Efficacy of Ceftazidime-Avibactam in the Treatment of Carbapenem-Resistant Klebsiella pneumoniae Infection After Kidney Transplantation

Figures & data

Table 1 Baseline Characteristics and Outcomes of Recipients with CRKP Infections Who Received Ceftazidime/Avibactam Compared with Other Antibiotic Treatment Regimens (Comparative Group)

Characteristics	CAZ-AVI Group	Comparative Group	P value
	N=22 (%)	N=32 (%)
Deceased donors	17 (77.3)	27 (84.4)	0.509
Age(years), mean±SD	37.2±9.8	41.1±10.0	0.164
Sex, male n (%)	13 (59.1)	19 (59.4)	0.983
BMI (kg/m2), mean±SD	21.3±3.0	22.2±2.0	0.194
Diabetes mellitus	6(27.3)	9(28.1)	0.945
Etiology of kidney failure, n (%)
HTA	2 (9.1)	4 (12.5)	0.695
DM	2 (9.1)	4 (12.5)	0.695
Glomerulonephritis	16 (72.7)	19 (59.4)	0.313
Others	2 (9.1)	5 (15.6)	0.482
Type of dialysis n (%)
Hematodialysis	15 (68.2)	19 (59.4)	0.510
Peritoneal dialysis	7 (31.8)	13 (40.6)	0.510
ATG induction n (%)	12 (54.5)	19 (59.4)	0.724
Types of infections
BSIs	11 (50.0)	12 (37.5)	0.361
UTIs	5 (22.7)	10 (31.3)	0.492
Pneumonia	9 (40.9)	12 (37.5)	0.801
SSIs	14 (63.6)	13 (40.6)	0.097
SOFA at infection onset, mean±SD	4.2±2.1	4.3±1.9	0.967
APACHE II at infection onset, mean±SD	9.7±3.2	10.6±3.0	0.299
Source control	6 (27.3)	9 (28.1)	0.945
Time from positive culture to study drug initiation(days), median (IQR)	2.0 (2.0–9.0)	3.0 (2.0–3.0)	0.369
Study drug within 48h, n (%)	11 (50.0)	15 (46.9)	0.821
Duration of study drug(days), mean±SD	10.7±4.4	10.4±4.8	0.821
Duration of infection after transplantation, mean±SD	11.5±6.2	11.5±5.4	0.977
Graft loss	1 (4.5)	5 (15.6)	0.207
Relapse, n (%)	2 (9.1)	7 (21.9)	0.215
14-day clinical cure, n (%)	18 (81.8)	17 (53.1)	0.030
14-day microbiological cure, n (%)	19 (86.4)	15 (46.9)	0.003
30-day mortality, n (%)	3 (13.6)	14 (43.8)	0.019

Notes: The variable marked in bold indicates that the difference between the two groups is statistically significant (P < 0.05).

Abbreviations: CRKP, carbapenem-resistant Klebsiella pneumoniae; CAZ-AVI, ceftazidime/avibactam; BMI, body mass index; HTA, hypertension; DM, diabetes mellitus; ATG, anti-human thymocyte immunoglobulin; BSIs, bloodstream infections; UTIs, urinary tract infections; SSIs, surgical site infections; SOFA, Sequential Organ Failure Assessment; APACHE II, Acute Physiologic Assessment and Chronic Health Evaluation II.

Table 2 Frequency of Antibiotic Regimen Used for Treatment of CRKP Infections in Kidney Transplantation

CAZ-AVI Group	N (%)	Comparative Group	N (%)
CAZ-AVI	16 (72.7)	Tigecycline/ carbapenem	13 (40.6)
CAZ-AVI/ carbapenem	6 (27.3)	Tigecycline	5 (15.6)
		Amikacin	4 (12.5)
		Tigecycline/ amikacin	3 (9.4)
		Colistin/ tigecycline	2 (6.3)
		Colistin	2 (6.3)
		Tigecycline/ phleomycin	1 (3.1)
		Tigecycline/ aztreonam	1 (3.1)
		Gentamicin	1 (3.1)

Table 3 Antimicrobial Susceptibility of Isolates from Recipients with CRKP Infections

Antibiotic	Number of Isolates Tested(N)	Susceptible (%)
Ceftazidime	54	0.0
Levofloxacin	54	9.3
Gentamycin	53	13.2
Imipenem	54	0.0
Meropenem	54	0.0
Amikacin	50	24.0
Polymyxin	52	96.2
Tigecycline	54	98.1
Ceftazidime-Avibatam	40	100.0

Table 4 Univariate and Multivariate Analysis of 30-Day Mortality of Recipients with CRKP Infection After Kidney Transplantation

Characteristics	Survivors	Non-Survivors	P value	Multivariate P value (OR, 95% CI)
	N=37(%)	N=17(%)
Deceased donors	31(83.8)	13(76.5)	0.523
Age(years), mean±SD	37.4±10.4	44.1±7.4	0.028
Sex, male n (%)	21(56.8)	11(64.7)	0.582
BMI (kg/m2), mean±SD	21.9±2.4	21.5±2.8	0.567
Diabetes	9(24.3)	6(35.3)	0.406
Etiology of kidney failure, n (%)
HTA	5(13.5)	1(5.9)	0.420
DM	4(10.8)	2(11.8)	0.918
Glomerulonephritis	25(67.6)	10(58.8)	0.533
Others	3(8.1)	4(23.5)	0.133
Type of dialysis n (%)
Hematodialysis	22(59.5)	12(70.6)	0.434
Peritoneal dialysis	15(40.5)	5(29.4)	0.434
ATG induction n (%)	21(56.8)	10(58.8)	0.887
Types of infections
BSIs	15(40.5)	8(47.1)	0.653
UTIs	11(29.7)	4(23.5)	0.637
Pneumonia	13(35.1)	8(47.1)	0.406
SSIs	20(54.1)	7(41.2)	0.381
SOFA at infection onset, mean±SD	3.8±2.1	5.3±1.0	0.012
APACHE II at infection onset, mean±SD	9.4±3.0	12.2±2.3	0.004
Source control	7(18.9)	8(47.1)	0.037
Time from positive culture to study drug initiation(days), median (IQR)	2(2–4.5)	3(2–4)	0.311
Study drug within 48h, n (%)	20(54.1)	6(35.3)	0.204
Duration of study drug(days), mean±SD	10.3±4.2	11.2±5.4	0.497
Duration of infection after transplantation, mean±SD	10.6±5.2	13.4±6.3	0.099
Relapse, n (%)	4(10.8)	5(29.4)	0.100
CAZ-AVI contamin, n (%)	19(51.4)	3(17.6)	0.026	0.026(0.148,0.027–0.800)

Notes: Bold values indicated that these variables were significant in univariate and multivariate analysis (P < 0.05).

Abbreviations: CRKP, carbapenem-resistant Klebsiella pneumoniae; CAZ-AVI, ceftazidime/avibactam; BMI, body mass index; HTA, hypertension; DM, diabetes mellitus; ATG, anti-human thymocyte immunoglobulin; BSIs, bloodstream infections; UTIs, urinary tract infections; SSIs, surgical site infections; SOFA, Sequential Organ Failure Assessment; APACHE II, Acute Physiologic Assessment and Chronic Health Evaluation II.

Figure 1 The survival curves for the two treatment groups between CAZ-AVI and comparative group.

Figure 2 Area under the receiver operating characteristic curve for this model.