Antibiotic resistance Flashcards
Define Antibiotic Resistance
The ability of an organism to survive treatment with an antibiotic (evade antibiotics)
How does Penicillin work?
Penicillin binds to the PBP (preventing the PBP from cross linking the amino acid strands in the cell wall)
When PBP is unable to cross link the amino acids in the cell wall …the cell wall is weakened and eventually leads to rupture of the bacteria (due to osmotic pressure)
what is the function of PBP?
PBP (penicillin binding protein) cross link the amino acid strands (in the cell wall of bacteria) to strengthen the cell wall.
What is the mechanism PRSP (?) uses for resistance and how did it probably acquire resistance?
Penicillin resistant S. pneumonia
Alterations in one or more penicillin binding proteins
Originated through the acquisition of foreign DNA leading to altered PBP’s that spread as a result of selective pressure and clonal dissemination
Probably from viridian strep
Define antibiotic selective pressure
Refers to impact of antimicrobial use on a population of organisms, in which organisms that are resistant to the antibiotic gain a survival advantage over those susceptible to an antibiotic
In DEVELOPING countries what is thought to have led to an increase in non-typhoidal floroquinolone resistant salmonella?
Unregulated antimicrobial dispensing for human use
In DEVELOPED countries what is thought to have led to the increase in non-typhoidal fluoroquinolone resistant Salmonella?
Extensive use of antimicrobials in food, animals to improve growth rate
Define MRSA
HA-MRSA
CA-MRSA
MRSA-methicillin resistant S.
HA-MRSA- hospital/healthcare acquired MRSA
CA-MRSA- Community acquired MRSA
Explain the differences between HA-MRSA and CA-MRSA
HA-MRSA. - more frequently carries and SCC mec element from groups I-III
Limited number of clones
Only five clones associated with HA-MRSA
These tend to be resistant to other antibiotics in addition to methicillin
tend to be associated with wound infection, surgical incision, opportunistic infection
CA-MRSA- more skin manifestation, distinguished by mobile chromosomal cassette SCC which carries the methicillin resistant gene mec contains a novel SCC mec type known as SCC mec type IV
SCC mec IV- Smaller in size and more mobile
Usually sensitive to antibiotics
Define clonal dissemination
Spread of specific clones of an organism throughout the community.
These clones are thought to be more transmissible than other clones
Why might a reduction in the use of antibiotics not lead to a reduction in infections that are caused by resistant organisms
If the expression of the resistant gene already exist -and there is no fitness cost component-then if you remove selection pressure (drug) –there is no incentive for the organism to remove the resistant gene
define protection of the target
when bacteria produce a different molecule (usually a protein) that protects the target
example: bacteria will produce a protein that alters the binding sites on its ribosome —this renders tetracycline ineffective because tetracyclines target is the ribosome.
explain altered target
some bacteria can express proteins with decreased affinity for an antibiotic
example : altered PBP –decreases the ability for penicillin to bind—rendering penicillin ineffective
explain efflux
proteins that pump drugs out of the cell
Expressed protiens that pump drugs out of the cell
this doesn’t allow drug to build up in the cell and renders drug ineffective
describe decreased cell permeability
porins particularly in gram neg cells
decreased porin expression- which decrease the amount of antibiotic that can ENTER the cell
Aminoglycosides (class of drugs)
- inhibits?
- resistant organisms produce?
- example (drug) name of an aminoglycoside?
- specific name of resistant enzyme?
- inhibits protien sysnthesis
- resistant enzyme: Aminoglycoside modifing enzyme
- Drug: Chloramphenicol
- Resistant enzyme: chloramphenicol acetyl transferase
explain how natural selection is at the heart of antibiotic resistance
Natural selection -> drug tx-> kills susceptible bacteria -> resistant bacteria are able to continue growing (BASIC SELECTION)
ON TOP OF THE BASIC SELECTION :
Drug tx -> kills normal flora in gut (commensal bacteria) creates opportunity for the growth of resistant bacteria
How do bacteria become resistant?
vertical transfer
horizontal transfer
societal pressures
selection pressure
explain vertical transfer
(parent to offspring)
1) spontaneous mutations (mistakes)
2) adaptive mutations (happens in cells that grow slowly or not at all )–stress response** slowly spread
horizontal transfer
1) Transformation- cell dies – naked DNA picked up by another cell
2) Conjugation – (direct transfer) – plasmid in one cell but not another the cell with the plasmid will develop a sex pillus and transfer the plasmid DNA containing the resistance to confer resistance
3) Transduction- virus mediated- virus incorporate their DNA into the bacterial genome .**look this one up to get a clearer definition ** (bacteriophages)
4) Outer membrane vesicles ( gram neg )- on the out membrane of the cell (blubs) can contain DNA , they are sloughed off into the intra-cellular space where they are sometimes picked up and incorporated into other cells.
societal pressures that increase resistance
1) Poor compliance (failing to take entire regimen)
2) Inappropriate use (prescribing antibiotics for viral infections etc)
3) Poor manufacturing/storage of antibiotics
4) Agricultural use of antibiotics (**1/2 of antibiotics manufactured are given to animals in the US.) subtherapeutic doses to promote growth, and improves feed efficiency (can feed animals less and they grow more)—METAPHALAXIS is when a few animals are sick so you tx the entire herd (all members whether or they are sick. (mass tx to treat a small # of sick animals) POOR REGULATION- no reg of drugs given to animals.
5) Decreased effective dose (drug interaction – pts on polyphamecutical regimen
6) Water pollution (run off from farms) – pharmaceuticals found in water supply.
explain selection pressure
environmental conditions leading to differential fitness in a population (the population is a bacteria)
list the 7 major threats (antibiotic resistant bacteria by name)
Extended spectrum Beta-lactamase (ESBL) Producing eterobacteriaceae
Carbepenem resistant enterobacteriaceae (CRE)
Multidrug resistant acinetobacter
drug resistant neisseria gonorrhoeae
vancomycin resistant enterococcus (VRE)
Methicillin resistant Staphyloccus aureus (MRSA)
Vancomycin resistant S. aureus (VRSA)
give details about Extended spectrum Beta –lactamase (ESBL) Producing eterobacteriaceae
these bacteria are resistant to nearly all penicillins and cephalosporins . (they tend to be resistant to aminoglycosides and quinolones)
RESISTANCE to the PENICILLINS is plasmid based
Because of the ESBL resistance THEY MUST BE TX-ED WITH CARBEPENEM
These tend to be Nosocomial infections (about 26 thousand infections/year in US)
give details about RESISTANT ENTEROBACTERIACEAE (CRE)
CDC LISTS AS TOP THEAT*
resistant to nearly all antibaiotics
typically Nosocomial infections
about 9000 cases/year
give details about RESISTANT ACINETOBACTER
Normally found in soil, water, and as commensals (become an issue when found in sx incision site)
63% are multidrug resistant
MEANING THEY ARE RESISTANT TO AT LEAST 3 CLASSES OF ANTIBIOTICS
As a group they produce inactivating enzymes
They will express altered porins
They will express altered target of drugs (quinolone drug)
They will express Efflux pumps
SOME ARE PLASMID BASED SOME ARE CROMOSOMAL BASED USUALLY NOSOCOMIAL
(may not all be present at one time in all isolates)
give details about RESISTANT NEISSERIA GONORRHOEAE
(***2ND MAJOR THREAT ACCORDING TO CDC)
About 800,000/year cases and about 240,000/year are resistant
1993 ->ciprofloxacin and cephalosporin (the bacteria used to be susceptible to cipro and cephalosporin)
2007-> almost 15% resistant to cipro now (concern that they will eventually become resistant to both)
give details about
Vancomycin RESISTANT ENTEROCOCCUS (VRE)
Resistant to nearly all antibiotics
Plasmid based
General nosocomial (but there can be community based infections)
About 66,000 infections/year 20,000 resistant infection/year
give details about RESISTANT STAPHYLOCOCCUS AUREUS (MRSA)
Nosocomial infections and community associated stains
About 80,000 severe MRSA infection/year and about 11,000 deaths
(are resistant to a lot of antibiotics
give details about RESISTANT S. AUREUS (VRSA)
resistant to everything MRSA is and also resistant to methicillin
13 cases in the US
How do microorganisms develop resistance to penicillin (what happens inside the cell)
Organisms produce a beta- lactamase (an enzyme that hydrolyzed beta lactam ring)
The beta-lactamase cleaves the beta lactam ring (opens it up and penicillin can no longer barring therefore penicillin is ineffective)
Which antibiotics are given to treat penicillin resistant organisms?
And which antibiotics are used as a last resort treat to penicillin resistant organisms?
Cephalosporins
Carbopenems ( last resort)
