Β-lactam resistance: Difference between revisions
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Β-lactam resistance
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*Based on amino acid sequences rather than function |
*Based on amino acid sequences rather than function |
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− | *Classes A, C, and D are serine ß-lactamases |
+ | *Classes A, C, and D are serine ß-lactamases, while class B are metallo-β-lactamases |
− | *'''Class A:''' original active-site serine ß-lactamases |
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− | *'''Class B:''' original metallo-ß-lactamases |
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− | *'''Class C:''' AmpC ß-lactamases |
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− | *'''Class D:''' OXA ß-lactamases |
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+ | {| class="wikitable" |
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+ | |+ |
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+ | !Ambler |
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+ | !Binding Site |
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+ | !Examples |
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+ | !Inhibitors |
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+ | |- |
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+ | |A |
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+ | |serine |
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+ | |TEM, SHV, KPC, CTX-M, GES |
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+ | |avibactam, vaborbactam, relebactam |
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+ | |- |
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+ | |B |
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+ | |metallo |
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+ | |VIM, NDM, IMP |
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+ | | |
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+ | |- |
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+ | |C |
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+ | |serine |
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+ | |AmpC, P99 |
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+ | |avibactam, vaborbactam, relebactam |
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+ | |- |
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+ | |D |
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+ | |serine |
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+ | |OXA (oxacillinase) enzymes |
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+ | |avibactam (OXA-48) |
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+ | |} |
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+ | <br /> |
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===Specific ß-lactamases=== |
===Specific ß-lactamases=== |
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====NDM-1==== |
====NDM-1==== |
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*Broad-spectrum metallo-beta-lactamase and carbapenemase |
*Broad-spectrum metallo-beta-lactamase and carbapenemase |
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− | *Can be treated empirically with [[ceftazidime-avibactam]] and [[aztreonam]] +/- [[colistin]] |
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==Efflux Pumps== |
==Efflux Pumps== |
Revision as of 07:06, 3 September 2020
Mechanisms
- ß-lactamase production: enzymatic breakdown of beta lactam antibiotic
- Penicillin binding protein mutations (e.g. MRSA)
- Efflux pump mutations
- Porin channel mutations that reduce antibiotic influx
β-lactamases
Ambler Classification of ß-lactamases
- Based on amino acid sequences rather than function
- Classes A, C, and D are serine ß-lactamases, while class B are metallo-β-lactamases
Ambler | Binding Site | Examples | Inhibitors |
---|---|---|---|
A | serine | TEM, SHV, KPC, CTX-M, GES | avibactam, vaborbactam, relebactam |
B | metallo | VIM, NDM, IMP | |
C | serine | AmpC, P99 | avibactam, vaborbactam, relebactam |
D | serine | OXA (oxacillinase) enzymes | avibactam (OXA-48) |
Specific ß-lactamases
NDM-1
- Broad-spectrum metallo-beta-lactamase and carbapenemase
Efflux Pumps
- Major cause of resistance in Pseudomonas aeruginosa and similar species
- e.g. MexAB-OprM, which confers broad antimicrobial resistance including cephalosporins and some carbapanems
Porin Loss
- Most common cause of carbapenem resistance in Pseudomonas aeruginosa