Nephrotoxicity and Efficacy Assessment of Polymyxin B Use in Renal Transplant Patients

Figures & data

Table 1 Demographics and Clinical Characteristics of the Study Cohort

Variables	Total Patients (N=235)	PMB-Nephrotoxicity (+) (N=45)	PMB-Nephrotoxicity (-) (N=190)	P-value*
Mean recipient age (year)	41.1±12.9	41.9±14.3	40.9±12.5	0.644
Gender (Male/Female)	171/64	38/7	133/57	0.050
Mean total hospital stay (days)	26(17.0–40.0)	42(29.5–102.0)	24(16.00–32.3)	<0.001
ICU admission	27(11.5%)	14(31.1%)	13(6.8%)	<0.001
Mechanical ventilation	13(5.5%)	10(22.2%)	3(1.6%)	<0.001
Vasoactive agents	58(24.7%)	20(44.4%)	38(20.0%)	0.001
The time after renal transplantation (month)	0.6 (0.0–7.0)	0.7(0.3–7.8)	0.4(0.0–6.6)	0.145
Infection site				0.061
Multiple	25(10.6%)	4(8.9%)	21(11.1%)
Single	120(51.1%)	30(66.7%)	90(47.7%)
Unclear	90(38.3%)	11(24.4%)	79(41.6%)
Source of infection
Respiratory tract	110(46.8%)	30(66.7%)	80(42.1%)	0.003
Blood	15(6.4%)	2(4.4%)	13(6.8%)	0.801
Urinary tract	33(14.0%)	4(8.9%)	29(15.3%)	0.385
Abdominal	4(1.7%)	1(2.2%)	3(1.6%)	0.575
Comorbidities
Cardiovascular and cerebrovascular diseases	80(34.0%)	20(44.4%)	60(31.6%)	0.101
Respiratory disease	6(2.6%)	0(0.0%)	6(3.2%)	0.495
Diabetes mellitus	37(15.7%)	8(17.8%)	29(15.3%)	0.677
Diseases of digestive system	50(21.3%)	11(24.4%)	39(20.5%)	0.564
Nutritional disease	18(7.7%)	6(33.3%)	12(66.7%)	0.111
Liver disease	30(12.7%)	11(24.4%)	19(10.0%)	0.009
Types of GR-GNB strains
Acinetobacter baumannii	5(2.1%)	1(2.2%)	4(2.1%)	1.000
Klebsiella pneumoniae	17(7.2%)	5(11.1%)	12(6.3%)	0.264
Pseudomonas aeruginosa	6(2.6%)	1(2.2%)	5(2.6%)	1.000
Immunosuppressant at time of PMB use
Prednisone	209(88.9%)	38(84.4%)	171(81.8%)	0.285
Dexamethasone	32(13.6%)	15(33.3%)	17(8.9%)	<0.001
Tacrolimus	177(75.3%)	25(55.6%)	152(80.0%)	0.001
Mycophenolate mofetil	161(68.5%)	22(48.9%)	139(73.2%)	0.002
Cyclosporine	25(10.6%)	8(17.8%)	17(8.9%)	0.084
Outcome
Hospital mortality	4(1.7%)	2(4.4%)	2(1.1%)	0.166
Microbiological cure	32/48(66.7%)	8(61.5%)	24(68.6%)	0.646
Clinical cure	230(97.9%)	42(93.3%)	188(98.9%)	0.019

Notes: Data were present as Mean ± standard deviation, No (%), or Median (IQR).*P value were shown as PMB-Nephrotoxicity (+) vs PMB-Nephrotoxicity (-). Bold font indicates data with significant differences.

Abbreviations: ICU, intensive care unit; APACHE II, Acute Physiology and Chronic Health Evaluation II; TMP-SMZ, trimethoprim/sulfamethoxazole; NSAIDS, nonsteroidal anti-inflammatory drugs; PMB, polymyxin B; CR-GNB, carbapenem-resistant Gram-negative bacteria; CRRT, continuous renal replacement therapy.

Table 2 The PMB and TGC Susceptibility of CR-GNB

Type of CR-GNB	Numbers of Strains	PMB MIC				TGC MIC
		≦0.5	≦1	1	2	≦1	4
CRKP	17	2	12	3	0	5	12
CRAB	5	3	1	1	0	2	3
CRPA	6	0	1	4	1	-	-

Abbreviations: PMB, polymyxin B; TGC, tigecycline; CR-GNB, carbapenem-resistant Gram-negative bacteria; MIC, minimum inhibitory concentration; CRKP, carbapenem-resistant Klebsiella pneumonia; CRPA, carbapenem-resistant Pseudomonas aeruginosa; CRAB, carbapenem-resistant Acinetobacter baumannii.

Table 3 Kidney Status and Nephrotoxic Agents Used in Kidney Transplant Patients

Variables	Total Patients (N=235)	PMB-Nephrotoxicity (+) (N=45)	PMB-Nephrotoxicity (-) (N=190)	P-value
Concomitant nephrotoxic agents
Aminoglycosides	6(2.6%)	4(8.9%)	2(1.1%)	0.013
Amphotericin B	24(10.2%)	10(22.2%)	14(7.4%)	0.003
TMP-SMZ	64(27.2%)	17(37.8%)	44(23.2%)	0.044
Fluorocytosine	9(3.8%)	4(8.9%)	5(2.6%)	0.125
Furosemide (>20mg/day)	55(23.4%)	12(26.7%)	43(22.6%)	0.705
Torasemide (>10mg/day)	15(6.4%)	7(15.6%)	8(4.2%)	0.005
NSAIDS	3(1.3%)	1(2.2%)	2(1.1%)	0.473
PMB use
Empiric treatment/Target treatment	187/48	33/12	154/36	0.248
Using loading dose	23(9.8%)	7(15.6%)	16(8.4%)	0.148
Loading dose (mg)	41.8±9.8	43.3±11.6	41.4±9.3	0.240
Maintenance dose q12h (mg)	40.0(40.0–50.0)	40.0(40.0–50.0)	40.0(40.0–50.0)	0.752
Maintenance dose in mg/kg (q12h)	0.7±0.2	0.7±0.2	0.7±0.2	0.902
Minimum maintenance dose (>1.25mg/kq, q12h)	3(1.3%)	0(0%)	3(1.6%)	1.000
Cumulative dose (mg)	640.0(450.0–960.0)	880.0(520.0–1110.0)	640.0(425.0–900.0)	0.006
Treatment duration time (days)	8.0(6.0–11.0)	11.0(7.0–15.0)	8.0(5.8–11.0)	0.003
Kidney status
Creatinine before PMB use (umol/L)	429.2±368.4	526.1±366.7	406.2±366.1	0.049
CRRT	10(4.3%)	10(22.2%)	0(0%)	<0.001
Hemodialysis	44(18.7%)	39(86.7%)	5(2.6%)	<0.001

Notes: Data were present as Mean ± standard deviation, No.(%), or Median (IQR). Bold font indicates data with significant differences.

Abbreviations: AKI, acute kidney injury; ICU, intensive care unit; APACHE II, Acute Physiology and Chronic Health Evaluation II; DM, diabetes mellitus; CR-GNB, carbapenem-resistant Gram-negative bacteria; TMP-SMZ, trimethoprim/sulfamethoxazole; NSAIDs, nonsteroidal anti-inflammatory drugs; PMB, polymyxin B; CRRT, continuous renal replacement therapy.

Table 4 Multivariate Logistic Regression of PMB-Nephrotoxicity in Kidney Transplant Patients

Variable	Adjusted OR	95% CI	P-value
Gender (Male/Female)	0.416	0.122–1.420	0.161
Mean total hospital stay (days)	1.029	1.013–1.044	<0.001
ICU admission	4.311	1.013–18.351	0.048
Mechanical ventilation	1.344	0.129–14.047	0.805
Vasoactive agents	2.779	1.034–7.465	0.043
Respiratory tract	0.958	0.287–3.205	0.945
Liver disease	3.118	0.969–10.028	0.056
Aminoglycosides	19.793	1.744–224.604	0.016
Amphotericin B	2.611	0.425–16.058	0.300
TMP-SMZ	0.818	0.224–2.985	0.761
Furosemide (>20mg/day)	0.600	0.200–1.796	0.361
Cumulative dose (mg)	0.999	0.996–1.001	0.375
Treatment duration time (days)	1.199	0.941–1.527	0.141
Dexamethasone	2.486	0.744–8.312	0.139
Tacrolimus	0.636	0.151–2.674	0.537
Mycophenolate mofetil	1.409	0.369–5.376	0.616
CCR before PMB use (mL/min.1.73m^2)	0.966	0.937–0.995	0.023

Note: Bold font indicates data with significant differences.

Abbreviations: ICU, intensive care unit; CCR, creatinine clearance rate; OR, odds ratio; CI, confidence interval; TMP-SMZ, trimethoprim-sulfamethoxazole.