Β-lactamases: Difference between revisions

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Β-lactamases
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(added Bush-Jacoby classification scheme)
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==Background==
  
==Background==
   
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* Includes a spectrum of molecules that hydrolyze [[β-lactams]], from penicillins to carbapenems
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*Includes a spectrum of molecules that hydrolyze [[β-lactams]], from penicillins to carbapenems
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** See also [[extended-spectrum β-lactamases]] and [[carbapenemases]]
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**See also [[extended-spectrum β-lactamases]] and [[carbapenemases]]
   
 
===Ambler Classification===
  
===Ambler Classification===
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|}
  
|}
   
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==== Serine β-lactamases ====
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====Serine β-lactamases====
   
 
*'''Amber classes A, B, and C''' are the serine β-lactamases
  
*'''Amber classes A, B, and C''' are the serine β-lactamases
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***Carbapenemases: OXA-23, OXA-48
  
***Carbapenemases: OXA-23, OXA-48
   
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==== Metallo-β-lactamases ====
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====Metallo-β-lactamases====
   
 
*'''Ambler Class B''' are the metallo-β-lactamases
  
*'''Ambler Class B''' are the metallo-β-lactamases
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***Verona integron-encoded metallo-β-lactamases (VIM)
  
***Verona integron-encoded metallo-β-lactamases (VIM)
 
***L1 β-lactamase, present in the [[Stenotrophomonas maltophilia]] chromosome
  
***L1 β-lactamase, present in the [[Stenotrophomonas maltophilia]] chromosome
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  +
=== Bush-Jacoby Classifications ===
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{| class="wikitable"
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! rowspan="2" |Group
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! rowspan="2" |Ambler
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! rowspan="2" |Substrates
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! colspan="2" |Inhibitors
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! rowspan="2" |Definition
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! rowspan="2" |Examples
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|-
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!CA/TZB
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!EDTA
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|-
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! colspan="7" |Group 1: Cephalosporinases
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|-
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|1
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| rowspan="2" |C
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|[[cephalosporins]]
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|—
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|—
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|hydrolyzes cephalosporins better than benzylpenicillin, and hydrolyzes cephamycins
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|''E. coli'' AmpC, P99, ACT-1, CMY-2, FOX-1, MIR-1
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|-
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|
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|[[cephalosporins]]
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|—
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|—
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|increased hydrolysis of ceftazidime and other oxyimino-β-lactams
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|GC1, CMY-37
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|-
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! colspan="7" |Group 2: β-Lactamases
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|-
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|2a
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| rowspan="7" |A
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|[[penicillins]]
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|yes
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|—
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|hydrolyzes benzylpenicillin better than cephalosporins
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|PC1
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|-
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|2b
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|[[penicillins]] and early [[cephalosporins]]
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|yes
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|—
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|hydrolyzes benzylpenicillin similar to cephalosporins
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|TEM-1, TEM-2, SHV-1
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|-
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|2be
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|extended-spectrum [[cephalosporins]], [[monobactams]]
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|yes
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|—
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|increased hydrolysis of oxyimino-β-lactams (third-generation plus monobactams)
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|TEM-3, SHV-2, CTX-M-15, PER-1, VEB-1
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|-
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|2br
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|[[penicillins]]
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|—
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|—
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|resistance to clavulanic acid, sulbactam, and tazobactam
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|TEM-30, SHV-10
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|-
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|2ber
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|extended-spectrum [[cephalosporins]], [[monobactams]]
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|—
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|—
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|increased hydrolysis of oxyimino-β-lactams plus resistance to clavulanic acid, sulbactam, and tazobactam
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|TEM-50
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|-
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|2c
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|[[carbenicillin]]
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|yes
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|—
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|increased hydrolysis of carbenicillin
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|PSE-1, CARB-3
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|-
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|2ce
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|[[carbenicillin]], [[cefepime]]
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|yes
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|—
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|increased hydrolysis of carbenicillin, cefepime, and cefpirome
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|RTG-4
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|-
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|2d
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| rowspan="3" |D
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|[[cloxacillin]]
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|variable
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|—
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|increased hydrolysis of cloxacillin or oxacillin
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|OXA-1, OXA-10
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|-
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|2de
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|extended-spectrum [[cephalosporins]]
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|variable
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|—
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|hydrolyzes cloxacillin or oxacillin and oxyimino-β-lactams
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|OXA-11, OXA-15
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|-
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|2df
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|[[carbapenems]]
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|variable
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|—
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|hydrolyzes cloxacillin or oxacillin and carbapenems
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|OXA-23, OXA-48
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|-
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|2e
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| rowspan="2" |A
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|extended-spectrum [[cephalosporins]]
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|yes
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|—
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|hydrolyzes cephalosporins, and inhibited by clavulanic acid but not aztreonem
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|CepA
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|-
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|2f
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|[[carbapenems]]
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|variable
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|—
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|increased hydrolysis of carbapenems, oxyimino-β-lactams, cephamycins
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|KPC-2, IMI-1, SME-1
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|-
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! colspan="7" |Group 3: Carbapenemases
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|-
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|3a
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| rowspan="2" |B
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|[[carbapenems]]
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|—
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|yes
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|broad-spectrum hydrolysis including carbapenems but not monobactams
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|IMP-1, VIM-1, CcrA, IND-1, L1, CAU-1, GOB-1, FEZ-1
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|-
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|3b
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|[[carbapenems]]
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|—
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|yes
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|preferential hydrolysis of carbapenems
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|CphA, Sfh-1
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|}
   
 
===Epidemiology===
  
===Epidemiology===
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*[[Carbapenems]], [[aminoglycosides]], [[fluoroquinolones]], and [[TMP-SMX]] typically work well
  
*[[Carbapenems]], [[aminoglycosides]], [[fluoroquinolones]], and [[TMP-SMX]] typically work well
   
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== Further Reading ==
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  +
* Updated Functional Classification of β-Lactamases. ''Antimicrob Agents Chemother''. 2010;54(3):969-976. doi: [https://doi.org/10.1128/AAC.01009-09 10.1128/AAC.01009-09]
 
{{DISPLAYTITLE:β-lactamases}}
  
{{DISPLAYTITLE:β-lactamases}}
 
[[Category:Antibiotics]]
  
[[Category:Antibiotics]]

Revision as of 17:04, 14 September 2020

Background

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
  • 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

Bush-Jacoby Classifications

Group Ambler Substrates Inhibitors Definition Examples
CA/TZB EDTA
Group 1: Cephalosporinases
1 C cephalosporins — — hydrolyzes cephalosporins better than benzylpenicillin, and hydrolyzes cephamycins E. coli AmpC, P99, ACT-1, CMY-2, FOX-1, MIR-1
cephalosporins — — increased hydrolysis of ceftazidime and other oxyimino-β-lactams GC1, CMY-37
Group 2: β-Lactamases
2a A penicillins yes — hydrolyzes benzylpenicillin better than cephalosporins PC1
2b penicillins and early cephalosporins yes — hydrolyzes benzylpenicillin similar to cephalosporins TEM-1, TEM-2, SHV-1
2be extended-spectrum cephalosporins, monobactams yes — increased hydrolysis of oxyimino-β-lactams (third-generation plus monobactams) TEM-3, SHV-2, CTX-M-15, PER-1, VEB-1
2br penicillins — — resistance to clavulanic acid, sulbactam, and tazobactam TEM-30, SHV-10
2ber extended-spectrum cephalosporins, monobactams — — increased hydrolysis of oxyimino-β-lactams plus resistance to clavulanic acid, sulbactam, and tazobactam TEM-50
2c carbenicillin yes — increased hydrolysis of carbenicillin PSE-1, CARB-3
2ce carbenicillin, cefepime yes — increased hydrolysis of carbenicillin, cefepime, and cefpirome RTG-4
2d D cloxacillin variable — increased hydrolysis of cloxacillin or oxacillin OXA-1, OXA-10
2de extended-spectrum cephalosporins variable — hydrolyzes cloxacillin or oxacillin and oxyimino-β-lactams OXA-11, OXA-15
2df carbapenems variable — hydrolyzes cloxacillin or oxacillin and carbapenems OXA-23, OXA-48
2e A extended-spectrum cephalosporins yes — hydrolyzes cephalosporins, and inhibited by clavulanic acid but not aztreonem CepA
2f carbapenems variable — increased hydrolysis of carbapenems, oxyimino-β-lactams, cephamycins KPC-2, IMI-1, SME-1
Group 3: Carbapenemases
3a B carbapenems — yes broad-spectrum hydrolysis including carbapenems but not monobactams IMP-1, VIM-1, CcrA, IND-1, L1, CAU-1, GOB-1, FEZ-1
3b carbapenems — yes preferential hydrolysis of carbapenems CphA, Sfh-1

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

Further Reading

  • Updated Functional Classification of β-Lactamases. Antimicrob Agents Chemother. 2010;54(3):969-976. doi: 10.1128/AAC.01009-09
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