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 ==
+==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
+*ß-lactamase production: enzymatic breakdown of beta lactam antibiotic
-== Ambler Classification of ß-lactamases ==
+*Penicillin binding protein mutations (e.g. MRSA)
+*Efflux pump mutations
+*Porin channel mutations that reduce antibiotic influx
+===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
-* Class B: original metallo-ß-lactamases
-* Class C: AmpC ß-lactamases
-* Class D: OXA ß-lactamases
-== Specific ß-lactamases ==
+*Also see [[Β-lactamases]]
-=== NDM-1 ===
+====Ambler Classification of ß-lactamases====
-* Broad-spectrum metallo-beta-lactamase and carbapenemase
-* Can be treated empirically with [[ceftazidime-avibactam]] and [[aztreonam]] +/- [[colistin]]
+*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="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]]