Β-lactam resistance: Difference between revisions
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Β-lactam resistance
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{{DISPLAYTITLE:β-lactam resistance}} |
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==Mechanisms== |
==Mechanisms== |
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*Porin channel mutations that reduce antibiotic influx |
*Porin channel mutations that reduce antibiotic influx |
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===β-lactamases=== |
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*Also see [[Β-lactamases]] |
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====Ambler Classification of ß-lactamases==== |
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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="wikitable" |
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*'''Class B:''' original metallo-ß-lactamases |
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!Class |
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*'''Class C:''' AmpC ß-lactamases |
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!Binding Site |
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*'''Class D:''' OXA ß-lactamases |
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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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|- |
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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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====Specific ß-lactamases==== |
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*TEM-1: most common β-lactamase in Gram-negative bacteria |
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*KPC: most common carbapenemase |
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*OXA-48: most common carbapenemase in [[Acinetobacter]] |
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=== |
===Efflux Pumps=== |
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====NDM-1==== |
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*Can be treated empirically with [[ceftazidime-avibactam]] and [[aztreonam]] +/- [[colistin]] |
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===Porin Loss=== |
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* |
*Most common cause of carbapenem resistance in [[Pseudomonas aeruginosa]] |
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== Management == |
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* See also [[Carbapenem-resistant organisms]] |
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[[Category:Antibiotics]] |
[[Category:Antibiotics]] |
Latest revision as of 16:10, 2 April 2022
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
- Also see 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
Class | 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
- TEM-1: most common β-lactamase in Gram-negative bacteria
- KPC: most common carbapenemase
- NDM-1: broad-spectrum metallo-β-lactamase and carbapenemase
- OXA-48: most common carbapenemase in Acinetobacter
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
Management
- See also Carbapenem-resistant organisms