Epidemiology, susceptibility, and risk factors for acquisition of MDR/XDR Gram-negative bacteria among kidney transplant recipients with urinary tract infections

Figures & data

Table 1 Demographic and clinical characteristics of 81 kidney transplant patients diagnosed with urinary tract infections due to MDR/XDR Gram-negative bacteria

Characteristics	Value
Age, mean years ± SD	41.4 ± 11.8
Sex, number of females, n (%)	49 (60.5)
Underlying kidney diseases
Chronic glomerulonephritis	62 (76.5)
Polycystic kidney disease	3 (3.7)
Diabetic nephropathy	2 (2.5)
Other/unknown	14 (17.3)
Re-transplant	4 (4.9)
Temperature of 38°C or greater, n (%)	25 (30.9)
Median body temperature of °C at infection onset	37.1 (36.6-38.4)
(IQR)
Nosocomial origin, n (%)	37 (45.7)
Inappropriate empirical antimicrobial use, n (%)	32 (39.5)
Average duration of days between transplant and	110 (36.5-
infection onset (IQR)	1158)
Type of organisms no. of cases (%)
Monomicrobial	74 (91.4)
Polymicrobial	7 (8.6)
Drug resistance, n (%)
MDR	70 (86.4)
XDR	11 (13.6)
PDR	0 (0)
Type of donor, no. of cases (%)
Donation after cardiac death	40 (49.4)
Living, related	25 (30.9)
Deceased	16 (19.8)
Use of antilymphocyte or antithymocyte globulin,	28 (34.6)
no. of cases (%)
Patient immunosuppressant treatment, no. of
cases (%)
Tacrolimus	66 (81.5)
Cyclosporine A	14 (17.3)
None	1 (1.2)
Laboratory variables from blood, no. of cases (%)
WBC count > 15,000/mm^3	14 (17.3)
Platelet count < 10,0000/mm^3	7 (8.6)
Lymphocyte count < 500/mm^3	12 (14.8)
Albumin level < 35 mg/dL	16 (19.8)
Creatinine level > 1.5 mg/dL	32 (39.5)
Septic shock at urinary tract infections onset	3 (3.7)
All-cause in-hospital mortality	5 (6.2)
Urinary tract infection-related mortality	1 (1.2)

Abbreviations: IQR, interquartile range; MDR, multiple drug resistant; PDR, pandrug resistant; WBC, white blood cell; XDR, extensively drug resistant.

Table 2 Classification and percentage of 88 MDR/XDR bacteria isolated from urinary tract specimens in kidney transplant recipients

Microorganism	Organisms (n = 88)	Percentage
Escherichia coli	55	62.5
Klebsiella pneumoniae	15	17
Acinetobacter baumannii	9	10.2
Pseudomonas aeruginosa	2	2.3
Enterobacter aerogenes	2	2.3
Proteus mirabilis	2	2.3
Enterobacter cloacae	1	1.1
Pseudomonas putida	1	1.1
Burkholderia pseudomallei	1	1.1

Abbreviations: MDR, multiple drug resistant; XDR, extensively drug resistant.

Table 3 Resistance rates of 88 MDR/XDR Gram-negative bacteria to 12 antibiotics (n, [%])

Antimicrobial	Escherichia coli (n=55)	Klebsiella pneumoniae (n= 15)	Non-fermenting bacteria (n= 13)	The other Enterobacteria (n=5)	Total drug resistance rate (%)
TIG	2 (3.6)	3 (20)	3 (23.1)	2 (40)	11.4
MEM	9 (16.4)	3 (20)	12 (92.3)	1 (20)	28.4
AN	8 (14.5)	5 (33.3)	11 (84.6)	1 (20)	28.4
LVF	35 (63.6)	9 (60)	11 (84.6)	0 (0)	62.5
SXT	35 (63.6)	10 (66.7)	13 (100)	4 (80)	70.5
PIT	19 (34.5)	6 (40)	12 (92.3)	2 (40)	44.3
ATM	54 (98.2)	11 (73.3)	13 (100)	4 (80)	93.2
CZO	54 (98.2)	13 (86.7)	13 (100)	5 (100)	96.6
CXM	54 (98.2)	13 (86.7)	13 (100)	5 (100)	96.6
CAZ	46 (83.6)	11 (73.3)	12 (92.3)	3 (60)	81.8
FEP	48 (87.3)	10 (66.7)	12 (92.3)	4 (80)	84.1
CFS	30 (54.5)	5 (33.3)	3 (23.1)	3 (60)	46.6

Abbreviations: AN, amikacin; ATM, aztreonam; CAZ, ceftazidime; CFS, cefoperazone/sulbactam; CXM, cefuroxime; CZO, cefazolin; FEP, cefepime; LVF, levofloxacin; MDR, multiple drug resistant; MEM, meropenem; PIT, piperacillin/tazobactam; SXT, trimethoprim/sulfamethoxazole; TIG, tigecycline; XDR, extensively drug resistant.

Table 4 Resistance rates of 12 XDR Gram-negative bacteria to five antibiotics that MDR/XDR bacteria remain relatively susceptible to (n, [%])

Antimicrobial	Acinetobacter baumannii (n=4)	Escherichia coli (n=3)	Klebsiella pneumoniae (n=2)	Pseudomonas spp.(n=3)^Table Footnotea,Table Footnoteb	Total drug resistance rate (%)
TIG	0 (0)	0 (0)	1 (50)	2 (66.7)	25
MEM	4 (100)	3 (100)	2 (100)	3 (100)	100
AN	4 (100)	1 (33.3)	1 (50)	3 (100)	75
PIT	4 (100)	3 (100)	2 (100)	3 (100)	100
CFS	2 (50)	2 (66.7)	2 (100)	1 (33.3)	58.3

Notes: ^a Including one isolate of Pseudomonas putida, one Burkholderia pseudomallei, and one Pseudomonas aeruginosa wherein Burkholderia pseudomallei is susceptible to TIG and Pseudomonas putida is resistant to CFS.

b P. aeruginosa is intrinsically resistant to tigecycline.

Abbreviations: AN, amikacin; CFS, cefoperazone/sulbactam; MDR, multiple drug resistant; MEM, meropenem; PIT, piperacillin/tazobactam; TIG, tigecycline; XDR, extensively drug resistant.

Table 5 Univariate and multivariate analysis of risk factors associated with the occurrence of MDR/XDR Gram-negative UTIs

Characteristics	MDR/ XDR UTIs	Non-MDR/ XDR UTIs	p-value^	OR (95% CI)
Total, n (%)	81 (87.1)	12 (12.9)
Univariate analysis, n (%)
Age ≥ 40 years	49 (60.5)	7 (58.3)	0.887	0.613 (0.065-5.808)
Male sex	32 (39.5)	4 (33.3)	0.682	4.893 (0.219-109.073)
Re-transplant	4 (4.9)	1 (8.3)	0.627	0.129 (0.003-5.266)
Polycystic kidney disease	3 (3.7)	0 (0)	0.498	0.423 (0.040-4.434)
Temperature ≥ 38°C	25 (30.9)	5 (41.7)	0.455	0.279 (0.024-3.183)
Nosocomial infection	37 (45.7)	1 (8.3)	0.014*	9.250 (1.140-75.031)
Graft from DCD donors	16 (19.8)	3 (25)	0.114	1.979 (0.227-17.235)
Early-onset infection	25 (30.9)	3 (25)	0.416	0.796 (0.033-19.297)
Non-fermenting bacteria	12 (14.8)	3 (25)	0.371	0.037 (0.001-1.569)
Use of antilymphocyte or antithymocyte globulin	28 (34.6)	3 (25)	0.512	1.508 (0.200-11.358)
Use of tacrolimus	66 (81.5)	8 (66.7)	0.235	2.134 (0.207-22.018)
Use of wide-spectrum antibiotics for 5 days or more within	49 (60.5)	3 (25)	0.021*	4.594 (1.155-18.269)
1 month before UTIs
Use of meropenem for 4 days or more within 1 month before UTIs	11 (13.4)	0 (0)	0.21	1.729 (0.203-14.744)
Septic shock	3 (3.7)	1 (8.3)	0.498	0.423 (0.040-4.434)
WBC count > 15,000/mm^3	14 (17.3)	2 (16.7)	0.958	2.029 (0.106-38.865)
Platelet count < 10,0000/mm^3	7 (8.6)	3 (25)	0.088	0.110 (0.002-5.634)
Lymphocyte count < 500/mm^3	12 (14.8)	3 (25)	0.371	0.071 (0.002-2.219)
Albumin level < 35 mg/dL	16 (19.8)	2 (16.7)	0.801	12.439 (0.351-440.472)
Creatinine level > 1.5 mg/dL	32 (39.5)	2 (16.7)	0.125	0.897 (0.055-14.676)
Multivariate analysis
Nosocomial infection			0.027*	11.429 (1.311-99.625)

Notes: ^{^}P-value from Pearson’s χ² test or Fisher’s exact test in univariate analysis and from multiple logistic regression in multivariate analysis. *The P-values are statistically significant.

Abbreviations: DCD, donation after cardiac death; MDR, multiple drug resistant; UTIs, urinary tract infections; WBC, white blood cell; XDR, extensively drug resistant.

Table 6 Univariate and multivariate analysis of risk factors associated with the occurrence of XDR Gram-negative UTIs

Characteristics	XDR UTIs	MDR UTIs	p-value^^	OR (95% CI)
Total, n (%)	11 (13.6)	70 (86.4)
Univariate analysis, n (%)
Age > 40 years	4 (36.4)	45 (64.3)	0.078	0.209 (0.027-1.630)
Male sex	6 (54.5)	26 (37.1)	0.272	0.637 (0.070-5.782)
Re-transplant	0 (0)	4 (36.4)	0.416	2.566 (0.022-283.083)
Polycystic kidney disease	2 (18.2)	1 (1.4)	0.006*	15.333 (1.260-186.600)
Temperature > 38°C	3 (27.3)	22 (31.4)	0.781	1.108 (0.151-8.140)
Nosocomial infection	9 (81.8)	28 (40)	0.01*	6.750 (1.356-33.603)
Graft from DCD donors	7 (63.6)	33 (47.1)	0.309	0.848 (0.129-5.567)
Early-onset infection	8 (72.7)	22 (31.4)	0.008*	5.818 (1.407-24.061)
Non-fermenting bacteria infection	6 (54.5)	6 (8.6)	<0.001*	11.627 (1.442-93.755)
Use of antilymphocyte or antithymocyte globulin	3 (27.3)	25 (35.7)	0.584	0.033 (0.001-1.071)
Use of tacrolimus	9 (81.8)	57 (81.4)	0.975	7.948 (0.365-172.903)
Use of wide-spectrum antibiotics for 5 days or more within	11 (100)	38 (54.3)	0.026*	8.421 (1.022-69.371)
1 month before UTIs
Use of meropenem for 4 days or more within	4 (36.4)	7 (10)	0.018*	5.143 (1.200-22.049)
1 month before UTIs
Septic shock	1 (9.1)	2 (2.9)	0.309	3.400 (0.282-41.031)
WBC count > 15,000/mm^3	1 (9.1)	13 (18.6)	0.439	0.438 (0.051-3.734)
Platelet count < 10,0000/mm^3	2 (18.2)	5 (7.1)	0.226	4.630 (0.298-71.833)
Lymphocyte count < 500/mm^3	2 (18.2)	10 (14.3)	0.735	1.786 (0.154-20.724)
Albumin level < 35 mg/dL	1 (9.1)	15 (21.4)	0.339	0.367 (0.043-3.096)
Creatinine level > 1.5 mg/dL	9 (81.8)	23 (32.9)	0.002*	7.474 (1.053-53.022)
Multivariate analysis
Creatinine > 1.5 mg/dL			0.023*	8.688 (1.354-55.747)
Non-fermenting bacteria			0.001*	20.161 (3.409-119.240)
Polycystic kidney disease			0.016*	39.871 (1.979-803.384)

Notes: ^P-value from Pearson’s χ² test or Fisher’s exact test in univariate analysis and from multiple logistic regression in multivariate analysis.

* The P-values are statistically significant.

Abbreviations: DCD, donation after cardiac death; MDR, multiple drug resistant; UTIs, urinary tract infections; WBC, white blood cell; XDR, extensively drug resistant.