Five years of fecal microbiota transplantation - an update of the Israeli experience

Table 1 Study population characteristics according to fecal microbiota implantation route

	Overall		Upper GI1		Lower GI		Capsules		P value
	n (valid)	% (IQR)	n	% (IQR)	n	% (IQR)	n	% (IQR)
Patients	111	100	24	222	50	45	37	33
Male gender	47 (111)	42	16	673	19	38	12	32
Age, median (IQR)	70 (111)	(53-82)	68	(51-86)	78	(61-83)	68	(45-75)	0.114
Charlson comorbidity score, median	6 (81)	3-7	5.5	(3-7.25)	6	(1.75-7.5)	5	(2-7)	0.734
CDI risk factors
Prior hospitalization	80 (111)	72	18	753	26	52	36	97	< 0.01
Prior antibiotics use	66 (108)	59	15	633	15	30	36	97	0.012
PPI usage	37 (110)	33	8	333	14	28	15	41	0.470
Chemotherapy	19 (111)	17	4	173	3	6	12	32	0.005
IBD	20 (111)	18	5	213	7	14	8	22	0.606
Previous CDI episode, median	2 (107)	(2-3)	2	(1-3)	2	(1-3)	3	(2-4)	0.275
Prior therapy
Metronidazole	89 (110)	80	17	713	41	82	31	84	0.365
Vancomycin	109 (110)	98	24	1003	48	96	37	100	0.534
Combination	31 (110)	28	10	423	15	30	6	16	0.099
Severe CDI	20 (111)	18	8	33.33	10	20	2	5.40	0.019
Indication
Refractory	29 (111)	26	6	253	19	38	4	11	0.017
Recurrent	82 (111)	74	18	753	31	62	33	89
Outpatient	78 (111)	70	12	503	36	72	30	81	0.032

¹Upper GI: Gastroscopy, nasogastric tube or through percutaneous endoscopic gastrostomy;

²Percentages refer to the total number of subjects in the cohort;

³Percentages refer to the number of subjects in the specific group. CDI: Clostridium difficile infection; IBD: Inflammatory bowel diseases; PPI: Proton pump inhibitor; GI: Gastrointestinal; FMT: Fecal microbiota implantation; IQR: Interquartile range; Prior hospitalization: Hospitalization in the 3 mo prior to the FMT; Prior antibiotics: Antibiotics use in the 3 mo prior to the FMT.

Table 2 Fecal microbiota implantation outcome and patients’ follow-up

	Overall		Upper GI		Lower GI		Capsules		P value
	n (valid)	%/IQR	n	%/IQR	n	%/IQR	n	%/IQR
Patients	111 (111)		24	222	50	45	37	33
Response within 7 d	94 (111)	84.72	17	713	42	84	34	92	0.198
Days to response, median	2 (111)	1-2	2	1-3	1	0-2	2	2-3	0.069
No. of patients in follow-up at 6 mo5	99 (99)	89.22	19	793	44	88	36	97
Recurrence at 6 mo	16 (99)	16.22	3	15.83	5	11.40	8	22.20	0.141
Total death	11 (111)	9.92	5	213	6	12	0	0	0.023
Death - unrelated	6 (11)	5.42	4	803	2	33	0	0
Death - CDI-related	3 (11)	2.72	1	203	4	66	0	0
No. of adverse events	19 (107)	17.12	1	43	14	28	4	11	0.006
Success4	97 (111)	87.42	19	793	44	88	34	92	0.338

¹Upper GI: Gastroscopy, nasogastric tube or through percutaneous endoscopic gastrostomy;

²Percentages refer to the total number of subjects in the cohort;

³Percentages refer to the number of subjects in the specific group;

⁴Success: diarrhea-free two months post-fecal microbiota implantation;

⁵Eleven patients died before this endpoint, and one had not yet reached it at study closure. Patients who died before this endpoint from a reason other than Clostridium difficile infection (CDI) and were diarrhea-free were regarded as success, while patients who died before this endpoint from their CDI were considered as failures. CDI: Clostridium difficile infection; IQR: Interquartile range; GI: Gastrointestinal.

Table 3 Fecal microbiota implantation success and failure

	Valid	No.	Success		Failure		P value
			Number	%	Number	%
Patients	111	111	97	87.42	14	12.6
Male gender	111	47	40	41.23	7	50.0	0.535
Ambulatory	111	78	72	92.32	6	7.7	0.016
Hospitalized	111	33	25	75.82	8	24.2
CDI risk factors
Prior hospitalization	111	80	68	70.13	12	85.7	0.224
Antibiotics use	108	89	77	81.13	12	92.3	0.318
PPI usage	110	37	32	33.33	5	35.7	0.86
Chemotherapy	111	19	17	17.53	2	14.3	0.764
IBD	111	20	18	18.63	2	14.3	0.698
Steroid usage	111	17	13	13.43	4	28.6	0.141
Fever	76	21	19	27.93	2	25.0	0.86
Severe disease	111	20	14	14.43	6	42.9	0.01
Death	111	11	6	6.23	5	37.5	0.001
Adverse events	107	19	15	16.03	4	30.8	0.19
Route: Lower GI FMT	111	50	45	88.02	5	12.0	0.338
Upper GI FMT1	111	24	19	79.22	5	20.8
Capsules FMT	111	37	34	91.92	3	8.1
Frozen stool	111	91	81	89.02	10	11.0	0.272
Fresh stool	111	20	16	80.02	4	20.0
0-1 Previous CDI	107	24	23	24.23	1	8.3	0.214
2+ previous CDI	107	83	72	74.23	11	78.6
Indication							0.824
Refractory	111	29	25	86.22	4	13.8
Recurrent	111	82	72	87.82	10	12.2
Prior therapy
Metronidazole	110	89	80	83.33	9	64.3	0.09
Vancomycin	110	109	95	99.03	14	100.0	0.701
Combination	109	31	27	28.13	4	30.8	0.843
	Valid		Mean	SD	Mean	SD	Sigma
Age (yr)	111		63.2	22.4	73.7	12.1	0.089
Charlson comorbidity score	81		4.82	3.18	6.6	2.32	0.048
Previous CDI episodes (n)	107		2.47	1.7	2.38	0.9	0.864
Time from 1st CDI (d)	89		140.4	200.8	108.56	120.3	0.643
Creatinine (mgl/dL)	76		1.37	1.2	2.19	2.6	0.098
Albumin (mg/L)	54		3.32	0.8	2.76	0.5	0.053
WBC (103/dL)	76		13.6	18.7	15.6	10.4	0.756

¹Upper GI: Gastroscopy, nasogastric tube or through percutaneous endoscopic gastrostomy;

²Percentages referral is the total number of subjects in the cohort;

³Percentages referral is the number of subjects in the specific group. CDI: Clostridium difficile infection; IBD: Inflammatory bowel diseases; PPI: Proton pump inhibitor; GI: Gastrointestinal; FMT: Fecal microbiota implantation; IQR: Interquartile range; WBC: White blood cells; Prior hospitalization: Hospitalization during the 3 mo prior to the FMT; Prior hospitalization: Antibiotics use in the 3 mo prior to the FMT.

Table 4 Multivariate analysis of the association between patient characteristics and a successful fecal microbiota implantation procedure

Patient characteristics	OR (95%CI)	P value
Hospitalized patient	0.19 (0.04-0.86)	0.032
Severe disease	0.14 (0.02-0.76)	0.023
Charlson score categories	0.82 (0.38-1.76)	0.622

Adjusted to previous hospitalization, metronidazole treatment prior to fecal microbiota implantation (FMT), previous Clostridium difficile infection (CDI), recurrent CDI, inflammatory bowel diseases, route of administration, stool preparation method (fresh/frozen) and FMT dosage.

Table 5 Comparison of patients’ characteristics by age

	Valid	No.	Below 60 yr		Above 60 yr		P value
			Number	%	Number	%
Patients	111	111	35	31.52	76	68.5
Male gender	111	47	15	42.93	32	42.1	0.941
Ambulatory	111	78	30	85.73	48	63.2	0.011
CDI risk factors
Prior hospitalization	111	80	22	62.93	58	76.3	0.142
Antibiotics use	108	89	28	80.03	61	83.6	0.649
PPI usage	110	37	9	25.73	28	37.3	0.230
Chemotherapy	111	19	7	20.03	12	15.8	0.584
IBD	111	20	14	40.03	6	7.9	0.000
Steroid usage	111	17	9	25.73	8	10.5	0.039
Fever	76	21	7	35.03	14	25.0	0.391
Severe	111	20	3	8.63	17	22.4	0.079
Route
Lower GI	111	50	12	34.33	38	50.0	0.254
Upper GI1	111	24	8	22.93	16	21.1
Capsules	111	37	15	42.93	22	28.9
0-1 Previous CDI	107	24	8	22.93	16	22.2	0.941
2+ previous CDI	107	83	27	77.13	56	77.8
Indication
Refractory	111	29	8	22.93	21	27.6
Recurrent	111	82	27	77.13	55	72.4
Prior therapy
Metronidazole	110	98	29	82.93	69	80.0	0.722
Vancomycin	109	109	35	100.03	74	98.7	0.493
Combination	109	31	12	34.33	19	25.7	0.352
Outcomes
Success	111	97	33	94.33	64	84.2	0.137
Recurrence by 6 m	99	16	7	203	9	14.1	0.443
Death	111	11	0	03	11	100.0	0.018
Adverse events	107	19	5	14.33	14	19.4	0.512
			Mean	SD	Mean	SD	Sigma
Age (yr)	111		37.26	14.72	77.07	8.9	0.000
Charlson comorbidity score	81		1.29	1.95	6.35	2.3	0.000
Previous CDI episodes (n)	107		2.63	1.9	2.38	1.51	0.455
Time from 1st CDI (d)	89		198.75	279.04	102.68	112.19	0.024
Creatinine (mg/dL)	76		0.91	0.51	1.67	1.63	0.051
Albumin (mg/L)	54		3.51	0.99	3.17	0.69	0.153
WBC (103/dL)	76		11.33	90.36	14.78	19.86	0.468

¹Upper GI: Gastroscopy, nasogastric tube or through percutaneous endoscopic gastrostomy;

²Percentages refer to the total number of subjects in the cohort;

³Percentages refer to the number of subjects in the specific group. CDI: Clostridium difficile infection; IBD: Inflammatory bowel diseases; PPI: Proton pump inhibitor; GI: Gastrointestinal; FMT: Fecal microbiota implantation; IQR: Inter quartile range; WBC: White blood cells; Prior hospitalization: Hospitalization in the 3 mo prior to the FMT; Prior hospitalization: Antibiotics use in the 3 mo prior to the FMT.

Table 6 Mortality

	Valid	No.	Alive		Dead		P value
			Number	%	Number	%
Patients			100	90.12	11	9.9
Male gender	111	47	38	38.03	9	81.8	0.005
Ambulatory	104	75	74	77.93	1	10.0	0.000
CDI risk factors
Prior hospitalization	111	80	69	69.03	11	100.0	0.030
Antibiotics use	108	89	81	82.73	8	80.0	0.834
PPI usage	110	37	31	31.33	6	54.5	0.122
Chemotherapy	111	19	19	19.03	0	0.0	0.112
IBD	111	20	20	20.03	0	0.0	0.101
Steroid usage	111	17	16	16.03	1	9.1	0.546
Fever	76	21	15	23.13	6	54.5	0.031
Severe	110	20	13	13.03	7	63.6	0.000
Adverse events	107	19	15	15.53	4	40.0	0.053
Route
Lower GI	111	50	44	44.03	6	54.5	0.023
Upper GI1		24	19	19.03	5	45.5
Capsules		37	37	37.03	0	0.0
0-1 previous CDI	107	24	19	19.83	5	45.5	0.053
2+ previous CDI		83	77		6
Indication	111						0.306
Refractory		23	19	19.03	4	36.4
Recurrent		82	76	76.03	6	54.5
Prior therapy
Metronidazole	110	89	80	80.83	9	81.8	0.936
Vancomycin	110	109	98	99.03	11	100.0	0.738
Combination	109	31	25	25.53	6	54.5	0.043
Outcomes
Adverse events	107	19	15	15.53	4	40.0	0.053
Response to FMT	111	94	88	88.03	6	54.5	0.003
			Mean	SD	Mean	SD	Sigma
Age (yr)	111		62.37	21.656	84	5.797	0.000
Charlson comorbidity score	81		4.57	2.98	8	2.4	0.001
Previous CDI episodes (n)	107		2.57	1.633	1.45	1.368	0.025
Time from 1st CDI (d)	89		138.47	197.991	110.75	63.036	0.493
Creatinine (mg/dL)	76		1.44	1.507	1.74	1.193	0.482
Albumin (mg/L)	54		3.34	0.782	2.4	0.408	0.010
WBC (103/dL)	76		13.65	18.87	15.64	78.62	0.564

¹Upper GI: Gastroscopy, nasogastric tube or through percutaneous endoscopic gastrostomy;

²Percentages refer to the total number of subjects in the cohort;

³Percentages refer to the number of subjects in the specific group. CDI: Clostridium difficile infection; IBD: Inflammatory bowel diseases; PPI: Proton pump inhibitor; GI: Gastrointestinal; FMT: Fecal microbiota implantation; IQR: Inter quartile range; WBC: White blood cells; Prior hospitalization: Hospitalization within the 3 mo prior to the FMT; Prior hospitalization: Antibiotics use in the 3 mo prior to the FMT.