Carbapenemases: A worldwide threat to antimicrobial therapy

Table 1 Carbapenemase classification

Bush-Jacoby	Bush-Jacoby-Medeiros	Molecular	Distinctive	Inhibited by		Characteristics	Representative
(2010)	(1995)	class	substrate	CA or TZB	EDTA		enzyme
2f	2f	A	Carbapenems	Variable	No	Increased hydrolysis of carbapenems, oxyamino-β-lactams, cephamycins	KPC-2, IMI-1, SME-1
2df		D	Carbapenems	Variable	No	Hydrolizes oxacillin and carbapenems	OXA-23, OXA-48
1e		C	Cephalosporins	No	No	Increased hydrolysis of ceftazidime and often other oxyimino-β-lactams	CMY-10
3a	3	B1	Carbapenems	No	Yes	Broad.spectrum hydrolysis including carbapenems but not monobactams	IMP-1, VIM-1, CcrA, IND-1
3a	3	B3	Cephalosporins	No	Yes	Broad.spectrum hydrolysis including carbapenems but not monobactams	L1, CAU-1, GOB-1, FEZ-1
3b	3	B2	Carbapenems	No	Yes	Preferential hydrolysis of carbapenems	CphA, SFh-1

CA: Clavulanic acid; TZB: Tazobactam; KPC: Klebsiella pneumoniae carbapenemase; IMI: Imipenem hydrolyzing Β-lactamase; SME: Serratia marcescens enzyme; VIM: Verona integron-encoded metallo-β-lactamase; EDTA: Ethylenediaminetetraacetic acid.

Table 2 Oxacillinase-type clusters

Cluster	Subfamily	Other members	Microorganisms associated
1	OXA-23	OXA-27, OXA-29	Acinetobacter spp.
2	OXA-24/40	OXA-25, OXA-26, OXA-72	Acinetobacter spp. and P. aeruginosa
3	OXA-51	OXA-64-71, OXA-75-78,OXA-83, OXA-84, OXA-86-89, OXA-91, OXA-92, OXA-94, OXA-95	Acinetobacter spp.
4	OXA-58		Acinetobacter spp.
5	OXA-55	OXA-SHE	Shewanella spp.
6	OXA-48	OXA-54, OXA-181, OXA-163, OXA-204, OXA-232, OXA-247, OXA-SAR2	Enterobacteriaceae
7	OXA-50	OXA-50a-d, POXB	P. aeruginosa.
8	OXA-60	OXA-60a-d	Ralstonia pickettii
9	OXA-62		Pandoraea pnomenusa

P. aeruginosa: Pseudomonas aeruginosa.

Table 3 Breakpoint and screening cut-off for carbapenemase-producing Enterobacteriaceae

	MIC (mg/L)				Disk-diffusion zone diameter (mm) using 10μg disks
	S breakpoint		Screening cut-off		S breakpoint		Screening cut-off
	EUCAST	CLSI	EUCAST	CLSI	EUCAST	CLSI	EUCAST	CLSI
Meropenem	≤ 2	≤ 1	> 0.12	2-4	≥ 22	≥ 23	< 25	16-21
Imipenem	≤ 2	≤ 1	> 1	2-4	≥ 22	≥ 23	< 23	-
Ertapenem	≤ 0.5	≤ 0.5	> 0.12	2-4	≥ 25	≥ 22	< 25	19-21

S: Susceptibility; MIC: Minimum inhibitory concentration; CLSI: Clinical Laboratory Standards Institute; EUCAST: European Committee on Antimicrobial Susceptibility Testing.