Ceftazidime-Avibactam as Salvage Treatment for Infections Due to Carbapenem-Resistant Klebsiella pneumoniae in Liver Transplantation Recipients

Figures & data

Table 1 Demographic and Clinical Data of 21 Liver Transplantation Recipients Receiving CZA for KPC-Producing Klebsiella pneumoniae Bacterial Infection

No.	Age(y) /Sex	Diagnosis	MELD Score/PELD Score	Procedure	Infection	SOFA Score	T from CRKP Onset to LT(d)	Carbapenemase	Prior Antibiotics	Source Control	Septic Shock	Sepsis	Prior Antibiotics Time (d)	T from CRKP Onset to CZA Initiation(d)	Concomitant Tx	Tx Duration (d)	M/O	C/O
1	48/M	HBV-LC	15	DDLT	BSI, IAI, PI	13	1	KPC-2	Initial: CPZ/SBT, CAZ, IMP, VAN, FOS, MEM, TGC; Second: MEM, POL	YES	YES	YES	32	10	Initial: MEM, second: POL+LEV+VAN	Initial: 6, Second:17	P	Die
2	45/M	HCC	7	DDLT	BSI, IAI	12	62	KPC-2	IMP, FOS, MEM, TGC, AMI, VAN, CAZ	YES	NO	YES	33	30	MEM	5	P	Die
3	54/M	HCV-LC	11	DDLT	BSI	17	3	KPC-2	CAZ	NO	NO	NO	5	3	MEM	19	E	Die
4	37/M	ACLF	35	DDLT	PI	15	1	KPC-2	CAZ, MEM, VAN	NO	NO	NO	13	10	VAN+LEV	8	P	Improve
5	41/M	ACLF	28	DDLT	IAI, PI	8	55	KPC-2	Initial: IMP Second: AMI, LEV, VAN, CPZ/SBT, PIP/TAZ	YES	NO	NO	36	1	Initial: MET; second: AZM+ MET	Initial:13, Second:10	P	Die
6	46/F	PLD	10	DDLT	CRBSI	2	6	KPC-2	MEM, TGC, VAN	NO	NO	NO	19	7	-	6	E	Improve
7	67/M	ACLF, ALD	21	DDLT	IAI, CRBSI	14	3	KPC-2	CAZ, IMP, VAN	YES	NO	NO	31	1	AZM	11	E	Improve
8	50/M	HBV-LC	18	DDLT	IAI	19	56	KPC-2	CPZ/SBT	YEA	NO	NO	9	6	AZM	9	E	Improve
9	65/M	HCC, HBV-LC	11	DDLT	BSI	5	81	KPC-2	CAZ	NO	NO	NO	4	1	-	9	E	Die
10	68/M	ACLF	24	DDLT	BSI, IAI, PI	15	3	KPC-2	Initial: MOX, LEV, CPZ/SBT, MEM Second: CPZ/SBT, TGC, VAN, MEM	YES	NO	YES	16	1	Initial:MEM, PIP/TAZ Second:-	Initial: 31 Second:4	P	Die
11	39/F	Wilson’s disease	32	DDLT	PI	14	5	KPC-2	CAZ, PIP/TAZ	NO	NO	NO	10	1	AZM	13	E	Improve
12	47/M	ACLF	41	DDLT	BSI, IAI	17	3	KPC-2	CAZ, LEV	YES	NO	NO	3	2	MEM	19	E	Improve
13	65/M	HCC	8	DDLT	BSI	8	4	KPC-2	CAZ, MET, CPZ/SBT	NO	NO	NO	5	4	-	11	E	Improve
14	59/M	HCC	6	DDLT	PI	9	45	KPC-2	MEM, MOX, LIN, VAN, IMP	NO	NO	NO	13	2	-	8	P	Die
15	55/M	ACLF	24	DDLT	PI	9	3	KPC-2	MEM, VAN, TGC	NO	NO	NO	5	1	MET, POL	13	E	Improve
16	19/M	Carol’s syndrome	20	LDLT	IAI	13	34	NDM-1	MEM, VAN, CPZ/SBT	YES	NO	NO	31	3	MET	10	P	Die
17	30/M	ACLF	35	DDLT	BSI	11	7	KPC-2	CPZ/SBT, TEI	NO	NO	NO	5	1	-	9	E	Improve
18	1/F	BA	23	LDLT	PI, IAI	12	3	NDM-1	PIP/TAZ, MEM, TGC, CPZ/SBT,	YES	YES	NO	27	26	-	3	P	Die
19	2/F	BA	7	LDLT	IAI	9	2	NDM-1	TEI, TGC, MEM, CPZ/SBT	YES	NO	NO	33	32	AZM	18	E	Improve
20	12/F	BA	28	DDLT	IAI	4	29	KPC-2	CEF, MEM, LNI, VAN, TGC,	YES	NO	NO	33	3	MET	14	E	Improve
21	0.5/F	BA	62	LDLT	IAI	7	7	NDM-1	MEM, TGC, CAZ	YES	NO	NO	37	9	-	7	E	Improve

Abbreviations: T, time; Tx, treatment; HBV-LC, hepatitis B-related liver cirrhosis; HCC, hepatocellular carcinoma; ACLF, acute-on-chronic liver failure; ALD, alcoholic liver disease; PLD, polycystic liver disease; BA, biliary atresia; DDLT, deceased donor liver transplantation; LDLT, living donor liver transplantation; BSI, bloodstream infection; VAP, ventilator-associated pneumonia; IAI, intraabdominal infection; CRBSI, catheter-related bloodstream infection; PI, pulmonary infection; AMI, amikacin; LIN, linezolid; POL, polymyxin; LEV, levofloxacin; MOX, moxifloxacin; AZM, aztreonam; CAZ, ceftazidime; MET, metronidazole; CPZ/SBT, cefoperazone-sulbactam; PIP/TAZ, piperacillin and tazobactam; LIN, linezolid; TEI, teicoplanin; CEF, cefepime; E, eradication; P, persistence; M/O, microbiological outcome; C/O, clinical outcome.

Table 2 Susceptibility Testing Results of Klebsiella pneumoniae Isolates to Antimicrobial Agents

Antimicrobial Agent	Klebsiella pneumoniae (n=21)
	S	I	R
Amikacin	11 (52.4%)	0	10 (47.6%)
Ampicillin	0	0	21 (100%)
Piperacillin‐tazobactam	0	0	21 (100%)
Imipenem	0	0	21 (100%)
Meropenem	0	0	21 (100%)
Cefoperazone‐sulbactam	0	1 (4.8%)	20 (95.2%)
Cefepime	0	0	21 (100%)
Aztreonam	0	0	21 (100%)
Levofloxacin	0	0	21 (100%)
Trimethoprim‐sulfamethoxazole	16 (76.2%)	0	9 (42.8%)
Tigecycline	19 (90.5%)	0	2 (9.5%)
Polymyxin B	20 (95.2%)	0	1 (4.8%)
Ceftazidime Avibactam	21 (100%)	0	0

Table 3 Description of Patients Infected by Carbapenem-Resistant Klebsiella Pneumoniae Who Experienced Clinical Failure

Age/Sex	Underlying Condition	Type of Infection	Clinical Presentation	Prior Therapy to CZA	Dose of CZA	CRRT	Combined Antibiotics	Reason for Clinical Failure
48/M	HBV-LC	BSI, IAI, HAP	Septic shock, sepsis	Initial: CPZ/SBT for 9d, IMP/VAN for 5d, TGC /MEM/FOS for 6d, Second: MEM/POL for 30d	Intial:2.5g q12h for 6d; Second:1.25g q12h for 17d	YES	Initial: MEM; Second: POL+ LEV	Recurrent infection; Death
45/M	HCC	BSI, IAI	Sepsis	IMP for 4d, MEM/FOS /TGC for 18d, IMP/FOS /TGC for 10d	2.5g q12h for 5d	NO	MEM	Respiratory failure, Death
54/M	HCV-LC UGIB	BSI	No sepsis	CAZ for 1d	2.5g q12h for 19d	YES	MEM	Gastrointestinal bleeding, Hemorrhagic shock, Death
41/M	HBV-LC	IAI HAP	No sepsis	Initial: IMP for 2d, Second: AMI/CPZ/SBT for 17d, LEV 7d, VAN /PIP/TAZ for 10d	Initial:2.5g q12h for 4d; Second:2.5g q12h for 7d	NO	Initial:MET; Second: AZM+MET	Recurrent infection; Death
65/M	HBV-LC, HCC	BSI	No sepsis	CAZ for 1d	2.5g q12h for 10d	NO	NO	Hepatic failure, Death
68/F	ACLF	BSI IAI PI	Sepsis	Initial: MOX for 5d, LEV for 2d, CPZ/SBT for 4d, MEM for 20d Second: PIP/TAZ for 6d, CPZ/SBT for 14d, TGC for 19d, VAN for 16d, MEM for 16d	Initial:2.5g q8h for 6d, 2.5g q12h for 25d; Second:2.5g q12h for 4d	NO	Initial:MEM, PIP/TAZ; Second: NO	Multiple organ failure, Recurrent infection, Death
59/M	HCC	HAP	No sepsis	MEM for 3d, MOX for 9d, LIN for 3d, VAN for 8d, IMP for 2d	2.5g q8h for 8d	NO	NO	Severe pulmonary infection, Gastrointestinal bleeding, Death
18/M	LC	IAI	No sepsis	MEM for 20d, VAN for 28d, CPZ/SBT for 8d	2.5g q8h for 10d	NO	MET	Recurrent infection, Severe pulmonary infection, Death
1/F	BA	HAP IAI	Septic shock	PIP/TAZ for 3d, MEM for 22d, TGC for 24d, CPZ/SBT for 5d	0.3g q8h for 3d	NO	NO	Multiple organ failure, Septic shock, Death

Abbreviations: IMP, imipenem; MEM, meropenem; TEI, teicoplanin; TMP-SMZ, trimethoprim-sulfamethoxazole; VAN, vancomycin; TGC, tigecycline; AMI, amikacin; LIN, linezolid; POL, polymyxin; LEV, levofloxacin; AZM, aztreonam; CAZ, ceftazidime; MET, metronidazole; CPZ/SBT, cefoperazone-sulbactam; PIP/TAZ, piperacillin and tazobactam.