Virulence Genotype and Correlation of Clinical Severeness with Presence of the Type VI Secretion System in Klebsiella pneumoniae Isolates Causing Bloodstream Infections

Figures & data

Table 1 Baseline Characteristics of Patients with Klebsiella pneumoniae Bloodstream Infection

Patient Characteristic	All (n = 119)	T6SS‐Positive (n = 20)	T6SS‐Negative (n = 99)	p-value
Age, years, mean ± SD	51.6±16.9	60.2±12.4	49.8±17.1	0.01
Gender, % male	83 (69.7)	14 (70)	69 (69.7)	0.97
CCI, median (IQR)	1.8 (0–6)	1.9 (0–4)	1.8 (0–6)	0.85
Underlying diseases, n (%)
Diabetes mellitus	32 (26.9)	8 (40.0)	24 (24.2)	0.14
Hypertension	22 (18.4)	8 (40.0)	14 (14.1)	0.007
Chronic cardiac insufficiency	7 (5.9)	1 (5.0)	6 (6.1)	0.85
End-stage renal disease	22 (18.4)	2 (10.0)	20 (20.2)	0.28
Chronic liver disease	11 (9.2)	1 (5.0)	10 (10.1)	0.47
Cerebrovascular diseases	6 (5.0)	1 (5.0)	5 (5.1)	0.99
Hematological malignancies	15 (12.6)	2 (10.0)	13 (13.1)	0.7
Solid tumor	15 (12.6)	3 (15.0)	12 (12.1)	0.72
Transplant	22 (18.4)	1 (5.0)	21 (21.2)	0.08
Underlying conditions
Immunosuppression	52 (43.7)	4 (20.0)	48 (48.5)	0.01
Previous surgery	41 (34.5)	5 (25.0)	36 (36.4)	0.32
Neutropenia	22 (18.4)	2 (10.0)	20 (20.2)	0.28
Hypoalbuminemia	98 (82.3)	16 (80.0)	82 (82.8)	0.76
ICU stay	47 (39.4)	9 (45.0)	38 (38.4)	0.58
Community-acquired BSI	40 (33.6)	9 (45.0)	31 (31.3)	0.23
Healthcare-associated	79 (66.4)	11 (55.0)	68 (68.7)	0.23
TTP	14.3±19.3	10.6±8.6	15.0±10.1	0.36
Hospitalization days	37.9±45.2	34.6±38.2	38.6±46.6	0.71
Multi-drug resistance bacteria	78 (65.5)	7 (35.0)	71 (71.7)	0.002
Initial appropriate antibiotics	83 (69.7)	17 (85.0)	66 (66.7)	0.10
Outcomes
7 day total mortality rate	26 (21.8)	3 (15.0)	23 (23.2)	0.41
30 day total mortality rate	39 (32.8)	2 (10.0)	37 (37.4)	0.01
In-hospital mortality (n,%)	43 (36.1)	5 (25.0)	38 (38.4)	0.25

Abbreviations: CCI, Charlson Comorbidity Index; IQR, interquartile range; TTP, time to positivity.

Table 2 Antimicrobial Resistance of T6SS‐positive and T6SS‐negative K. pneumoniae Bloodstream Isolates

Antimicrobial Susceptibility, n (%)	All (n = 119)	T6SS‐Positive (n = 20)	T6SS‐Negative (n = 99)	p
Aztreonam	65 (54.6)	6 (30.0)	59 (59.6)	0.01
Gentamicin	58 (48.7)	5 (25.0)	53 (53.5)	0.02
Tobramycin	45 (37.8)	3 (15.0)	42 (42.4)	0.02
Trimethoprim sulfamethoxazole	51 (42.8)	5 (25.0)	46 (46.5)	0.07
Amikacin	38 (31.9)	3 (15.0)	35 (35.4)	0.07
Cefepime	56 (47.0)	6 (30.0)	50 (50.5)	0.09
Ceftriaxone	75 (63.0)	8 (40.0)	67 (67.7)	0.01
Cefotaxime	76 (63.8)	8 (40.0)	68 (68.7)	0.015
Ceftazidime	62 (52.1)	6 (30.0)	56 (56.6)	0.03
Cefoperazone‐sulbactam	57 (47.8)	4 (20.0)	53 (53.5)	0.006
Ciprofloxacin	68 (57.1)	4 (20.0)	64 (64.6)	<0.001
Levofloxacin	58 (48.7)	3 (15.0)	55 (55.6)	0.001
Imipenem	50 (42.0)	4 (20.0)	46 (46.5)	0.029
Meropenem	50 (42.0)	4 (20.0)	46 (46.5)	0.029
Ampicillin‐sulbactam	79 (66.3)	8 (40.0)	71 (71.7)	0.006
Piperacillin‐tazobactam	54 (45.3)	4 (20.0)	50 (50.5)	0.01
Minocycline	11 (9.2)	0	11 (11.1)	0.118
Piperacillin	85 (71.4)	9 (45.0)	76 (76.8)	0.004
Tigecycline	1 (0.8)	0	1 (1.0)	0.652
Ceftazidime - avibatan	11 (9.2)	1 (5.0)	10 (10.1)	0.473
CRKP	49 (41.2)	4 (20.0)	45 (45.4)	0.03
ESBL	24 (20.2)	4 (20.0)	20 (20.2)	0.98

Abbreviations: CRKP, carbapenem-resistant KP; ESBL, extended-spectrum β-lactamase.

Table 3 Capsular Serotypes and Virulence Factors Between T6SS‐positive and T6SS‐negative K. pneumoniae Bloodstream Isolates

Variable, n (%)	Total n = 119	T6SS‐Positive (n = 20)	T6SS‐Negative (n = 99)	p-value
Capsular serotype
K1	13 (10.9)	5 (25.0)	8 (8.1)	0.027
K2	9 (7.5)	1 (5.0)	8 (8.1)	0.653
Non K1/K2	97 (81.5)	14 (70.0)	83 (83.8)	0.146
Virulence genes
rmpA	60 (50.4)	13 (65.0)	47 (47.5)	0.153
rmpA2	54 (45.3)	12 (60.0)	42 (42.4)	0.307
aerobactin	28 (23.5)	11 (55.0)	17 (17.2)	<0.001
iroB	27 (22.6)	9 (45.0)	18 (18.2)	0.009
hvkp	26 (21.8)	10 (50.0)	16 (16.2)	0.001

Abbreviation: K, capsular polysaccharide (K antigen).

Figure 1 Mean ± standard deviation optical density at 600 nm of T6SS-positive and T6SS-negative Klebsiella pneumoniae isolates stained with crystal violet in the biofilm formation assay.

Figure 2 Serum resistance assay for all T6SS-positive and T6SS-negative K. pneumoniae isolates. Serum resistance as a viability ratio (colony forming units [CFUs] of serum-bacterial suspension/CFUs of bacterial suspension without normal human serum).

Figure 3 In vitro competitive index (CI) values of T6SS K. pneumoniae isolates. Each circle represents one of the CI values obtained from the number of ampicillin-resistant CFUs (K. pneumoniae) divided by the number of ampicillin-susceptibility CFUs (E. coli).