Resistance phenotype and clinical molecular epidemiology of carbapenem-resistant

Figures & data

Figure 1 The variation of CRKP isolates from January 2016 to December 2017.

Abbreviations: CRKP, carbapenem-resistant Klebsiella pneumoniae; KPC, K. pneumoniae carbapenemases; MβL, metallo-β-lactamase; OXA-48, oxacillinase type 48.

Table 1 Antimicrobial susceptibility and MIC distributions of CRKP isolates

Antibiotics	Breakpoint μg/mL)		MIC μg/mL)			Antimicrobial susceptibility
	S	R	Range	MIC50	MIC90	R (%)	S (%)
ETP	≤0.5	≥2	≤0.25-≥32	>32	>32	99.41	0.59
IPM	≤1	≥4	1—≥ 16	>16	>16	95.88	0.59
MEM	≤1	≥4	1—≥ 16	>16	>16	95.29	1.76
CAZ	≤4	≥16	>32	>32	>32	100	0
CTX	≤1	≥4	>32	>32	>32	100	0
CMZ	≤16	≥64	8-≥64	>64	>64	86.47	8.24
CXM	≤4	≥32	>64	>64	>64	100	0
CSL	≤16	≥64	32—≥128	>128	>128	100	0
AMK	≤16	≥64	≤l-≥128	>128	>128	58.24	41.75
GEN	≤4	≥16	≤l-≥128	>128	>128	61.76	36.47
NIT	≤32	≥128	0.5-≥ 128	128	>128	66.47	21.76
SXT	≤2/38	≥4/76	≤0.25/4.75-≥32/608	>32/608	>32/608	81.76	18.24
ATM	≤4	≥16	≤l-≥128	>128	>128	94.71	5.29
CIP	≤1	≥4	≤0.06-≥8	4	>8	62.94	32.35
LVX	≤2	≥8	≤0.125—≥ 16	16	>16	61.68	38.32
TGC	≤1	>2	≤0.125-2	0.5	1	0.59	85.88
COL	≤2	>2	0.25-16	1	1	2.94	97.06

Note: The two sets of data for SXT values show: 1:19 ratio (trimethoprim:sulfamethoxazole).

Abbreviations: AMK, amikacin; ATM, aztreonam; CAZ, ceftazidime; CIP, ciprofloxacin; CMZ, cefmetazole; COL, colistin; CRKP, carbapenem-resistant Klebsiella pneumoniae; CSL, cefoperazone–sulbactam; CTX, cefotaxime; CXM, cefuroxime; ETP, ertapenem; GEN, gentamicin; IPM, imipenem; LVX, levofloxacin; MEM, meropenem; MIC, minimum inhibitory concentration; NIT, nitrofurantoin; R, resistance; SXT, sulfamethoxazole/trimethoprim; TGC, tigecycline

Table 2 Antimicrobial activity of 17 agents against carbapenemase-producing Klebsiella pneumoniae isolates by the microdilution broth method

Antibiotics	KPC (n=30)				MβL (n=67)				OXA-48 (n=72)
	Range (μg/mL)	MIC50 (μg/mL)	MIC90 (μg/mL)	R (%)	Range (μg/mL)	MIC50 (μg/mL)	MIC90 (μg/mL)	R (%)	Range (μg/mL)	MIC50 (μg/mL)	MIC90 (μg/mL)	R (%)
ETP	>32	>32	>32	100	16->32	>32	>32	100	≤0.25->32	>32	>32	98.61
IPM	>16	>l6	>l6	l00	8->l6	>l6	>l6	l00	l-> l6	>l6	>l6	90.27
MEM	>16	>l6	>l6	100	16->l6	>l6	>l6	l00	l-> l6	>l6	>l6	88.89
CAZ	>32	>32	>32	l00	>32	>32	>32	l00	>32	>32	>32	100
CTX	>32	>32	>32	l00	>32	>32	>32	l00	>32	>32	>32	100
CMZ	>64	>64	>64	l00	>64	>64	>64	l00	8->64	>64	>64	68.06
CXM	>64	>64	>64	l00	>64	>64	>64	l00	>64	>64	>64	100
CSL	>128	>l28	>l28	l00	>l28	>l28	>l28	l00	32->l28	>l28	>l28	100
AMK	≤l->128	>l28	>l28	76.67	≤l->l28	≤l	≤l	4.48	≤l->l28	>l28	>l28	100
GEN	≤l->128	>l28	>l28	80	≤ l->l28	≤l	≤l	l3.43	≤l->l28	>l28	>l28	100
NIT	0.5-> 128	>l28	>l28	90	8->l28	64	128	35.82	32->l28	128	>l28	86.11
SXT	≤0.25/4.75->32/608	>32/608	>32/608	86.67	≤0.25/4.75->32/608	32/608	>32/608	6l.l9	>32/608	>32/608	>32/608	100
ATM	>l28	>l28	>l28	l00	≤l->l28	>l28	>l28	88.06	32->l28	l28	>l28	100
CIP	>8	>8	>8	96.67	≤0.06->8	0.5	4	ll.94	>8	>8	>8	100
LVX	l6->l6	l6	>l6	96.67	≤0.l25->l6	0.5	2	7.46	l6->l6	>l6	>l6	100
TGC	0.25-2	0.5	l	0	≤0.l25-2	0.25	0.5	0	≤0.l25-8	l	2	l.39
COL	0.5-l	l	l	0	0.5-l6	l	l	l.49	0.25-8	l	l	5.56

Note: SXT: 1:19 Ratio (trimethoprim:sulfamethoxazole)

Abbreviations: AMK, amikacin; ATM, aztreonam; CAZ, ceftazidime; CIP, ciprofloxacin; CMZ, cefmetazole; COL, colistin; CSL, cefoperazone–sulbactam; CTX, cefotaxime; CXM, cefuroxime; ETP, ertapenem; GEN, gentamicin; IPM, imipenem; LVX, levofloxacin; MEM, meropenem; NIT, nitrofurantoin; R, resistance; SXT, sulfamethoxazole/trimethoprim; TGC, tigecycline.

Table 3 Distribution of different CRKP genotypes from 2016 to 2017

Genotype	2016 (n=101)n (%)	2017(n=69)n (%)	Total(n=170)n (%)
blaNDM-l	13 (12.87)	22 (31.88)	35 (20.59)
blaNDM-5	10 (9.9)	18 (26.09)	28 (16.47)
blaKPC-2	19 (18.81)	11 (15.94)	30 (17.65)
blaOXA-232	55 (54.46)	17 (24.64)	72 (42.35)
blaIMP-4	2 (1.98)	0	2 (1.18)
blaKPC-2 + blaIMPIMP-4	1 (1.0)	0	1 (0.59)
blaKPC-2 + blaNDMNDM-,1	1 (1.0)	0	1 (0.59)
Undetermined	0	1 (1.45)	1 (0.59)

Abbreviation: CRKP, carbapenem-resistant Klebsiella pneumoniae.

Table 4 Genotypes and MLST of 170 CRKP isolates

STs	Resistance genes	Number of isolates
ST11 (n=30)	KPC-2, TEM-1, SHV-11, CTX-M-14	13
	KPC-2, TEM-1, SHV-12, CTX-M-14	7
	KPC-2, SHV-11, CTX-M-14	5
	KPC-2, TEM-1, SHV-11	3
	KPC-2, SHV-12, CTX-M-14	2
	KPC-2, NDM-1, SHV-12, CTX-M-14, CMY-6	1
ST14 (n=11)	NDM-1, TEM-1, SHV-1, CTX-M-15	7
	NDM-1, TEM-1, SHV-12, CTX-M-15	2
	NDM-5, TEM-1, SHV-5, CTX-M-15	1
	DHA-1, TEM-1, SHV-11, CTX-M-15	1
ST15 (n=71)	OXA-232, SHV-1, CTX-M-15	71
ST17 (n=4)	NDM-1, DHA-1, SHV-11, CTX-M-14	2
	NDM-1, DHA-1, SHV-1, CTX-M-14	1
	NDM-5, DHA-1, TEM-1, SHV-1, CTX-M-14	1
ST18 (n=1)	KPC-2, TEM-1, SHV-11, CTX-M-15	1
ST37 (n=13)	NDM-1, TEM-1, SHV-1	11
	NDM-1, SHV-1	2
ST43 (n=1)	NDM-1, SHV-12	1
ST45 (n=2)	NDM-1, TEM-1, SHV-11, CTX-M-15	1
	NDM-1, TEM-1, SHV-1	1
ST48 (n=30)	NDM-5, SHV-11, CTX-M-15	27
	NDM-1, TEM-1, SHV-1, CTX-15	2
	NDM-1, DHA-1, SHV-11, CTX-M-15	1
ST101 (n=1)	IMP-4, TEM-1, SHV-1, CTX-M-15	1
ST105 (n=1)	NDM-1, TEM-1, CTX-M-14	1
ST198 (n=1)	IMP-4, SHV-11	1
ST2673 (n=1)	KPC-2, IMP-4, DHA-1, TEM-1	1
ST3245 (n=1)	OXA-232, TEM-1, SHV-1, CTX-M-15	1
ST3246 (n=1)	NDM-1, TEM-1, SHV-1	1
ST3247 (n=1)	NDM-1, SHV-1	1

Abbreviations: CRKP, carbapenem-resistant Klebsiella pneumoniae; MLST, multilocus sequence typing; STs, sequence types.

Table 5 Characteristics of patients colonized or infected by CRKP

Characteristics	n=170
Age (<3 m)	118 (69.41)
Male gender	93 (54.71)
Length of hospital stay (days)^a	27 (12-62)
Length from admission to cRKP isolated (days)^a	8 (4-21)
neonatal information	112 (65.88)
Birth weight (g)^a	2090 (1330-2999)
gestational age (weeks)^a	35 (30-39)
Very low birth weight	12 (10.71)
Premature	71 (63.39)
Cesarean/natural vaginal delivery	78 (69.64)
Premature rupture of membrane	19 (16.96)
Total parenteral nutrition	76 (67.86)
Low Apgar score at 5 minutes (≤7)	18 (16.07)
History of drug use during pregnancy	27 (24.11)
GDM	5 (4.46)
PIH	7 (6.25)
Source of isolates
Respiratory	116 (68.23)
Urine	18 (10.59)
Blood	18 (10.59)
Secretions	7 (4.12)
Vein detained needle	3 (1.76)
Other^b	8 (4.71)
Wards of hospitalization
NICU	112 (65.88)
PICU	28 (16.47)
Charity ward	14 (8.33)
Gastroenterology	4 (2.35)
Respiratory medicine	4 (2.35)
Other^c	8 (4.71)
Underlying conditions/diseases
Pneumonia	84 (49.41)
Congenital heart disease	54 (31.76)
Gastroenteritis	18 (10.58)
NRDS	7 (4.12)
Invasive procedures
Central venous catheter	132 (77.65)
Intubation/mechanical ventilation	127 (75.71)
Surgery	45 (26.47)
Urinary catheterization	41 (24.12)
Thoracic tube drainage	6 (3.53)
CRKP colonizations	58 (34.12)
CRKP infections	112 (65.88)
Lower respiratory tract infection	58 (51.72)
Bloodstream	21 (18.75)
Urinary tract infection	18 (16.07)
Intra-abdominal infection	8 (7.14)
Skin and soft tissues infection	7 (6.25)
Antibiotic exposure
Carbapenems	76 (44.71)
β-lactam/β-lactamase inhibitor combinations	91 (53.53)
Third generation cephalosporin	50 (29.41)
Fosfomycin	4 (2.35)
Vancomycin	6 (3.53)

Notes: Data shown as n (%) unless otherwise specified. ^aMedian and interquartile ranges (25th and 75th percentile).

b Other source of isolates, including ascites and pus.

c Other wards of hospitalization, including cardiothoracic surgery, cardiovasology, urology, gastroenterology.

Abbreviations: CRKP, carbapenem-resistant Klebsiella pneumoniae; GDM, gestational diabetes mellitus; m, months; NICU, neonatal intensive care unit; NRDS, neonatal respiratory distress syndrome; PICU, pediatric intensive care unit; PIH, pregnancy induced hypertension; wk, weeks.