Hypervirulent Klebsiella pneumoniae is emerging as an increasingly prevalent K. pneumoniae pathotype responsible for nosocomial and healthcare-associated infections in Beijing, China

Figures & data

Table 1. Clinical characteristics of hvKp infection.

	Community-acquired infection (n = 10)		Healthcare-associated infection (n = 31)		Nosocomial infection (n = 117)
Clinical characteristic	HvKp(7)	cKp(3)	HvKp(19)	cKp(12)	HvKp(53)	cKp(64)	P value^※
Basic demographics
Age	75.29 ± 9.12	76.00 ± 22.52	76.84 ± 17.95	80.67 ± 11.55	78.21 ± 18.09	78.52 ± 12.65	0.914
Metastatic infection	2(28.6%)	0(0%)	8(42.1%)	0(0%)	21(39.6%)	14(21.9%)	0.037
Male	5(71.4%)	2(66.7%)	18(94.7%)	11(91.7%)	45(84.9%)	52(81.3%)	0.601
Underlying diseases
Pulmonary disease	5(71.4%)	2(66.7%)	16(84.2%)	9(75.0%)	30(56.6%)	47(73.4%)	0.056
Diabetes	5(71.4%)	2(66.7%)	11(57.9%)	7(58.3%)	25(47.2%)	25(39.1%)	0.378
Cardiovascular disease	5(71.4%)	1(33.3%)	10(52.6%)	5(41.7%)	38(71.7%)	43(67.2%)	0.599
Cerebrovascular disease	1(14.3%)	0(0%)	7(36.8%)	6(50.0%)	35(66.0%)	28(43.8%)	0.016
Cancer	1(14.3%)	0(0%)	5(26.3%)	5(41.7%)	12(22.6%)	21(32.8%)	0.224
Surgery within 3 months	0(0%)	0(0%)	3(15.8%)	6(50.0%)	17(32.1%)	24(37.5%)	0.590
Digestive disease	3(42.9%)	0(0%)	7(36.8%)	5(41.7%)	30(56.6%)	35(54.7%)	0.836
Urinary disease	2(28.6%)	1(33.3%)	3(15.8%)	4(33.3%)	21(39.6%)	26(40.6%)	0.912
Usage of Glucocorticoid within 7 days	1(14.3%)	0(0%)	1(5.2%)	0(0%)	16(30.2%)	10(15.6%)	0.059
Antibiotics exposure within 90 d	0(0%)	0(0%)	9(47.4%)	4(33.3%)	49(92.5%)	61(95.3%)	0.516
Immunosuppression	1(14.3%)	0(0%)	5(26.3%)	5(41.7%)	21(39.6%)	30(46.9%)	0.431
Catheter
Central intravenous catheter	0(0%)	0(0%)	8(42.1%)	0(0%)	42(79.2%)	42(65.6%)	0.103
Urinary catheter	0(0%)	0(0%)	7(36.8%)	5(41.7%)	48(90.6%)	49(76.6%)	0.045
Endotracheal tube	0(0%)	0(0%)	3(15.8%)	0(0%)	34(64.2%)	30(46.9%)	0.062
Gastrostomy tube	0(0%)	0(0%)	8(42.1%)	7(58.3%)	48(90.9%)	48(75.0%)	0.029
Drainage tube	0(0%)	0(0%)	1(5.2%)	4(33.3%)	19(35.8%)	22(34.4%)	0.868
Infection type
Wound	1(14.3%)	0(0%)	0(0%)	1(8.3%)	2(3.8%)	5(7.8%)	0.599
Pneumonia	5(71.4%)	2(66.7%)	13(57.9%)	10(83.3%)	42(79.2%)	49(76.6%)	0.728
Urinary infection	1(14.3%)	1(33.3%)	8(21.1%)	1(8.3%)	17(32.1%)	17(26.6%)	0.513
Bacteremia	0(0%)	0(0%)	0(0%)	0(0%)	6(11.3%)	8(12.5%)	0.845
Liver abscess	0(0%)	0(0%)	1(5.2%)	0(0%)	1(1.9%)	2(3.1%)	1.000
Other abscess	1(14.3%)	0(0%)	5(26.3%)	0(0%)	3(5.7%)	1(1.6%)	0.225
Abdominal infection	1(14.3%)	0(0%)	0(0%)	0(0%)	7(13.2%)	7(10.9%)	0.706
Sepsis	2(28.6%)	0(0%)	10(52.6%)	4(33.3%)	43(81.1%)	38(59.4%)	0.011
WBC	13.29 ± 10.72	9.27 ± 2.05	14.55 ± 11.76	9.03 ± 3.68	9.87 ± 3.77	11.00 ± 5.25	0.192
NEU%	68.00 ± 15.56	68.47 ± 3.88	73.76 ± 19.67	78.08 ± 9.58	77.22 ± 10.06	77.73 ± 11.30	0.779
TP	72.14 ± 6.34	64.33 ± 4.51	63.63 ± 14.12	66.27 ± 5.06	63.86 ± 6.39	64.26 ± 5.49	0.712
ALB	40.29 ± 3.25	37.33 ± 1.53	34.53 ± 9.38	34.74 ± 4.19	33.19 ± 3.62	33.33 ± 4.39	0.852
CCI>4	2(28.6%)	0(0%)	8(42.1%)	8(66.7%)	29(54.7%)	39(60.9%)	0.497
SOFA>6	2(28.6%)	0(0%)	11(57.9%)	5(41.7%)	35(66.0%)	26(40.6%)	0.006
Admitted in the ICU^#	1(14.3%)^#	0(0%)	4(21.1%)^#	1(8.3%)	15(28.3%)	26(40.6%)	0.164
30 day mortality *	1(14.3%)	0(0%)	1(5.2%)	3(25.0%)	8(15.1%)	13(20.3%)	0.464

The P value <0.05 was shown in the bold values. TP: Total protein; ALB: Albumin; WBC: White blood cell count; NEU%: Neutrophils percentage; CCI: Charlson comorbidity index; SOFA: Sequential organ failure assessment.*: Death or life-sustaining therapy withheld due to poor prognosis; #: patient with community-acquired infection or healthcare-associated infection was admitted or transferred to the ICU. ^※: statistical tests were performed only for the nosocomial group.

Figure 1. The phylogenetic tree of ST11 and ST23 strains isolated in this study.

Table 2. Virulence phenotype and genotype of hvKp.

	Community-acquired infection (n = 10)		Healthcare-associated infection (n = 31)		Nosocomial infection (n = 117)
Virulence	HvKp(7)	cKp(3)	HvKp(19)	cKp(12)	HvKp(53)	cKp(64)	P value ^※
K serotype
K1	0(0%)	0(0%)	7(36.8%)	0(0%)	9(17.0%)	0 (0%)	0.001
K2	1(14.3%)	0(0%)	1(5.2%)	0(0%)	7(13.2%)	1(1.6%)	0.034
K5	0(0%)	0(0%)	0(0%)	0(0%)	0(0%)	0(0%)
K20	1(14.3%)	0(0%)	0(0%)	0(0%)	1(1.9%)	1(1.6%)	1.000
K54	1(14.3%)	0(0%)	0(0%)	1(8.3%)	0(0%)	1(1.6%)	1.000
K57	1(14.3%)	1(33.3%)	1(5.2%)	1(8.3%)	3(5.7%)	1(1.6%)	0.482
rmpA	5(71.4%)	0(0%)	11(57.9%)	0(0%)	32(60.4%)	0(0%)	#
rmpA2	5(71.4%)	0(0%)	12(63.2%)	0(0%)	41(77.4%)	0(0%)	#
crmpA	2(28.6%)	0(0%)	1(5.2%)	0(0%)	2(3.8%)	0(0%)	0.203
Hypermucoviscosity	7(100.0%)	0(0%)	16(84.2%)	1(8.3%)	38(71.7%)	3(4.7%)	0.000
iucA	5(71.4%)	0(0%)	14(73.7%)	0(0%)	43(81.1%)	0(0%)	#
iroB	6(85.7%)	0(0%)	15(78.9%)	0(0%)	22(41.5%)	0(0%)	#
peg-344	6(85.7%)	0(0%)	14(73.7%)	0(0%)	22(41.5%)	0(0%)	#
peg-589	4(57.1%)	0(0%)	13(68.4%)	0(0%)	31(58.5%)	0(0%)	0.000
rmpA+rmpA2+ iucA+iroB+peg-344	4(57.1%)	0(0%)	8(42.1%)	0(0%)	12(22.6%)	0 (0%)	0.000
iucA+rmpA2^&	1(14.3%)	0(0%)	1(5.3%)	0(0%)	9(17.0%)	0 (0%)	0.000
pLVPK-like*	1(14.3%)	0(0%)	5(26.3%)	0(0%)	6(11.3%)	0 (0%)	*
pVir-CR-HvKP4-like*	0(0%)	0(0%)	3(15.8%)	0(0%)	8(15.1%)	0 (0%)	*

The P value <0.05 was shown in the bold values. &: Strains that only have these two genes among iucA, rmpA, rmpA2, iroB, peg-344. *: The pLVPK-like and pVir-CR-HvKP4-like plasmids were achieved by the ST11 and ST23 strains. Due to the potential gaps of Next-generation Sequencing, statistical analysis for plasmids was not conducted. ^#: HvKp are defined on the basis of possession of one or more of these markers (the combination of iroB, iucA, rmpA/A2 and peg-344). Therefore, it doesn’t make sense to test for differences of hvKp vs cKp. ^※:statistical tests were performed only for the nosocomial group.

Table 3. Risk factors for nosocomial hvKp infection.

Variable	Univariate OR (95% CI)	P-value	Multivariate OR (95% CI)	P-value
Metastatic infection	2.344(1.044–5.262)	0.039
Cerebrovascular disease	2.500(1.177–5.309)	0.017	2.415(1.072–5.437)	0.033
Gastrostomy tube	3.200(1.086–9.432)	0.035
SOFA>6	2.842(1.334–6.054)	0.007	2.304(1.029–5.158)	0.042

Table 4. Antibiotics resistance patterns of hvKp.

	Community-acquired infection (n = 10)		Healthcare-associated infection (n = 31)		Nosocomial infection (n = 117)
Antibiotic agent	hvKp(7)	cKp(3)	hvKp(19)	cKp(12)	hvKp(53)	cKp(64)	P-value^※
MDR	0(0%)	0(0%)	4(21.1%)	6(50.0%)	27(50.9%)	44(68.8%)	0.050
ESBLs Amikacin Gentamicin Ampicillin/Sulbactam Aztreonam Cefazolin Cefotetan Cefepime Ceftriaxone Ceftazidime Ciprofloxacin Levofloxacin Trimethoprim/Sulfamethoxazole Piperacillin/Tazobactam Imipenem Meropenem Tobramycin	1(14.3%) 0(0%) 0(0%) 2(28.6%) 0(0%) 1(14.3%) 0(0%) 0(0%) 1(14.3%) 0(0%) 0(0%) 0(0%) 0(0%) 0(0%) 0(0%) 0(0%) 0(0%)	1(33.3%) 0(0%) 0(0%) 0(0%) 0(0%) 1(33.3%) 0(0%) 0(0%) 0(0%) 0(0%) 0(0%) 0(0%) 0(0%) 0(0%) 0(0%) 0(0%) 0(0%)	5(26.3%) 0(0%) 2(10.5%) 6(31.6%) 4(21.1%) 5(26.3%) 3(15.8%) 2(10.5%) 5(26.3%) 4(21.1%) 4(21.1%) 4(21.1%) 3(15.8%) 2(10.5%) 2(10.5%) 2(10.5%) 2(10.5%)	4(33.3%) 0(0%) 1(8.3%) 5(41.7%) 2(16.7%) 6(50.0%) 1(8.3%) 2(16.7%) 5(41.7%) 1(8.3%) 4(33.3%) 4(33.3%) 5(41.7%) 1(8.3%) 1(8.3%) 1(8.3%) 3(25.0%)	25(47.2%) 6(11.3%) 16(30.2%) 31(58.5%) 23(43.4%) 27(50.9%) 15(28.3%) 22(41.5%) 25(47.2%) 23(43.4%) 25(47.2%) 24(45.3%) 14(26.4%) 15(28.3%) 13(24.5%) 14(26.4%) 16(30.2%)	43(67.2%) 13(20.3%) 29(45.3%) 47(73.4%) 29(45.3%) 48(75.0%) 17(26.6%) 21(32.8%) 42(65.6%) 29(45.3%) 32(50.0%) 29(45.3%) 34(53.1%) 23(35.9%) 18(28.1%) 19(29.7%) 25(39.1%)	0.029 0.189 0.038 0.088 0.094 0.007 0.834 0.331 0.045 0.836 0.760 0.997 0.003 0.380 0.661 0.695 0.317

The P value <0.05 was shown in the bold values. ^※:statistical tests were performed only for the nosocomial group.