(05) Antibiotic Resistance Flashcards
Differentiate between acquired and innate drug resistance.
Innate:
- exists prior to the use of the drug
Acquired:
- selection and accumulation of resistant strains
Gram (-) bacteria is mostly resistant to ß-lactams. what type of resistance does this bacteria have?
- Innate, most gram (-) and intracellular bacteria are ß-lactam resistant because of the barrier created by the cytoplasmic membrane
What are the 3 most common ways for a bacteria to acquire resistance to an antibiotic?
- which occur horizontally
- Chromosomal Mutations
- Transposons
- R-factor transfer
**R-factor much more likely to account for horizontal transfer than the other two
T or F: patients can only have infections that are multidrug resistant to drugs they’ve been treated with.
False, they can acquire MDR strains from other people
**NOTE: often the R-factor contains several MDR genes
5 basic tenants of antibiotic resistance
- It will emerge
- it will get more resistant
- likely to become resistant to other antibiotic
- They will persist
- use of antibiotics by one person affects other in extended and immediate healthcare environment
When would you use bactericidal antibiotics?
For:
- Potentially lethal infections
- Chronic infections
- Those involving Biofilms
When do you use bacteriostatic antibiotics?
When the immune system can be relied upon to assist in clearance.
What is the MIC?
- Minimum inhibitory concentration
- Lowest bacterial concentration that inhibits growth
How do we test for MIC?
- Kirby-Bauer method
- E Strip Test
How does E-strip test work?
- how do you find MIC?
- how do you find MBC (minimum bactericidal conc.)?
Stick contains serial dilutions
- Point where bacteria touch the stick = MIC
- MBC - bascially the same but might be a little bit more concentrated
T or F: antibiotic resistant bacteria is more virulent than other bacteria
False, just because its antibiotic resistant doesn’t mean its better at establishing infection
- in a world with no antibiotics the course of the infection would be the same
What is the reason for using multidrug therapy on bacteria?
- You double the unlikely hood of a favorable mutation conferring resistance
- Probably Synergy
- Likely Polymicrobial infection
- Uncertain Diagnosis
- Reduction of therapeutic levels of toxic drug
What are the 4 different mechanisms by which antibiotic resistance can be conferred?
- Exclusion
- Active Export
- MDR pumps - Target Alteration
- Drug inactivation
Exclusion
- Gram (-) approach
- Gram (+) approach
Gram (-)
- remove porins from surface
- remove transport system
- Alteration of membrane lipids
Gram (+)
- increased cell wall thickness (traps vancomycin)
Multidrug-Resistance Efflux Pumps
- what induces these?
- class?
- IMPORTANT FOR RES. TO WHAT DRUG?
- Induced in presence of drug
- ABC transporter
- TETRACYCLINE
Altered Targets
- targets that are most often altered?
- Ribosomes, topoisomerases, RNA polymerases, and TRANSPEPTIDASES (ignore ß-lacatams)
How does MRSA work?
- what is it resistant to?
- Resistant to ALL ß-lactams
- Have aqcuired TRANSPOSON containing mecA gene
- Encodes minor transpeptidase that works while the principle ones are being inhibited by ß-lacatams
Why are newer drugs designed to binds multiple sites?
- They prevent a Knockout alteration
What are VRE and VRSA
- how are they antibiotic resistant?
Vancomycin Resistant:
- Enterococci
- Staphylococcus Aureus
PLASMID containing VanA gene encodes an enzyme that makes D-Ala D-Lactate (instead of D-Ala D-Ala)
- Vancomycin can bind D-Ala D-lactate
What happens of MRSA aquired VanA plasmid?
You’re screwed because Vancomycin is usually used for MRSA infections
How does Chloramphenicol Resistance Arise?
- Methylation of 50S subunit prevents Chloramphenicol from binding
Why is antibiotic inactivation the most potent form of inactivation?
- 2 types of inactivation
- It doesn’t require sacrifice on any working part of the bacteria
2 types:
- Modification
- Destruction
Types of antibiotic inactivation through modification?
- what antibiotic is particularly susceptible to this?
- Acetylation, Phophorylation, adenylation of OH or NH groups
- Aminoglycosides are very susceptible
**Overall causes reduction of affinity for target
Why antibiotic type undergoes inactivation by destruction?
- enzyme responsible
- how do we prevent this?
ß-lactams by ß-lactamases (1st. found in S. aureus)
- Prevent by using Methicllin, Oxacillin or Cephalosporins that are bound by clavulanic acid
Where are ß-lactamases found?
- gram (+)
- gram (-)
- what modality does this resistance travel by?
Gram (+)
- secreted into immediate environment
Gram (-)
- Periplasmic space
*Travels via plasmid
Why are ß-lactamases more significant in Gram (-) bacteria?
- ß-lactamase gene is on a plasmid
- gram (-) bacteria are much more likely to exchange plasmids
What are ESBLs?
- what does they do?
- Associated bacteria?
Extended Spectrum ß-lactamases
- Can kill later generation drugs like cephalosporins
Associated with Gram (-) rods, including:
- E. Coli
- Klebsiella
- Pseudomonas
*many of these are MDR
What are 3 common types of ESBLs?
- TEMs
- SHVs
- CTX-M
Carbapenemase
- why is it worse than ESBL?
- Associated bacteria?
Cleaves:
- Carbapenems (alt. treatment for ESBL infects.)
- Penicillins
- Cephalosporins
Gram (-) rods:
- Klebsiella pneumoniae cabapenemase (KPC)
- NDM-1
**New MDR bacteria of hospitals
what are CRE?
Carbapenemase-resistan Enterobacteriaceae
MDR strains are often associated with…
Plasmid Transmission
Why should you limit use of fluroquinolone when treating gram (-) enteric infections?
Because of Multidrug Resistance Plasmids that also contain ß-lacatamases and aminoglycoside resistant gener
What are two primary factors that lead to antibiotic resistance?
- why?
- Overuse of antibiotics
- Antibiotic use for livestock
- antibiotic resistant bacteria become a part of their normal flora
What are the 5 keys to controlling antibiotic resistance?
- Developement of New Antibiotics
- Prudent use of existing antibiotics
- Development of more vaccines
- Better infection control in hosipitals
- Reduction of antibiotic use in the livestock industry
