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 |
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*'''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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|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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|B |
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|metallo |
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|VIM, NDM, IMP |
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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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|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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===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== |
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Revision as of 11:06, 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
