Β-lactam resistance: Difference between revisions

From IDWiki
Β-lactam resistance
m (Aidan moved page Antimicrobial Beta-lactam resistance to Beta-lactam resistance without leaving a redirect)
No edit summary
 
(13 intermediate revisions by the same user not shown)
Line 1: Line 1:
= Beta-lactam resistance =
{{DISPLAYTITLE:β-lactam resistance}}


== Mechanisms ==
==Mechanisms==


* ß-lactamase production: enzymatic breakdown of beta lactam antibiotic
*ß-lactamase production: enzymatic breakdown of beta lactam antibiotic
* Penicillin binding protein mutations (e.g. MRSA)
*Penicillin binding protein mutations (e.g. MRSA)
* Efflux pump mutations
*Efflux pump mutations
* Porin channel mutations that reduce antibiotic influx
*Porin channel mutations that reduce antibiotic influx


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


*Also see [[Β-lactamases]]
* Based on amino acid sequences rather than function

* Classes A, C, and D are serine ß-lactamases
* Class A: original active-site serine ß-lactamases
====Ambler Classification of ß-lactamases====

* Class B: original metallo-ß-lactamases
*Based on amino acid sequences rather than function
* Class C: AmpC ß-lactamases
* Class D: OXA ß-lactamases
*Classes A, C, and D are serine ß-lactamases, while class B are metallo-β-lactamases

{| class="wikitable"
!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]]

[[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