Exploring effectiveness of Metronidazole, Bismuth, and Rifaximin in treating small intestinal bacterial overgrowth and irritable bowel syndrome: A systematic review

Table 1 Characteristics of studies using Metronidazole, n (%)

Number	Ref.	Year of publication	Study design and setting	Number of patients enrolled with summary	Intervention used	Comparison used	Patients achieved outcome (intervention group)	Patients achieved outcome (comparison group)
1	Marie et al[23]	2009	Non-randomized, uncontrolled, prospective	51	Intermittent rotating antibiotics (7 days/month for 3 months)	None	21/49	N/A
2	Feng et al[24]	2021	Non-randomized, prospective	14	Antibiotic course	Placebo	6	2
3	Menees et al[25]	2012	Non-randomized, uncontrolled, prospective	51	Norfloxacin and Metronidazole intermittently	None	11	N/A
4	Tauber et al[27]	2014	Non-randomized, uncontrolled, prospective	37	Amoxicillin, Ciprofloxacin, and Metronidazole in succession	None	6	N/A
5	Mouillot et al[26]	2020	Retrospective cohort study	101	Gentamicin/Metronidazole and Metronidazole alone	None	20	23
6	García-Collinot et al[28]	2020	Clinical pilot study	40	Metronidazole alone	Saccharomyces boulardii alone	2	4
7	Tahan et al[29]	2013	Noncontrolled open clinical trial, community-based	20	Trimethoprim-sulfamethoxazole (30 mg/kg/day) and Metronidazole (20 mg/kg/day) for 14 days	None	19	N/A
8	Marie et al[23]	2009	Prospective observational cohort study, single tertiary care center	51	Rotating antibiotic therapy (Norfloxacin/Metronidazole)	None	22	N/A
9	Lauritano et al[30]	2009	Randomized controlled trial, catholic university of Rome	142	Metronidazole 750 mg/day for 7 days	Rifaximin 1200 mg/day for 7 days	31	45
10	Lauritano et al[31]	2008	Randomized controlled trial	142	Metronidazole 750 mg/day	Rifaximin 1200 mg/day	53 patients (Metronidazole)	67 patients (Rifaximin)
11	Lauritano et al[31]	2008	Cross-sectional study	51	Rotating antibiotic therapy (Norfloxacin/Metronidazole)	None	22 patients (improvement)	N/A
12	Dear et al[32]	2005	Clinical trial, hospital-based	12	Metronidazole	No fiber diet	6 patients: Significant reduction in hydrogen and methane production	N/A
13	Di Stefano et al[33]	2005	RCT, hospital setting	14	Metronidazole	Rifaximin	12 patients showed greater improvement in symptom severity	7 patients showed improvement (Rifaximin)
14	Di Stefano et al[33]	2005	RCT, hospital setting	14	Metronidazole	Rifaximin	12 patients showed greater improvement in symptom severity	7 patients showed improvement (Rifaximin)
15	Di Stefano et al[33]	2005	RCT, hospital setting	14	Metronidazole	Rifaximin	12 patients showed greater improvement in symptom severity	7 patients showed improvement (Rifaximin)
16	Melchior et al[34]	2017	Pilot controlled phase II study	16	Metronidazole (n = 8, 10 days)	Subcutaneous (n = 8, 10 days)	7 patients (87.5%) showed > 50% reduction in flatus incontinence episodes (from 18.2 ± 16.2 to 3.5 ± 3.1 episodes)	1 patient (12.5%) showed > 50% reduction in flatus incontinence episodes (from 11.1 ± 12 to 8 ± 9.7 episodes)
17	Thakur et al[35]	2009	Randomized, controlled	24	Metronidazole, 7 days	None	9 (improvement in stool scores)	0 (not reported)
18	Richard et al[36]	2021	Retrospective, single-center study	223	Metronidazole (500 mg, 3 ×/day for 10 days/month for 3 months)	Single antibiotic (Metronidazole) vs rotating antibiotics	36/69 (52.2%) achieved remission	62/124 (50.0%) achieved remission
19	Richard et al[36]	2021	Retrospective, single-center study	223	Metronidazole (500 mg, 3 ×/day for 10 days/month for 3 months) + Norfloxacin (400 mg, 2 ×/day for 10 days/month for 3 months) or Metronidazole + Ofloxacin	Rotating antibiotics vs single antibiotics	21/30 (70.0%) achieved remission	62/124 (50.0%) achieved remission
20	Pérez Aisa et al[37]	2019	Prospective cohort study, single-center	60	Rifaximin, Metronidazole, Ciprofloxacin	None	12 patients (small intestinal bacterial overgrowth + group, after treatment)	N/A
21	Konrad et al[38]	2018	Randomized single-blind clinical trial	116	Pantoprazole 2 × 40 mg, Amoxicillin 2 × 1000 mg, Metronidazole 2 × 500 mg for 10 days	Pantoprazole 2 × 40 mg, Amoxicillin 2 × 1000 mg, Rifaximin 3 × 400 mg for 10 days	18 (normal LHBT); 19 (UBT < 4.0‰); pain reduced below 3 points in 16	21 (normal LHBT); 19 (UBT < 4.0‰); pain reduced below 3 points in 18
22	Peinado Fabregat et al[39]	2022	Retrospective cohort study	54	Antibiotics (Metronidazole, Rifaximin, other) + probiotics	None	39 (partial/full symptom improvement)	N/A
23	Peinado Fabregat et al[39]	2022	Retrospective cohort study	54	Metronidazole + probiotics	None	13 (81.2)	10 (32.3)
24	Peinado Fabregat et al[39]	2022	Retrospective cohort study	54	Metronidazole	None	7 (36.8)	7 (36.8)
25	Peinado Fabregat et al[39]	2022	Retrospective cohort study	54	Antibiotics (Metronidazole, Rifaximin, other)	None	12 (63.2)	9 (32.0)
26	Peinado Fabregat et al[39]	2022	Retrospective cohort study	54	Metronidazole, Rifaximin	None	12 (71.4)	N/A
27	Lauritano et al[30]	2009	Open-Label randomized trial	71 intervention each group	Rifaximin (1200 mg/day)	Metronidazole (750 mg/day)	45	31
28	Castiglione et al[22]	2003	Open-Label randomized trial	15 intervention, 14 placebo	Metronidazole (750 mg/day)	Ciprofloxacin (1000 mg/day)	13	14

LHBT: Lactulose hydrogen breath test; N/A: Not available; RCT: Randomized controlled trial; UBT: Urease breath test.