Molecular Mechanisms and Epidemiology of Carbapenem-Resistant Enterobacter cloacae Complex Isolated from Chinese Patients During 2004–2018

Figures & data

Table 1 Carbapenem Susceptibility of ECC Clinical Isolates

Time of Isolation	No. of Isolates	CNS (R+I) (n)	NS(%)	R (%)	I (%)	S (%)
2004	32	0	0	0	0	100
2005	46	0	0	0	0	100
2006	47	0	0	0	0	100
2007	47	0	0	0	0	100
2008	60	0	0	0	0	100
2009	41	0	0	0	0	100
2010	40	1(1+0)	2.5	2.5	0	97.5
2011	34	5(4+1)	14.7	11.8	2.9	85.3
2012	82	6(5+1)	7.3	6.1	1.2	92.7
2013	36	1(1+0)	2.8	2.8	0	97.2
2014	36	4(4+0)	11.1	11.1	0	88.9
2015	177	20(19+1)	11.3	10.7	0.6	88.7
2016	214	31(25+6)	14.5	11.7	2.8	85.5
2017	221	20(16+4)	9.0	7.2	1.8	91.0
2018	201	25(24+1)	12.4	11.9	0.5	87.6
Total	1314	113(99+14)	8.6	7.5	1.1	91.4

Abbreviations: ECC, Enterobacter cloacae complex; No., number; CNS, carbapenem-nonsusceptible strains; S, sensitivity; I, intermediate; R, resistance; NS; R and I.

Table 2 Minimum Inhibitory Concentrations (MICs) of 113 Carbapenem-Nonsusceptible ECC Isolates

Isolates	MIC (μg/mL)
	ATM	CRO	CAZ	FEP	ETP	IPM	MEM	CIP	LVX	GEN	TOB	AMK	SXT	NIT	COL
Y509	≤1	≥64	≥64	≥64	16	2	4	1	1	≥16	≥16	8	≥320	/	0.25
Y541	64	≥32	≥128	32	2	0.5	≤0.125	0.06	0.06	4	2	4	≥320	64	8
Y542	32	≥32	≥128	4	2	0.5	0.25	0.25	0.06	2	0.5	2	20	64	0.125
Y569	32	≥32	≥128	4	1	≤0.125	≤0.125	0.06	0.06	2	0.5	2	≤5	32	0.125
Y572	32	≥32	≥128	1	2	0.5	0.5	0.06	0.06	2	2	8	10	32	0.25
Y573	≥128	≥32	≥128	8	2	0.5	0.25	≥8	≥16	64	16	≥512	≥320	128	0.25
CG35	0.5	≥32	≥128	16	2	8	4	0.25	0.5	8	8	4	≥320	32	0.125
CG38	1	≥32	≥128	32	64	64	64	0.5	1	16	8	4	≥320	32	0.25
CG64	32	≥32	≥128	32	8	4	4	≥8	≥16	4	16	4	≥320	32	0.25
CG80	64	≥32	≥128	8	1	1	0.25	1	1	4	4	1	≥320	64	0.125
CG85	0.5	4	16	0.06	4	2	0.25	0.5	0.06	4	4	8	≤5	64	0.125
CG98	64	16	8	8	128	8	16	≥8	≥16	32	4	4	≥320	≥1024	0.5
CG175	4	≥32	≥128	≥128	>128	64	64	1	1	8	8	4	≥320	128	>64
CG371	≥128	≥32	≥128	8	8	2	4	0.5	0.25	≥128	64	16	≥320	32	0.25
CG380	64	≥32	≥128	4	2	0.25	≤0.125	0.25	0.03	1	0.5	2	40	64	0.125
CG389	≥128	≥32	16	64	2	1	0.25	≥8	≥16	≥128	≥128	≥512	≥320	256	0.25
CG417	32	≥32	64	2	4	0.5	0.25	4	8	1	0.5	4	80	128	1
CG586	≤1	≥64	≥64	≥64	16	2	4	1	1	≥16	≥16	8	≥320	64	0.5
CG604	≥64	32	≥64	4	2	0.5	0.25	2	4	8	≥16	16	≥320	128	0.5
CG648	16	16	4	4	4	4	4	≤0.25	≤0.25	≤1	≤0.25	≤0.25	≤5	32	>64
CG652	32	≥32	≥128	2	2	0.25	≤0.125	0.25	0.5	2	1	4	≤5	64	0.25
CG662	8	≥32	≥128	8	2	4	1	0.25	0.25	64	4	4	≥320	16	0.5
CG666	32	≥64	≥64	4	2	0.25	0.25	≤0.25	≤0.25	≤1	≤1	≤2	≤20	32	0.25
CG698	≤1	≥64	≥64	8	2	1	0.5	≤0.25	1	8	4	≤2	≥320	64	>64
CG709	1	16	≥128	2	2	0.5	≤0.125	0.5	0.25	32	16	2	≥320	32	0.5
CG721	≥64	≥64	≥64	≥64	2	1	0.25	≥4	≥8	≤1	8	≤2	≤20	256	0.5
CG727	≥64	≥64	≥64	≤1	1	0.5	0.25	≤0.25	≤0.25	≤1	≤1	≤2	≤20	64	>64
CG737	≤1	4	2	≤1	4	0.5	≤0.125	≥4	≥8	≤1	8	≤2	≥320	64	>64
CG741	≤1	4	2	≤1	4	0.25	≤0.125	≥4	≥8	≤1	8	≤2	≥320	64	64
CG745	≥128	≥32	≥128	16	4	0.5	1	≥8	≥16	1	1	2	≥320	64	0.5
CG749	≤1	≥64	≥64	≥64	128	8	16	≥4	≥8	≥16	≥16	4	≥320	64	0.5
CG780	8	≥32	64	0.5	4	0.5	≤0.125	≥8	≥16	1	1	2	≥320	128	0.5
CG804	≥128	≥32	≥128	64	32	4	4	≥8	≥16	2	1	4	≥320	32	0.5
CG815	≥64	≥64	16	8	16	16	4	≤0.25	≤0.25	≤1	≤1	≤2	≤20	64	0.5
CG817	≥64	32	16	2	8	4	1	≤0.25	≤0.25	≤1	≤1	≤2	≤20	32	0.5
CG701	2	≥64	2	32	2	2	0.25	≤0.25	1	≥16	8	≤2	≥320	32	>64
CG718	≤1	≤1	≤1	≤1	0.25	4	≤0.125	0.5	1	≤1	≤1	≤2	≤20	64	0.5
CG824	≥64	≥64	≥64	2	1	0.25	≤0.125	≤0.25	≤0.25	≤1	≤1	≤2	≤20	64	0.5
CG848	≥64	≥64	≥64	16	4	0.5	0,25	≥4	4	≤1	≤1	≤2	≤20	64	0.5
CG864	≥64	≥64	≥64	4	8	0.5	≤0.125	≤0.25	≤0.25	≤1	≤1	≤2	≤20	/	>64
CG871	≥64	≥64	≥64	2	2	0.5	0.125	≤0.25	0.5	≤1	≤1	≤2	≤20	/	0.5
CG884	≥64	≥64	≥64	≤1	2	0.5	≤0.125	≤0.25	1	≤1	≤1	≤2	≤20	/	32
CG901	64	≥32	≥128	64	16	2	2	≥8	8	64	≥128	≥512	≥320	256	0.5
CG911	≥64	≥64	16	16	16	8	4	0.5	1	≥16	≥16	16	≥320	64	0.5
CG914	≥64	≥64	16	16	32	4	4	0.5	1	≥16	≥16	16	≥320	64	0.5
CG916	≥64	≥64	≥64	≥64	128	16	16	0.5	1	≥16	≥16	≤2	≥320	64	0.5
CG934	≥64	≥64	≥64	≤1	2	0.25	≤0.125	≤0.25	≤0.25	≤1	≤1	≤2	≤20	≤16	>64
CG937	16	≥64	≥64	≤1	2	0.5	≤0.125	≥4	≥8	≥16	≥16	≥64	≥320	256	0.5
CG939	≥64	≥64	≥64	4	1	0.5	≤0.125	1	1	8	≥16	16	≥320	64	0.5
CG945	≥64	≥64	≥64	16	4	0.5	≤0.125	1	2	8	≥16	16	≥320	64	0.5
CG947	≥64	≥64	≥64	16	1	0.5	0.25	1	2	8	≥16	16	≥320	64	0.5
CG950	≥64	≥64	≥64	4	2	0.5	≤0.125	1	2	8	≥16	16	≥320	64	0.5
CG952	≥64	≥64	≥64	4	4	0.5	0.5	1	2	8	≥16	16	≥320	64	0.5
CG983	16	≥64	≥64	≥64	128	8	16	≥4	≥8	≥16	≥16	≥64	≤20	256	0.5
CG996	4	≥64	≥64	16	8	2	1	≤0.25	≤0.25	≥16	≥16	≤2	≤20	64	0.5
CG1005	≥64	≥64	≥64	≥64	>256	64	128	≥4	4	≥16	≥16	4	≥320	≥512	1
CG1015	≥64	≥64	≥64	2	1	0.25	≤0.125	≤0.25	≤0.25	≤1	≤1	≤2	≤20	32	0.25
CG1038	≥64	≥64	4	4	2	4	1	≤0.25	≤0.25	≤1	≤1	≤2	≤20	32	32
CG1041	≥64	≥64	≥64	2	1	0.25	≤0.125	≤0.25	≤0.25	≤1	≤1	≤2	≤20	33	0.5
CG1045	≥64	≥64	≥64	≥64	8	1	2	≥4	≥8	8	≥16	16	≥320	≤16	0.5
CG1050	≥64	≥64	≥64	≤1	2	0.5	≤0.125	1	1	≤1	≤1	≤2	≤20	32	16
CG1051	≥64	≥64	≥64	2	4	0.25	≤0.125	1	1	≤1	≤1	≤2	≤20	32	>64
CG1070	2	16	4	≤1	16	0.5	0.25	≥4	4	≤1	≤1	≤2	≤20	128	0.125
CG1075	≥64	≥64	≥64	≥64	32	2	2	≥4	≥8	≥16	8	≤2	≥320	64	0.25
CG1079	≥64	≥64	≥64	≤1	4	0.5	0.5	≥4	4	4	2	8	≤20	128	0.125
CG1081	≥64	≥64	≥64	8	8	0.25	0.25	≥4	≥8	≥16	≥16	≤2	≥320	32	0.125
CG1090	≥64	≥64	≥64	≥64	16	1	4	≥4	≥8	≥16	8	≤2	≥320	64	0.125
CG1043	≤1	8	4	≤1	1	1	0.5	≥4	2	≥16	8	≤2	≥320	128	0.25
CG1159	4	32	4	2	4	0.25	≤0.125	1	1	8	4	≤2	≥320	64	0.5
CG1181	≥64	≥64	≥64	≤1	2	1	0.25	≤0.25	≤0.25	≤1	≤1	≤2	≤20	32	0.5
CG1208	≥64	≥64	≥64	4	4	0.5	0.25	2	4	4	4	≤2	≥320	128	0.5
CG1212	≥64	≥64	≥64	2	2	0.25	≤0.125	1	1	≤1	≤1	≤2	≤20	32	0.125
CG1231	≥64	≥64	≥64	2	4	0.25	0.25	≤0.25	≤0.25	≤1	≤1	≤2	≤20	32	0.25
CG1236	32	≥64	≥64	≤1	4	1	2	≤0.25	≤0.25	≤1	≤1	≤2	≤20	32	0.25
CG1244	≥64	≥64	≥64	≤1	2	0.25	0.5	≤0.25	≤0.25	≤1	≤1	≤2	≤20	32	0.125
CG1249	≥64	≥64	≥64	4	16	0.5	4	0.5	0.5	≤1	≤1	≤2	≤20	32	>64
CG1250	≥64	≥64	≥64	8	2	0.25	0.25	2	1	≤1	≤1	≤2	≥320	64	0.25
CG1252	16	16	16	≤1	1	0.5	≤0.125	≤0.25	≤0.25	≤1	≤1	≤2	≤20	64	0.5
CG1257	≤1	≥64	≥64	≥64	4	8	4	≤0.25	1	4	8	≤2	≥320	64	0.5
CG1280	≥64	≥64	≥64	2	1	0.25	≤0.125	≤0.25	≤0.25	≤1	≤1	≤2	≤20	64	0.125
CG1281	≥64	≥64	≥64	2	1	0.25	≤0.125	≤0.25	≤0.25	≤1	≤1	≤2	≤20	64	0.125
CG1330	≥64	≥64	≥64	≥64	16	4	4	≥4	≥8	4	4	≤2	≥320	64	0.125
CG1376	64	≥32	≥128	32	16	4	4	1	1	4	16	4	≥320	64	0.25
CG1381	≥64	≥64	≥64	≥64	16	16	8	0.5	1	4	8	≤2	≥320	32	0.25
CG1400	≥64	≥64	≥64	32	2	1	2	≥4	≥8	≥16	≥16	4	≥320	64	>64
CG1457	≥64	≥64	≥64	≥64	4	0.25	0.5	≤0.25	1	≤1	≤1	≤2	≤20	64	0.5
CG1461	≥64	≥64	≥64	16	4	2	1	≤0.25	1	≤1	≤1	≤2	≤20	128	0.5
CG1144	≥128	8	≥128	4	≤0.125	2	≤0.125	0.5	0.25	1	1	2	≤5	31	0.5
CG1479	≥64	≥64	≥64	8	128	16	8	≤0.25	≤0.25	≤1	≤1	≤2	≤20	32	>64
CG1498	16	≥64	≥64	≥64	4	16	1	2	1	4	8	≤2	≥320	32	0.5
CG1506	≥64	≥64	≥64	4	4	8	2	1	1	≥16	≥16	16	≤20	≤16	>64
CG1522	≥64	≥64	≥64	8	4	2	0.25	≤0.25	≤0.25	≤1	≤1	≤2	≤20	256	0.5
CG1532	≥64	≥64	≥64	4	2	1	0.25	0.5	1	8	8	≤2	≥320	64	0.5
CG1547	≥64	≥64	≥64	≥64	16	16	16	≥4	4	≤1	≤1	4	≥320	128	0.5
CG1563	≥128	≥32	≥128	1	2	1	0.25	1	1	2	1	2	≤5	16	0.25
CG1565	≥64	≥64	≥64	32	4	0.25	0.25	2	2	8	≥16	32	≥320	64	0.5
CG1574	2	≥64	≥64	32	8	16	8	1	1	≤1	≤1	≤2	≤20	64	>64
CG1581	≥64	≥64	≥64	32	4	0.5	0.25	≥4	≥8	8	≥16	16	≥320	128	1
CG1589	≥128	≥32	≥128	4	2	0.5	0.25	≥8	≥16	≥128	≥128	≥512	≥320	128	0.5
CG1591	≥64	≥64	≥64	≥64	16	4	4	≥4	≥8	≤4	≥16	≤16	≥320	≤16	0.25
CG1593	32	≥64	≥64	≥16	2	8	2	0.5	1	≤1	8	≤2	≤20	≤16	0.5
CG1601	16	≥64	≥16	≤2	1	2	≤0.125	2	1	≥16	8	≤2	≥320	64	0.5
CG1606	≥64	≥64	≥64	≥64	8	2	1	≥4	≥8	≥16	≥16	≥64	≥320	256	1
CG1608	64	≥32	≥128	16	16	16	8	1	4	≥128	8	2	≤5	32	0.5
CG1640	≥64	≥64	16	8	>128	64	64	≥4	1	≤1	8	≤2	≤20	32	0.5
CG1728	≥64	≥64	≥64	4	4	0.25	0.25	≤0.25	≤0.25	≤1	≤1	≤2	≤20	64	0.5
CG1737	≤1	≥64	≥64	≥64	64	8	8	≥4	≥8	8	≥16	≤2	≥320	64	0.5
CG1746	≥128	≥32	64	32	4	0.5	≤0.125	≥8	≥16	≥128	32	4	≥320	64	0.5
CG1778	≤4	≥64	≥64	≥64	32	8	8	≥4	≥8	≤1	≤1	≤2	≥320	64	0.5
CG1779	≤1	≥64	≥64	≥64	16	8	8	≥4	≥8	≤1	≤1	≤2	≥320	/	0.5
CG1781	≤1	≥64	≥64	≥64	16	8	4	≥4	≥8	≤1	≤1	≤2	≥320	/	0.5
CG1813	8	≥64	≥64	32	16	2	4	1	2	8	8	≤2	≥320	/	0.25
CG1819	≤1	≥64	≥64	≥64	32	4	8	≤0.25	≤0.25	≤1	≤1	≤2	≤20	/	>64

Abbreviations: ECC, Enterobacter cloacae complex; ATM, aztreonam; CRO, ceftriaxone; CAZ, ceftazidime; IPM, imipenem; MEM, meropenem; ETP, ertapenem; CIP, ciprofloxacin; LVX, levofloxacin; GEN, gentamicin; TOB, tobramycin; AMK, amikacin; COL, colistin; NIT, nitrofurantoin; SXT, trimethoprim-sulfamethoxazole; FEP, cefepime; /, not available.

Figure 1 Antibiotic resistant mechanisms determined in the Enterobacter cloacae complex (ECC) isolates and multilocus sequence typing (MLST) in this study. (A) Carbapenem resistance genes; (B) extended-spectrum β-lactamases (ESBLs) phenotypic test for the phenotypic detection of ESBLs production; (C) β-lactam resistance genes; (D) expression of outer membrane porins genes and cephalosporinase gene ampC; (E) carbonyl cyanide 3-chlorophenylhydrazone (CCCP) was used to detect the activity of efflux pumps in carbapenem-nonsusceptible ECC isolates; (F) sequence typing (ST) of ECC. Blue, purple, and yellow squares represent positive. Gray squares represent negative. The purple square with an up arrow represents the overexpression of genes, and the purple square with a down arrow represents the low expression of genes.

Figure 2 Performing goeBURST analysis on the molecular epidemiological characteristics of 79 ECC isolates. The population snapshot indicates the clonal assignment of the sequence typing (ST) presented in this study. Each green dot represents one ST, the numbers in the dot represent ST types, and the dot size represents their abundance in the ST set.