Β-lactam resistance: Difference between revisions

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Β-lactam resistance
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{{DISPLAYTITLE:β-lactam resistance}}

==Mechanisms==
==Mechanisms==


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*Porin channel mutations that reduce antibiotic influx
*Porin channel mutations that reduce antibiotic influx


== β-lactamases ==
===β-lactamases===


===Ambler Classification of ß-lactamases===
*Also see [[Β-lactamases]]

====Ambler Classification of ß-lactamases====


*Based on amino acid sequences rather than function
*Based on amino acid sequences rather than function
*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
{| class="wikitable"
*'''Class B:''' original metallo-ß-lactamases
!Class
*'''Class C:''' AmpC ß-lactamases
!Binding Site
*'''Class D:''' OXA ß-lactamases
!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]]


===Specific ß-lactamases===
===Efflux Pumps===
====NDM-1====


*Major cause of resistance in [[Pseudomonas aeruginosa]] and similar species
*Broad-spectrum metallo-beta-lactamase and carbapenemase
*e.g. MexAB-OprM, which confers broad antimicrobial resistance including cephalosporins and some carbapanems
*Can be treated empirically with [[ceftazidime-avibactam]] and [[aztreonam]] +/- [[colistin]]


== Efflux Pumps ==
===Porin Loss===


* Major cause of resistance in [[Pseudomonas aeruginosa]] and similar species
*Most common cause of carbapenem resistance in [[Pseudomonas aeruginosa]]
* e.g. MexAB-OprM, which confers broad antimicrobial resistance including cephalosporins and some carbapanems


== Porin Loss ==
== Management ==


* See also [[Carbapenem-resistant organisms]]
* Most common cause of carbapenem resistance in [[Pseudomonas aeruginosa]]


[[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

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

Management