Baseline characteristics
We collected 615 patients’ clinical data with CR-KP humor infections diagnosed between January 2018 and December 2019. 135 patients who did not meet the requirements were excluded, and the remaining 480 patients were enrolled in the study. Baseline characteristics of study cohort are reported in Table 1.
The total 30-day mortality of patients with CR-KP was 37.3%. Of all patients, the majority were male (289, 60.2%) and the female were 191 (39.8%). 379 patients (78.9%) were pulmonary infection and 68 patients (14.2%) were bloodstream infection. Hypertension, coronary heart disease, and neurological diseases were the most common underlying diseases (47.7%, 35.2% and 21.9%, respectively). Stroke (188, 39.2%) was the most common in acute complications, followed by AKI (117, 24.4%) and septic shock (108, 22.5%), and septic shock was significantly more frequent among patients in the death group than those in the survival group (46.3% vs. 8.3%, p<0.001). Most of patients (430, 89.6%) were intubation or tracheotomy and 387 patients (80.6%) carried a central venous catheter. A proportion of patients got steroid therapy (93, 19.4%) and continuous renal replacement therapy (CRRT, 58, 12.1%). Finally, 116 patients’ rectal swabs were collected and screened for the presence of carbapenem-resistant enteric bacteria, but only 35 patients were detected positive (30.2%).
Table 1 Demographic and clinical characteristics of the study cohort
Variables
|
30-days outcome
|
ALL, 480
|
Death, 179
|
Survival, 301
|
χ2
|
p-value
|
Gender
|
▪ Female
|
191
|
70
|
121
|
0.06
|
0.813
|
▪ Male
|
289
|
109
|
180
|
|
|
Age
|
▪ ≤60
|
209
|
53
|
166
|
29.51
|
<0.001
|
▪ >60
|
271
|
126
|
135
|
|
|
Wards
|
▪ Respiratory ICU
|
104
|
34
|
70
|
1.2
|
0.273
|
▪ General ICU
|
110
|
47
|
63
|
1.8
|
0.18
|
▪ Surgical ICU
|
119
|
48
|
71
|
0.63
|
0.428
|
▪ Neurological ICU
|
111
|
34
|
77
|
2.74
|
0.098
|
▪ Emergency ICU
|
36
|
16
|
20
|
0.85
|
0.356
|
Specimens
|
|
|
|
|
|
▪ BALF
|
379
|
120
|
259
|
24.41
|
<0.001
|
▪ Blood and catheter tips
|
68
|
45
|
23
|
28.27
|
<0.001
|
▪ Drainage liquid
|
21
|
7
|
14
|
|
|
▪ Urine
|
9
|
1
|
8
|
|
|
▪ Cerebrospinal fluid
|
3
|
3
|
0
|
|
|
Comorbidities
|
|
|
|
|
|
▪ COPD
|
85
|
33
|
52
|
0.04
|
0.84
|
▪ Solid tumors
|
81
|
46
|
35
|
4.01
|
0.045
|
▪ Hematopathy
|
20
|
16
|
4
|
16.27
|
<0.001
|
▪ Chronic liver disease
|
42
|
24
|
18
|
6.85
|
0.009
|
▪ Organ transplantation
|
20
|
11
|
9
|
2.06
|
0.15
|
▪ Coronary heart disease
|
169
|
72
|
97
|
2.81
|
0.094
|
▪ Hypertension
|
229
|
91
|
138
|
0.93
|
0.335
|
▪ Diabetes
|
97
|
49
|
48
|
8.4
|
0.004
|
▪ Infectious disease
|
87
|
36
|
51
|
0.56
|
0.454
|
▪ Tuberculosis
|
15
|
5
|
10
|
0.10
|
0.747
|
▪ CNS sequelae
|
105
|
35
|
70
|
0.70
|
0.404
|
Acute comorbidities
|
|
|
|
|
|
▪ Septic shock
|
108
|
83
|
25
|
91.09
|
<0.001
|
▪ Acute kidney injure
|
117
|
86
|
31
|
84.72
|
<0.001
|
▪ Stroke
|
188
|
45
|
143
|
22.64
|
<0.001
|
▪ Acute heart failure
|
39
|
17
|
22
|
0.72
|
0.396
|
Pre-infection variables
|
|
|
|
|
|
▪ Central venous catheter
|
387
|
159
|
228
|
12.29
|
<0.001
|
▪Intubation or tracheotomy
|
430
|
165
|
265
|
2.06
|
0.151
|
▪ CRRT
|
58
|
36
|
22
|
17.32
|
<0.001
|
▪ Steroid therapy
|
93
|
40
|
53
|
1.61
|
0.2
|
▪ Immunosuppressive
|
23
|
14
|
9
|
5.74
|
0.017
|
▪ Chemoradiotherapy
|
19
|
13
|
6
|
8.20
|
0.004
|
Table 2 Therapies in the death and survive groups
Variables
|
30-days outcome
|
ALL
|
Death
|
Survive
|
Previous antibiotic therapy
|
|
▪Penicillins &cephalosporins
|
158
|
109
|
166
|
▪ Carbapenems
|
184
|
69
|
115
|
▪ Tigecycline
|
69
|
20
|
49
|
▪ Quinolones
|
153
|
60
|
93
|
▪ Others
|
63
|
35
|
28
|
Definitive therapy
|
|
|
|
▪ Carbapenems
|
339
|
150
|
189
|
▪ Tigecycline
|
327
|
143
|
184
|
▪ Polymyxin B
|
40
|
27
|
13
|
▪ Ceftazidime avibactam
|
23
|
14
|
9
|
▪ Other cephalosporins
|
124
|
36
|
88
|
▪ Fosfomycin
|
60
|
43
|
17
|
Therapies
The empirical and definitive therapies for patients with CR-KP in the survivor and death group are summarized in Table 2. The most frequently used antibiotics for both empirical and definitive therapy were carbapenems in two groups. Then, we did a statistical analysis for the different antibiotic therapeutic regimens and the results were listed in Table 3.
Table 3 Different antibiotic therapeutic regimens
Antibiotic therapeutic regimens
|
30-days outcome
|
ALL
|
Death
|
Survive
|
survival rate
|
A: Ceftazidime avibactam & Tigecycline
|
24
|
7
|
17
|
70.8%
|
B: Carbapenems & Tigecycline & Polymyxin B
|
28
|
9
|
19
|
67.9%
|
C: Carbapenems & Polymyxin B
|
33
|
19
|
14
|
42.4%
|
D: Carbapenems & Tigecycline
|
198
|
87
|
111
|
56.1%
|
E: Carbapenems & Tigecycline & Fosfomycin
|
44
|
18
|
26
|
59.1%
|
Chi-square test showed that both antibiotic regimen B (carbapenems plus tigecycline and polymyxin B, χ2=3.96, p=0.04) and antibiotic regimen A (ceftazidime avibactam plus tigecycline, χ2=4.52, p=0.033) were superior to antibiotic regimen C (carbapenems combined with polymyxin B) and the differences were of statistical significance. However, there was no statistically significant difference among antibiotic regimen D (carbapenems plus tigecycline), antibiotic regimen C (carbapenems plus polymyxin B) and regimen E (carbapenems plus tigecycline plus fosfomycin). It seemed that polymyxin B and tigecycline have synergistic effect and carbapenems plus polymyxin B was not a recommended therapeutic regimen (Figure 1). Ceftazidime avibactam-based antimicrobial regimens also had no advantage over other therapeutic regimens.
In addition, we investigated the efficacy of tigecycline combination with other different antibiotics in the treatment of CR-KP. The different antibiotic therapeutic regimens were listed in Table 4.
Table 4 Tigecycline combination with other different antibiotics
Tigecycline and
other antibiotics
|
30-days outcome
|
ALL
|
Death
|
Survive
|
Survive rate
|
χ2
|
p-value
|
Imipenem
|
97
|
45
|
52
|
53.6%
|
5.432
|
0.246
|
Meropenem
|
39
|
12
|
27
|
69.2%
|
|
Biapenem
|
62
|
30
|
32
|
51.6%
|
|
Ceftazidime avibactam
|
24
|
7
|
17
|
70.8%
|
|
3rd or 4th ephalosporins
|
39
|
16
|
21
|
56.8%
|
|
Chi-square test showed that there was no statistically significant difference among different antibiotic regimens. Considering the price of antibiotics, we recommend biapenem combined with tigecycline as a therapeutic regimen.
Prognostic factors
In the multivariate logistic regression analysis, hemopathy, age (>60 years), solid tumors, diabetes, septic shock, acute kidney injury and stroke were independent predictors associated with the 30-day mortality (Table 5).
Table 5 Multivariate analysis of risk factors for mortality
Variables
|
B
|
OR (95% CI)
|
p-value
|
Hemopathy
|
2.218
|
9.191 (2.555-33.053)
|
0.001
|
Age(>60 years)
|
0.992
|
2.696 (1.584-4.590)
|
<.001
|
Solid tumors
|
0.835
|
2.305 (1.169-4.546)
|
0.016
|
Diabetes
|
0.677
|
1.968 (1.152-3.361)
|
0.013
|
Septic shock
|
1.796
|
6.024 (3.027-11.989)
|
<0.001
|
AKI
|
1.218
|
3.381 (1.784-6.406)
|
<0.001
|
Stroke
|
-0.573
|
0.564 (0.329-0.966)
|
.037
|
Correlation analysis and ROC curves
Multivariate linear regression was performed in APACHE II score, SOFA score, lymphocyte absolute value (LYM) and survival time. Survival time was negatively correlated with APACHE II score and SOFA score, and positively correlated with LYM (Figure 2 and 3). In addition, ROC curves were also drawn for APACHE II score, SOFA score and LYM, with AUC of 0.825, 0.876 and 0.797, and with cut-off value of 17, 6 and 0.775
Survival analysis
Survival analysis showed that pulmonary and drainage fluid infections were statistically significance differences from bloodstream infection with CR-KP (Figure 4).