Clinical and Microbiological Characteristics of Community-Onset Carbapenem-Resistant Enterobacteriaceae Isolates

Figures & data

Figure 1 The study design flow chart.

Table 1 Overview of Clinical Characters and Antimicrobial Resistance Genes of 28 Patients with Community-Onset CRE Infections

Patients’ Clinical Characters									Gene Characters of Isolates
		Specimen	Age/Gender (M/F)	Department	Underlying Conditions	Surgery		Prior Antibiotic Use Within 90 Days	Carba NP Test	ST	AmpC	Carbapenems Genes	Other Beta-Lactam Genes
						Within 90days	Beyond 90days
K. pneumoniae	CA02	urine	71/F	Urology Surgery	Malignancy	N	Y	N	+	11	N	KPC-2	CTX-M-65, SHV-155, SHV-172, SHV-31, TEM-1B
	CA03	sputum	65/M	Emergency Department	N	N	N	N	+	11	N	KPC-2	CTX-M-65, SHV-12, TEM-1B
	CA04	urine	86/M	Urology Surgery	N	N	N	N	+	11	N	KPC-2	CTX-M-65, SHV-182
	CA05	urine	82/F	Urology Surgery	Malignancy	N	Y	Fosfomycin	+	11	N	KPC-2	CTX-M-65, SHV-12, SHV-129, SHV-13, SHV-155, SHV-172, SHV-31, TEM-1B
	CA07	urine	73/M	Urology Surgery	Obstructive urinary tract disease	N	N	N	+	11	N	KPC-2	CTX-M-3, SHV-182, TEM-1B,
	CA08	blood	77/M	Emergency Department	N	N	N	N	+	11	N	KPC-2	CTX-M-14b, SHV-182, TEM-1B
	CA11	swab	45/F	Nephrology Center	Acute myeloid leukemia	N	N	N	+	11	N	KPC-2	CTX-M-65, SHV-182, TEM-1B
	CA12	urine	87/F	Urology Surgery	N	N	Y	N	+	11	N	KPC-2	CTX-M-65, SHV-11
	CA15	urine	75/M	Urology Surgery	N	N	Y	Macrolides	+	147	N	NDM-5	SHV-11, CTX-M-3, SHV-11, SHV-67, TEM-1B
K. pneumoniae	HCA01	sputum	23/M	Nephrology Center	Acute myeloid leukemia	N	N	Cefoperazone/Sulbactam, moxifloxacin, linezolid, imipenem, faropenem, cefuroxime, azithromycin	+	11	N	KPC-2	SHV-12, SHV-129
	HCA06	urine	32/F	Emergency Department	N	Y	N	Piperacillin/tazobactam, levofloxacin, fosfomycin	+	11	N	KPC-2	CTX-M-65, SHV-182, TEM-1B
	HCA09	sputum	19/M	Nephrology Center	Acute myeloid leukemia	N	N	N	－	11	N	N	CTX-M-65, SHV-182, TEM-1B
	HCA10	secretions	70/M	Anorectal Surgery	Malignancy	Y	N	Cefoperazone/Sulbactam	+	11	N	KPC-2	SHV-182
	HCA13	secretions	45/F	Anorectal Surgery	N	Y	N	Cefoperazone/Sulbactam	+	11	N	KPC-2	CTX-M-65, SHV-12, SHV-129, TEM-1B
	HCA14	urine	53/M	Nephrology Center	Chronic kidney disease, cerebral infarction	Y	Y	Moxifloxacin, amikacin	+	15	N	NDM-1	CTX-M-15, OXA-1, SHV-106, SHV-28, TEM-1B
E. coli	CA17	urine	59/F	Nephrology Center	N	N	Y	N	+	2705	N	NDM-1	CTX-M-55, CTX-M-14b, TEM-176
	CA19	urine	47/F	Nephrology Center	Obstructive urinary tract disease	N	N	N	+	354	N	NDM-5	CTX-M-14, NDM-5, TEM-1B
	CA20	urine	35/F	Urology Surgery	Renal abscess	N	N	N	+	410	N	NDM-5	CTX-M-65, TEM-1B
	CA21	urine	35/F	Nephrology Center	Chronic kidney disease	N	Y	Aztreonam	+	617	N	NDM-1	CTX-M-55, TEM-176
	CA23	urine	78/F	Nephrology Center	N	N	N	N	+	69	N	NDM-5	N
E. coli	HCA16	urine	69/F	Respiratory Medicine	Malignancy/diabetes mellitus	N	N	Cephalosporin, macrolides, meropenem	+	69	N	NDM-5	N
	HCA18	urine	92/M	Emergency Department	Chronic kidney disease, diabetes mellitus, heart failure	N	Y	Cephalosporin, macrolides	+	167	N	KPC-2, NDM-5	CTX-M-15, OXA-1, SHV-12, SHV-13, SHV-155, SHV-172, SHV-31
	HCA22	urine	69/F	Nephrology Center	Atherosclerosis	N	N	N	+	10*	N	NDM-5	TEM-1B
E. cloacae	HCA24	urine	66/M	Urology Surgery	Obstructive urinary tract disease	N	N	Cephalosporin, clarithromycin	－	93	Y	N	ACT-7, TBM-1B
	HCA25	urine	62/M	Infectious Disease	Obstructive urinary tract disease	N	N	Cephalosporin, fosfomycin	－	93	Y	N	ACT-7, TBM-1B
E. asburiae	HCA26	urine	77/F	Urology Surgery	Obstructive urinary tract disease, schistosomiasis hepatopathy	N	N	Cephalosporin, fosfomycin	－	1065	Y	N	ACT-6
C. freundii	HCA27	urine	59/M	Urology Surgery	Obstructive urinary tract disease, diabetes mellitus, chronic kidney disease	N	N	Biapenem, nitrofural, cephalosporin, macrolides	+	116	N	NDM-1	SHV
	CA28	urine	46/M	Nephrology Center	Chronic kidney disease	N	Y	N	+	118	N	NDM-1	TEM

Abbreviations: Y, yes; N, no; +, positive; －, negative.

Table 2 Comparisons of Clinical Characters Among CA-CRE, HCA-CRE, and HA-CRE^a with All 64 CRE Cases

Variable	No.(%) of CA-CRE (n=15)	No.(%) of HCA-CRE (n=13)	No.(%) of HA-CRE (n=36)	P-value	P^b	P^c	P^d
Age>65	7(46.7)	6(46.2)	14(38.9)	0.832
Male	6(40.0)	8(61.9)	23(63.9)	0.320
Pathogens
K. pneumoniae	9(60.0)	6(46.2)	30(83.3)	0.028*	0.705	0.144	0.024*
E. coli	5(33.3)	3(23.1)	3(8.3)	0.068
Other pathogens	1(6.7)	4(3.1)	3(8.3)	0.086
Underlying conditions
Malignancy	2(13.3)	2(15.4)	10(27.8)	0.549
Diabetes mellitus	0	3(23.1)	4(11.1)	0.121
Chronic kidney disease	2(13.3)	4(30.8)	2(5.6)	0.054
Surgery history	6(40.0)	4(30.8)	23(63.9)	0.081
Obstructive urinary tract disease	2(13.3)	4(30.8)	4(11.1)	0.286
Invasive operation within 90 days
Catheter	0	9(69.2)	10(27.8)	<0.001*	N/A	N/A	0.018*
Bone marrow aspiration	0	2(15.4)	3(8.3)	0.293
Abdominal/Pelvic drainage tube	0	3(23.1)	7(19.4)	0.148
Invasive blood pressure monitoring	0	1(7.7)	1(2.8)	0.420
Lumbar puncture	0	1(7.7)	0	0.203
PICC ^d	0	0	4(11.1)	0.388
Mechanical ventilation	0	0	1(2.8)	1.000
Cystoscope	0	1(7.7)	1(2.8)	0.420
Prior antibiotic use within 90 days
Carbapenems	0	3(23.1)	17(47.2)	0.001*	N/A	N/A	0.191
Cephalosporin	0	10(76.9)	11(30.6)	<0.001*		N/A	0.008*
Macrolides	1(6.7)	3(23.1)	0	<0.001*	0.311	N/A	N/A
Moxifloxacin	0	2(15.4)	8(22.2)	0.132
Fosfomycin	1(6.7)	2(15.4)	1(2.8)	0.141
Amikacin	0	1(7.7)	1(2.8)	0.420
Linezolid	0	1(7.7)	1(2.8)	0.420
Piperacillin/tazobactam	0	1(7.7)	4(11.1)	0.589
Aztreonam	1(6.7)	3(23.1)	0	0.010*	0.311	N/A	N/A

Notes: ^aCA-CRE, HCA-CRE, and HA-CRE: abbreviations of “community-acquired CRE, healthcare-associated CRE, and hospital-acquired CRE”; ^bP: comparison between CA-CRE & HA-CRE; ^cP: comparison between HCA-CRE & HA-CRE; ^dP: comparison between CA-CRE & HCA-CRE; *P < 0.05.

Abbreviation: N/A, not applicable.

Figure 2 (A) Antibiotic-resistance rate comparisons of 9 community-acquired K. pneumoniae (CA-KP) and 6 healthcare-associated K. pneumoniae (HCA-KP) isolates to 20 common agents, with no significant difference (P>0.05). The red dotted line provides a reference with a rate of 50%. (B) Antibiotic-resistance rate comparisons of 5 community-acquired E. coli (CA-EC) and 6 healthcare-associated E. coli (HCA-EC) isolates to 20 common agents, with no significant difference (P>0.05). The red dotted line provides a reference with a rate of 50%. (C) Nonsusceptible rate comparisons of 15 community-onset K. pneumoniae (CO-KP) and 8 community-onset E. coli (CO-EC) isolates to 20 common agents. The significant P-value is marked above the bar chart (P<0.05). The red dotted line provides a reference with a rate of 50%.

Figure 3 (A) Minimum spanning tree of core genome sequences of K. pneumoniae collected from 2015~2018 (n = 25, 15CO-KP and 10HA-KP). The cluster distance threshold is 15 alleles. Each circle (node) represents one or multiple identical sequences. The number between the nodes illustrates the number of target genes with different alleles. The text in each circle indicates the case identifier. The sequence types were labeled above the circles. (B) Minimum spanning tree of core genome sequences of E. coli collected from 2015~2018 (n =11, 8 CO-EC and 3 HA-EC). The cluster distance threshold is 10 alleles. Each circle (node) represents one or multiple identical sequences. The number between the nodes illustrates the number of target genes with different alleles. The text in each circle indicates the case identifier.

Figure 4 The number of single-nucleotide polymorphisms (SNPs) between each ST11 K. pneumoniae strain heatmap. The deeper the color is, the larger the SNP quantity scale. # indicates core genome SNP differences ≤10.