β-lactamases

From IDWiki
Β-lactamases /
Revision as of 06:04, 29 September 2022 by Aidan (talk | contribs) ()
(diff) ← Older revision | Latest revision (diff) | Newer revision → (diff)

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 Classification

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

Common β-Lactamases

β-lactamase[1] AMX AMC TIC TIM PIP TZP CFZ FOX CRO
TEM-1 R S R S I/R S S/I/R S S
TEM-1 hyperproduction R I/R R I/R R S/I/R I/R S S
OXA-1 R I/R R I/R R I/R R S S
IRT type R I/R I/R I/R S/I/R S/I/R S S S
CMT type R R R I/R R I/R I/R S I/R
ESBL type R S/I R S I/R S/I R S R
AmpC hyperproduction R R I/R I/R I/R I/R R I/R S/I/R

Management

Further Reading

  • Updated Functional Classification of β-Lactamases. Antimicrob Agents Chemother. 2010;54(3):969-976. doi: 10.1128/AAC.01009-09
  1. Cantón R, Morosini MI, de la Maza OM, de la Pedrosa EG. IRT and CMT beta-lactamases and inhibitor resistance. Clin Microbiol Infect. 2008 Jan;14 Suppl 1:53-62. doi: 10.1111/j.1469-0691.2007.01849.x. PMID: 18154528.