Β-lactamases: Difference between revisions

Revision as of 09:08, 12 September 2020

Background

Includes a spectrum of molecules that hydrolyze β-lactams, from penicillins to carbapenems
- See also extended-spectrum β-lactamases and carbapenemases

Ambler Classification

Classification based on amino acid sequences rather than function

Class	Binding Site	Examples	Inhibitors
A	serine	TEM, SHV, KPC, CTX-M, GES	clavulanic acid, tazobactam, avibactam, vaborbactam, relebactam
B	metallo	VIM, NDM, IMP
C	serine	AmpC, P99	avibactam, vaborbactam, relebactam
D	serine	OXA (oxacillinase) enzymes	avibactam (OXA-48), ±clavulanic aciid

Serine β-lactamases

Amber classes A, B, and C are the serine β-lactamases
Contain a serine residue at the active site
Class A: inhibited by clavulanic acid or tazobactam
- Constitutively expressed plasmid
- Most common ESBL in Gram-negative bacteria
- Resistance to 2nd and 3rd generation cephalosporins
- Common in E. coli, Klebsiella, and Proteus spp.
- Examples include:
  - Penicillinases: TEM-1 (common in GNBs), SHV-1
  - ESBLs: CTX-M, TEM-3
  - Carbapenemases: K. pneumoniae carbapenemase (KPC)
Class C: not inhibited by clavulanic acid or EDTA, resistant to cefoxitin, inhibited by cloxicillin in vitro
- AmpC = chromosomal
- Often an inducible AmpC gene present in the genome
- Common in Citrobacter, Serratia, and Enterobacter
Class D: not inhibited by EDTA, variably inhibited by clavulanic acid; hard to identify
- Common in Pseudomonas
- Difficult to detect with routine screening
- Examples include:
  - ESBLs: OXA-11
  - Carbapenemases: OXA-23, OXA-48

Metallo-β-lactamases

Ambler Class B are the metallo-β-lactamases
Contain a zinc ion at the active site
Inhibited by EDTA, not inhibited by clavulanic acid
Examples include:
- Carbapenemases:
  - New Delhi metallo-beta-lactamase (NDM-1)
  - Imipenemases (IMP)
  - Verona integron-encoded metallo-β-lactamases (VIM)
  - L1 β-lactamase, present in the Stenotrophomonas maltophilia chromosome

Epidemiology

The most common β-lactamase is TEM-1
The most common carbapenemases in the US are KPCs, followed by NDM and OXA-48-like carbapenemases

Management

Antibiotic therapy tailored to the resistance pattern
Carbapenems, aminoglycosides, fluoroquinolones, and TMP-SMX typically work well

@@ Line 1: / Line 1: @@
 ==Background==
+* Includes a spectrum of molecules that hydrolyze [[β-lactams]], from penicillins to carbapenems
-===Classification===
+** See also [[extended-spectrum β-lactamases]] and [[carbapenemases]]
+===Ambler Classification===
-*Classes A, B, and C: serine β-lactamases
-**'''Class A''': inhibited by clavulanic acid or tazobactam
+*Classification based on amino acid sequences rather than function
-***Constitutively expressed plasmid
-***Most common ESBL in Gram-negative bacteria
+{| class="wikitable"
-***Resistance to 2nd and 3rd generation cephalosporins
+!Class
-***Common in ''[[E. coli]]'', ''[[Klebsiella]]'', and ''[[Proteus]]'' spp.
+!Binding Site
-***Examples include:
+!Examples
-****Penicillinases: TEM-1 (common in GNBs), SHV-1
+!Inhibitors
-****ESBLs: CTX-M, TEM-3
+|-
-****Carbapenemases: ''K. pneumoniae'' carbapenemase (KPC)
+|A
-**'''Class C''': not inhibited by clavulanic acid or EDTA, resistant to cefoxitin, inhibited by clox in vitro
+|serine
-***AmpC = chromosomal
+|TEM, SHV, KPC, CTX-M, GES
-***Often an inducible AmpC gene present in the genome
+|clavulanic acid, tazobactam, avibactam, vaborbactam, relebactam
-***Common in ''[[Citrobacter]]'', ''[[Serratia]]'', and ''[[Enterobacter]]''
+|-
-**'''Class D''': not inhibited by EDTA, variably inhibited by clavulanic acid; hard to identify
+|B
-***Common in ''[[Pseudomonas]]''
+|metallo
-***Difficult to detect with routine screening
+|VIM, NDM, IMP
-***Examples include:
+|
-****ESBLs: OXA-11
+|-
-****Carbapenemases: OXA-23, OXA-48
+|C
-*'''Class B''': metallo-β-lactamase, inhibited by EDTA, not inhibited by clavulanic acid
+|serine
+|AmpC, P99
+|avibactam, vaborbactam, relebactam
+|-
+|D
+|serine
+|OXA (oxacillinase) enzymes
+|avibactam (OXA-48), ±clavulanic aciid
+|}
+==== Serine β-lactamases ====
+*'''Amber classes A, B, and C''' are the serine β-lactamases
+*Contain a serine residue at the active site
+*'''Class A''': inhibited by [[clavulanic acid]] or [[tazobactam]]
+**Constitutively expressed plasmid
+**Most common ESBL in [[Gram-negative bacteria]]
+**Resistance to 2nd and 3rd generation [[cephalosporins]]
+**Common in ''[[E. coli]]'', ''[[Klebsiella]]'', and ''[[Proteus]]'' spp.
 **Examples include:
+***Penicillinases: TEM-1 (common in GNBs), SHV-1
-***Carbapenemases:
+***ESBLs: CTX-M, TEM-3
-****New Delhi metallo-beta-lactamase (NDM-1)
+***Carbapenemases: ''K. pneumoniae'' carbapenemase (KPC)
-****Imipenemases (IMP)
+*'''Class C''': not inhibited by [[clavulanic acid]] or EDTA, resistant to [[cefoxitin]], inhibited by [[cloxicillin]] in vitro
-****Verona integron-encoded metallo-β-lactamases (VIM)
+**AmpC = chromosomal
+**Often an inducible AmpC gene present in the genome
+**Common in ''[[Citrobacter]]'', ''[[Serratia]]'', and ''[[Enterobacter]]''
+*'''Class D''': not inhibited by EDTA, variably inhibited by [[clavulanic acid]]; hard to identify
+**Common in ''[[Pseudomonas]]''
+**Difficult to detect with routine screening
+**Examples include:
+***ESBLs: OXA-11
+***Carbapenemases: OXA-23, OXA-48
+==== Metallo-β-lactamases ====
+*'''Ambler Class B''' are the metallo-β-lactamases
+*Contain a zinc ion at the active site
+*Inhibited by EDTA, not inhibited by [[clavulanic acid]]
+*Examples include:
+**Carbapenemases:
+***New Delhi metallo-beta-lactamase (NDM-1)
+***Imipenemases (IMP)
+***Verona integron-encoded metallo-β-lactamases (VIM)
+***L1 β-lactamase, present in the [[Stenotrophomonas maltophilia]] chromosome
-=== Epidemiology ===
+===Epidemiology===
-* The most common β-lactamase is TEM-1
+*The most common β-lactamase is TEM-1
-* The most common carbapenemases in the US are KPCs, followed by NDM and OXA-48-like carbapenemases
+*The most common carbapenemases in the US are KPCs, followed by NDM and OXA-48-like carbapenemases
 ==Management==