Β-lactam resistance: Difference between revisions

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

@@ Line 1: / Line 1: @@
+{{DISPLAYTITLE:β-lactam resistance}}
 ==Mechanisms==
@@ Line 6: / Line 8: @@
 *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
-*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]]