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21 Cards in this Set
- Front
- Back
5 ways bacteria can develop antibiotic resistance:
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Mutation
Plasmid Transposon, insertion elements Transformation - from environment Transduction - from bacteriophage |
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4 Antibiotic resistance mechanisms:
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*Drug does not reach its target
*Drug is inactivated *Target is altered *Alternative metabolic pathway (competition of substrates) |
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Drug doesn't reach its target; how does this happen?
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*Permeability
*Porins (outer membrane gram negative) *Transport proteins -import (aminoglycosides) -export (efflux) |
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Resistance Mechanisms--The Drug is Inactive, how does this happen?
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*Antibiotic is inactivated (destroyed)
*Antibiotic is not activated |
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Resistance Mechanisms--Altered Target; how does this happen?
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*Target is altered so that the drug (antibacterial agent) no longer binds to the target
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Describe ß-Lactam resistance: 4 general mechanisms:
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*Beta-lactamases (inactivate drug)
*Porins (entry; drug does not reach its target) *Efflux pumps (drug does not reach its target) *Altered penicillin binding proteins (altered target) |
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Significance of ß-lactamases:
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*Beta-lactamases inactivate beta-lactam ring so that the compound is no longer active
*Very common mechanism of resistance *Many (>1,000) beta-lactamases *e.g. penicillinase (1% of dry weight) in Staphylococcus aureus carried on a plasmid, inducible *In gram negative bacteria the beta-lactamase is located in the periplasmic space *Numerous beta-lactamases in gram negative organisms |
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How do porin alterations confer antibiotic resistance to ß-lactams?
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*Porins in gram negative bacteria allow passage of beta-lactam antibiotic through the outer membrane
*Pseudomonas aeruginosa lacks classical high-permeability porins; hence beta-lactam can not reach its target in the periplasmic space *Mutations in porins |
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How do efflux pumps confer resistance to ß-lactams?
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*Not a common mechanism for beta-lactam resistance
*Pseudomonas aeruginosa contains efflux pumps that actively removes beta-lactam antibiotics from the periplasmic space |
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Describe the significance of altered PBPs in ß-lactam resistance:
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*Altered target
*Differences in binding affinity of specific PBP (penicillin binding proteins) may explain differences in activity among different bacteria *Alteration of several PBPs must decrease for an organism to be resistant *MRSA transposon with PBP2b *S. pneumoniae mosaic genes (transformation) |
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Describe Vancomycin Resistance:
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*Enterococci that are vancomycin resistant (VRE) contain a plasmid with at least seven genes involved in the production of D-alanyl-D-lactate that does not bind to vancomycin
*S. aureus (VRSA) contain enterococcal vancomycin resistance genes |
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What are the 4 mechanisms of macrolide resistance?
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*Modified ribosome (altered target) methylated
*Efflux pumps *Modified ribosome: point mutation (rRNA) *Modified ribosome: ribosomal protein |
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How are targets altered to develop macrolide resistance?
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*Phenotype MLSB
*Resistance to macrolides, lincosamides and streptogramin type-B *Bacterial ribosome is methylated (A2058) so that these antibiotics do not bind to their target *Methylase expressed constitutively or inducibly in strep and staph *Cross resistance to all MLSB compounds: macrolides, lincosamides, and streptogramin type-B |
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How do efflux pumps cause macrolide resistance?
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*Remove macrolides from the cell’s interior
*Energy dependent *mef gene in streptococci uses proton motive force; most common mechanism of resistance in S. pneumoniae in United States |
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How do altered ribosomes contribute to macrolide resistance?
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*Point mutations A2059G
*Mutations/insertions of ribosomal protein L4 or L22 in Streptococcus pneumoniae |
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Clinical Significance of Antibiotic Resistance:
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*Delay in instituting appropriate treatment
*Increased morbidity and mortality *Must use costlier antibiotics *Newer antibiotics result in new toxicities and selection pressure *Not always clear how to best use antibiotics *Role of combination therapy to prevent emergence of resistance *Antibiotics in animal feeds and other uses |
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General rules for treatment of infections:
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*Remove foreign body
*Drain abscess and remove necrotic tissue *Appropriate antibacterial -Most active against infecting bacteria -Narrow spectrum -Least toxic -Cost |
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Describe misuse and overuse of antibiotics:
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*Using antibiotics to treat untreatable infections, e.g. viral infection
*Using antibiotics to treat bacterial infections when there is no impact on natural history of infection *Treating fever of undetermined origin with antibiotics *Improper dosing -too much -too little *Relying on antibiotics alone -removal of foreign body -surgical drainage of abscess *Lack of adequate bacteriological information -Cultures not obtained -Or cultures obtained after antibiotics are started |
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History of staph aureus resistance:
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*Penicillin
Penicillinase (1945) *Methicillin MRSA (1961) multidrug resistant *Vancomycin VRSA (2002) vancomycin resistant MRSA |
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What all can strep pneumoniae be resistant to?
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Penicillin
Cefotaxime/ceftriaxone Erythromycin (macrolides) TMP/SMX Tetracycline Chloramphenicol Quinolones Rifampin |
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What drug must you use in resistant klebsiella pneumonia?
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tigecycline (a bacteriostatic)
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