Betalactamases

Bush-Jacoby-Medeiros group¹

Ambler
class²

Representative
enzymes (examples)

Preferred
substrates

Inhibited by

Organisms

Location

CA³

EDTA⁴

1

C

AmpC

Cephalosporins

-

-

Gramnegative rods

Chromosome
(Plasmid)

2a

A

PC1

Penicillins

+

-

Grampositive cocci (and rods)

Plasmid

2b

A

TEM-1, 2

SHV-1

Penicillins
cephalosporins

+

-

Gramnegative rods Gramnegative cocci

Plasmid

Chromosome

2be

A

D

TEM-derivates
SHV-derivates
CTX-M-1-26

PER
GES-1
OXY-1/2 (K1)

OXA-11,14,16,17

Penicillins
narrow- and extended-spectrum cephalosporins

+

±

-

-

-

-

Gramnegative rods

P.aeruginosa
P.aeruginosa
K.oxytoca

Acinetobacter spp
P.aeruginosa

Plasmid

Chromosome

Plasmid

2br

A

TEM-30-36, TRC-1, SHV-49

Penicillins

±

-

E.coli,
K.pneumoniae (inhibitor-resistant)

Plasmid

2c

A

PSE-1,3 4

BRO-1-3

Penicillins,
carbenicillin

+

-

P.aeruginosa
A.baumanii

M.catarrhalis

Variable

2d

D

OXA-1-10
PSE-2

Penicillins
cloxacillin

±

-

Enterobacteriaceae
P.aeruginosa

Variable

2e

A

CepA
FPM-1

L2

Cephalosporins

+

-

Bacteroides sp
Proteus sp

S.maltophilia (inducible)

Variable

2f

A

D

NMC-A
Sme-1-3
Imi-1-3

KPC-1,2

GES-2

OXA-24-26,40, 51,58,72

Penicillins
cephalosporins
carbapenems

+

±

E.cloacae
S.marcescens

K.pneumoniae

P.aeruginosa

A.baumanii

Chromosome

Plasmid

Plasmid

Chromosome

3

B

VIM, IMP, SPM, GIM

L1
CcrA

Penicillins cephalosporins
carbapenems

-

+

P.aeruginosa
A.species
Enterobacteriacae
S.maltophilia
Bacteroides sp

Variable

¹Functional classification based on substrate profile
²Structural classification based on amino acid sequence similarities³CA, clavulanic acid (for inhibition of betalactamase activity)
⁴EDTA, metal chelator (for the inactivation of zinc-dependant enzymes)

References

Bush K, Jacoby GA, Medeiros AA. A functional classification scheme for betalactamases and its correlation with molecular structure. Antimicrobial Agents and Chemotherapy 39:1211-1233, 1995.
Bradford P. Extended-spectrum beta-lactamases in the 21st century: characterization, epidemiology, and detection of this important resistance threat. Clinical Microbiology Reviews 14: 933-951, 2001.
Lahey Clinic Studies at www.lahey.org/studies/webt.htm

RAF & RAF-M (SRGA & SRGA-M)
Revised 2005-04-14 /C Giske

Bush-Jacoby-Medeiros group¹	Ambler class²	Representative enzymes (examples)	Preferred substrates	Inhibited by		Organisms	Location
Bush-Jacoby-Medeiros group¹	Ambler class²	Representative enzymes (examples)	Preferred substrates	CA³	EDTA⁴	Organisms	Location
1	C	AmpC	Cephalosporins	-	-	Gramnegative rods	Chromosome (Plasmid)
2a	A	PC1	Penicillins	+	-	Grampositive cocci (and rods)	Plasmid
2b	A	TEM-1, 2 SHV-1	Penicillins cephalosporins	+	-	Gramnegative rods Gramnegative cocci	Plasmid Chromosome
2be	A D	TEM-derivates SHV-derivates CTX-M-1-26 PER GES-1 OXY-1/2 (K1) OXA-11,14,16,17	Penicillins narrow- and extended-spectrum cephalosporins	+ ± -	- - -	Gramnegative rods P.aeruginosa P.aeruginosa K.oxytoca Acinetobacter spp P.aeruginosa	Plasmid Chromosome Plasmid
2br	A	TEM-30-36, TRC-1, SHV-49	Penicillins	±	-	E.coli, K.pneumoniae (inhibitor-resistant)	Plasmid
2c	A	PSE-1,3 4 BRO-1-3	Penicillins, carbenicillin	+	-	P.aeruginosa A.baumanii M.catarrhalis	Variable
2d	D	OXA-1-10 PSE-2	Penicillins cloxacillin	±	-	Enterobacteriaceae P.aeruginosa	Variable
2e	A	CepA FPM-1 L2	Cephalosporins	+	-	Bacteroides sp Proteus sp S.maltophilia (inducible)	Variable
2f	A D	NMC-A Sme-1-3 Imi-1-3 KPC-1,2 GES-2 OXA-24-26,40, 51,58,72	Penicillins cephalosporins carbapenems	+ ±		E.cloacae S.marcescens K.pneumoniae P.aeruginosa A.baumanii	Chromosome Plasmid Plasmid Chromosome
3	B	VIM, IMP, SPM, GIM L1 CcrA	Penicillins cephalosporins carbapenems	-	+	P.aeruginosa A.species Enterobacteriacae S.maltophilia Bacteroides sp	Variable