Outcomes and Risk Factors of Bloodstream Infections Caused by Carbapenem-Resistant and Non-Carbapenem-Resistant Klebsiella pneumoniae in China

Figures & data

Table 1 Characteristics of Patient Cohorts

Characteristic	Complete Cohort
	CSKP (n=47)	CRKP (n=56)	P-value
Age (median, IQR)	10 (0–61)	27 (0–61)	0.48
Sex			0.764
Female	13 (27.7%)	17 (30.4%)
Male	34 (72.3%)	39 (69.6%)
Underlying disease/comorbid conditions
Hypertensive	0 (0%)	3 (5.4%)	0.248
Diabetes diseases	8 (17.0%)	6 (10.7%)	0.352
Coronary heart disease	1 (2.1%)	4 (7.1%)	0.372
Congestive heart failure	5 (10.6%)	3 (5.4%)	0.464
Connective tissue disease	0 (0%)	2 (3.6%)	0.499
Chronic pulmonary disease	3 (6.4%)	1 (1.8%)	0.329
Chronic kidney failure	1 (2.1%)	5 (8.9%)	0.216
End-stage liver disease	1 (2.1%)	0	0.456
Cancer	6 (12.8%)	5 (8.9%)	0.530
Hematogenous tumor	6 (12.8%)	2 (3.6%)	0.138
Charlson comorbidity index > 2	8 (17.0%)	8 (14.3%)	0.703
Location before admission
Home	27 (57.4%)	24 (42.9%)	0.14
Transfer from other hospital	13 (27.7%)	29 (51.8%)	0.013
Born this episode	7 (14.9%)	3 (5.4%)	0.18
Health-care exposures before BSI onset
Antibiotic exposure (within 30 days)	35 (74.5%)	50 (89.3%)	0.055
ICU admission (within 30 days)	13 (25.5%)	24 (42.9%)	0.147
Surgery (within 30 days)	14 (29.8%)	20 (35.7%)	0.524
Corticosteroid therapy (within 30 days)	6 (12.8%)	7 (12.5%)	0.968
Radiation therapy or chemotherapy	6 (12.8%)	2 (3.6%)	0.138
Immunosuppressive therapy (within 3 months)	9 (19.1%)	11 (19.6%)	0.950
Tracheal cannula or tracheotomy (within 30 days)	15 (31.9%)	34 (69.4%)	0.004
Central venous catheterization (within 30 days)	27 (57.4%)	40 (71.4%)	0.138
Previous hospitalization (within 12 months)	42 (89.4%)	51 (91.1%)	1
ICU at time of BSI onset	13 (27.7%)	20 (35.7%)	0.383
Epidemiological classification			0.235
Community acquired	11 (23.4%)	8 (14.3%)
Hospital acquired	36 (76.6%)	48 (85.7%)
Source
Primary	12 (25.5%)	12 (21.4%)	0.624
Central-line associated	3 (6.4%)	6 (10.7%)	0.504
Cardiovascular system infection	1 (2.1%)	0	0.456
Gastrointestinal system infection	11 (23.4%)	13 (23.2%)	0.982
Pneumonia or ventilator-associated event	14 (29.8%)	16 (28.6%)	0.892
Surgical site infection	1 (2.1%)	1 (1.8%)	1
Skin and soft tissue infection	1 (2.1%)	3 (5.4%)	0.623
Urinary tract infection	4 (8.5%)	5 (8.9%)	1
Mechanical ventilation after BSI onset	16 (34%)	31 (55.4%)	0.031
Hemodialysis treatment	5 (10.6%)	10 (17.9%)	0.301
Temperature ≥ 39°C or < 36°C after BSI onset	21 (44.7%)	27 (48.2%)	0.72
Severe sepsis	20 (42.6%)	26 (46.4%)	0.694
Septic shock	14 (29.8%)	17 (30.4%)	0.950
Active empiric antibiotic therapy	44 (93.6%)	25 (44.6%)	< 0.001
Active directed antibiotic therapy	41 (87.2%)	39 (69.6%)	0.033
Combination therapy	3 (6.4%)	3 (5.4%)	1.000
Carbapenem-including treatment	31 (66.0%)	40 (71.4%)	0.55
Polymyxin-including treatment	0	5 (8.9%)	0.036
Tigecycline-including treatment	1 (2.1%)	12 (21.4%)	0.003
Length of hospitalization before the onset of BSI	11 (1–19)	12 (3.25–28)	0.216
Length of hospitalization after the onset of BSI	15 (8–27)	14 (8.25–23.5)	0.366
Total length of stay (days)	28 (16–51)	28.5 (16–50.75)	0.783
Outcome
7-day mortality	7 (14.9%)	10 (17.9%)	0.687
14-day mortality	7 (14.9%)	16 (28.6%)	0.097
28-day mortality	9 (19.1%)	20 (35.7%)	0.063
In-hospital mortality	9 (19.1%)	22 (39.3%)	0.026

Note: P values less than 0.05 are bolded.

Abbreviations: KP, Klebsiella pneumoniae; CRKP, carbapenem-resistant KP; CSKP, carbapenem susceptible KP; BSI, bloodstream infection.

Table 2 Antimicrobial Spectrum Evaluation Percentage of Carbapenem-Resistant Klebsiella pneumoniae Isolates Resistance to Various Antibiotics

Antimicrobial Agents	CRKP Isolates (n=56)			CSKP Isolates (n=47)			P-value
	MIC50	MIC90	R%	MIC50	MIC90	R%
CTX	256	>256	100	48	>128	74.5	<0.01
CAZ	>256	>256	100	8	128	55.3	<0.01
FEP	128	>256	100	8	16	61.7	<0.01
CT	0.25	0.5	1.8	0.5	0.5	0	0.362
TGC	1	4	12.5	1	2	8.5	0.519
IMP	16	>32	89.3	≤0.25	0.375	2.1	<0.01
ETP	>16	>16	100	≤0.25	≤0.25	2.1	<0.01
MEM	16	>16	94.6	≤0.25	0.25	0	<0.01
CIP	2	128	57.1	1	64	42.6	0.134
FOS	512	>512	92.9	>512	>512	97.9	0.24
SXT	2/38	16/304	48.2	>16	>16	59.6	0.254
PTZ	512	>512	94.6	4	12	8.5	<0.01
AMK	4	>256	48.2	2	4	6.4	<0.01
GEN	128	>256	60.7	≤1	128	38.3	0.023
ATM	>128	>128	96.4	12	128	55.3	<0.01

Note: P values less than 0.05 are bolded.

Abbreviations: CTX, cefotaxime; CAZ, ceftazidime; FEP, cefepime; CT, colistin; TGC, tigecycline; IMP, imipenem; ETP, ertapenem; MEM, meropenem; CIP, ciprofloxacin; FOS, fosfomycin; SXT, trimethoprim-sulfamethoxazole; PTZ, piperacillin-tazobactam; AMK, amikacin; GEN, gentamicin; ATM, aztreonam.

Figure 1 (A) Isolation of CRKP and CSKP over the past 9 years. CRKP isolates increased almost every year, and most strains were isolated in 2017. (B) Age distribution of patients with CRKP strains. (C) Age distribution of patients with CSKP strains.

Abbreviations: KP, Klebsiella pneumoniae; CRKP, carbapenem-resistant KP; CSKP, carbapenem-susceptible KP.

Figure 2 Resistance rate of CRKP and CSKP to antimicrobial agents.

Abbreviations: CTX, cefotaxime; CAZ, ceftazidime; FEP, cefepime; CT, colistin; TGC, tigecycline; IMP, imipenem; ETP, ertapenem; MEM, meropenem; CIP, ciprofloxacin; FOS, fosfomycin; SXT, trimethoprim-sulfamethoxazole; PTZ, piperacillin-tazobactam; AMK, amikacin; GEN, gentamicin; ATM, aztreonam.

Figure 3 (A) Survival rates between CRKP and CSKP infections with G. mellonella infection model. (B) Fatality rates between CRKP and CSKP infections with G. mellonella infection model. (C) Kaplan–Meier survival curves of CRKP infections (11 strains) with G. mellonella infection model. (D) Kaplan–Meier survival curves of CSKP infections (11 strains) with G. mellonella infection model. Klebsiella pneumoniae strain HvKP4 as a positive control. *Means P < 0.05, ***Means P < 0.001.

Figure 4 (A) Survival curve between CRKP and CSKP on Days from BSI onset. (B) Survival curve between CRKP and CSKP on Length of hospitalization after the onset of BSI.

Abbreviations: KP, Klebsiella pneumoniae; CRKP, carbapenem-resistant KP; CSKP, carbapenem-susceptible KP.

Table 3 Risk Factors for CRKP BSIs with Multivariate Logistic Regression Analysis

Covariate	Univariate Analysis		Multivariate Analysis	P value
	OR (95% CI)	P value	OR (95% CI)
Transfer from other hospital	2.809 (1.229–6.420)	0.014	0.374 (0.127–1.101)	0.074
Tracheal cannula or tracheotomy (within 30 days)	3.297 (1.460–7.446)	0.004	0.295 (0.102–0.852)	0.024
Active empiric antibiotic therapy	0.055 (0.015–0.198)	<0.01	0.008 (0.001–0.118)	<0.01
Active directed antibiotic therapy	0.336 (0.120–0.939)	0.038	0.085 (0.007–1.083)	0.058
Tigecycline-including treatment	0.080 (0.010–0.639)	0.017	0.061 (0.004–0.855)	0.038

Note: P values less than 0.05 are bolded.

Abbreviations: KP, Klebsiella pneumoniae; CRKP, carbapenem-resistant KP; CSKP, carbapenem susceptible KP; BSI, bloodstream infection; OR, odds ratio; CI, confidence interval.

Table 4 Risk Factors for Mortality of KP, CRKP and CSKP BSI with Multivariate Logistic Regression Analysis

Mortality		Items	p-value	OR	95% CI
28-day mortality	KP	Tracheal cannula or tracheotomy (within 30 days)	0.005	0.038	0.004–0.371
	KP	Septic shock	0.021	0.066	0.006–0.666
	KP	Length of hospitalization after the onset of BSI	0.002	0.838	0.748–0.939
	CRKP	Tracheal cannula or tracheotomy (within 30 days)	0.018	0.014	0.000–0.476
	CRKP	Severe sepsis	0.048	0.012	0.000–0.953
	CRKP	Length of hospitalization after the onset of BSI	0.004	0.699	0.550–0.889
In-hospital mortality	KP	Tracheal cannula or tracheotomy (within 30 days)	0.005	0.038	0.004–0.371
	KP	Septic shock	0.021	0.066	0.006–0.666
	KP	Length of hospitalization after the onset of BSI	0.002	0.838	0.748–0.939
	CRKP	Carbapenem-resistant Enterobacterales bacteremia	0.023	0.009	0.00–0.520
	CRKP	Length of hospitalization after the onset of BSI	0.018	0.816	0.689–0.965

Note: P values less than 0.05 are bolded.

Abbreviations: KP, Klebsiella pneumoniae; CRKP, carbapenem-resistant KP; CSKP, carbapenem susceptible KP; BSI, bloodstream infection; OR, odds ratio; CI, confidence interval.