Resistance mechanisms and molecular epidemiology of carbapenem-nonsusceptible Escherichia coli in Taiwan, 2012-2015

Figures & data

Table 1 Antimicrobial resistance rates of carbapenem-nonsusceptible E. coli isolates in Taiwan

	2012	2013	2014	2015	Total
	(N=50)	(N=62)	(N=81)	(N=44)	(N=237)
ETP	96.00	96.77	95.06	97.73	96.2
IPM	74.00	77.42	72.84	72.73	74.26
MEM	62.00	62.90	56.79	68.18	61.6
ATM	94.00	98.39	96.30	93.18	95.78
DOR	50.00	50.00	44.44	45.45	47.26
TZP	78.00	91.94	90.12	90.91	88.19
CFZ	100	100	100	100	100
FOX	98.00	100	97.53	97.73	98.31
CTX	96.00	96.77	100	100	98.31
CAZ	100	98.39	98.77	97.73	98.73
FEP	60.00	79.03	85.19	81.82	77.64
CIP	80.00	75.81	79.01	86.36	79.75
LVX	74.00	67.74	76.54	86.36	75.53
GEN	42.00	54.84	48.15	38.64	46.84
AMK	0.00	4.84	8.64	6.82	5.49
SXT	70.00	72.58	65.43	72.73	69.62
COL	2.00	1.61	4.94	4.55	3.38
TGC	6.00	0.00	0.00	2.27	1.69

Abbreviations: ETP, ertapenem; IPM, imipenem; MEM, meropenem; ATM, aztreonam; DOR, doripenem; TZP, piperacillin-tazobactam; CFZ, cefazolin; FOX, cefoxitin; CTX, cefotaxime; CAZ, ceftazidime; FEP, cefepime; CIP, ciprofloxacin; LVX, levofloxacin; GEN, gentamicin; AMK, amikacin; SXT, trimethoprim-sulfamethoxazole; COL, colistin; TGC, tigecycline.

Figure 1 The MIC distribution for three carbapenems for CnsEC isolates in Taiwan.

Abbreviations: IPM, imipenem; MEM, meropenem; DOR, doripenem; MIC, minimal inhibitory concentration; CnsEC, carbapenem-nonsusceptible E. coli.

Figure 2 Distribution of carbapenemases among carbapenem-nonsusceptible E. coli isolates in Taiwan.

Figure 3 Dendrogram generated by pulsed-field gel electrophoresis (PFGE) patterns of the 18 isolates of carbapenemase-producing carbapenem-nonsusceptible E. coli using the BioNumerics software.

Table 2 Outer membrane profiles for carbapenem-nonsusceptible E. coli isolates

β-lactamases	Outer membrane profile
	2012 (n=50)				2013 (n=62)				2014 (n=81)				2015 (n=44)				Total
	F/C	∆C	∆F	∆C/F	F/C	∆C	∆F	∆C/F	F/C	∆C	∆F	∆C/F	F/C	∆C	∆F	∆C/F	F/C	∆C	∆F	∆C/F	All
Carbapenemase ^a	1	1	1	0	1	1	2	0	0	1	4	1	0	0	4	1	2	3	11	2	18
KPC-2	1	1	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1	1	1	0	3
NDM-1,5	0	0	1	0	1	1	1	0	0	1	1^b	0	0	0	1	1	1	2	4	1	8
IMP-8	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	1	1	2
VIM-1	0	0	0	0	0	0	0	0	0	0	2	0	0	0	1	0	0	0	3	0	3
OXA-48	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	2	0	2
AmpC^c																					195
CMY	4	7	6	30	0	4	12	36	1	4	12	49	0	0	9	21	4	15	38	136	193
DHA	0	0	0	1	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0	2	2
ESBL^c																					102
CTX-M	2	1	0	9	0	2	7	17	0	0	7	31	0	0	6	10	2	3	20	67	92
SHV	0	0	1	3	0	0	2	2	0	0	0	0	0	0	0	2	0	0	3	7	10

Notes: ^aFor carbapenemase-producing E. coli strains, there was no duplicate calculation for each isolate. ^bThe isolate harbored both NDM-1 and OXA-181. ^cFor the columns that show the numbers of AmpC and ESBL genes, only non-carbabapenemase-producing isolates were included (n=219). Isolates that harbored multiple β-lactamases were duplicately calculated. ^d∆C, ∆F, ∆C/F represent loss of OmpC, loss of OmpF, and loss of both OmpC and F, respectively.

Table 3 Association of outer membrane proteins loss and antimicrobial resistance rates (%) among the 219 carbapenem-nonsusceptible E. coli isolates without carbapenemase

	OmpF+	OmpF-		OmpC+	OmpC-
	(N=20)	(N=199)	p-value	(N=47)	(N=172)	p-value
EPT	80.00	97.49	0.0002*	89.36	97.67	0.011*
IPM	60.00	73.37	0.2037	46.81	79.07	<0.0001*
MEM	45.00	60.30	0.1849	36.17	65.12	0.0004*
DOR	30.00	44.72	0.2053	17.02	50.58	<0.0001*
ATM	90.00	97.99	0.0369*	97.87	97.09	<0.0001*
FEP	55.00	78.39	0.0191*	74.47	76.74	0.74519
TZP	90.00	86.93	0.6956	78.72	89.53	0.0492*
	OmpF+C-	OmpF-C-		OmpF-C+	OmpF-C-
	(N=15)	(N=157)	p-value	(N=42)	(N=157)	p-value
EPT	86.67	99.36	0.0203*	88.10	99.36	0.0017*
IPM	66.67	80.25	0.2164	50.00	80.25	<0.0001*
MEM	46.67	68.15	0.0926	35.71	68.15	0.0001*
DOR	26.67	54.14	0.0574	14.29	54.14	<0.0001*
ATM	93.33	98.73	0.3081	100.00	98.73	1
FEP	46.67	79.61	0.0039*	73.81	79.61	0.4165
TZP	93.33	89.17	1.0000	78.57	89.17	0.0702

Note: *Statistical significance.

Figure 4 Comparisons of resistance mechanisms and antibiotics resistance rates between pan-carbapenem-resistant E. coli (pCREC) and non-pCREC. The 18 isolates of carbapenemase-producing E. coli are excluded. *Statistical significance. (A) The distribution of ESBL and AmpC genes. (B) The resistance rates of COL (colistin), TGC (tigecycline), and AMK (amikacin). (C) The percentages of outer membrane protein (Omp) loss: including the loss of only one Omp (OmpF or OmpC) and the loss of both OmpF and OmpC.

Table 4 The prevalence rates and genotypes of carbapenemase-producing E. coli among carbapenem-nonsusceptible E. coli isolates

Study period	Geographical area	Carbapenemase-producing E. coli (number of isolates)^a	Genotypes of carbapenemases (number of isolates)	Reference
2008–2014	Global^b	35.8% (149/408)	NDM (57) OXA-48-like (46) KPC (42) IMP (3), VIM (2)	^Citation9
2012–2013	USA	21.9% (7/32) ^c	KPC (7)	^Citation7
2013–2014	Europe^d	40% (77/194)	OXA-48-like enzymes (43) NDM (20), KPC (14)	^Citation21
2012–2015	Taiwan	7.59% (18/237)	NDM-type (8) KPC-2 (3), VIM-1 (3) OXA-48 (2), IMP-8 (2)	Present study
2015	Korea	8.33% (3/36)	OXA-232 (1) KPC-2 (1) NDM-1 (1)	^Citation8
2015	China^e	76.9%(30/39)^f	NDM-type (29)	^Citation22

Notes: ^aThe numbers represent: carbapenemase-producing E. coli isolates/carbapenem-nonsusceptible E. coli isolates. ^bThe Study for Monitoring Antimicrobial Resistance Trends (SMART) global surveillance program: The data from Asian area excluded isolates from mainland China (all years) and India (most isolates from 2010 and all isolates from 2011 to 2014). ^cAmong 89 isolates of carbapenemase-nonsusceptible E. coli, only 32 isolates were tested for carbapenemase. ^dThe European Survey on Carbapenemase-producing Enterobacteriaceae (EuSCAPE): 455 sites from 36 countries. ^eChina CRE Network. ^f Among 110 isolates of carbapenemase-nonsusceptible E. coli, only 39 isolates were tested for carbapenemase.

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