Welcome to SCIRE Professional
 

Alternative Approaches for UTI Prevention

Table 30 Alternative Approaches for Preventing UTIs

Author Year

Country
Research Design
Score Total Sample Size

MethodsOutcome
Hess et al. 2008

USA

PEDro=9

RCT

N=47

Population: Mean age: 53 yr; Gender: males=47, females=0; Level of injury: tetraplegia=23, paraplegia=24; Severity of injury: AIS A=27, B=10, C=10

Intervention: SCI individuals with neurogenic bladder were divided into two groups. Each group was randomly selected to receive either 6 mo of cranberry extract tablet 500 mg BID, or placebo and then the alternate for the next 6 mo. Bladder management methods: condom catheter=35, intermittent catheterization (IC)=8, and indwelling catheter=4.

Outcome Measures: Incidence of urinary tract infection (UTI) (>104 organisms, one+new symptoms, evidence of tissue invasion – hematuria or pyuria; urine pH.

1.   No significant difference was seen between the two groups in the incidence of bacteriuria; however UTI were fewer in the period of cranberry treatment (7 UTI/6 mo) versus placebo (21 UTI/6 mo) (p=0.01).

2.   34% of individuals in the placebo period experienced at least one UTI; while only 13% experienced at least one UTI in the cranberry tablet consumption period (p=0.03).

3.   Urine pH was not significantly different between the two periods.

4.   The 22 participants with a high glomerular filtration rate (GFR) reported no incidence of UTIs during the cranberry period, while 9 had 11 UTIs during the placebo period.

Lee et al. 2007

Australia

RCT

PEDro=7

N=305

Population: SCI with Neurogenic bladder and stable management: Mean age: 43.5 yr; Gender: males=253, females=52; Level of injury: tetraplegia=168; Severity of injury: complete=150

Intervention: Double-blinded comparison of methenamine hippurate (MH, 2g) with cranberry (1600mg), MH (2g) with cranberry placebo, cranberry (1600mg) with MH placebo or MH placebo with cranberry placebo).

Outcome Measures: Time to symptomatic urinary tract infection (UTI) (culture), predictors of UTIs, adverse events collected for up to 6 mo.

1.   The Kaplan-Meier curves for MH and Cranberry compared to placebo showed no evidence of a treatment effect.

2.   The unadjusted analysis confirms that there was no statistically significant effect of MH tablets (HR 0.94, 95% confidence interval 0.68-1.32) or cranberry tablets (HR 0.93, 95% CI 0.66-1.29).

3.   The only significant predictor of a future UTI was found to be the number of UTIs in the preceding 6 mo.

4.   Common adverse effects included diarrhea or constipation.

5.   There was no difference in adverse event rates between the groups.

Linsemeyer et al. 2004 USA

RCT

PEDro=6

Ninitial=37; Nfinal=21

Population: SCI with neurogenic bladder: Gender: males=16, females=5; Level of injury: C4-L1; Number of UTIs=0 to 2.

Intervention: Randomized, crossover: placebo or cranberry tablets (400 mg) 3 times daily for 4 weeks.

Outcome Measures: Urinary bacterial counts, white blood cell counts, combination of both counts.

1.   No statistically significant findings for the effect of cranberry tablets versus placebo:

·       Urinary bacterial count (p=0.96),

·       White blood cell count (p<0.27)or

·       Urinary bacterial + white blood cell count combination (p<0.27).

Waites et al. 2004

USA

RCT

PEDro=5

Ninitial=74; Nfinal=48

 

Population: SCI with neurogenic bladder: Age range 20-73 yr; Gender: males=42, females=6; Severity of injury: complete=40, incomplete=6; Time post-injury=1-30 yr.

Intervention: Randomized to cranberry versus placebo capsules.

Outcome Measures: Bacterial counts and urinalysis.

1.   No significant differences between groups:

·       Bacterial colony counts, bladder management method, or within groups over time (p=0.758).

·       Urinary leukocyte counts /mL urine, bladder management method, or within groups over time (p=0.929).

·       pH of urine, or within groups over time (p=0.659).

·       For each outcome, no interaction between groups, bladder management method, and time (p>0.05).

2.   pH higher for external collection versus intermittent catheter (p=0.046) for all time periods for both groups combined.

Pannek et al. 2018a

Switzerland

Prospective Controlled Trial

NInitial=46

NFinal=35

 

Population: Homeopathy (HT): Median age=23.9yr (3.6 – 49.9); Gender: males=16, females=9; Etiology: SCI=25; Median time since injury=13.8yr (1.4 – 45.0).

Control (CG): Median age=47yr (37 – 73); Gender: males=7, females=3; Etiology: SCI=10; Median time since injury=22.0±13.9yr.

Intervention: Participants were allocated to either HT or CG. CG consisted of the standard of practice at the authors’ institution which consisted of urine acidification with either L-methionine, 3×500 mg, or one teaspoon of cider vinegar in 1 glass of water with cranberry extracts 3x daily. Participants in the HT group received one of 6 different homeopathic remedies; Staphysagria, Nux-vomica, Lycopodium clavatum, Hypericum, Sulpher, and Acidum nitricum. Outcomes measures were assessed at baseline and 1x/mo, for 4 yr.

Outcome Measures: UTIs per yr.

1.     HT was more effective for prophylaxis of UTI compared to CG (p<0.001).

2.     HT showed a significant decrease in the number of UTIs per year at the end of the study compared to the pre-study rate (p<0.001).

3.     There was no significant difference in UTI rate when comparing pre- and post-study for the CG (p>0.05).

Pannek et al. 2018b

Switzerland

Prospective Controlled Trial

NInitial=46

NFinal=35

 

Population:  Homeopathy (HT): Median age=23.9yr (3.6 – 49.9); Gender: males=16, females=9; Etiology: SCI=25; Median time since injury=13.8yr (1.4 – 45.0).

Control (CG): Median age=47yr (37 – 73); Gender: males=7, females=3; Etiology: SCI=10; Median time since injury=22.0±13.9yr.

Intervention: Sub-analysis of Pannek et al. 2018a. Data was organized relative to UTI treatment to assess antibiotic vs non-antibiotic treatment success rate. Antibiotic treatment methods included; Ciprofloxacin, Nitrofurantoin, Norfloxacin, other. Non-antibiotic treatment methods included; homeopathy (Staphysagria, Lycopodium clavatum, Hypericum, Nux vomica, Sulphur, Acidum nitricum), Bladder tea, bladder irrigation with saline, cranberry products, increased fluid intake.

Outcome Measures: Treatment success rate.

1.     There was no difference antibiotic and non-antibiotic success rates (p>0.05).
Reid et al. 2001

Canada

Pre-Post

N=15

Population: SCI: Age range 21-78 yr; Gender: males=10, females=4, not determined=1.

Intervention: 250 mL water and cranberry juice with meals successively, each for 7 d treatment arms separated by 2 days.

Outcome Measures: Biofilm load, bacterial adhesion collected at 0, 7 and 15 days, gram negative counts.

Cranberry juice versus water significantly reduces:

1.     Biofilm load (p=0.028); and compared to baseline (p=0.013,).

2.     Bacterial Adhesion counts (p<0.033).

3.     Gram positive counts (p=0.022).

4.     Gram negative counts (p=0.054).

Pannek et al. 2014

Switzerland

Case Series

N=8

Population: Neurogenic lower urinary tract dysfunction; Mean age: 38.75 yr; Gender: males; Level of injury: cervical=3, thoracic=5; Severity of injury: complete=4, incomplete=4.

Intervention: In addition to standard urologic prophylaxis consisting of 4 mo antibiotic treatment (Nitrofuracin or Trimethoprim) and urine acidification with L-Methionine and Cranberry tablets (twice/day), individuals underwent homeopathic case taking by experienced homeopaths.

Outcomes: Description of cases, UTI frequency, adverse events, reduction of standard treatment.

1.     At a median follow-up of 15 mo, 5 participants did not experience new UTIs, and UTI frequency was reduced in 3 participants.

2.     Standard prophylactic treatment could be reduced in 4 participants.

3.     No side effects or adverse drug reactions were observed.

4.     Bladder management and standard prophylactic measured remained unchanged for all participants.

Discussion

Cranberry (in various forms) is in widespread use for UTI prevention and many clinicians recommend it for this purpose. This remains the fact despite uncertainty as to its effectiveness, especially in persons requiring ongoing catheterization as reported in a Cochrane systematic review (Jepson & Craig 2008). However, Hess et al. (2008) conducted a study in which subjects were given either cranberry tablets or placebo for 6 months, and then crossed to the opposite arm, showing a significant reduction in UTI incidence for those on cranberry treatment. These authors chose a robust definition of UTI (see above), and explained in their conclusion that they presume the treatment effect arose from an effect on cell wall adherence to the uroepithelial cell wall, an effect that they propose takes >1 month to develop. As such, shorter studies may fail to note benefit from cranberry treatment (see Linsemeyer et al. 2004). While Reid et al. (2001) employed a short study, significant results were noted in biofilm load and bacterial adhesion (though this study was not designed to determine effect on significant UTI). These hypotheses help build our understanding of the potential mechanisms of action cranberry may have in preventing UTI.

As noted in the section on antiseptic agents above, Lee et al. (2007) conducted a well-designed double-blind, placebo-controlled RCT (n=305) that examined the effectiveness of cranberry tablets (1600 mg) for UTI prevention alone or in combination with oral methenamine hippurate (2 g). Neither treatment alone or in combination was effective in preventing symptomatic UTIs as assessed over a 6 month study period. This rigorous study incorporated intention-to-treat and multiple analysis methods including survival analysis and multivariate analysis using Cox proportional hazards regression and investigated outcomes associated with both symptomatic UTIs (primary) and bacteriuria (secondary). These results were confirmed by two additional RCTs. Linsenmeyer et al. (2004) found that cranberry tablets (400 mg) were not effective in changing bacterial or white blood cell counts of 21 participants who underwent a 9-week placebo-controlled, crossover trial. Similar results were obtained by Waites et al. (2004) in community residing persons with SCI of greater than 1 years duration (n=48) which showed no difference between cranberry extract or placebo taken for 6 months in reducing bacteriuria or pyuria nor for reducing symptomatic UTI rates. In contrast to these findings, a pre-post study (n=15) conducted by Reid et al. (2001) showed that cranberry juice intake significantly reduced the adhesion of bacteria to bladder cells whereas water intake did not significantly reduce the bacterial adhesion or biofilm presence in individuals with SCI. These conflicting conclusions may be influenced by the variation in “dose” and formulation of cranberry product (i.e., tablet versus juice) and the outcome measures used across the various studies. Notably, this study (Reid et al. 2001) was not designed or intended to assess the effect of cranberry on asymptomatic UTI.

Hess et al. (2008) comment in their discussion that subjects in the Waites et al. (2004) study may have been non-compliant given that study medication was mailed to subjects, that the UTI definition may not have been as robust, and that there was an imbalance in bladder management methods between groups. It is important to be note that the studies by Hess et al. (2008), Linsenmeyer et al. (2004), and Waites et al. (2004) lack intent-to-treat statistical analyses which reduces the quality of these investigations. The lack of consistency between results underscores the need for yet further efforts to convincingly prove or disprove the potential value of cranberry prophylaxis.

Conclusion

There is conflicting level 1a evidence (from four RCTs; Lee et al. 2007; Linsenmeyer et al. 2004; Waites et al. 2004; Hess et al. 2008) to support the effectiveness of cranberry in preventing UTI in patients with neurogenic bladder due to SCI.

It is uncertain if cranberry is effective in preventing UTIs in persons with SCI.