urinary tract infections

Image result My last post discussed Lactobacillus crispatus as an important bacteria for womens' vaginal health and as a possible treatment for bacterial vaginosis (BV) - a condition where the vaginal microbes are out of whack (dysbiosis). It appears that Lactobacillus crispatus may also be a possible treatment for women with urinary tract infactions (UTIs), a condition where again microbes are out of whack. The bacteria Lactobacillus crispatus is part of the vaginal microbiome of many healthy women and thought to be protective. It is unknown whether L. crispatus would also work for men with UTIs.

In the US, the vaginal suppository product Lactin-V (containing the freeze dried human vaginal strain of L. crispatus CTV-050) is currently being tested for both bacterial vaginosis and recurring urinary tract infections (UTIs). So far there are positive results for this product (manufactured by Osel, Inc.) in phase 2 clinical trials, but it may be years away from FDA approval. The following article excerpts are from April 2011, but these are still the most recent published research results for this probiotic (beneficial bacteria). The results are pretty convincing that beneficial bacteria might some day replace standard medical treatment (antibiotics) for UTIs.  The Lactin-V treatment in women with recurrent UTIs resulted in "robust and prolonged colonization with Lcrispatus" in the vagina, which resulted in reducing the incidence of UTIs by about 50%. But...the results also showed that which strain of L. crispatus the women had was important - some women had lots of one strain of "endogenous" L. crispatus - naturally occurring in them - that was not protective. Or...it could be that other microbes that are not being looked at are also important.

Of course researchers are also looking at other beneficial bacteria and there has been more recent research. D-Mannose and cranberry supplements have also been found to be effective in treating UTIs of many women (see herehere, and here), as well as changing the urine's acidity through diet. While studies typically focus on women, these other products also work for UTIs in men (D-Mannose and cranberry supplements seem to be especially effective). Looks like probiotics and alternative treatments (D-mannose, cranberry supplements, etc.) are the future in treating UTIs!

From Medscape: Probiotic May Help Prevent Recurrent Urinary Tract Infection

In a randomized, double-blind phase 2 study, an intravaginal probiotic composed of Lactobacillus crispatus CTV-05 (Lactin-V, Osel Inc) reduced the rate of recurrent urinary tract infection (rUTI) in UTI-prone women by roughly one half, which compares favorably with historical data on antimicrobial prophylaxis, the researchers say. They add that larger trials are warranted to see whether use of vaginal Lactobacillus could replace long-term antimicrobial preventive treatments in women susceptible to rUTI.

UTIs are common in women and frequently recur, Ann Stapleton, MD, from the University of Washington in Seattle, and colleagues note in their report. It has been shown, they add, that women with rUTIs [recurrent UTIs] often have alterations in vaginal microbiota, including depletion of lactobacilli.

A phase 1 study of Lactobacillus crispatus CTV-05 showed that the probiotic can be given as a vaginal suppository with minimal adverse effects to healthy women with a history of rUTI. In the phase 2 study, 100 premenopausal women (median age, 21 years) with a history of rUTI received antimicrobials for acute UTI and then were randomly assigned to receive either Lactobacillus crispatus CTV-05 or placebo vaginal suppository gelatin capsules administered once daily for 5 days, followed by once weekly for 10 weeks.

"We found that Lactin-V reduced the risk of rUTI approximately as effectively as antimicrobial prophylaxis, achieved high-level vaginal colonization in most women, and was well tolerated," Dr. Stapleton and colleagues report. According to the investigators, culture-confirmed rUTI occurred in 7 (15%) of 48 of women who received Lactobacillus crispatus CTV-05 compared with 13 (27%) of 48 women who received placebo.

A high level of vaginal colonization with L crispatus throughout follow-up was associated with a significant reduction in rUTI only among women receiving Lactobacillus crispatus CTV-05. What was "striking," the investigators add, was that placebo-treated women often had high concentrations of vaginal L crispatus during follow-up, yet this failed to protect them from rUTI. In contrast, women who received Lactobacillus crispatus CTV-05 and achieved high colonization were protected from rUTI. "Lactin-V after treatment for acute UTI," they conclude, "confers a significant advantage over repopulation of the vaginal microbiota with endogenous L. crispatus." [The original study.]

Image result Lactobacillus crispatus  Credit:MicrobeWiki

Image result Today I read an interesting article about bacterial vaginosis and research on bacteria that could finally treat it effectively. Bacterial vaginosis (BV) appears to be a problem with the microbial community of a woman's vagina being out of whack (dysbiosis). Common symptoms include increased white or gray vaginal discharge that often smells like fish, there may be burning with urination and sometimes itching, and the discharge has higher than normal vaginal pH (alkaline). One bacteria that seems to be very important and beneficial for vaginal health is Lactobacillus crispatus. Research suggests that L. crispatus may be a treatment for both bacterial vaginosis and urinary tract infections. Currently the treatment for BV is a course of antibiotics, but the problem recurs frequently.

In the US, the vaginal product Lactin-V (containing the freeze dried human vaginal strain of L. crispatus CTV-05, and used as an vaginal suppository) is currently being tested (with so far positive results in phase 2 clinical trials) for both bacterial vaginosis and recurrent urinary tract infections (UTIs). But it may be years away from FDA approval. The biopharmaceutical company Osel Inc. is currently conducting research on this product, and as of May 2016 is recruiting women for a phase 2b clinical study of this product in the US.

Other sources that I know of for the bacteria L. crispatus are: the probiotic Ordesa DonnaPlus+Intimate Flora (manufactured in Spain) and NaturaMedicatrix LactoGyn Crispatus Bio (made in Luxembourg). However, these are different strains of L. crispatus than what has been successfully tested using Lactin-V. (It is unknown whether this makes a difference.) Both are meant to be taken orally (swallowed daily) - which may or may not be an effective way to get L. crispatus in the vagina (it is unknown which way works best).

Other probiotics, especially Lactobacillus species, may also benefit vaginal health. One way to get an idea of products women find helpful is to look at user comments after products listed on Amazon. (By the way - douches, sprays, wipes, deodorizers, and special soaps will not help bacterial vaginosis.... Not at all.).

The following article was written by science journalist Kendall Powell. Do click on the link and read the entire article to get an idea of the complexity of the problem, the role of various bacteria in vaginal health, other health problems that occur with BV, ethnic differences, and how certain bacteria can alter vaginal mucus (leaving women vulnerable to infection). It is clear that much is unknown, but it looks like vaginal health depends on a "healthy microbial community". Excerpts from Mosaic:

The superhero in your vagina

The aisle is marked with a little red sign that says “Feminine Treatments”. Squeezed between the urinary incontinence pads and treatments for yeast infections, there is a wall of bottles and packages in every pastel shade imaginable. Feminine deodorant sprays, freshening wipes, washes for your “intimate area”.

Vaginal odor might be the last taboo for the modern woman.....The companies behind these products know that many women are looking for ways to counter embarrassing and debilitating symptoms such as vaginal odor and discharge. The culprit is often bacterial vaginosis, the most common vaginal infection you’ve probably never heard of. Nearly one-third of US women of reproductive age have it at any given time. The sad truth is that these sprays, soaps and wipes will not fix the problem. They will – in many cases – actually make it worse.

But while women try to mask embarrassing smells, a more sinister truth also remains under cover: the bacteria responsible are putting millions of women, and their unborn babies, at risk from serious health problems. All of which is making researchers look anew at the most private part of a woman’s body, to understand what it means to have a healthy – some prefer “optimal” – vagina and why that is so important for wider health.

Compared with those of other mammals, the human vagina is unique. As warm, moist canals exposed to all sorts of things including penises, babies and dirt, most mammalian vaginas harbour a diverse mix of bacteria. However, for many women, one or another species of Lactobacillus has become the dominant bacterial resident. Lactobacillus bacteria pump out lactic acid, which keeps the vaginal environment at a low, acidic pH that kills or discourages other bacteria, yeast and viruses from thriving. There are even hints that certain Lactobacillus species reinforce the mucus in the vagina that acts as a natural barrier to invaders.

For the most part, we’ve been happily cohabitating ever since, but it’s a delicate balancing act. Normal intrusions to the vaginal environment, such as semen (which causes vaginal pH to rise) or menstruation, can reduce numbers of Lactobacillus and allow other microbes, including those associated with bacterial vaginosis (BV), to flourish.

Her doctor explained that BV is a disturbance of the natural balance of bacteria that live inside the vagina. Sex with someone new, having multiple partners, and douching – rinsing out the vagina with a bag or bottle of liquid – can all contribute to getting BV, but it is not classified as a sexually transmitted disease. Mostly, how a woman develops BV is still a big mystery.

And if the embarrassment and discomfort weren’t enough, BV has a far more menacing side. Women affected have a higher risk of contracting sexually transmitted infections (STIs) like gonorrhoea and chlamydia, acquiring and transmitting HIV, and having pelvic inflammatory disease (which can lead to infertility) and other vaginal and uterine infections. During pregnancy, BV gives a woman a greater chance of having a preterm birth or passing infections to her baby, both of which can lead to lifelong problems for the baby.

Holmes felt the syndrome should be renamed bacterial vaginosis, which loosely translates to “too much bacteria”. And fulfilling three of the four Amsel criteria – thin vaginal discharge, vaginal pH greater than 4.5, positive whiff test and clue cells – is still used by many doctors today to diagnose BV.

They are realising that all Lactobacillus bacteria – long thought to keep vaginas healthy – are not created equal. For some researchers, L. crispatus is emerging as the vagina’s superhero. It not only pumps out the best mix of two different types of lactic acid to keep the vagina inhospitable to other bugs, but it also fortifies a woman’s vaginal mucus to trap and keep at bay HIV and other pathogens.

In 2011, Larry Forney, an evolutionary ecologist at University of Idaho in Moscow, and Jacques Ravel, a microbial genomicist from the University of Maryland School of Medicine in Baltimore, sequenced the bacterial species found in the vaginas of nearly 400 North American women who didn’t have the symptoms of BV. They found five different types of bacterial community. Four of these were dominated by different Lactobacillus species, but the fifth contained a diverse mix of microbes (including Gardnerella, Sneathia, Eggerthella and Mobiluncus species), many of which have been associated with BV. 

The African studies leave researchers clamouring for better solutions for these women. Like others, van de Wijgert believes that the solution lies in getting the right bacteria to set up house in women’s vaginas. In 2014, she found that Rwandan sex workers with L. crispatus dominant in their vaginas were less likely to have HIV and other STIs. This bacterium may have even protected the clients of HIV-positive sex workers somewhat, because these women were also less likely to shed HIV in the vagina.

Image result Lactobacillus crispatus Credit: MicrobeWiki

Image result for antibiotics This article by Dr. Thomas E. Finucane lays out nicely a paradigm shift in how to view uncomplicated urinary tract infections (UTIs) - as a case of dysbiosis (microbial community out of whack), and that antibiotics to kill bacteria are generally not needed or helpful. (He doesn't mention it, but the next step in his argument should be that probiotic or beneficial bacteria or other microbes may improve the microbial community and symptoms.) A main point of the article is that we now know the urinary tract is not sterile - instead diverse microbiota live there (the microbial community is the microbiome) including bacteria and viruses (the virome), and that these stable microbial communities are generally beneficial. Standard cultures do not pick up all the microbes living in the urinary tract.

He points out that: UTI symptoms are usually self-limited, of brief duration and only slightly shortened by antibiotic treatment; that cystitis rarely progresses to pyelonephritis (which does need antibiotic treatment); and that randomized trials show no reduction in the risk of progression to pyelonephritis with antibiotic treatment. He stresses the "generally benign (other than symptoms) nature of “symptomatic UTI” is suggested by the billions of persons around the world and over the years who have suffered “UTI” without access to antibiotics and have recovered fully". And that "urinary tract dysbiosis" may be a better description of what a woman is experiencing.

However, I would like to add that to a person experiencing an UTI, the pain does not at all feel "benign". So look at the posts on UTIs and treatments and perhaps try something like D- mannose  or cranberry supplements, or both. From The American Journal of Medicine:

“Urinary tract infection” and the microbiome

The current paradigm for managing uncomplicated “urinary tract infection” (“UTI”) is deeply flawed. “UTI” is ambiguously defined and, coupled with a belief that “bacteria are not normal inhabitants of the urinary tract, the diagnosis often leads to unnecessary, harmful antibiotic treatment. Although bacteriuria identified by standard clinical cultures (which we will call standard bacteriuria) is central to most definitions, more sensitive diagnostic tests now demonstrate that “urine is not sterile2 and that standard bacteriuria represents a fraction of the diverse microbiota hosted by the urinary tract. Knowledge of this complex, generally beneficial microbiome deeply undermines the current paradigm, which relies on the findings of standard culture. By acknowledging this microbiome a successor paradigm will generate new questions about relationships among host, microbiome and antibiotic use and will almost surely show additional serious harms from antibiotic overtreatment.

This discussion concerns medically stable, non-pregnant adults with normal urinary tract structure and function. The role of antibiotics in patients with abnormalities of anatomy or physiology, such as spinal cord injury, urinary obstruction, or catheters, will require careful investigation. New insight into pyelonephritis and bacteremic bacteriuria is likely to develop.

The ambiguous definition of “UTI” seems to promote antibiotic overuse. In one common usage, “urinary tract infection is defined as microbial infiltration of the normally sterile urinary tract.” With this definition, asymptomatic bacteriuria is a “UTI” and is often treated, even in patient groups where strong evidence shows lack of benefit.4 A second common definition, “significant bacteriuria in a patient with symptoms or signs attributable to the urinary tract and no alternate source” seems more restrictive but does not define what symptoms or signs may be attributed to the urinary tract. This ambiguity creates opportunities for overtreatment....Antibiotic treatment of “UTI” often follows even though no data have shown these changes respond to treatment.

Canonically, “all symptomatic UTI should be treated” but actual benefit is limited. Hooton emphasizes that in acute uncomplicated cystitis “the primary goal of treatment is to ameliorate symptoms.” Foxman summarizes that symptoms are usually self-limited, of brief duration and only slightly shortened by antibiotic treatment; that cystitis rarely progresses to pyelonephritis; and that randomized trials show no reduction in the risk of progression to pyelonephritis with antibiotic treatment.7 The generally benign (other than symptoms) nature of “symptomatic UTI” is suggested by the billions of persons around the world and over the eons who have suffered “UTI” without access to antibiotics and have recovered fully.

With its various meanings, convenient diagnosis, long tradition, suggestive link to treatment and uncritical acceptance by clinicians, patients, families and insurers, “UTI” remains heavily embedded in practice, “one of the most common bacterial infections worldwide”. The paradigm provides tidy management for a patient with “UTI” who expects antibiotics. Further, the current paradigm does account for several findings. Standard bacteriuria is associated with pyuria, fever and dysuria, for example, and these often improve with treatment, as do a wide variety of findings seemingly unconnected with the urinary tract. Antibiotic treatment improves outcomes for asymptomatic pregnant women who have standard bacteriuria. Pyelonephritis and bacteremic bacteriuria probably arise in the urinary tract and do require antibiotic treatment.

To diagnose “UTI” and determine antibiotic sensitivity based on results of standard cultures, however, is to rely on familiar, accessible data and to ignore the dozens of bacterial speciesas well as intracellular bacterial colonies and urinary virome known to reside in the urinary tract. Current discussions of symptomatic or asymptomatic bacteriuria or sterile urine are similarly problematic. To attribute delirium to standard bacteriuria seems unjustifiable, knowing that most or all people with or without delirium have bacteriuria. The current paradigm is defensible only if all pathogenic organisms are identified with standard cultures and all organisms more difficult to identify can be safely ignored.

We propose instead that urinary symptoms, bacteremia, pyelonephritis, and other recognizable disturbances of the urinary tract are the dysbiotic tip of a much larger iceberg of complex host-microbe interactions that are occurring out of sight of standard cultures. As expected in the era of the microbiome, stable bacterial communities are generally beneficial. For example, compared with the instillation of sterile saline, “bladder colonization with (the nonpathogenic) E. coli HU2117 safely reduces the risk of symptomatic urinary tract infection in patients with spinal cord injury”.8 Of 699 young women with asymptomatic bacteriuria, half of whom were randomized to receive no antibiotic treatment, “treatment was associated with a higher rate of symptomatic UTI… (thus) asymptomatic bacteriuria … may play a protective role in preventing symptomatic recurrence” during 12-month follow-up.9

Costello and colleagues outline a broader paradigm shift in the general approach to infection; “transitioning clinical practice from the Body-as-Battleground to the Human-as-Habitat perspective will require rethinking how one manages the human body.10 To help in this transition, mindful language will be important. We suggest that authors use “UTI” only within quotation marks and that clinicians use the bimanual “air quotes” gesture in discussions. This small, repetitive annotation is intended to disrupt the term’s complacent usage and encourage rethinking of how one manages bacteriuria. The term “urinary tract dysbiosis” may be useful for otherwise well patients with urinary tract symptoms.

“UTI” is an ill-defined, glibly overdiagnosed and overtreated “infection”. Current management ignores modern science. The associated antibiotic overuse causes serious harm to patient safety and to public health. Instead of the current-paradigm question, “Does this patient have a UTI?” the successor-paradigm question will be, “Does evidence show that antibiotic treatment is likely to benefit this patient?” Shifting the paradigm is an urgent matter.

 A study found that a combination of cranberry supplement (120 mg cranberries, with a minimum proanthocyanidin content of 32mg), the probiotic Lactobacillus rhamnosus, and vitamin C (750 mg) three times a day was enough to prevent the recurrence of urinary tract infections (UTIs) for the majority of women in this small (36 patient) study. At 6 months there was a 61% success rate. No side effects were reported.

These are wonderful results, but why aren't more studies also being done on the effective product D-Mannose? The one study (see post) that I found looking at D-Mannose found an 85% success rate at 6 months. It is especially effective against E.coli, which is the cause of the majority of UTIs. But the great news is that finally women have some effective and safe treatments to try, and the wonderful possibility of getting off the vicious cycle of repeated courses of antibiotics. The article abstract from Pubmed.gov (National Library of Medicine):

Effectiveness of a Combination of Cranberries, Lactobacillus rhamnosus, and Vitamin C for the Management of Recurrent Urinary Tract Infections in Women: Results of a Pilot Study.

Urinary tract infections (UTIs) are common in women and many patients with recurrent UTIs do not eradicate the condition albeit being treated with multiple courses of antibiotics. The use of nutritional supplements might reduce the risk of recurrent UTIs. However, the role of supplements taken as single agents appears to be limited. We hypothesized that a combination of cranberries, Lactobacillus rhamnosus, and vitamin C might produce a clinical benefit due to their additive or synergistic effects. We prospectively enrolled 42 consecutive women with recurrent UTIs treated with 120mg cranberries (minimum proanthocyanidin content: 32mg), 1 billion heat-killed L. rhamnosus SGL06, and 750mg vitamin C thrice daily for 20 consecutive days. Patients were advised to stop taking these supplements for 10 d and then to repeat the whole cycle three times. Patients were contacted three mo and six mo following the end of the administration of these supplements and evaluated with a semistructured interview and urinalysis. Responders were defined as the absence of symptoms and negative urinalysis or urine culture. Follow-up data were available for 36 patients. Overall, 26 (72.2%) and 22 patients (61.1%) were responders at the 3-mo and 6-month follow-up. No major side effects were recorded. The administration of cranberries, L. rhamnosus, and vitamin C might represent a safe and effective option in women with recurrent UTIs.

PATIENT SUMMARY: We evaluated the effectiveness of cranberries, Lactobacillus rhamnosus, and vitamin C thrice daily for 20 consecutive d monthly for 3 mo for the management of recurrent urinary tract infections in women. Our results show that this approach might represent a safe and effective option.

 This new research suggests possible future treatments in treating urinary tract infections (UTIs) by manipulating the person's diet and so influencing gut microbes and urinary pH (how acidic is the urine). These possible future treatments are different than what others are looking for, which are bacteria (probiotics) that one can take to prevent or treat UTIs. (Earlier posts on treating UTIs are here and here,)

The researchers found that during UTIs, humans secrete siderocalin which helps the body fight infection by depriving bacteria of iron (a mineral necessary for bacterial growth), and that samples that were less acidic, and closer to the neutral pH of pure water, showed higher activity of the protein siderocalin and were better at restricting bacterial growth than the more acidic samples. The researchers found that the presence of small metabolites called aromatics, which vary depending on a person's diet, also contributed to variations in bacterial growth. Samples that restricted bacterial growth had more aromatic compounds, and urine that permitted bacterial growth had fewer. Stay tuned for follow-up research. 

One of the researchers, Dr. Jeffrey P. Henderson, pointed out that physicians already know how to raise urinary pH with things like calcium supplements, and alkalizing agents are already used in the U.K. as over-the-counter UTI treatments. But knowing how to encourage the metabolites is trickier, but will involve dietary changes. Some good food sources include those rich in antioxidants: coffee, tea, colorful berries, cranberries, and red wine.From Science Daily:

A person's diet, acidity of urine may affect susceptibility to UTIs

The acidity of urine -- as well as the presence of small molecules related to diet -- may influence how well bacteria can grow in the urinary tract, a new study shows. The research may have implications for treating urinary tract infections, which are among the most common bacterial infections worldwide. Urinary tract infections (UTIs) often are caused by a strain of bacteria called Escherichia coli (E. coli), and doctors long have relied on antibiotics to kill the microbes. But increasing bacterial resistance to these drugs is leading researchers to look for alternative treatment strategies.

"Many physicians can tell you that they see patients who are particularly susceptible to urinary tract infections," said senior author Jeffrey P. Henderson​, MD, PhD,...With this in mind, Henderson and his team, including first author Robin R. Shields-Cutler, a graduate student in Henderson's lab, were interested in studying how the body naturally fights bacterial infections. They cultured E. coli in urine samples from healthy volunteers and noted major differences in how well individual urine samples could harness a key immune protein to limit bacterial growth. "We could divide these urine samples into two groups based on whether they permitted or restricted bacterial growth," Henderson said. "Then we asked, what is special about the urine samples that restricted growth?"

The urine samples that prevented bacterial growth supported more activity of this key protein, which the body makes naturally in response to infection, than the samples that permitted bacteria to grow easily. The protein is called siderocalin, and past research has suggested that it helps the body fight infection by depriving bacteria of iron, a mineral necessary for bacterial growth. Their data led the researchers to ask if any characteristics of their healthy volunteers were associated with the effectiveness of siderocalin.

"Age and sex did not turn out to be major players," Shields-Cutler said. "Of all the factors we measured, the only one that was really different between the two groups was pH -- how acidic or basic the urine was."Henderson said that conventional wisdom in medicine favors the idea that acidic urine is better for restricting bacterial growth. But their results were surprising because samples that were less acidic, closer to the neutral pH of pure water, showed higher activity of the protein siderocalin and were better at restricting bacterial growth than the more acidic samples.

Importantly, the researchers also showed that they could encourage or discourage bacterial growth in urine simply by adjusting the pH, a finding that could have implications for how patients with UTIs are treated."Physicians are very good at manipulating urinary pH," said Henderson, who treats patients with UTIs. "If you take Tums, for example, it makes the urine less acidic. But pH is not the whole story here. Urine is a destination for much of the body's waste in the form of small molecules. It's an incredibly complex medium that is changed by diet, individual genetics and many other factors."

After analyzing thousands of compounds in the samples, the researchers determined that the presence of small metabolites called aromatics, which vary depending on a person's diet, also contributed to variations in bacterial growth. Samples that restricted bacterial growth had more aromatic compounds, and urine that permitted bacterial growth had fewer.

Henderson and his colleagues suspect that at least some of these aromatics are good iron binders, helping deprive the bacteria of iron. And perhaps surprisingly, these molecules are not produced by human cells, but by a person's gut microbes as they process food in the diet."Our study suggests that the body's immune system harnesses dietary plant compounds to prevent bacterial growth," Henderson said. "We identified a list of compounds of interest, and many of these are associated with specific dietary components and with gut microbes."

Indeed, their results implicate cranberries among other possible dietary interventions. Shield-Cutler noted that many studies already have investigated extracts or juices from cranberries as UTI treatments but the results of such investigations have not been consistent.

My last post was about a recent Medscape article discussing whether probiotics can be used to treat urinary tract infections (UTIs) (answer: probiotics are promising, but too little is known right now to recommend any). Two alternative treatments that the article did not discuss were drinking cranberry juice or taking cranberry supplements (studies are currently mixed regarding their effectiveness in UTIs - possibly due to varying cranberry products and doses used) and taking D-mannose supplements (whether as a powder or pill).

D-mannose is recommended on alternative medical sites as an effective treatment for UTIs caused by E.coli, including recurrent UTIs. Studies show that up to 90% of UTIs are caused by E. coli.The majority of both males and females writing comments about UTI treatments on these sites and for D-mannose product reviews (on Amazon) rave about D-mannose as the only treatment that worked for them after suffering from recurrent UTIs (antibiotics typically did not work well for them). D-mannose is a naturally occurring sugar found in a number of fruits, especially cranberries and blueberries. D-mannose is effective because it attaches to E. coli bacteria, and prevents them from attaching to the walls of the urinary tract. (Researchers write that D-mannose "inhibits bacterial adhesion to uroepithelial cells.") Persons taking D-mannose are also advised to drink plenty of water, which then flushes out the bacteria.

The typical dose of D-mannose for UTI treatment is 500 mg, in capsule or powder form, taken in a glass of water or juice, every few hours for five days (perhaps 5 or 6 tablets a day). Then continue taking for a few days after all symptoms go away to make sure all the bacteria are flushed out of the urinary tract. Many long-term recurrent UTI sufferers continue taking D-mannose at lower doses to prevent the UTIs from recurring. There are no known side-effects. D-mannose is easily found at stores such as Whole Foods and online (Amazon).

After doing a D-mannose and urinary tract infection search using PubMed (from Medline, the National Institute of Health), I found that currently there is only one published study looking at the use of D-Mannose in urinary tract infections.

The 2014 study by B. Kranjcec, D. Papes, and S. Altarac looked at the effectiveness of D-mannose powder for recurring urinary tract infections in women. 308 women with a history of recurrent UTIs were first treated with an antibiotic (ciprofloxacin) for an UTI, and then were randomly assigned to one of 3 groups for 6 months. The 3 groups were: D-mannose (2 g of D-mannose in 200 ml water daily), or prophylactic antibiotics (50 mg Nitrofurantoin daily) or a control group that didn't take anything (no prophylaxis). Results were that 98 patients (31.8%) had a recurrent UTI. Of those 98, 14.6% (15 women) were in the D-mannose group, 20.4% (21 women) in the Nitrofurantoin antibiotic group, and 60.8%  (62 women) in the no treatment (no prophylaxis) group. In other words, the D-mannose group did the best in preventing recurrences, even better than the antibiotic. From World Journal of Urology:

D-mannose powder for prophylaxis of recurrent urinary tract infections in women: a randomized clinical trial.

Overall 98 patients (31.8%) had recurrent UTI: 15 (14.6) in the D-mannose group, 21 (20.4) in Nitrofurantoin group, and 62 (60.8) in no prophylaxis group, with the rate significantly higher in no prophylaxis group compared to active groups (P < 0.001). Patients in D-mannose group and Nitrofurantoin group had a significantly lower risk of recurrent UTI episode during prophylactic therapy compared to patients in no prophylaxis group (RR 0.239 and 0.335, P < 0.0001). In active groups, 17.9% of patients reported side effects but they were mild and did not require stopping the prophylaxis. Patients in D-mannose group had a significantly lower risk of side effects compared to patients in Nitrofurantoin group (RR 0.276, P < 0.0001), but the clinical importance of this finding is low because Nitrofurantoin was well tolerated.

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How does the medical profession currently view probiotics in the prevention and treatment of urinary tract infections (UTIs), especially recurrent infections? Answer: Only a few studies have been done, but what little is known is promising, which is good because traditional antibiotic treatment has problems (especially antibiotic resistance). The following article excerpts are from Medscape. Medscape is a popular web resource for physicians and health professionals. It features peer-reviewed original medical journal articles, CME (Continuing Medical Education), daily medical news, drug information, etc. To read the entire article without registering with Medscape (registration is free for everyone), just Google the title and then click on it. From Medscape:

Probiotics in Preventing Recurrent Urinary Tract Infections in Women: A Literature Review

Increasing antibiotic resistance and increasing resistance to commonly used antibiotics makes treatment and prevention of urinary tract infections difficult. Although more research is needed, probiotics should be considered a useful and safe alternative to antibiotics. Urinary tract infections (UTIs) are one of the most common bacterial infections in women, accounting for over 6 million primary care visits annually (Zak, 2014). Approximately 50% to 60% of women will develop a UTI in their lifetime...

Treatment is often complicated by the high rates of reoccurrence. Approximately 20% to 30% of women with a UTI will have a reoccurrence (Beerepoot, Geerlings, van Haarst, van Charante, & ter Riet, 2013)... Ikaheimo et al. (1996) found that in the primary care setting, 53% of women over 55 years of age and 36% of younger women will have a reoccurrence within a year. Women are diagnosed with recurrent UTIs if they have three UTIs with three positive urine cultures within a 12-month period or two infections in the previous six months (Al-Badr & Al-Shaikh, 2013).

Symptoms of UTIs include dysuria, frequency, urgency, nocturia, suprapubic pain, and hematuria, all of which significantly affect the quality of life. Contributing factors to UTIs include inadequate hydration, voiding patterns, diaphragm and spermicide use, tight undergarments, wiping technique, immuno-suppression, postmenopausal women, diabetes mellitus, and frequent sexual intercourse (Al-Badr & Al-Shaikh, 2013). Escheria coli (E. coli) causes the majority of UTIs in women, accounting for 75% to 95% of infections (Al-Badyr & Al-Shaikh, 2013; Nosseir, Lind, & Winkler, 2012). Recurrent UTIs are most often (~80% of time) caused by reinfection with the same pathogen (Al-Badyr & Al-Shaikh, 2013; Nosseir et al., 2012).

Continuous antibiotics are currently used as treatment and prophylaxis for recurrent UTIs. The literature recommends treating anywhere from 6 to 12 months to 2 to 5 years (Zak, 2014). However, the long-term effects of antibiotics are unknown. We are currently in an age of increasing antibiotic resistance, and increasing resistance to commonly used antibiotics, such as trimethoprim-sulfamethoxazole (Gupta, Hooton, & Stamm, 2001), makes treatment and prevention of infections difficult. Therefore, finding safe and effective alternatives to preventing recurrent UTIs in women is imperative. 

The literature provides low-to-moderate evidence that probiotics are effective in preventing UTIs in women. Abdulwahab, Abdulazim, Nada, and Radi (2013) examined the effect of vaginal Lactobacillus from 100 healthy women on the growth of uropathogenic E. coli isolates from 100 women with recurrent UTIs. They found that the majority of Lactobacilli in healthy women without UTIs were L. acidophilus, L. fermentum, and L. delburekii. In addition, they found that all vaginal Lactobacilli strains (from asymptomatic women) could inhibit the growth of E. coli on the agar plate. The weakness of this study, however, is that it was done in a laboratory. 

Two studies went one step further by examining human prophylaxis with Lactobacilli, either orally or vaginally, as means to prevent recurrent UTIs. Beerepoot et al. (2012) compared the effects of oral L. rhamnosus and L. reuteri (109 CFU twice daily) with trimethoprim-sulfamethoxazole (TMP-SMX, 480 mg daily) on preventing recurrent UTIs in 252 postmenopausal women. In their randomized control trial, they found that after 12 months of prophylaxis, the mean number of symptomatic UTIs decreased form 7.0 (from the previous year) to 2.9 in the TMP-SMX group and from 6.8 to 3.3 in the Lactobacilli group.

Antibiotic resistance from E. coli (causing UTI and in urine and feces of asymptomatic women) to sulfamethoxazole, trimethoprim and amoxicillin increased...after 12 months of TMP-SMX prophylaxis, 100% of urinary E. coli was found resistant to trimethoprim and sulfamethoxazole. No antibiotic resistance occurred in the Lactobacilli group.

Stapleton et al. (2011) considered the effect of an intravaginal probiotic, L. crispatus, for prevention of recurrent UTIs in 100 premenopausal women. In their randomized, placebo-controlled phase 2 trial, they found that L. crispatus was associated with reduced symptomatic UTIs. Fifteen percent of women taking L. crispatus and 27% of women taking placebo experienced recurrent UTIs. 

Each of the three studies above examined different species of Lactobacilli. Abdulwahab et al. (2013) investigated the effects of L. acidophilus, L. fermentum, and L. delburekii. Beerepoot et al. (2012) studied L. rhamnosus and L. reuteri and Stapleton et al. (2011) investigated L. crispatus....However, all three studies provide evidence that even with different strains of Lactobacilli and different routes of receiving the probiotic, Lactobacilli can reduce recurrent UTIs in women.

The literature review reveals that Lactobacillus probiotics, taken either orally or vaginally, are likely effective in reducing recurrent UTIs in women. Lactobacilli may be especially useful for women with a history of recurrent, complicated UTIs or prolonged antibiotic use. Although Lactobacilli are found slightly less effective to antibiotics in reducing recurrent UTIs (at least in the dose and frequency studied), probiotics do not cause antibiotic resistance and may offer other health benefits due to vaginal re-colonization with Lactobacilli. In addition, long-term health effects of continual antibiotic use are still lacking. 

Future studies should examine optimum frequency, duration, species, and route of Lactobacilli... In an age of increasing antimicrobial resistance, other non-antibiotic methods of preventing recurrent UTIs, such as cranberry tablets, herbs, and acupuncture, should also be further studied, especially in comparative effectiveness research with Lactobacilli. 

EscherichiaColi NIAID.jpgE. coli bacteria.  Photo:Wikipedia, Rocky Mountain Laboratories

This is very exciting research if it holds up. Basically a bacterial cause for urologic chronic pelvic pain syndrome (UCPPS), also known as non-bacterial chronic prostatitis, means that it is really a urinary tract infection. Bacteria were found that can only be found with state of the art genome sequencing, and NOT with ordinary cultures. From American Microbiome Institute:

Bacteria may be responsible for chronic prostatitis

Some people suffer from an enigmatic diagnosis known as ), also known as non-bacterial chronic prostatitis.  UCPPS’s symptoms are rather similar to urinary tract infections (UTI’s), with a conspicuous lack of a bacterial cause.  In order to diagnose UCPPS doctors must do a bacterial culture of the urine, and if no bacteria grow then the UCPPS diagnosis may be given. 

While many believe that this disease may be caused by stress or hormone imbalances, a team of researchers from across the U.S. and Canada investigated if there was a bacterial cause.  As we know, much of the microbiome is unculturable, and can only be identified through genome sequencing.  These researchers hypothesized that bacteria are the true cause of UCPPS, and that UCPPS is similar to UTI, only the bacteria are unculturable, and so basic hospital screens for the bacteria fail to identify them.  The scientists recently published the results of their study in The Journal of Urology.

The researchers did genome analyses on 110 urine samples from male patients suffering from UCPPS and 115 urine samples from normal males with no UCPPS diagnosis.  The results showed that both the groups had approximately 75 bacteria in their urine, all of which would unlikely have cultured in normal hospital assays.  When they compared the types of bacteria between the groups they noticed that Burkholderia cenocepacia was highly abundant in patients with UCPPS but not the control group.  Interestingly, this species had been previously identified as a possible urologic pathogen.

The study had a number of limitations, and the authors admit as much.  For example, it is unclear their sampling procedures would adequately identify any bacteria causing biofilms, and they limited the study to bacteria so fungi and viruses went untested.  Still, it is compelling evidence for a bacterial cause to a disease that had previously been thought to not have a bacterial origin.  These findings really speak to what prominent microbiome scientist, and member of the AMI’s scientific advisory board, Rob Knight recently said in an interview with NPR:  “When you consider the number of diseases where, just over the last five years, it went from being crazy to think the microbes were involved to now being crazy to think the microbes aren't involved, it's amazing how rapidly the evidence has been accumulating.”