically used for?
Severe infections like Typhoid or Rocky Mountain Fever, due to causing anemia because of nonselectivity.
- inhibits pepidyl transferase
What kind of bacteria does Clindamycin usually treat?
Gram Positive - Community MRSA and S. Aureus (skin)
–binds 50S preventing elongation– Bacteriostatic
What kind of cross reactivity does Clindamycin have?
If the bacterium is resistant to Macrolids, then they are also resistant to Clindamycin.
How does Linezolid work?
Binds a unique site of the 50S Ribosome preventing formation of the 70S complex.
Gram Positive Only
When would someone use Linezolid?
Used with complicated skin and structure infections, can become resistant by a single point mutation of the ribosome. Usually Staph strains.
What are the inhibitors of DNA synthesis?
1st Generation - Nalidixic Acid - narrow
2nd Generation - Fluoroquinolones - Broad
- Cipro, Levo, Moxi
What is the mechanism of action of DNA synthesis antibiotics?
Binds DNA Gyrase/Topoisomerase disrupting DNA replication and repair.
Resistance: Point mutations and Drug modification
What is Metronidazole commonly used to treat?
Typically Anaerobic infections due to targeting DNA with free radicals.
– C. Difficle Treatment
What are two RNA Polymerase inhibitors?
Rifampin and Fidaxomicin
-binds RNA Polymerase inhibiting it’s action
What are two inhibitors of the Tetrahydrofolate pathway?
Sulfonamides - similar to p-aminobenzoic acid
Trimethoprim - inhibits dihydrofolate reductase
When two antibiotics complement one another’s action they are thought to be?
Synergistic
Why do bacteriostatic and bactericidal drugs not work well together?
Due to the bactericidal drugs killing the bacterium when they are dividing, but bacteriostatic prevent them from dividing.
Where are biofilms typically located and how do they effective treatment?
Biofilms are usually found on implanted devices or tubes and the bacteria can reside there unaffected by antibiotics. Only cure is to remove the device.
