The Efficacy and Influencing Factors of Polymyxin B in High-Level Carbapenem-Resistant Klebsiella pneumoniae Infections

Figures & data

Table 1 Clinical Characteristics of Patients and Univariate Analysis of Factors Associated with Microbiological Clearance and All-Cause Discharge Mortality

Related Indicators	Overall (N=92)	Clearance (N=42)	Failure (N=50)	P value	Non-Survivors (N=21)	Survivors (N=71)	P value
Demographics
Age (years)	63.5 [52.0, 71.5]	69 [67.0, 78.0]	74 [67.0, 78.0]	0.520	76 [69.0, 91.0]	72 [67.0, 74.5]	0.020
Admission to ICU	25 [16.25, 36.75]	35 [20.0, 43.5]	21 [12.0, 31.0]	0.375	32 [21.0, 43.0]	21 [15.0, 36.5]	0.416
Hospitalization days	35 [26.0, 46.0]	37 [28.0, 66.0]	28 [20, 38]	0.540	38 [32.0, 88.0]	29 [22.0, 44.0]	0.907
APACHE II score	17 [12.75, 24.0]	13 [7.5, 19.0]	16 [14, 24]	0.039	17 [15.0, 24.0]	14 [8.0, 21.5]	0.229
Gender (male)	75 (81.5)	33 (78.6)	42 (84.0)	0.504	17 (81.0)	58 (81.7)	1.000
Comorbidities
Septic shock	25 (27.2)	12 (28.6)	13 (26.0)	0.782	7 (33.3)	18 (25.4)	0.577
Sepsis	27 (29.3)	11 (26.2)	16 (32.0)	0.542	9 (42.9)	18 (25.4)	0.172
Hypoproteinemia	35 (38.0)	18 (42.9)	17 (34.0)	0.383	10 (47.6)	25 (35.2)	0.318
Mechanical Ventilation	26 (28.3)	13 (31.0)	13 (26.0)	0.599	6 (28.6)	20 (28.2)	1.000
Pulmonary disease	4 (4.3)	0 (0)	4 (8.0)	0.122	0 (0)	4 (5.6)	0.570
Cardiovascular diseases	27 (29.3)	13 (31.0)	14 (28.0)	0.757	8 (38.1)	19 (26.8)	0.414
Hypertension	36 (39.1)	18 (42.9)	28 (36.0)	0.502	8 (38.1)	28 (29.4)	1.000
Cerebrovascular diseases	44 (47.8)	19 (45.2)	25 (50.0)	0.649	9 (42.9)	35 (49.3)	0.629
Solid tumor	14 (15.2)	5 (11.9)	9 (18.0)	0.563	5 (23.8)	9 (12.7)	0.297
Hematological malignant disease	5 (5.4)	2 (4.8)	3 (6.0)	1.000	2 (9.5)	3 (4.2)	0.320
Diabetes	23 (25.0)	11 (26.2)	12 (24.0)	0.809	5 (23.8)	18 (25.4)	1.000
Kidney disease	4 (4.3)	0 (0)	4 (8.0)	0.122	0 (0)	4 (5.6)	0.570
Liver disease	6 (6.5)	2 (4.8)	4 (8.0)	0.684	2 (9.5)	4 (5.63)	0.617
Digestive system diseases	12 (13.0)	8 (19.0)	4 (8.0)	0.134	3 (14.3)	8 (12.7)	1.000
Transplantation history	2 (2.2)	1 (2.4)	1 (2.0)	1.000	0 (0)	2 (2.8)	1.000
Surgery	49 (53.3)	21 (50.0)	28 (56.0)	0.566	10 (47.6)	39 (54.9)	0.623
Electrolyte disturbance	29 (31.5)	9 (21.4)	20 (40.0)	0.056	6 (28.6)	23 (32.4)	0.769
Infection variables
≥2 sites of infection	40 (43.5)	18 (42.9)	22 (44.0)	0.912	7 (33.3)	33 (46.5)	0.326
Pneumonia	85 (92.4)	38 (90.5)	47 (94.0)	0.525	21 (100)	64 (90.1)	0.345
Bloodstream	28 (30.4)	11 (26.2)	17 (34.0)	0.417	5 (23.8)	23 (32.4)	0.592
Abdominal	4 (4.3)	1 (2.4)	3 (6.0)	0.623	1 (54.8)	3 (4.2)	1.000
Urinary tract	8 (8.7)	5 (11.9)	3 (6.0)	0.463	1 (4.8)	7 (9.9)	0.677
Intracranial infection	2 (2.2)	4 (9.5)	3 (6.0)	0.698	0 (0)	7 (9.9)	0.345
Other site infections	7 (7.6)	2 (4.8)	5 (10.0)	0.448	2 (9.5)	5 (7.0)	0.675
Co-infection with other pathogens	38 (41.3)	18 (42.9)	20 (40.0)	0.782	9 (42.9)	29 (40.8)	1.000
Acinetobacter baumannii	17 (18.5)	6 (14.3)	11 (22.0)	0.424	2 (9.5)	15 (21.1)	0.341
Pseudomonas aeruginosa	20 (21.7)	10 (23.8)	10 (20.0)	0.807	6 (28.6)	14 (19.7)	0.383
Other pathogens	2 (2.2)	2 (4.8)	0 (0)	0.206	1 (4.8)	1 (1.4)	0.406
Fever (°C)	38.1 [37.6, 38.9]	38 [37.3, 38.6]	38 [37.6, 39.7]	0.727	38 [36.9, 38.0]	38.3 [37.7, 38.7]	0.937
White blood cell count (x10^9/L)	10.75 [7.8, 13.4]	10.6 [7.35, 14.89]	9.99 [7.9, 12.35]	0.473	10.0 [7.1, 14.7]	10.8 [8.5, 10.8]	0.086
Procalcitonin (μg/L)	1.36 [0.51, 6.57]	0.74 [0.28, 1.57]	2.23 [0.70, 3.21]	0.946	0.568 [0.075, 0.700]	1.73 [0.79, 3.02]	0.713
C-reactive Protein (mg/L)	99.01 [43.12, 134.59]	82.39 [22.05, 137.12]	143.87 [69.09, 200.5]	0.098	56.3[18.06, 143.87]	127 [71.98, 195.7103]	0.371
Polymyxin B treatment
Duration days	12 [8.0, 16.75]	16 [10.5, 21.0]	10 [7.0, 15.0]	0.229	14 [10.5, 20.0]	11[8.0, 16.0]	0.037
Daily dose (WIU)	150 [100, 150]	150 [100, 150]	150 [100, 150]	0.333	150 [100, 150]	150 [100, 150]	0.904
100 WIU/day	41 (44.6)	19 (45.2)	22 (44.0)	0.905	10 (47.6)	31 (43.7)	0.806
150 WIU/day	35 (45.2)	19 (45.2)	18 (32.0)	0.193	8 (38.1)	27 (38.0)	1.000
200 WIU/day	16 (17.4)	4 (9.5)	12 (24.0)	0.098	3 (14.3)	13 (18.3)	1.000
Concomitant drugs
Anti-positive bacteria drugs^a	26 (28.3)	13 (31.0)	13 (26.0)	0.599	11 (52.4)	15 (21.1)	0.011
Antifungal drugs^b	37 (40.2)	15 (35.7)	22 (44.0)	0.419	14 (66.7)	23 (32.4)	0.010
Polymyxin B monotherapy	7 (7.6)	4 (9.5)	3 (6.0)	0.698	2 (9.5)	5 (7.0)	0.657
Tigecycline	43 (46.7)	17 (40.5)	26 (52.0)	0.270	14 (66.7)	29 (40.8)	0.048
Carbapenem	58 (63.0)	25 (59.5)	33 (66.0)	0.522	14 (66.7)	44 (62.0)	0.800
Concomitant β-lactams other than carbapenems^c	20 (21.7)	16 (38.1)	4 (8.0)	0.001	4 (19.0)	16 (22.5)	1.000
Aminoglycoside	5 (5.4)	3 (7.1)	2 (4.0)	0.657	1 (4.8)	4 (5.6)	1.000
Fosfomycin	14 (15.2)	5 (11.9)	9 (18.0)	0.563	3 (14.3)	11 (15.5)	1.000
Immunosuppressant	4 (4.3)	2 (4.8)	2 (4.0)	1.000	1 (4.8)	3 (4.2)	1.000
Glucocorticoids	36 (39.1)	16 (38.1)	20 (40.0)	0.853	9 (42.9)	27 (38.0)	0.800
Outcome
Mortality	37 (40.2)	16 (38.1)	21 (42.0)	0.704	10 (47.6)	15 (21.1)	0.025
Incidence of AKI	25 (27.2)	13 (31.0)	12 (24.0)	0.488	10 (47.6)	32 (45.1)	1.000

Notes: Data are presented as n (%) mean ± SD, or median [IQR]. ^aIncluding teicoplanin, vancomycin, desmethyl vancomycin, linezolid; ^bIncluding Voriconazole, posaconazole, caspofungin; ^cIncluding cefoperazone-sulbactam, piperacillin-tazobactam, ceftazidime and cefepime.

Table 2 Susceptibility Profile and Minimal Inhibitory Concentration (MIC) of CRKP to Various Antibiotics

Antimicrobial Agents	No. of Susceptible Isolates (%)
Amikacin	8 (8.7)
Ceftazidime	1 (1.1)
Piperacillin-tazobactam	0 (0)
Cotrimoxazole	18 (19.6)
Minocycline	25 (27.2)
Doxycycline	9 (9.8)
Ciprofloxacin	0 (0)
Polymyxin B or Colistin	90 (91.8)
Tigecycline	85 (92.4)
Antimicrobial Agents	MIC range (mg/L)
	≤ 0.5	0.5–2.0	>2.0
Polymyxin B or Colistin	40 (43.5)	51 (55.4)	1 (1.1)
Tigecycline	7 (7.6)	77 (83.7)	8 (8.7)

Figure 1 Schematic diagram of the patient screening process.

Table 3 Comparison of Patient Conditions Before and After Therapy

Parameter	Baseline	After Therapy	P value
Fever (°C)	38.0 (37.6, 38.8)	37.5 (36.8, 38.2)	< 0.001
White blood cell count	10.6 (7.85, 13.39)	9.5 (7.32, 12.5)	0.214
C-reactive Protein (mg/L)	99.01 (44.18, 133.55)	32.4 (16.55, 95.54)	< 0.001
Procalcitonin (μg/L)	1.4 (0.504, 5.465)	0.776 (0.193, 4.365)	0.041

Table 4 Multivariate Analysis of Factors Associated with Microbiological Clearance

Risk Factor	Unadjusted OR (95% CI)	P-value	Adjusted OR (95% CI)	P-value
APACHE II score	0.932 (0.874, 0.995)	0.034	0.888 (0.799, 0.986)	0.027
Concomitant β-lactams other than carbapenems^a	7.077 (2.139, 23.415)	0.001	15.757 (2.528, 98.215)	0.003
C-reactive Protein (mg/L)	0.994 (0.988, 1.001)	0.085	0.989 (0.976, 1.001)	0.084
Electrolyte disturbance	0.409 (0.162, 1.036)	0.059	0.127 (0.021, 0.754)	0.023
PMB 200 WIU/day	0.333 (0.099, 1.126)	0.077	0.195 (0.025, 1.531)	0.120

Note: ^aIncluding cefoperazone-sulbactam, piperacillin-tazobactam, ceftazidime and cefepime.

Table 5 Multivariate Analysis of Factors Associated with All-Cause Discharge Mortality

Risk Factors	Unadjusted OR (95% CI)	P value	Adjusted OR (95% CI)	P value
Age (years)	1.052 (1.009, 1.098)	0.018	1.078 (1.025, 1.135)	0.004
Duration days	1.062 (0.994, 1.135)	0.073	1.076 (0.992, 1.167)	0.077
Concomitant anti-positive bacteria drugs^a	4.107 (1.468, 11.487)	0.007	3.442 (0.976, 12.147)	0.055
Concomitant antifungal drugs^b	4.174 (1.483, 11.744)	0.007	4.226 (1.129, 15.821)	0.032
Concomitant tigecycline	2.897 (1.041, 8.059)	0.042	4.253 (1.157, 15.628)	0.029
Incidence of AKI	3.394 (1.213, 9.494)	0.020	3.197 (1.056, 14.523)	0.041

Notes: ^aIncluding teicoplanin, vancomycin, desmethyl vancomycin, linezolid; ^bIncluding voriconazole, posaconazole, caspofungin.