Risk Factors for Mortality of Inpatients with Pseudomonas aeruginosa Bacteremia in China: Impact of Resistance Profile in the Mortality

Figures & data

Table 1 Demographic, Clinical Characteristics and Outcomes of 215 Patients with P. aeruginosa Bacteremia^a

Characteristics	Total N=215	Died N=61	Alive N=154	OR	95% CI	P-value
Age (years), (mean, SD)	60.5, 19.0	65.1, 16.1	58.7, 19.8			0.016
Male gender, n (%)	159 (74.0)	47 (77.0)	112 (72.7)	1.259	0.629–2.520	0.515
Underlying disease, n (%)	154 (71.6)	59 (96.7)	95 (61.7)	18.321	4.314–77.806	<0.001
Diabetes mellitus	54 (25.1)	21 (34.4)	33 (21.4)	1.925	1.001–3.701	0.048
Chronic lung disease	35 (16.3)	19 (31.1)	16 (10.4)	3.902	1.844–8.255	<0.001
Chronic renal failure	22 (10.2)	5 (8.2)	17 (11.0)	0.720	0.253–2.045	0.535
Liver disease	29 (13.5)	1 (1.6)	28 (18.2)	0.075	0.010–0.564	0.003
Solid organ cancer	39 (18.1)	9 (14.8)	30 (19.5)	0.715	0.318–1.612	0.418
Cardiovascular disease	81 (37.7)	42 (68.9)	39 (25.3)	6.518	3.395–12.515	<0.001
Solid-organ transplantation	3 (1.4)	1 (1.6)	2 (1.3)	1.267	0.113–14.230	1.000
Hematological Disease	50 (23.3)	11 (18.0)	39 (25.3)	0.649	0.307–1.369	0.254
Benign biliary tract disease	32 (14.9)	2 (3.3)	30 (19.5)	0.140	0.032–0.606	0.005
Primary site of infection, n (%)
Lung	64 (29.8)	32 (52.5)	32 (20.8)	4.207	2.228–7.944	<0.001
Soft-tissue	2 (0.9)	1 (1.6)	1 (0.6)	2.550	0.157–41.427	1.000
Biliary tract	12 (5.6)	0 (0.0)	12 (7.8)	1.085	1.036–1.135	0.021
Urinary tract	10 (4.7)	0 (0.0)	10 (6.5)	1.069	1.026–1.115	0.066
Catheter-related	48 (22.3)	8 (13.1)	40 (26.0)	0.430	0.188–0.983	0.041
Peritoneum	9 (4.2)	0 (0.0)	9 (5.8)	1.062	1.021–1.105	0.063
Unknown	70 (32.6)	20 (32.8)	50 (32.5)	1.015	0.539–1.909	0.964
Nosocomial infection^b, n (%)	176 (81.9)	49 (80.3)	127 (82.5)	0.868	0.408–1.848	0.714
Comorbid condition, n (%)
Corticosteroid use	60 (27.9)	15 (24.6)	45 (29.2)	0.790	0.401–1.557	0.495
Immune deficiency^c	54 (25.1)	10 (16.4)	44 (28.6)	0.490	0.229–1.051	0.063
Neutropenia^d	40 (18.6)	10 (16.4)	30 (19.5)	0.810	0.369–1.779	0.600
Intravenous catheterization	146 (67.9)	20 (32.8)	126 (81.8)	0.108	0.055–0.213	<0.001
Blood transfusion	87 (40.5)	33 (54.1)	54 (35.1)	2.183	1.195–3.987	0.010
Coinfection with other bacteria	44 (20.5)	18 (29.5)	26 (16.9)	2.061	1.030–4.122	0.039
Hospitals, n (%)
CJFH	69 (32.1)	42 (68.9)	27 (17.5)	10.398	5.253–20.581	<0.001
Henan Provincial People’s Hospital	79 (36.7)	2 (3.3)	77 (50.0)	0.034	0.008–0.144	<0.001
Ningbo Medical Center Lihuili Hospital	30 (14.0)	6 (9.8)	24 (15.6)	0.591	0.229–1.526	0.273
Wuhan Forth Hospital	36 (16.7)	11 (18.0)	25 (16.2)	1.135	0.520–2.478	0.750
Weifang No.2 People’s Hospital	1 (0.5)	0 (0.0)	1 (0.6)	1.007	0.994–1.019	1.000
Antimicrobial therapy regimen, n (%)	209 (97.2)	60 (98.4)	149 (96.8)	2.013	0.230–17.596	0.853
Monotherapy^e	91 (42.3)	18 (29.5)	73 (47.4)	0.464	0.246–0.876	0.017
Combined antibiotic therapy^f	118 (54.9)	42 (68.9)	76 (49.4)	2.269	1.212–4.248	0.010
LOS (days), median (IQR)	20.0 (12.0–31.8)	14.0 (9.0–31.0)	22.0 (14.0–32.0)			0.422
Received mechanical ventilation, n (%)	69 (32.1)	43 (70.5)	26 (16.9)	11.761	5.880–23.522	<0.001
Admitted to ICU, n (%)	88 (40.9)	51 (83.6)	37 (24.0)	16.127	7.451–34.904	<0.001

Notes: ^aP. aeruginosa bacterium was defined as the presence of P. aeruginosa in blood culture and the clinical features related to the P. aeruginosa infection. Only the first P. aeruginosa bacterium event was enrolled in the analysis if a patient presented ≥2 positive P. aeruginosa bacteremia during the study period. ^bNosocomial infection was defined as the occurrence of P. aeruginosa bacterium (1) that occurred more than 48 h after admission to hospital (2) that occurred less than 48 h after admission to hospital in cases who had been in other hospitals within the 2 weeks prior to admission. ^cThe presence of immune deficiency was defined as the receipt of immunosuppressive therapy (immunosuppressive agent, chemotherapy or radiotherapy) during the P. aeruginosa bacteremia. ^dNeutropenia was defined that an absolute neutrophil count of <500/mL. ^eAntibiotic monotherapy was defined as the treatment with only one of the following antibiotics: aztreonam, cefoperazone-sulbactam, ceftazidime, ticarcillin-clavulanate, piperacillin-tazobactam, cefepime, imipenem, meropenem, amikacin, levofloxacin, ciprofloxacin, colistin, and so on. ^fCombination therapy consisted of the treatment with two or more antibiotics.

Abbreviations: SD, standard deviation; IQR, interquartile range; ICU, intensive care unit; LOS, length of hospital stay; CJFH, China-Japan Friendship Hospital; OR, odds ratio; CI, confidence interval.

Figure 1 Risk factors for mortality of 215 hospitalized patients with P. aeruginosa bacteremia in China. Cardiovascular disease (OR=3.978, P=0.001), blood transfusion (OR=5.855, P<0.001) and hospitalization in China-Japan Friendship Hospital (CJFH) (OR=9.031, P<0.001) were demonstrated to be independently associated with the mortality among all patients.

Table 2 Demographic, Clinical Characteristics and Outcomes of 69 Patients with P. aeruginosa Bacteremia^a

Characteristics	Total N=69	Died N=42	Alive N=27	P-value	OR	95% CI
Age (years), (mean, SD)	64.6, 17.4	63.1, 16.7	66.8, 18.5	0.395
Male gender, n (%)	55 (79.7)	35 (83.3)	20 (74.1)	0.351	1.750	0.536–5.712
Underlying disease, n (%)	68 (98.6)	41 (97.6)	27 (100.0)	1.000	0.976	0.931–1.023
Diabetes mellitus	23 (33.3)	14 (33.3)	9 (33.3)	1.000	1.000	0.359–2.789
Chronic lung disease	24 (34.8)	18 (42.9)	6 (22.2)	0.079	2.625	0.879–7.838
Chronic renal failure	13 (18.8)	11 (26.2)	2 (7.4)	0.103	4.435	0.899–21.884
Solid organ cancer	16 (23.2)	7 (16.7)	9 (33.3)	0.109	0.400	0.128–1.250
Cardiovascular disease	45 (65.2)	32 (76.2)	13 (48.1)	0.017	3.446	1.222–9.715
Solid-organ transplantation	3 (4.3)	1 (2.4)	2 (7.4)	0.693	0.305	0.026–3.538
Hematological Disease	7 (10.1)	4 (9.5)	3 (11.1)	1.000	0.842	0.173–4.096
Benign biliary tract disease	3 (4.3)	0 (0.0)	3 (11.1)	0.056	1.125	0.985–1.285
Primary site of infection, n (%)
Lung	44 (63.8)	32 (76.2)	12 (44.4)	0.007	4.000	1.415–11.310
Soft-tissue	1 (1.4)	1 (2.4)	0 (0.0)	1.000	0.976	0.931–1.023
Biliary tract	4 (5.8)	0 (0.0)	4 (14.8)	0.020	1.174	1.003–1.374
Urinary tract	1 (1.4)	0 (0.0)	1 (3.7)	0.391	1.038	0.964–1.118
Catheter-related	4 (5.8)	1 (2.4)	3 (11.1)	0.324	0.195	0.019–1.983
Unknown	15 (21.7)	8 (19.0)	7 (25.9)	0.499	0.672	0.212–2.134
Nosocomial infection^b, n (%)	53 (76.8)	33 (78.6)	20 (74.1)	0.666	1.283	0.413–3.985
Comorbid condition, n (%)
Corticosteroid use	18 (26.1)	14 (33.3)	4 (14.8)	0.153	2.875	0.832–9.940
Immune deficiency^c	5 (7.2)	5 (11.9)	0 (0.0)	0.148	0.881	0.788–0.985
Neutropenia^d	7 (10.1)	6 (14.3)	1 (3.7)	0.311	4.333	0.492–38.191
Intravenous catheterization	8 (11.6)	3 (7.1)	5 (18.5)	0.291	0.338	0.074–1.553
Blood transfusion	23 (33.3)	20 (47.6)	3 (11.1)	0.004	7.273	1.896–27.895
Coinfection with other bacteria	17 (24.6)	13 (31.0)	4 (14.8)	0.218	2.578	0.741–8.971
Antimicrobial therapy regimen, n (%)	67 (97.1)	42 (100.0)	25 (92.6)	0.150	1.080	0.971–1.202
Monotherapy^e	13 (18.8)	5 (11.9)	8 (29.6)	0.066	0.321	0.092–1.117
Combined antibiotic therapy^f	54 (78.3)	37 (88.1)	17 (63.0)	0.014	4.353	1.288–14.707
Resistance profile
CRPA	40 (58.0)	30 (71.4)	10 (37.0)	0.005	4.250	1.519–11.889
MDRPA	41 (59.4)	29 (69.0)	12 (44.4)	0.042	2.788	1.024–7.596
LOS (days), median (IQR)	17.0 (10.8–27.3)	12.5 (9.0–27.0)	22.0 (14.0–33.5)	0.184
Received mechanical ventilation, n (%)	33 (47.8)	30 (71.4)	3 (11.1)	<0.001	20.000	5.060–79.047
Admitted to ICU, n (%)	37 (53.6)	34 (81.0)	3 (11.1)	<0.001	34.000	8.168–141.520

Note: The definitions of ^aP. aeruginosa bacterium, ^bnosocomial infection, ^cimmune deficiency, ^dneutropenia, ^eantibiotic monotherapy and ^fcombination therapy are seen in the annotation of Table 1.

Abbreviations: SD, standard deviation; IQR, interquartile range; ICU, intensive care unit; LOS, length of hospital stay; CRPA, carbapenem-resistant P. aeruginosa; MDRPA, multidrug-resistant P. aeruginosa; OR, odds ratio; CI, confidence interval.

Figure 2 Risk factors for mortality of 69 in-hospital patients with P. aeruginosa bacteremia in China-Japan Friendship Hospital (CJFH). Cardiovascular disease (OR=5.329, P=0.010), blood transfusion (OR=7.938, P=0.011) and carbapenem-resistant P. aeruginosa (CRPA) phenotype (OR=4.485, P=0.038) were found to be associated with increased odds of death there.

Figure 3 The resistance profile of P. aeruginosa strains from 42 non-survivors in China-Japan Friendship Hospital. P. aeruginosa resistance is serious given that a total of 30 carbapenem-resistant P. aeruginosa (CRPA) strains and 29 multidrug-resistant P. aeruginosa (MDRPA) strains were found in 42 non-survivors.

Abbreviations: ND, not done; S, susceptible; I, intermediate; R, resistant; ATM, aztreonam; GN, gentamicin; TOB, tobramycin; CAZ, ceftazidime; SCF, cefoperazone-sulbactam; FEP, cefepime; PIP, piperacillin; TZP, piperacillin-tazobactam, TCA, ticarcillin-clavulanate; IPM, imipenem; MEM, meropenem; AMK, amikacin; LEV, levofloxacin; CIP, ciprofloxacin; COS, colistin.

Figure 4 Kaplan–Meier analysis of 5-day mortality in patients in China-Japan Friendship Hospital. (A) Kaplan-Meier analysis of 5-day mortality in patients with carbapenem-resistant P. aeruginosa (CRPA) bacteremia (N=40) and in patients with carbapenem- susceptible P. aeruginosa (CSPA) bacteremia (N=29). (B) Kaplan–Meier analysis of 5-day mortality in patients with multidrug-resistant P. aeruginosa (MDRPA) bacteremia (N=41) and without (N=28). The survival curve showed that CRPA and MDRPA phenotypes were significantly associated with 5-day mortality (P<0.05).

Abbreviation: NMDRPA, no MDRPA.