Table 3.
Outcomes of clinical trials of cranberry (A), D-Mannose (B), combination cranberry and D-Mannose (C) and NSAIDs (D).
| A. Outcomes of Cranberry Trials | ||||
|---|---|---|---|---|
| Name Year | UTI Threshold (CFU/mL) Bacteria Isolated |
Outcome Reported | Side Effects Reported | Reported Success * |
| A1. Koradia, 2019 [41] | ≥ 103 N/A |
No of UTIs: BKProCyan vs. placebo: 4 (9.1%) vs. 33.3% (p = 0.005) Time to first UTI: Median time: 174 vs. 90 days (p = 0.001) UTI free: BKPro-Cyan group vs. placebo group (90.9 vs. 66.7%) Duration of UTI:N/A Symptom Scores:N/A |
3 (6.8%) had abdominal distention (n = 1) and diarrhoea (n = 2) All reported TEAEs were mild in severity, considered related to the study drug and resolved without corrective treatment |
Yes |
| A2. Maki, 2016 [44] | ≥ 103 E. coli |
No of UTIs: Cranberry vs. placebo: 39 vs. 67 (p = 0.016) Time to first UTI: Cranberry vs. placebo: 33 (17.8%) vs. 50 (26.6%) first UTI with pyuria (p = 0.131) UTI free: Cranberry vs. Placebo: 33 subjects (17.8%) vs. 50 (26.6%) (HR: 0.67; 95% CI: 0.43, 1.05; p = 0.078) Duration of UTI:N/A Symptom Scores:N/A |
GI issues: 3 (1.6%) with nausea (p = 0.044) Headache [cranberry group: n = 16 (8.6%); sinusitis [cranberry group: n = 10 (5.4%)] and upper respiratory infection [cranberry group: n = 13 (7.0%); All serious AEs unlikely related to cranberry product |
Yes |
| A3. Bruyère, 2019 [45] | ≥ 105 E. coli |
No of UTIs: Frequency of cystitis in first 3 mo: 0.7 ± 1.1 propolis + cranberry group vs. 1.3 ± 1.1 placebo (p = 0.0257), but not in the first 6 months Total cystitis episodes within first 3 mo: 1.4 ± 1.0 vs. 2.0 ± 1.0 (p = 0.0680) Time to first UTI: 69.9 ± 45.8 days vs. 43.3 ± 45.9 (p = 0.0258) UTI free: 47.1% in the propolis and cranberry vs. 36.1% in the placebo group (p = 0.3527) Duration of UTI:N/A Symptom Scores:N/A |
3 events: Sigmoid diverticulitis, acute pyelonephritis and hallux valgus corrective surgery. All unrelated to treatment | Yes |
| A4. Vostalova, 2015 [46] | ≥ 105 E. coli |
No of UTIs: Average UTIs/subject: 0.12 (10/83 vs. 0.32 (30/93) (p = 0.03) >1 UTI: 9/83 (10.84%) in cranberry vs. 24/93 (25.81%) in placebo (p = 0.04) Time to first UTI: 133 days in the cranberry group vs. 65 days in placebo group (p = 0.04) UTI free:N/A Duration of UTI:N/A Symptom of scores:N/A |
None reported | Yes |
| A5. Ledda, 2015 [47] | N/A N/A |
No of UTIs: 73.3% reduction in freq. of UTI (p < 0.05) 15.4% reduction in control group (p = 0.012) Time to first UTI:N/A UTI free: N/A Duration of UTIs: 2.5 ± 1.3 vs. 3.6 ± 1.7 days (p < 0.05) Symptom scores:N/A |
3 (13.6%) in cranberry group required medical consultation for UTI symptoms (p < 0.05). However, no AEs reported | Yes |
| A6. Kontiokari, 2001 [48] | ≥ 105 E. coli |
No of UTIs: Difference between cranberry and control] (0.36 UTIs /person year) (95% CI 0.03–0.68, p = 0.03) [Cranberry: 0.45: Lactobacillus: 0.91: Control: 0.81 Time to first UTI: N/A UTI free: 8 (16%), 19 (39%) and 18 (36%): 20% reduction in cranberry vs. control (95% CI: 3% to 36%, p = 0.023) Duration of UTI:N/A Symptom scores: N/A |
No AEs reported except for occasional complaint of the bitter taste of cranberry juice |
Yes |
| A7. Stothers, 2002 [49] | ≥ 105 N/A |
No of UTIs: Mean no. UTIs was 0.72 in placebo group, 0.30 in juice group (p < 0.05) and 0.39 in tablet group (p < 0.05) Time to first UTI: N/A UTI free: Placebo: 16 (32%), Juice: 10 (20%, p < 0.05) and tablet 9 (18%, p < 0.05) Duration of UTI:N/A Symptom scores:N/A |
Juice: reflux; tablet: mild nausea, increased frequency of bowel movements | No |
| A8. Stapleton, 2012 [42] | ≥ 103 E. coli |
No of UTIs: Cranberry vs. placebo: (33/120, 27.5%) vs. placebo group (17/56; 30.4%) Time to first UTI: N/A UTI free: Not significantly different between groups (p = 0.41) Duration of UTI:N/A Symptom scores:N/A |
3 discontinued due to GI symptoms: including constipation, heartburn, vaginal (itching, dryness) and other (migraine) symptoms | No |
| A9. Barbosa-Cesnik, 2011 [43] | ≥ 103 E. coli |
No of UTIs: Cranberry vs. placebo: vs. cumulative incidence rate: 19.3% vs. 14.6% (p = 0.21) Time to first UTI: N/A UTI free: N/A Duration of UTI:N/A Symptom scores:N/A |
SAEs unrelated to treatment | No |
| A10. Gbinigie, 2021 [33] |
>105 N/A |
No of UTIs: N/A Time to first UTI: Reduced in group 2 (adjusted mean difference: 0.6; 95%CI: −4.0 to 5.3) and increased in group 3 (adjusted mean diff: 7.9; 95%CI 2.6–13.2) vs. control UTI free: Reduced in group 2 (adjusted HR 1.7. 95% CI: 0.7 to 4.1) but increased in group 3 (adjusted HR 0.6; 95% CI: 0.2 to 1.4), compared with controls Duration of symptoms:N/A Symptom scores:N/A |
7 total events: Immediate antibiotics and immediate cranberry: suprapubic pain, dysuria, backache, cloudy urine. Immediate cranberry and delayed antibiotics: feeling unwell, ache in lower back, backache, stomach-ache, headache and nausea |
No |
| A11. Beerepoot, 2011 [50] | ≥ 103 E. Coli |
No of UTIs: TMP-SMX vs. Cranberry: After 3 mo: 0.5 (95% CI:0.3–0.7) and 0.7 (95% CI: 0.4–0.9) (p = 0.30) After 12 mo: 1.8 (95% CI: 0.8–2.7) vs. 4.0 (2.3–5.6) (p = 0.02) Time to first UTI: N/A UTI free: TMP-SMX vs. cranberry: Median time: 8 mo vs. 4 mo (p = 0.03) >1 UTI TMP-SMX vs. cranberry: After 3 months: 32.1 (19.7.42.5) and 36.9 (22.9–48.3) (p = 0.75) Duration of UTI:N/A Symptom scores:N/A |
None | No |
| A12. Babar, 2021 [51] | ≥ 103 N/A |
No of UTIs: High dose vs. low PAC: 45 vs. 59 Time to first UTI: N/A UTI free: Median high dose vs. low PAC: 24.0 wks vs. 16.6 Duration of UTI:N/A Symptom scores:N/A |
No serious AEs. Only one person reported dyspepsia, leading to a discontinuation | No |
| B. Outcomes of D-mannose trials | ||||
| Name Year | UTI threshold (CFU/mL) | Outcome reported | Side effects reported |
Reported
Success * |
| B1. Kranjčec, 2014 [52] | ≥ 103 E. coli |
No of UTIs: D-mannose: 15 (14.6%) Nitrofurantoin:21 (20.4%) No prophylaxis:62 (60.8%) (p < 0.001 comparing prophylaxis to control) Time to first UTI: Median time: Mannose: 43 days (IQR: 15–50) vs. Nitrofurantoin: 24 days (IQR: 15–36) vs. no prophylaxis: 28 (20–42) (p = 0.12) UTI free:N/A Duration of UTI:N/A Symptom scores:N/A |
7.8% (p < 0.001) Diarrhoea (8/103) |
Yes |
| B2. Porru, 2014 [53] | ≥ 105 E. coli |
No of UTIs: Of the 60 women, 45 (75%) had 1 recurrence, 10/60 (16.6%) had 2 recurrences, 5/60 (8.3%) had no r-UTI Time to first UTI: 52.7 days (D-mannose) vs. 200 days (antibiotics) (p < 0.0001) Time to first UTI: N/A UTI free:N/A Duration of symptoms:N/A Symptom scores:N/A |
None reported | Yes |
| C. Outcomes of combination cranberry and D-mannose trials | ||||
| Name Year | UTI threshold (CFU/mL) | Outcome reported | Side effects reported | Reported Success * |
| C1. Mainini, 2020 [54] | ≥ 103 E. coli |
No of UTIs: Group 1 (active): 6-month follow-up: 8/48 (p = 0.0057) 12-month follow-up: 11/48 (p = 0.0005) Group 2 (placebo): 6-month follow-up: 3/46 (p = 0.2418) 12-month follow-up: 4/46 (p = 0.1168 Time to first UTI:N/A UTI free: Patients without r-UTI: Group 1 (active): 6-month follow-up: 8/48 (p = 0.0057) 12 months: 11/48 (p = 0.0005)Group 2 (placebo): 6-month follow-up: 3/46 (p = 0.2418) 12 months:4/46 (p = 0.1168) Duration of symptoms:N/A Symptom scores:N/A |
None reported | Yes |
| C2. Murina, 2021 [55] | ≥ 103 E. coli |
No of UTIs: Group 1:16% Group 2:15.5% Group 3:52.9% (p < 0.01) UTI Free: Day 90: Group 1:87.7% Group 2:84.9%. Group 3:42% Day 150: Group 1:65.8% Group 2:68.8% Group 3:36.9% UTI free:N/A Duration of symptoms:N/A Symptom scores:N/A |
None reported | Yes |
| D. Outcomes of NSAID trials | ||||
| Name Year | UTI threshold (CFU/mL) | Outcome reported | Side effects reported |
Reported
Success * |
| D1. Moore, 2019 [77] | N/A N/A |
No of UTIs: N/A Time to first UTI:N/A UTI free:N/A Duration of symptoms:N/A Symptom score: Freq. symptom severity on days 2–4, showed no difference in symptom severity between factorial groups |
No UUT infections | Yes |
| D2. Gágyor, 2015 [56] | >102 E. coli |
No of UTIs: N/A After day 14: Fosfomycin: 11% vs. 6% Ibuprofen (p = 0.049) Time to first UTI:N/A UTI free:N/A Duration of symptoms:N/A Symptom score: Higher symptom burden on days 0–7 in ibuprofen group |
4 in ibuprofen needed hospital admission; 1 GI haemorrhage likely due to Ibuprofen |
No |
| D3. Vik, 2018 [57] | ≥103 E. coli |
No of UTIs: N/A Time to first UTI:N/A UTI free:N/A Duration of symptoms:N/A Symptom score: Mean symptom sum score: 2.3 for Ibuprofen and 0.7 for pivmecillinam, estimated difference of 1.6 (95% CI 0.8–2.4) |
7 pyelonephritis cases in ibuprofen group | No |
| D4. Bleidorn, 2010 [58] | >102 E. coli |
No of UTIs: Follow up: Day 28, 1 ciprofloxacin patient and 2 ibuprofen patients (p = 1.0) reported relapse Time to first UTI:N/A UTI free:N/A Duration of UTI:N/A Symptom course (SD): ibuprofen vs. ciprofloxacin. Day 7: 0.7 (1.26) vs. 0.6 (0.86) (p = 0.816) |
Mostly GI disorders and upper respiratory tract infections, headaches likely unrelated to treatment | No |
| D5. Ko, 2018 [59] | ≥104 E. coli |
No of UTIs: N/A Time to first UTI:N/A UTI free:N/A Duration of UTI:N/A Symptom score: Faster symptom resolution in combination therapy at 1.5 days (p = 0.035) |
N/A | No |
* Reported success: the decision about the success of the trial was based on the conclusions reported by the author of the original studies.