Clinical characteristics of ABA and PAE bacteraemia
Of the 545 cases identified during the 1-year study period, 304 were ABA bacteraemia and 241 were PAE bacteraemia. Of the 304 ABA bacteraemia cases, 216 (71%) were CR-ABA and 88 (29%) were carbapenem-susceptible ABA (CS-ABA). Of the 241 PAE bacteraemia cases, 55 (23%) were CR-PAE and 186 (77%) were carbapenem-susceptible PAE (CS-PAE).
The clinical characteristics of ABA bacteraemia according to carbapenem susceptibility are described in Table S1. Catheter related bloodstream infection and pneumonia were more frequent in the CR-ABA group than in the CS-ABA group (42.1% vs. 28.4%, P = 0.026; 36.1% vs. 9.1%, P < 0.001). The CR-ABA group showed significantly higher percentages of severe sepsis or septic shock (53.2% vs. 21.6%, P < 0.001) and inappropriate empirical therapy (75.0% vs. 19.3%, P < 0.001) than the CS-ABA group. All-cause 30-day mortality and treatment failure rates were significantly higher in the CR-ABA group than the CS-ABA group (57.5% vs. 15.5%, P < 0.001; 60.6% vs. 15.9%, P < 0.001).
The clinical characteristics of PAE bacteraemia according to carbapenem susceptibility are described in Table S2. The CR-PAE group showed significantly higher percentages of HAI (61.8% vs. 45.2%, P = 0.030) and underlying liver disease (25.5% vs. 14.0%, P = 0.044) than the CS-PAE group. The CR-PAE group showed significantly higher percentages of inappropriate empirical therapy than the CS-PAE group (52.7% vs. 26.3%, P < 0.001). There was no significant difference in treatment failure between the CR-PAE and CS-PAE groups (34.5% vs. 24.7%, P = 0.150).
Comparisons of clinical characteristics of the CR-ABA and CR-PAE groups are shown in Table 1. The CR-ABA group showed significantly higher percentages of severe sepsis or septic shock than the CR-PAE group. Inappropriate empirical therapy was more frequent in the CR-ABA group than the CR-PAE group. All-cause 30-day mortality and treatment failure were significantly higher in the CR-ABA group than the CR-PAE group.
Table 1
Clinical characteristics of patients with carbapenem-resistant Acinetobacter baumannii (CR-ABA) and carbapenem-resistant Pseudomonas aeruginosa (CR-PAE) bacteraemia
Variables
|
Total
(n=271)
|
CR-ABA
(n=216)
|
CR-PAE
(n=55)
|
P
|
Age, mean (±SD)
|
65.6 (±16.9)
|
66.0 (±17.2)
|
64.1 (±15.4)
|
0.469
|
Male
|
177 (65.3)
|
143 (66.2)
|
34 (61.8)
|
0.542
|
ICU stay
at bacteraemia onset
|
139 (51.3)
|
127 (58.8)
|
12 (21.8)
|
<0.001
|
Hospital-acquired infection
|
218 (80.4)
|
184 (85.2)
|
34 (61.8)
|
<0.001
|
Healthcare-associated infection
|
260 (95.9)
|
211 (97.7)
|
49 (89.1)
|
0.004
|
Mixed bacteraemia
|
29 (10.7)
|
18 (8.3)
|
11 (20.0)
|
0.012
|
Site of infection
|
Primary bacteraemia
|
76 (28.0)
|
58 (26.9)
|
18 (32.7)
|
0.387
|
CRBSI
|
103 (38.0)
|
91 (42.1)
|
12 (21.8)
|
0.006
|
Pneumonia
|
82 (30.3)
|
78 (36.1)
|
4 (7.3)
|
<0.001
|
Urinary tract infection
|
55 (20.3)
|
45 (20.8)
|
10 (18.2)
|
0.662
|
Intra-abdominal infection
|
26 (9.6)
|
16 (7.4)
|
10 (18.2)
|
0.015
|
Underlying medical condition
|
Charlson’s WIC ≥ 3
|
216 (79.7)
|
172 (79.6)
|
44 (80.0)
|
0.951
|
Heart disease
|
28 (10.3)
|
24 (11.1)
|
4 (7.3)
|
0.404
|
Lung disease
|
27 (10.0)
|
26 (12.0)
|
1 (1.8)
|
0.024
|
Chronic kidney disease
|
51 (18.8)
|
43 (19.9)
|
8 (14.5)
|
0.364
|
Liver disease
|
56 (20.7)
|
42 (19.4)
|
14 (25.5)
|
0.326
|
Diabetes mellitus
|
79 (29.2)
|
69 (31.9)
|
10 (18.2)
|
0.045
|
Malignancy
|
78 (28.8)
|
55 (25.5)
|
23 (41.8)
|
0.017
|
Cerebrovascular disease
|
59 (21.8)
|
48 (22.2)
|
11 (20.0)
|
0.721
|
Transplantation
|
16 (5.9)
|
11 (5.1)
|
5 (9.1)
|
0.332
|
Immunosuppressant use
|
37 (13.7)
|
28 (13.0)
|
9 (16.4)
|
0.512
|
Clinical severity
|
Severe sepsis or septic shock
|
136 (50.2)
|
115 (53.2)
|
21 (38.2)
|
0.046
|
Pitt score, median (IQR)
|
4.00 (2.00-6.00)
|
5.00 (2.00-7.00)
|
2.00 (1.00-4.00)
|
<0.001
|
Inappropriate empirical antibiotics
|
191 (70.5)
|
162 (75.0)
|
29 (52.7)
|
0.001
|
All-cause 30-day mortality
|
135 (51.1)
|
122 (57.5)
|
13 (25.0)
|
<0.001
|
Treatment failure
|
150 (55.4)
|
131 (60.6)
|
19 (34.5)
|
0.001
|
SD, standard deviation; ICU, intensive care unit; CRBSI, catheter-related bloodstream infection; WIC, weighted index of comorbidity; IQR, interquartile range |
Antibiotic susceptibility of carbapenem-resistant isolates
Antibiotic susceptibility of carbapenem-resistant isolates is described in Table 2. Not all results of susceptibility tests were available for carbapenem-resistant isolates. For all antibiotics except colistin and trimethoprim/sulfamethoxazole, the percentages of non-susceptible isolates were significantly different between the CR-ABA and CR-PAE groups. The percentages of non-susceptible isolates, except for tigecycline and minocycline, were significantly higher in the CR-ABA group than the CR-PAE group.
Table 2
Antibiotic susceptibility of carbapenem-resistant Acinetobacter baumannii (CR-ABA) and carbapenem-resistant Pseudomonas aeruginosa (CR-PAE) isolates
Non-susceptible (I+R) isolate No. (%)
|
Total*
(n=271)
|
CR-ABA
(n=216)
|
CR-PAE
(n=55)
|
P
|
Ceftazidime
|
240/268 (89.6)
|
209 (97.2)
|
31 (58.5)
|
<0.001
|
Cefepime
|
242/265 (91.3)
|
211 (98.6)
|
31 (60.8)
|
<0.001
|
Ciprofloxacin
|
239/269 (88.8)
|
210 (97.2)
|
29 (54.7)
|
<0.001
|
Amikacin
|
66/130 (50.8)
|
58 (70.7)
|
8 (16.7)
|
<0.001
|
Gentamicin
|
175/245 (71.4)
|
161 (77.8)
|
14 (36.8)
|
<0.001
|
Tobramycin
|
45/88 (51.1)
|
40 (74.1)
|
5 (14.7)
|
<0.001
|
Piperacillin/tazobactam
|
225/243 (92.6)
|
191 (99.0)
|
34 (68.0)
|
<0.001
|
Trimethoprim/sulfamethoxazole
|
145/174 (83.3)
|
134 (82.2)
|
11 (100.0)
|
0.215
|
Imipenem
|
252/260 (96.9)
|
211 (99.1)
|
41 (87.2)
|
0.001
|
Meropenem
|
254/261 (97.3)
|
213 (99.5)
|
41 (87.2)
|
<0.001
|
Tigecycline
|
24/118 (20.3)
|
16 (14.5)
|
8 (100.0)
|
<0.001
|
Colistin
|
4/217 (1.8)
|
3 (1.7)
|
1 (2.7)
|
0.529
|
Minocycline
|
47/174 (27.0)
|
38 (23.2)
|
9 (90.0)
|
<0.001
|
I, intermediate; R, resistant; *Not all isolate susceptibility test results were available, and results were presented as non-susceptible isolate number/available total (%). |
Risk factors for treatment failure
The results of univariate analysis between risk factors and treatment failure in ABA are listed in Table S3. We stratified the patients’ data according to carbapenem resistance and the appropriateness of empirical therapy in the multivariate analyses of risk factors for treatment failure, because of the significant interaction between those factors.
Table 3 shows the risk factors for treatment failure in ABA identified using multivariate analysis according to the appropriateness of empirical therapy. While severe sepsis or septic shock and high Pitt bacteraemia score were independent risk factors for treatment failure in the inappropriate empirical antibiotics group, pneumonia, and Charlson’s WIC ≥ 3 were independent risk factors for treatment failure in the appropriate empirical antibiotics group.
Table 3
Risk factors for treatment failure in patients with Acinetobacter baumannii bacteraemia, according to the appropriateness of empirical therapy
Risk factors
|
Inappropriate empirical antibiotics (n=179)
|
Appropriate empirical antibiotics (n=125)
|
aOR (95% CI)
|
P
|
aOR (95% CI)
|
P
|
Male
|
-
|
-
|
2.36 (0.89-6.23)
|
0.084
|
ICU stay at
bacteraemia onset
|
-
|
-
|
1.23 (0.36-4.25)
|
0.746
|
Healthcare-associated infection
|
5.14 (0.43-61.37)
|
0.196
|
-
|
-
|
Site of infection
|
Primary bacteraemia
|
-
|
-
|
1.50 (0.47-4.78)
|
0.489
|
CRBSI
|
2.35 (0.98-5.64)
|
0.055
|
-
|
-
|
Pneumonia
|
-
|
-
|
10.56 (2.68-41.57)
|
0.001
|
Underlying medical condition
|
Charlson’s WIC ≥ 3
|
-
|
-
|
4.66 (1.07-20.36)
|
0.041
|
Heart disease
|
2.72 (0.66-11.31)
|
0.168
|
-
|
-
|
Lung disease
|
-
|
-
|
4.32 (0.65-28.67)
|
0.130
|
Clinical severity
|
Severe sepsis or septic shock
|
22.70 (9.48-54.39)
|
<0.001
|
1.67 (0.60-4.66)
|
0.330
|
Pitt score
|
1.58 (1.36-1.83)
|
<0.001
|
1.15 (0.94-1.41)
|
0.169
|
Carbapenem resistance
|
6.17 (1.13-33.75)
|
0.036
|
4.15 (1.16-14.84)
|
0.029
|
aOR, adjusted odds ratio; CI, confidence interval; ICU, intensive care unit; CRBSI, catheter related bloodstream infection; WIC, weighted index of comorbidity; -, the variable was not included in the multivariate analysis model, because it was not significant in univariate analysis (P > 0.10). |
The results of multivariate analysis between risk factors and treatment failure in ABA according to carbapenem susceptibility are listed in Table S4. In the CR-ABA group, severe sepsis or septic shock (adjusted odds ratio [aOR]: 9.70, 95% confidence interval [CI]: 5.02-18.76, P<0.001) and high Pitt bacteraemia score (aOR: 1.44, 95% CI: 1.27-1.63, P<0.001) were significantly associated with treatment failure.
The results of univariate analysis between risk factors and treatment failure in PAE bacteraemia are listed in Table S5. Significant risk factors for treatment failure in PAE identified by multivariate analysis are listed by the appropriateness of empirical therapy in Table 4. HAI, severe sepsis or septic shock, and high Pitt score were independent risk factors for treatment failure in both the inappropriate and appropriate empirical antibiotics groups. Urinary tract infection was associated with decreased treatment failure in the appropriate antibiotics group. Table S6 shows the significant risk factors for treatment failure in PAE by multivariate analysis according to carbapenem susceptibility. In the CR-PAE group, HAI (aOR: 25.03, 95% CI: 2.15-291.99, P = 0.010), use of immunosuppressant (aOR: 32.08, 95% CI: 1.58-652.62, P = 0.024), and high Pitt bacteraemia score (aOR: 1.47, 95% CI: 1.05-2.07, P = 0.025) were significantly associated with treatment failure.
Carbapenem resistance and treatment failure
In ABA, carbapenem resistance was independently associated with treatment failure in both the inappropriate (aOR: 6.17; 95% CI: 1.13-33.75; P = 0.036) and appropriate empirical treatment groups (aOR: 4.15; 95% CI: 1.16-14.84; P = 0.029; Table 3). In PAE, carbapenem resistance was not significantly associated with treatment failure in both the inappropriate (aOR: 0.91, 95% CI: 0.27-3.03, P = 0.879) and appropriate empirical antibiotics groups (aOR: 1.76, 95% CI: 0.45-6.87, P = 0.418; Table 4).
Table 4
Risk factors for treatment failure in patients with Pseudomonas aeruginosa bacteraemia, according to the appropriateness of empirical therapy
Risk factors
|
Inappropriate empirical antibiotics (n=78)
|
Appropriate empirical antibiotics (n=163)
|
aOR (95% CI)
|
P
|
aOR (95% CI)
|
P
|
Male
|
-
|
-
|
3.61 (1.23-10.65)
|
0.020
|
ICU stay
at bacteraemia onset
|
-
|
-
|
1.32 (0.41-4.29)
|
0.645
|
Hospital-acquired infection
|
4.57 (1.34-15.54)
|
0.015
|
2.88 (1.09-7.65)
|
0.033
|
Site of infection
|
Primary bacteraemia
|
-
|
-
|
2.79 (0.94-8.25)
|
0.064
|
Pneumonia
|
4.61 (0.68-31.20)
|
0.117
|
3.82 (1.09-13.32)
|
0.036
|
Urinary tract infection
|
-
|
-
|
0.13 (0.02-0.79)
|
0.027
|
Underlying medical condition
|
Malignancy
|
2.09 (0.55-7.91)
|
0.276
|
1.81 (0.66-4.96)
|
0.251
|
Immunosuppressant use
|
3.31 (0.78-14.11)
|
0.105
|
1.58 (0.54-4.63)
|
0.406
|
Clinical severity
|
Severe sepsis or septic shock
|
5.43 (1.42-20.76)
|
0.013
|
10.33 (3.56-29.94)
|
<0.001
|
Pitt score
|
1.59 (1.21-2.10)
|
0.001
|
1.59 (1.27-1.99)
|
<0.001
|
Carbapenem resistance
|
0.91 (0.27-3.03)
|
0.879
|
1.76 (0.45-6.87)
|
0.418
|
aOR, adjusted odds ratio; CI, confidence interval; ICU, intensive care unit