Alternative Approaches for UTI Prevention
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.
Individuals who have had less than optimal results from traditional treatments for neurogenic lower urinary tract dysfunction will sometimes seek alternative options such a homeopathy. In a series of 8 cases, individuals who received standard antibiotic prophylaxis and urine acidification also received homeopathic care and were reported to have reduced prophylactic treatments in half of the participants and reduced UTI frequency in 3/8 participants while bladder management remained unchanged in all participants.
In a first study to prospectively consider the efficacy of homeopathic treatment for UTI prevention in SCI, Pannek et al 2018a concluded that adjunctive homeopathic treatments decrease UTI in SCI. Although the decrease was reported as significant (P<0.001 from medical history and P=0.008 from completed questionnaires), it is important to note that complete recruitment was not achieved for the study. Due to participants not wanting to be randomized to the control group, only 10 controls were recruited for comparison to 25 homeopathy participants. As well, since homeopathy is individualized, 12 different homeopathic remedies were included in the study analysis. Because the homeopathic group had statistically fewer UTIs accompanied by a high satisfaction with the homeopathic treatments, the Pannek team suggested that classical homeopathy be considered for people with SCI who have recurrent UTIs.
Pannek et al 2018b reported that 67.8% of individuals were free of symptoms after choosing homeopathic treatment as compared to 78.8% of individuals choosing first-line antibiotic treatments for UTI in SCI. Although the latter was based on 104 episodes of UTIs treated with antibiotics, the smaller homeopathic group only contributed 59 UTIs treated with homeopathic remedies. The Pannek team felt that non-antibiotic therapy was feasible as a first-line treatment option even in complicated UTI provided the individual was febrile. This conclusion was further supported by the reduced risk for serious complications as a result of homeopathic treatments.
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.
There is level 2 evidence (from two prospective studies: Pannek et al 2018a and 2018b) suggesting that homeopathy might be a treatment consideration for people with SCI who suffer from recurrent UTIs.
There is level 4 evidence (from one case series: Pannek et al. 2014) that suggests adjunctive homeopathic care may be able to reduce standard antibiotic prophylaxis and UTI frequency in some individuals.
