Successful Treatment of Ventriculitis Caused by MDR/XDR Gram-Negative Bacillus Using Ceftazidime/Avibactam: Case Series and Literature Review

Figures & data

Table 1 Susceptibility Results for Klebsiella pneumoniae in Cerebrospinal Fluid Collected on Different Date in case 1

Day 3		Day 4 and 6		Day 13
Antibiotic	MIC (mg/L)	Antibiotic	MIC (mg/L)	Antibiotic	MIC (mg/L)
Tigecycline	2	Tigecycline	2	Tigecycline	2
Ceftazidime/avibactam	21mm*	Ceftazidime/avibactam	21mm*	Ceftazidime/averbatan	21 mm*
Levofloxacin	≥8	Imipenem	≥16	Meropenem	6
Cefuroxime sodium	≥64	Levofloxacin	≥8	Ampicillin	6
Cefuroxime axetil	≥64	Minocycline	≥16	Aztreonam	6
Compound sulfamethoxazole	≤20	Compound sulfamethoxazole	≤20	Ciprofloxacin	6
Ceftazidime	≥64	Ceftazidime	≥64	Gentamicin	6
Cefepime	≥32	Tobramycin	≥16	Cefazolin	6
Piperacillin/tazobactam sodium	≥128	Cefepime	≥32	Cefepime	≥32
Cefoperazone/sulbactam	≥64	Piperacillin/tazobactam sodium	≥128	Piperacillin/tazobactam sodium	≥128
Ertapenem	≥8	Meropenem	≥16	Cefoperazone/sulbactam	≥64
Imipenem	≥16	Cefoperazone/sulbactam	≥64	Ertapenem	≥8
Cefoxitin	≥64	Polymyxin	≤0.5	Ceftazidime	≥64
Cefatriaxone	≥64	Ciprofloxacin	≥4	Compound sulfamethoxazole	≤20
Amikacin	≥64	Aztreonam	≥64	Cefuroxime axetil	≥64
Amoxicillin/clavulanate potassium	≥32	Amikacin	≥64	Levofloxacin	≥8
KPC	+	KPC	+	Imipenem	≥16
				Cefoxitin	≥64
				Cefatriaxone	≥64
				Amikacin	≥64
				Amoxicillin/clavulanate potassium	≥32
				Cefuroxime sodium	≥64

Note: *Antibacterial circle diameter.

Abbreviations: MIC, minimum inhibitory concentration; KPC, Klebsiella pneumoniae carbapenemase.

Table 2 CSF Analyses of Case 1 on Different Date

Day	CSF RBC Count (Cells/mm3)	CSF WBC Count (Cells/mm3)	CSF % Neutrophil	CSF Glucose (g/L)	CSF Protein (mmol/L)
1	NA	NA	NA	0.1	4.377
3	100	4500	96	0.1	5.011
5	30	800	60	2.0	3.095
8	4480	60	46	1.4	3.997
11	3000	15	NA	0.9	3.743
12	1040	40	60	0.6	4.511
14	250,000	9000	85	0.6	3.398
15	2500	300	75	1.1	3.301
16	7500	30	40	0.7	3.666
18	1150	12	NA	1.0	3.293
20	500	110	20	1.3	1.609
21	100	8	NA	1.3	3.278
23	10	90	20	2.2	1.768
25	0	140	6	2.2	1.415
31	20	20	NA	2.2	1.086

Abbreviations: CSF, cerebrospinal fluid; RBC, red blood cell; WBC, white blood cell; NA, not available.

Figure 1 Brain computed tomography scan of case 1. (A and B) CT images show pus gathering in the subcutaneous tissues. (C) CT images show the pus gathering in the cisterns of interhemispheric fissure (red arrows).

Figure 2 Summary of the clinical treatment process of Case 1.

Table 3 Susceptibility Results for Klebsiella pneumoniae in Cerebrospinal Fluid Collected on Different Date in case 2

Drug	MIC (mg/L)
	9/7	9/10	9/12
Ceftazidime/avibactam	4	4	4
Polymyxin	1	1	1
Imipenem	≥16	≥16	≥16
Levofloxacin	≥8	≥8	≥8
Cefuroxime Sodium	≥64	≥64	≥64
Cefuroxime Axetil	≥64	≥64	≥64
Sulfamethoxazole	≥320	≥320	≥320
Ceftazidime	≥64	≥64	≥64
Cefepime	≥32	≥32	≥32
Piperacillin/tazobactam sodium	≥128	≥128	≥128
Cefoperazone/sulbactam	≥64	≥64	≥64
Tigecycline	2	2	2
Ertapenem	≥8	≥8	≥8
Cefoxitin	≥64	≥64	≥64
Cefatriaxone	≥64	≥64	≥64
Amikacin	≤2	≤2	≤2
Amoxicillin/clavulanic acid	≥32	≥32	≥32

Abbreviation: MIC, minimum inhibitory concentration.

Table 4 Susceptibility Results for Pseudomonas aeruginosa in Sputum Collected on Different Date

Drug	MIC (mg/L)
	Day 2	Day 3	Day 4	Day 6
Ciprofloxacin	≥4	≥4	≥4	≥4
Polymyxin	4	4	4	4
Imipenem	≥16	≥16	≥16	≥16
Cefoperazone/Sulbactam	≥64	≥64	≥64	≥64
Ceftazidime	32	32	32	32
Ticarcillin/Potassium Clavulanate	≥128	≥128	≥128	≥128
Tobramycin	≤1	≤1	≤1	≤1
Cefepime	≥32	≥32	≥32	≥32
Meropenem	≥16	≥16	≥16	≥16
Amikacin	4	4	4	4
Levofloxacin	≥8	≥8	≥8	≥8

Abbreviation: MIC, minimum inhibitory concentration.

Table 5 CSF Analyses of Case 2 on Different Date

Day	CSF RBC Count (Cells/mm3)	CSF WBC Count (Cells/mm3)	CSF % Neutrophil	CSF Glucose (g/L)	CSF Protein (mmol/L)
1	8250	1950	93	2.5	2.0
2	2000	400	80	2.6	1.69
4	3700	1900	92	4.0	2.51
5	10,000	1700	90	4.9	2.01
6	630	100	88	6.5	2.49
7	200	3	NA	3.6	2.66
8	30	2	NA	5.2	2.85
11	270	20	NA	2.5	2.85
12	700	200	70	2.5	3.32
14	6000	380	88	4.4	12.01
16	120	10	NA	2.6	9.86
19	2000	0	NA	1.8	2.24
21	300	30	70	3.2	30.08
22	50	250	60	2.5	27.47
26	150	220	80	8.4	22.92
32	12,000	200	90	3.9	32.1
37	70	8	NA	3.0	0.62
39	1	3	NA	4.0	2.14
42	750	6	NA	4.1	1.41
50	33	1	NA	3.7	1.14

Abbreviations: CSF, cerebrospinal fluid; RBC, red blood cell; WBC, white blood cell; NA, not available.

Figure 3 Brain computed tomography scan of case 2. (A) The CT images show blocking of the right lateral ventricle but with obvious enlargement of the left lateral ventricle and the fourth ventricle, which indicate separation of the ventricular system. (B) Red arrow show the drainage tube.

Figure 4 Schematic presentation of the clinical treatment process for Case 2.

Table 6 CSF Analyses of Case 3 on Different Date

Day	CSF RBC Count (Cells/mm3)	CSF WBC Count (Cells/mm3)	CSF % Neutrophil	CSF Glucose (g/L)	CSF Protein (mmol/L)
1	8	9000	92	0.1	2.630
3	40	1000	85	0.2	2.390
6	5	1	NA	0.4	1.700
8	44	20	NA	0.1	1.510
11	45	113	10	0.0	2.660
17	20	450	96	3.8	2.230
18	4500	430	95	4.2	2.620
19	4644	230	90	3.5	2.510
20	40	15	NA	0.7	2.270
24	1902	13,302	81	3.1	3.900
25	90	15	NA	2.6	2.810
28	3089	840	95	3.5	1.330
29	240	212	95	3.3	1.160
30	0	20	NA	3.4	1.730
34	270	6	NA	3.6	0.990
38	69	5	NA	2.6	1.070
47	120	5	NA	3.2	0.520
52	20	6	NA	3.0	0.510
79	500	20	NA	2.8	0.280

Abbreviations: CSF, cerebrospinal fluid; RBC, red blood cell; WBC, white blood cell; NA, not available.

Table 7 Susceptibility Results for Pseudomonas aeruginosa in Cerebrospinal Fluid Collected on Different Date

Drug	MIC (mg/L)
	Day 10	Day 17	Day 34
Ciprofloxacin	≥4	≥4	≥4
Polymyxin	≤0.5	≤0.5	≤0.5
Imipenem	≥16	≥16	≥16
Cefoperazone/Sulbactam	≥64	32	≥64
Ceftazidime	8	16	32
Ticarcillin/Potassium Clavulanate	≥128	≥128	≥128
Tobramycin	≤1	≤1	≤1
Cefepime	16	16	16
Meropenem	≥16	≥16	≥16
Amikacin	≤2	≤2	16
Levofloxacin	≥8	≥8	≥8

Abbreviation: MIC, minimum inhibitory concentration.

Figure 5 Schematic presentation of the clinical treatment process for Case 3.

Table 8 Summary of Ceftazidime–Avibactam Used for CNS Infections Caused by MDR K. pneumoniae and MDR P. aeruginosa

First Author	Country	Numbers	CSF Cultures	Drugs	Outcome
Holyk^Citation7	USA	1	MDR K. pneumoniae	CAZ/AVI 2.5g IV 21 days and gentamicin 15 days intraventricular	Cured
Samuel^Citation5	USA	1	KPC-producing K. pneumoniae	CAZ/AVI 2.5g IV q6h 14 days	Cured
Gofman^Citation8	USA	1	Carbapenem-resistant K. pneumoniae and Pseudomonas aeruginosa	Intrathecal amikacin 30 mg qd 4 weeks and CAZ/AVI 2.5 g IV q8h 6 weeks	Cured
Yasmin^Citation6	UAS	1	KPC-producing MDR K. pneumoniae	CAZ/AVI 2.5g IV q8h 10 days	Cured
Xipell^Citation9	Spain	1	XDR Pseudomonas aeruginosa	CAZ/AVI 2.5g and colistin 2 MU IV q8h 30 days	Cured
Rodríguez-Núñez^Citation10	Spain	1	XDR Pseudomonas aeruginosa	CAZ/AVI 31 days	Alive at 90 days

Abbreviations: CSF, cerebrospinal fluid; KPC, Klebsiella pneumoniae carbapenemase; MDR, multidrug-resistant; XDR, extensively drug-resistant; CAZ/AVI, ceftazidime/avibactam; IV, intravenously.

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