Urinary Tract Infection (UTI)

Urinary Tract Infection (UTI)

1 Overview

Summary and Quick Facts

  • Urinary tract infections (UTIs) are common and may cause troublesome symptoms, such as urinary urgency or uncomfortable urination. Bacteria cause most UTIs, so they are generally treatable with antibiotics.
  • This protocol reviews the types of UTI, how they are treated and how to reduce the risk of future infections. Several natural compounds that may help minimize the use of antibiotics in the treatment of UTIs are covered as well, which are important because overuse of powerful antibiotics leads to antibiotic resistance.
  • Cranberries contain powerful natural compounds that help combat UTI-causing bacteria. Several clinical trials have shown that cranberry juice and extracts help reduce UTI recurrence and frequency.

What is a Urinary Tract Infection?

A urinary tract infection (UTI) is a common infection that occurs along the urinary tract. Bacterial (or, rarely, fungal) infections can arise in the lower urinary tract (ie, bladder and urethra) or the upper urinary tract (ie, kidneys and ureters), which is more severe.

The bacteria that cause UTIs adhere to mucous membranes in the urinary tract, preventing bacteria from being cleared by the flow of urine, which is normally a deterrent to bacterial colonization. Antibiotics are generally used to treat UTIs; however, overuse of antibiotics can contribute to antibiotic resistance.

Natural interventions such as cranberry and probiotics may help prevent infection and support a healthy urinary tract.

What are the Risk Factors for Urinary Tract Infections?

  • Female gender
  • Family/personal history
  • Sexual intercourse
  • Pregnancy
  • Low estrogen levels
  • Allergies
  • Recent antibiotic use
  • Incontinence
  • Diabetes
  • Urinary flow abnormalities
  • Urinary catheters

What are the Signs and Symptoms of a Urinary Tract Infection?

Lower urinary tract infection:

  • Painful stinging or burning while urinating
  • More frequent urination
  • Strong odor, cloudy, and/or off-colored urine
  • Discomfort or pressure in lower abdomen or rectum
  • Fever

Upper urinary tract infection:

  • High fever
  • Chills
  • Vomiting
  • Flank/abdominal pain
  • Frequent painful urination

What are Conventional Medical Treatments for Urinary Tract Infections?

  • Antibiotics

What are Emerging Therapies for Urinary Tract Infections?

  • Topical estrogen for recurring UTI, as low estrogen increases the risk of UTI
  • FimH is a protein that is crucial for bacterial adherence to the urinary tract. FimH inhibitors have shown promise in animal models of UTI.
  • Hyaluronic acid and chondroitin sulfate are substances the bladder uses to make glycosaminoglycans, which line the inner surface of the bladder. As damage to this layer may play a role in recurrent UTIs, injecting hyaluronic acid and chondroitin sulfate into the bladder may reduce recurrence.

What Dietary and Lifestyle Changes May Be Beneficial for Urinary Tract Infections?

  • Increase fluid intake
  • Do not delay urination—urinate as soon as possible after feeling the need
  • Wear cotton underwear
  • Wipe front-to-back to avoid transporting bacteria from anus to urethra

What Natural Interventions May Be Beneficial for Urinary Tract Infections?

  • Cranberry. Evidence suggests compounds found in cranberries may interfere with the adhesion of bacteria to the urinary tract. Consumption or supplementation with cranberry is linked to reduced incidence of UTI.
  • D-mannose. This sugar can bind to the cells that line the urinary tract and prevent bacteria from adhering to the lining.
  • Blueberry. Blueberries, like cranberries, contain compounds that can inhibit the adhesion of bacteria to the cells that line the urinary tract. Both blueberries and cranberries also contain compounds that prevent large aggregates of bacteria from forming.
  • Probiotics. Probiotics may prevent UTIs by competing with other bacteria for resources, secreting natural antibacterial chemicals, and preventing pathogenic bacteria from adhering to the urinary tract.
  • Berberine. Berberine, a plant alkaloid, has natural antibacterial properties. It is not recommended for pregnant women or for long-term use.
  • Hibiscus. Hibiscus plants contain many compounds that have antibacterial, antifungal, and antioxidant properties. A clinical study showed that women taking hibiscus extracts experienced fewer UTIs and overall improvement in urinary comfort.
  • Vitamin C. Vitamin C is not only essential for immune function, it may also acidify the urine, which helps inhibit the growth of infectious bacteria in the urinary tract. Supplementation during pregnancy has been shown to reduce the incidence of UTI.
  • Pumpkin seed extract. Pumpkin seed extract has been shown to support bladder function and combat symptoms associated with an overactive bladder, which may contribute to UTIs.

2 Introduction

A “urinary tract infection” or “UTI” is a common infection that occurs along the urinary tract, which includes the bladder, kidneys, ureters, and urethra; they are usually caused by bacteria (A.D.A.M. 2011; Hooton 2012; Schollum 2012; Mayo Clinic 2012a; MedlinePlus 2011a). Infections of the lower urinary tract (ie, bladder and urethra) commonly cause urinary urgency, pain during urination, or cloudy, pink, or red-colored urine (Hooton 2012; Mayo Clinic 2012b). Less common and potentially more severe are infections of the upper urinary tract, which comprises the kidneys and ureters; kidney infection (pyelonephritis) is associated with fever, vomiting, and flank pain (Schollum 2012; Gupta 2012; National Kidney and Urologic Diseases Clearinghouse 2012b).

In 2007, UTIs accounted for 8.6 million doctor’s office visits, making them one of the most common bacterial infections encountered by out-patient caregivers; costs associated with UTI management have been estimated to be $1.6 billion annually (Hooton 2012; Foxman 2003). UTIs are considerably more common among women, nearly half of whom will experience a UTI during their lifetime (Schollum 2012; Gupta 2012; Schaeffer 2011a; Hooton 2012).

Doctors routinely prescribe powerful antibiotics to treat UTIs, and individuals with recurrent UTI may be prescribed a longer course of treatment (Hooton 2012; National Kidney and Urologic Diseases Information Clearinghouse 2012a). This may lead to the emergence of antibiotic-resistant bacterial strains, which can cause UTIs that are more serious and difficult to treat (Sanchez 2012; Gupta 2011; Hooton 2012).

Scientific studies suggest natural compounds such as those found in extracts of Hibiscus sabdariffa and cranberry may reduce adherence of bacteria to the urinary tract, thereby reducing UTI recurrence (Mounnissamy 2002; Hess 2008; Bailey 2007; Allaert 2009). In addition, probiotics represent a potential treatment option, as these “good bacteria” may be able to displace pathogenic bacteria and modulate the immune system to help fight infections (Darouiche 2012; Stapleton 2011; Beerepoot 2012).

This protocol will outline the biology and development of UTIs, and explain how they are conventionally treated; some novel and emerging treatment strategies will also be examined. Dietary and lifestyle considerations that may reduce UTI risk will be discussed, as will a number of scientifically-studied natural interventions that may support the health of the urinary tract.

3 Biology and Development of Urinary Tract Infections

A UTI typically arises when microorganisms like bacteria or fungi enter the urinary tract through the urethra (Hooton 2012). UTIs can also occur in association with use of urinary catheters, which are medical devices that drain the bladder (Hooton 2010; Medline Plus 2011b).

There are many different bacteria that can cause UTIs, with Escherichia coli (E. coli) being the most common (Ronald 2002; Ferri 2011). Less commonly, fungi (esp. Candida species) may cause UTIs; this is more frequent in hospital settings or individuals with predisposing diseases and/or structural abnormalities of the urinary tract (Ronald 2002; Wildenfels 2010; Fisher 2011).

The bacteria that cause UTIs are similar to those naturally found in the colon and other areas of the body, but they have some characteristics that allow them to cause UTIs (Hooton 2012). One of the most important, especially in the case of E. coli, is the ability of these bacteria to adhere to the mucous membranes in the urinary tract (Schoolnik 1989; National Kidney and Urologic Diseases Information Clearinghouse 2012a; Roberts 1987). The mucous membranes of the lower urinary tract contain a variety of molecules, including mannose, a sugar. Strains of E. coli can adhere (or attach to) these mannose molecules using small projections, called fimbriae (Roberts 1987; Klemm 2010; Ohlsen 2009; Ermel 2012; Jorgensen 2012). This binding prevents bacteria from being cleared from the urinary tract by the flow of urine, which is normally a deterrent to bacterial colonization (Mulvey 2002). Once the bacteria have bound to the cells that line the urinary tract, they may then invade these cells. This process also helps the bacteria avoid being killed by antibiotics or the immune system (Jorgensen 2012; Mulvey 2001, 2002; Dhakal 2008).

Although most research has focused on E. coli infections of the urinary tract in otherwise healthy individuals, the general process is similar for other forms of UTI (Reid 1996). In the case of catheter-associated UTIs, which account for up to 40% of hospital-acquired infections, bacteria can gain access to the urinary tract via the catheter itself (Hooton 2010).

4 Causes and Risk Factors

In women, symptomatic UTIs are typically caused by the spread of potentially pathogenic bacteria from the bowel to the urinary tract (Hooton 2012; Schaeffer 2011b). Although UTIs can occur in anyone, certain factors increase risk, including female gender, sexual intercourse, family and personal history of UTIs, pregnancy, allergies, diabetes, abnormalities in the flow of urine, sustained urinary catheterization, incontinence, low estrogen levels, and antibiotic use.

Female Gender

UTIs are more common in women than men; the majority of females report having had a UTI by 32 years of age (Hooton 2012; National Kidney and Urologic Diseases Information Clearinghouse 2012a). This may be because: (1) women have shorter urethras than men, which makes it easier for bacteria to access their bladders, and (2) the urethral opening is closer to the external genitalia and anus, thus increasing the risk of bacterial cross-contamination (Mayo Clinic 2012a; University of Maryland Medical Center 2011; University Health Service 2012; National Kidney and Urologic Diseases Information Clearinghouse 2012a).

Sexual Intercourse

Sexual intercourse is a risk factor for UTIs (Hooton 1996, 2012; Mayo Clinic 2012a). This is particularly true for women that have sexual intercourse more than once per week (Hu 2004). Women that use diaphragms for contraception also have an increased risk of developing UTIs (Hooton 1996). A new sexual partner in the past year is another sexually related risk factor for UTI in women (Scholes 2005).

Family History

Having one or more first-degree female relatives (mother or sister) with a history of UTIs increases personal risk (Hooton 2012).

Personal History

Having a personal history of UTIs, either recurrent or otherwise, is another major risk factor for the development of a subsequent UTI (Hooton 1996; Hu 2004; Scholes 2005).

Pregnancy

Pregnancy appears to increase the risk that a UTI will spread and cause pyelonephritis, a serious infection of the kidneys associated with fever, chills, and flank pain. This is because pregnancy can cause hormonal changes, as well as shifts in the position of the urinary tract, which make it easier for bacteria to spread to the kidneys (University of Maryland Medical Center 2011; National Kidney and Urologic Diseases Information Clearinghouse 2012a).

Allergies

Women who are allergic to compounds that may come in contact with the genital area, such as bubble baths, vaginal creams, and soaps may be at greater risk of developing UTIs because irritation of this sensitive region may allow bacteria access to the urinary tract (University of Maryland Medical Center 2011).

Diabetes

Patients being treated for diabetes have an increased risk of developing asymptomatic bacteriuria (bacteria in the urine that does not cause symptoms), UTIs, and pyelonephritis (Hu 2004; A.D.A.M. 2011). Diabetes impairs the immune system and makes it harder for the body to fight off infections (Mayo Clinic 2012a). In addition to the more common UTIs caused by E. coli, people with diabetes are also more likely to acquire UTIs caused by other bacteria, including Klebsiella and group B Streptococcus (Ronald 2002).

Urinary Flow Abnormalities

Disruptions in urinary flow can also predispose people to UTIs. Anatomical abnormalities that affect the urinary tract can lead to recurring urinary tract infections in children. Anything else that blocks the flow of urine, such as kidney stones, a narrow urethra, or an enlarged prostate, also increases the risk of UTI (Mayo Clinic 2012a; A.D.A.M. 2011; WomensHealth.gov 2008).

Urinary Catheters

People who require a urinary catheter have a higher incidence of UTI (Ronald 2002). Use of a urinary catheter disrupts the body’s natural defense against bacterial infections and provides an easier route by which bacteria can travel to the bladder. As a result, it is recommended that urinary catheters be used for the shortest possible time to reduce the risk of UTIs (Hooton 2010, National Kidney and Urologic Diseases Information Clearinghouse 2012a; A.D.A.M. 2011; WomensHealth.gov 2008).

Incontinence

Incontinence is associated with an increase in UTIs (Hu 2004), as well as acute pyelonephritis (Scholes 2005).

Low Estrogen Levels

The risk of UTI increases after menopause as estrogen levels in the body drop. Estrogen is responsible for maintaining the health of vaginal walls; when estrogen levels are low, either due to menopause, surgery, or congenital problems, vaginal walls become thin, which increases susceptibility to invading bacteria (WomensHealth.gov 2008; University of Maryland Medical Center 2011). Some studies have found that estrogen prescriptions, such as creams and vaginal rings, may help prevent UTIs (Raz 2011).

Antibiotic Use

Patients who have taken antibiotics recently may have an increased risk of developing a UTI. Antibiotics deplete the urinary tract of the beneficial bacteria Lactobacilli, which are protective against E. coli and other infectious bacteria (University of Maryland Medical Center 2011).

5 Signs and Symptoms

A variety of signs and symptoms may suggest lower and/ or upper urinary tract infection (UTI).

Cystitis involves the lower urinary tract, and typical signs/ symptoms include (Mayo Clinic 2012a; University of Maryland Medical Center 2011; WomensHealth.gov 2008)

  • A painful stinging or burning sensation during urination
  • The need to urinate more frequently
  • Cloudy, red, pink, or dark-colored urine
  • Discomfort or pressure in the lower abdomen
  • Urine with a strong odor
  • Pain in the pelvic area (women) or rectum (men)
  • Fever

Pyelonephritis is a serious infection involving the upper urinary tract (kidneys). Signs/ symptoms of pyelonephritis include (Hooton 2012; National Kidney and Urologic Diseases Information Clearinghouse 2012a; Mayo Clinic 2011)

  • High fever
  • Flank/Abdominal pain
  • Chills
  • Vomiting
  • Frequent/Painful urination

Interstitial Cystitis/ Painful Bladder Syndrome

While pelvic pain, urinary urgency, and nighttime urination are associated with UTI, these symptoms may be the result of a different, somewhat more obscure condition called interstitial cystitis or, sometimes, painful bladder syndrome (Vij 2012; Moutzouris 2009; Miller 2012; Quillin 2012; Ching 2012).

As with UTIs, interstitial cystitis affects women more often than men and can considerably decrease quality of life. Unfortunately, opinions about interstitial cystitis, and the techniques used to diagnose and treat it, are somewhat inconsistent within conventional medicine; this leads to delayed diagnosis in many cases. One reason for this is that a specific cause has not been identified; upon examination, bacteria are not present in the urine of those with interstitial cystitis. Inflammatory damage to the bladder lining (urothelial cell barrier) and some level of immune system derangement are thought to be involved, but the origins of these phenomena are unclear (Moutzouris 2009; Vij 2012; Quillin 2012; Miller 2012).

Since little is understood about the development of interstitial cystitis, protocols for its treatment lack a robust evidence base and often hinge upon physicians’ clinical experience or data from relatively small clinical trials. After diagnosing a patient with interstitial cystitis, which can only be accomplished by ruling out other causes of symptoms since no laboratory test can identify the condition, physicians may prescribe a number of therapies, including (Moutzouris 2009; Vij 2012; Quillin 2012; Miller 2012)

  • Some antidepressants (eg, amitriptyline)
  • DMSO (injected into the bladder)
  • Antihistamines
  • Behaviorial therapy (eg, retraining voiding patterns) (Parsons 1991)
  • Pentosan polysulfate sodium (Elmiron®)
  • Transcutaneous electrical nerve stimulation (TENS)
  • Intravescial lidocaine (ie, injection of the local anesthetic lidocaine into the bladder)
  • Corticosteroids
  • and many others

Despite the fact that an estimated 180 different strategies have been tried as potential treatments for interstitial cystitis, only very few have been shown to be effective. One such drug is pentosan; it is FDA-approved to treat interstitial cystitis and is marketed under the brand name Elmiron® (Moutzouris 2009). Pentosan is thought to work by supporting the integrity of the urothelial layer in the bladder (Teichman 2002).

6 Diagnosis and Conventional Treatment

Diagnosis

UTIs may be difficult to diagnose in some cases, since patients may not always have typical symptoms (Wilson 2004). Also, other conditions have symptoms in common with UTI (eg, gonorrhea, chlamydia, interstitial cystitis, and diabetes).

The presence of red or white blood cells, bacteria or certain chemicals in the urine usually indicates a UTI (Fihn 2003; A.D.A.M. 2011). Most frequently, a urine dipstick test is used to confirm the diagnosis of UTI in individuals with suggestive symptoms. This test evaluates a urine sample to detect nitrites, which are chemicals produced by E. coli, a bacteria that can cause UTIs; it also measures levels of proteins produced by immune cells responding to the infection. In some complicated cases, a urine culture may be used to help guide treatment (Wilson 2004).

Conventional Treatment

Antibiotics. The standard treatment for a UTI is a course of one or more antibiotics. No single antibiotic is recommended for treating every UTI, but nitrofurantoin (Furadantin®), trimethoprim-sulfamethoxazole (Bactrim™), pivemecillinam (Selexid®), fosfomycin trometamol (Monurol®), fluoroquinolone (eg, Cipro®), and beta-lactam (eg, Augmentin®) may all be used (Gupta 2012; McKinnell 2011).

Although many antibiotics can be used to treat UTIs, one of the main factors that determines which antibiotics are chosen is the bacterial resistance pattern. There are strains of E. coli that are resistant to antibiotics and are found throughout the world (Hooton 2012; Kahlmeter 2003; Nicolle 2008). Other strains of bacteria that cause UTIs, including species of Proteus and Klebsiella, have also developed resistance to specific antibiotics (Kahlmeter 2003). As a result, the choice of antibiotic is usually governed by susceptibility of the pathogenic organism responsible for an individual’s case and/or community history of microbial antibiotic resistance (Hooton 2012). This is typically determined by regional rates reported by local hospitals, although this information can overestimate the prevalence of resistance among bacteria in a region (Hooton 2012; Gupta 2011a). Some guidelines recommend avoiding a particular antibiotic if local resistance rates to that antibiotic are greater than 20% (Gupta 2011).

7 Novel and Emerging Treatments

Topical Estrogen for Recurring UTI

Low estrogen levels thin the walls of the vagina, increasing a woman’s risk of developing UTIs (University of Maryland Medical Center 2011). As a result, topical estrogen may represent a treatment option in some cases of UTI among women.

Two different methods of administering topical estrogen have been effective at reducing the frequency of recurring UTIs in postmenopausal women. These include an estradiol-releasing ring and intravaginal estriol cream (Raz 1993; Eriksen 1999; Krause 2009). Estradiol-releasing rings may also acidify the urine, which may help combat intravaginal bacterial growth. As of late 2012, a Phase 4 clinical trial is examining the efficacy of intravaginal estrogen and lactobacilli for preventing recurrent UTIs (ClinicalTrials.gov 2009).

FimH Inhibitors

One of the most important early steps for bacteria to infect the urinary tract is their adhesion to the outside of the cells that line the urinary tract. Bacteria use small finger-like projections, called fimbriae, to bind to the urinary tract lining. Fimbriae are coated with proteins, called lectins, which mediate this process (Klemm 2010). Researchers have discovered that one of these lectins, known as FimH, is crucial for this process; they have therefore developed medications that inhibit the activity of FimH (Jiang 2012; Klein 2010).

To make even better therapies, scientists have developed many different compounds that can inhibit FimH and are continuously tweaking the molecules to improve their effectiveness. The most promising compounds have a similar core structure and are called alpha-D-mannosides. Although these drugs have not yet been tested in humans, studies have found that these chemicals can significantly reduce the amount of bacteria that colonize the bladder in animal models of UTI (Jiang 2012; Klein 2010). In some studies, the FimH blockers drastically reduce the amount of bacteria in the bladder by approximately as much as standard antibiotic treatments (Jiang 2012). These FimH blockers have also been effective in animal models of catheter-associated UTIs (Guiton 2012).

Hyaluronic Acid and Chondroitin Sulfate Injections

Another emerging treatment focuses on the bladder wall. The cells that line the inside of the bladder, known as urothelial cells, are an important part of the body’s defense against UTIs (Bassi 2012; Khandelwal 2009). These cells help to keep undesirable substances (eg, bacteria) from penetrating into the deeper layers of the bladder and also make substances, known as proteoglycans, which form a layer of glycosaminoglycans (GAGs) on the inner surface of the bladder. Any damage to the GAG layer facilitates the adhesion of bacteria to the bladder wall and may play a role in recurrent UTIs (Damiano 2011; Bassi 2012).

New treatments that focus on restoring the integrity of the GAG wall are being developed for preventing recurrent UTIs. These treatments involve injecting some of the substances used to construct GAG, such as hyaluronic acid and chondroitin sulfate, directly into the bladder. This process is also known as intravesical administration. Intravesical administration of hyaluronic acid and chondroitin sulfate has been shown to reduce the number of UTIs in women with recurrent UTIs (Constantinides 2004; Damiano 2011; Bassi 2012; DeVita 2012). Mild bladder irritation has been reported as a side effect of this treatment in some patients (Constantinides 2004; Bassi 2012). Although this treatment is available in Canada and Europe, it has not been approved by the Food and Drug Administration (FDA) for use in patients because of limited clinical trial data.

8 Dietary and Lifestyle Considerations

Fluid Intake

Physicians often recommend that patients with UTIs increase their fluid intake. The theory behind this recommendation is that increasing fluid intake will increase the amount of urine produced, which will help flush out bacteria (Denman 1992). Although this is a common physician suggestion, it is not clear how effective it is at treating or preventing UTIs. Some early studies found that more frequent urination reduces the amount of bacteria in the urine. However, studies examining whether increased urination reduces the incidence of UTI have not yielded conclusive results (Denman 1992; Beetz 2003). Regardless, poor fluid intake is a risk factor for recurrent UTI in female children (Stauffer 2004; Rudaitis 2009), and increased fluid intake does appear to be protective against more serious upper UTIs that can affect the kidneys (Beetz 2003).

Behavioral Measures

Some behavioral changes may also help prevent UTIs, particularly in children. Recurrent UTIs in female children are associated with infrequent urination, delaying urination after the urge to urinate manifests, and delaying of defecation, but not poor bathroom hygiene (Rudaitis 2009; Stauffer 2004). Similarly, women who delay urination for more than one hour post-urge have an increased risk of developing UTIs, which suggests that urinating shortly after feeling the need to urinate could help prevent UTIs. Avoiding diaphragms and spermicide as contraception methods may also prevent UTIs (Stapleton 1997). Although some sources suggest that urinating shortly before and after intercourse also helps to reduce a female’s risk of developing UTIs (University of Maryland Medical Center 2011; Hudson 2006), there is no conclusive evidence that frequent voiding or voiding after intercourse significantly reduces UTI risk (Stapleton 1997; Hooton 2012). Other behavioral interventions that may reduce the risk of developing a UTI include wearing cotton underwear, avoiding tight-fitting clothing, and wiping from front-to-back to prevent transportation of bacteria from the anus to the urethra (WomensHealth.gov 2008).

9 Targeted Natural Interventions

Cranberry

Cranberries contain substances that may be able to treat or prevent UTIs. Cranberry juice and powders made from cranberry extract have been used for decades to prevent or treat UTIs. Originally, it was hypothesized that one of the components in cranberry – quinic acid – increased the levels of a natural antibacterial agent in the urine, known as hippuric acid. However, it is not clear if there is a significant increase in hippuric acid levels in the urine after cranberry consumption (Jepson 2007, 2012).

Evidence suggests that substances known as proanthocyanidins, which are found in cranberries, may interfere with the adhesion of bacteria (particularly E. coli) to the walls of the urinary tract (Jepson 2007, 2012; McMurdo 2005). By preventing E. coli from binding to the urinary tract cells, proanthocyanidins can keep bacteria from fully colonizing and invading the urinary tract. One of the advantages of using cranberry juice or related products is that cranberries are relatively inexpensive, natural, and should not contribute to the growing problem of antibiotic resistance (McMurdo 2005).

One study found that both cranberry juice and cranberry tablets were effective at reducing urinary tract infections (compared to placebo) in women who developed at least one UTI per year. This study also found that cranberry tablets were a more cost-effective option compared to cranberry juice (Stothers 2002). Another study found that consuming cranberry juice three times per day produced a trend towards reducing the incidence of UTIs during pregnancy (Wing 2008). Yet another study compared cranberry extract to low-dose trimethoprim (a commonly used antibiotic) for prevention of recurrent UTIs in older women. This study found that regular use of trimethoprim was only slightly better than 500 mg of cranberry extract daily for preventing the recurrence of UTIs. It also found that women taking trimethoprim were more likely to withdraw from the study due to side effects (McMurdo 2009).

Although there are many studies that have examined the potential benefits of cranberry for UTIs, a recent comprehensive review concluded that the benefits of consuming cranberry juice for UTIs were minimal. However, many of the studies included in this review used sugar-laden cranberry juice cocktails; the high sugar content and the fact that many of these beverages are blends of different juices (reducing the proanthocyanidin content) may also obscure the benefits of cranberries (Jepson 2012).

D-mannose

D-mannose is a sugar that can be found in, among other things, cranberries. One of the interesting aspects of D-mannose is that it is able to bind to the cells that line the urinary tract (Hudson 2006) and to prevent bacteria, such as E. coli, from adhering to the lining of the urinary tract (Hudson 2006; Schaeffer 1980).

Blueberry

Much like cranberries, blueberries also contain compounds that can inhibit the adhesion of E. coli to the cells that line the urinary tract (Ofek 1991). In addition, both blueberries and cranberries contain compounds that are able to help prevent large aggregates of bacteria from forming (Weiss 2002). The clinical effect of blueberries on UTIs has yet to be thoroughly investigated.

Probiotics

Probiotics – beneficial bacteria that reside in the gut and positively impact the health of their host – are a promising natural treatment for UTIs. There are many possible ways that probiotics may prevent UTIs: they may compete with other bacteria for resources, secrete natural antibacterial chemicals (called bacteriocin), and prevent pathogenic bacteria from adhering to the urinary tract (Darouiche 2012).

Bacteria in the Lactobacillus family, normally found in the female vagina, are thought to prevent UTI (Darouiche 2012). Taking antibiotics or using spermicidal agents can kill off these Lactobacilli, which can then increase the risk of UTI (Reid 2001). In addition, recurrent UTIs are often associated with decreased levels of Lactobacillus bacteria and increased colonization with E. coli (Stapleton 2011). As a result, supplementing the vaginal flora with probiotic Lactobacilli may represent a viable technique for preventing UTIs (Reid 2001; Stapleton 2011; Kwok 2006). In particular, there is evidence that the Lactobacillus rhamnosus GR-1 and Lactobacillus reuterii RC-14 strains are clinically effective (Reid 2006).

Lactobacillus bacteria also may prevent UTIs by stimulating the immune system and producing substances that kill infectious bacteria, such as hydrogen peroxide and lactic acid (Darouiche 2012). A study comparing Lactobacillus bacteria to regular doses of trimethoprim-sulfamethoxazole (an antibiotic combination) found that the antibiotics were only slightly more effective than the probiotic treatment for uncomplicated UTI; however, probiotics were more effective in complicated cases, which was likely due to the presence of baseline antibiotic resistance rates in these cases. The authors also point out that probiotics had the advantage of not increasing the risk of antibiotic-resistant microorganisms (Beerepoote 2012).

Berberine

Berberine, a chemical known as a plant alkaloid, has historically been used in Chinese and Ayurvedic medicine. It can be found in many plants, including goldenseal, Orgeon grape, coptis, barberry, and turmeric (Head 2008). Berberine has natural antibacterial properties and is effective at inhibiting the growth of many opportunistic pathogens, including E. coli (Cernakova 2002). Some studies have found that berberine prevents E. coli from adhering to cells that line the urinary tract, thus providing a possible mechanism of action for its UTI-preventative properties (Sun 1988). One study suggested that berberine may represent a new target for the development of pharmaceuticals (Domadia 2008). Berberine may not be safe for pregnant women, however, because it can induce uterine contractions and may cause jaundice in newborns (Head 2008).

Although berberine has been studied in human clinical trials and shown to have several metabolic benefits, concerns about long-term use of berberine have been raised on the basis of certain preclinical studies (Kysenius 2014; Mikes 1985; Mikes 1983). Some evidence suggests that long-term berberine use, especially at high doses, may impair particular aspects of cellular metabolism in specific types of cells. The implications of this preclinical research are yet to be determined by long-term human clinical trials, therefore Life Extension currently recommends short-term use of berberine.

Hibiscus

Hibiscus is a family of plants that has traditionally been used to treat many different infections, including UTIs. Hibiscus plants contain many compounds that have antibacterial, antifungal, and antioxidant properties (Maganha 2010). One compound in particular, gossypetin, has been shown to have antibacterial activity against common UTI-causing bacteria, including E. coli and Pseudomonoas aeurginosa (Mounnissamy 2002). In a double-blind, placebo-controlled clinical trial, 61 women with a history of frequent UTIs were randomly assigned to one of 3 groups receiving a daily dose of 200 mg of hibiscus extract standardized to 90% polyphenols, 200 mg of hibiscus extract standardized to 60% polyphenols, or placebo. Compared to the control group, women taking the hibiscus concentrations experienced 77% fewer incidence of UTIs, as well as overall improvement in urinary comfort (Allaert 2009).

Vitamin C

Vitamin C, also known as ascorbic acid, is one of the most commonly used vitamin supplements and it has a variety of effects on the human body. One potential benefit is that it may acidify the urine, which helps inhibit the growth of infectious bacteria in the urinary tract (Carlsson 2001). This acidification may also convert bacterial nitrites into nitric oxide, which is toxic to bacteria (Hudson 2006). In addition, vitamin C is important for the function of the immune system (Hudson 2006). Studies have found that taking 100 mg of vitamin C daily during pregnancy can reduce the incidence of UTIs (Ochoa-Brust 2007).

General Support for Healthy Bladder Function

Pumpkin seed extract. Urinary urgency and/or frequency are often associated with UTI. To this end, for those afflicted by UTIs, especially chronic UTI sufferers, taking steps to improve bladder tone and support healthy voiding patterns may be beneficial.

Although not studied specifically in the context of UTI, pumpkin seed extract has been shown to support bladder function and combat the symptoms associated with an overactive bladder. In an animal study, rats supplemented with pumpkin seed extract exhibited significantly improved bladder function and decreased urinary frequency (Hata 2005). In a human study involving 39 postmenopausal women, 6 weeks of supplementation with pumpkin seed extract plus soybean germ extract lead to significant decreases in daytime and nighttime urination (Sogabe 2001). In a similar study among 45 men, this same combination extract lead to reduced nighttime urination and improved sleep satisfaction after 6 weeks of supplementation (Terado 2004).

A.D.A.M. Medical Encyclopedia. Urinary tract infection - adults. U.S. National Library of Medicine, http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001549/ Updated Sept. 13th, 2011. Accessed Nov. 14th, 2012.

Allaert F. Double-blind, placebo-controlled study of Hibiscus sabdariffa L extract in the prevention of recurrent cystitis in women. Poster presented at the Federative Pelviperineal Diagnostics and Procedures Meeting: Convergences in Pelviperineal Pain. Nantes, France: December 16-18, 2009.

Bailey DT, Dalton C, Joseph Daugherty F, et al. Can a concentrated cranberry extract prevent recurrent urinary tract infections in women? A pilot study. Phytomedicine 2007;14(4):237-41.

Bassi PF, Tarricone R, Ciani O, Lazzeri M, Romancik M. Glycosaminoglycan therapy - a new approach to the prevention of recurrent urinary tract infections. European Urological Review. 2012;7(1):1-5 [epub ahead of print].

Beerepoot MA, ter Riet G, Nys S, et al. Lactobacilli vs. antibiotics to prevent urinary tract infections. Archives of Internal Medicine. 2012;172(9):704-712.

Beetz R. Mild dehydration: a risk factor of urinary tract infection? European Journal of Clinical Nutrition. 2003;57(Sup 2):S52-S58.

Carlsson S, Wiklund NP, Engstrand L, Weitzberg E, Lundberg JON. Effects of pH, nitrite, and ascorbic acid on nonenzymatic nitric oxide generation and bacterial growth in urine. Nitric Oxide: Biology and Chemistry. 2001;5(6):580-586.

Cernakova M and Kostalova D. Antimicrobial activity of berberine – a constitutent of mahonia aquifolium. Folia Microbioligia. 2002;47(4):375-378.

Ching C. Interstitial cystitis. MD Consult; First Consult. Copyright © 2012 Elsevier Inc. Available at: http://www.mdconsult.com/das/pdxmd/body/389600735-4/1391374580?type=med&eid=9-u1.0-_1_mt_1010371#Contributors. Accessed 12/17/2012.

ClinicalTrials.gov. Low dose estriol with lactobacilli treatment for preventing recurrent urinary tract infection in postmenopausal women. http://clinicaltrials.gov/ct2/show/NCT00900653 Updated May 2009. Accessed 18 Nov. 2012.

Constantinides C, Manousakas T, Nikolopoulos P, Stanitsas A, Haritopoulos K, Giannopoulos A. Prevention of recurrent bacterial cystitis by intravesical administration of hyaluronic acid: a pilot study. BJU International. 2004;22:1262-1266.

Damiano R and Cicione A. The role of sodium hyaluronate and sodium chondroitin sulphate in the management of bladder disease. Therapeutic Advances in Urology. 2011;3(5):223-232.

Darouiche RO and Hull RA. Bacterial interference for prevention of urinary tract infection. Clinical Infectious Diseases. 2012;1-8.

Denman SJ and Burton JR. Fluid intake and urinary tract infection in the elderly. JAMA. 1992;267(16):2245-2246.

Devita DD, Antell H, Giordano S. Effectiveness of intravesical hyaluronic acid with or without chondroitin sulfate for recurrent bacterial cystitis in adult women: a meta-analysis. International Urognyecology Journal. 2012;Epub ahead of print.

Dhakal BK, Kulsesus RR, Mulvey MA. Mechanisms and consequences of bladder cell invasion by uropathogenic Escehrichia coli. European Journal of Clinical Investigation. 2008;38(S2):2-11.

Domadia PN, Bhunia A, Sivaraman J, Swarup S, Dasgupta D. Berberine targets assembly of escherichia coli cell division protein FtsZ. Biochemistry. 2008;47:3225-3234.

Eriksen BC. A randomized, open, parallel-group study on the preventive effect of an estradiol-releasing vaginal ring (estrong) on recurrent urianry tract infections in postmenopausal women. American Journal of Obstetrics and Gynecology. 1999;180:1072-1079.

Ermel W, Georgeault S, Inisan C, Besnard M. Inhibition of uropathogenic Escherichica coli bacteria to uroepithelial cells by extracts from cranberry. Journal of Medicinal Food. 2012;15(2):126-134.

Ferri F. Urinary Tract Infection (UTI). In: Ferri: Practical Guide to the Care of the Medical Patient, 8th ed. Copyright © 2011 Mosby, Inc. MD Consult website. Available at: http://www.mdconsult.com/books/page.do?eid=4-u1.0-B978-0-323-07158-1..00003-1--s14710&isbn=978-0-323-07158-1&uniqId=388881570-2#4-u1.0-B978-0-323-07158-1..00003-1--s14710. Accessed December 12, 2012.

Fihn SD. Acute uncomplicated urinary tract infection in women. The New England Journal of Medicine. 2003;349(3):259-266.

Fisher JF, Kavanagh K, Sobel JD, et al. Candida Urinary Tract Infection: Pathogenesis. Clin Infect Dis. 2011;52 (suppl 6): S437-S451.

Foxman B. Epidemiology of urinary tract infections: incidence, morbidity, and economic costs. Dis Mon. 2003;42(2):53-70.

Guiton PS, Cusumano CK, Kline KA, et al. Combinatorial small-molecule therapy prevents uropathogenic Escherichia coli catheter-associated urinary tract infections in mice. Antimicrobial Agents and Chemotherapy. 2012;56(9):4738-4745.

Gupta K and Trauter B. Urinary tract infection. Annals of Internal Medicine. March 2012:ITC3-1-16.

Gupta K, Hooton TM, Miller L. Managing uncomplicated urinary tract infection---making sense out of resistance data. Clinical Infectious Diseases. 2011a;53(10):1041-1042.

Gupta K, Hooton TM, Naber KG, et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: a 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clinical Infectious Diseases. 2011b;52(5):e103-e120.

Hata K Tanahashi S, Wakida Y, Tatsuzaki M, Koide A. Effect of Pumpkin seed extract on urinary bladder function in anesthetized rats. Jpn J Med Pharm Sci. 2005;54(3):339-45.

Head, KA. Natural approaches to prevention and treatment of infections of the lower urinary tract. Alternative Medicine Review. 2008;13(3):227-244.

Hess MJ, Hess PE, Sullivan MR, Nee M, Yalla SV. Evaluation of cranberry tablets for the prevention of urinary tract infections in spinal cord injured patients with neurogenic bladder. Spinal Cord. 2008 Sep;46(9):622–6.

Hooton TM, Bradley SF, Cardenas DD, et al. Diagnosis, prevention and treatment of catheter-associated urinary tract infection in adults: 2009 international clinical practice guidelines from the Infectious Diseases Society of America. Clinical Infectious Diseases. 2010;50:625-663.

Hooton TM, Scholes D, Hughes JP, et al. A prospective study of risk factors for symptomatic urinary tract infection in young women. The New England Journal of Medicine. 1996;335(7):468-474.

Hooton TM. Clinical practice. Uncomplicated urinary tract infection. The New England journal of medicine. Mar 15 2012;366(11):1028-1037.

Hu KK, Boyko EJ, Scholes D, et al. Risk factors for urinary tract infections in postmenopausal women. Archives of Internal Medicine. 2004;164:989-993.

Hudson T. Treatment and prevention of bladder infections. Alternative and Complementary Therapies. 2006;297:302.

Jepson RG and Craig JC. A systematic review of the evidence for cranberries and blueberries in uti prevention. Molecular Nutritional Food Research. 2007;51:738-745.

Jepson RG, Williams G, Craig JC. Cranberries for preventing urinary tract infections. Cochrane Database of Syst Rev. 2012;10:CD001321.

Jiang X, Abgottspon D, Kleeb S, et al. Antiadhesion therapy for urinary tract infections---a balanced pk/pd profile proved to be key for success. Journal of Medicinal Chemistry. 2012;55:4700-4713.

Jorgensen I and Seed PC. How to make it in the urinary tract: a tutorial by Escherichia coli. PLOS Pathogens. 2012;8(10):1-4.

Kahlmeter G. An international survey of the antimicrobial susceptibility of pathogens from uncomplicated urinary tract infections: the ECOSENS project. Journal of antimicrobial Chemotherapy. 2003;51:69-76.

Khandelwal P. et al. Cell biology and physiology of the uroepithelium. Am J Physiol Renal Physiol. 2009 December; 297(6): F1477–F1501.

Klein T, Abgottspon D, Wittwer M. et al. FimH antagonists for the oral treatment of urinary tract infections: from design and synthesis to in vitro and in vivo evaluation. Journal of Medicinal Chemistry. 2010;53:8627-8641.

Klemm P, Hancock V, Schembri MA. Fimbrial adhesins from extraintestinal Escherichia Coli. Environmental Microbiology Reports. 2010;2(5):628-640.

Krause M, Wheeler TL, Snyder TE, Richter HE. Local effects of vaginally administered estrogen therapy: a review. Journal of Pelvic Medicine and Surgery. 2009;15(3):105-114.

Kwok L, Stapleton AE, Stamm WE, Hillier SL, Wobbe CL, Gupta K. Adherence of Lactobacillus crispatus to vaginal epithelial cells from women with or without a history of recurrent urinary tract infection. The Journal of Urology. 2006;176:2050-2054.

Kysenius K, Brunello CA, Huttunen HJ. Mitochondria and NMDA receptor-dependent toxicity of berberine sensitizes neurons to glutamate and rotenone injury. PloS one. 2014;9(9):e107129.

Maganha EG, Halmenschlager RC, Rosa RM, Henriques JAP, Ramos ALL, Saffi J. Pharmacological evidences for the extracts and secondary metabolites from plants of the genus Hibiscus. Food Chemistry. 2010;118:1-10.

Mayo Clinic. Kidney infection. Definition. Mayo Foundation for Medical Education and Research. Available at: http://www.mayoclinic.com/health/kidney-infection/DS00593. Last updated Aug. 9, 2011. Accessed December 14, 2012.

Mayo Clinic. Urinary Tract Infection. Definition. Mayo Foundation for Medical Education and Research. http://www.mayoclinic.com/health/urinary-tract-infection/DS00286 Last Updated 29 Aug. 2012a. Accessed 14 Nov. 2012.

Mayo Clinic. Urinary Tract Infection. Symptoms. Mayo Foundation for Medical Education and Research. Available at: http://www.mayoclinic.com/health/urinary-tract-infection/DS00286/DSECTION=symptoms. Last updated Aug. 2012b. Accessed December 13, 2012.

McKinnell JA, Stollenwerk NS, Jung CW, Miller LG. Nitrofurantoin compares favoriably to recommended agents as empirical treatment of uncomplicated urinary tract infections in a decision and cost analysis. Mayo Clinic Proceedings. 2011;86(6):480-488.

McMurdo MET, Argo I, Phillips G, Daly F, Davey P. Cranberry or trimethoprim for the prevention of recurrent urinary tract infections? a randomized controlled trial in older women. Journal of Antimicrobial Chemotherapy. 2009;63:389-395.

McMurdo MET, Bissett LY, Price RJG, Phillips G, Crombie IK. does ingestion of cranberry juice reduce symptomatic urinary tract infections in older people in hospital? a double-blind, placebo-controlled trial. Age and Ageing. 2005;34:256-261.

MedlinePlus. Urinary catheters. Available at: http://www.nlm.nih.gov/medlineplus/ency/article/003981.htm. Last updated Sep. 26, 2011b. Accessed December 14, 2012.

MedlinePlus. Urinary tract infection – adults. Available at: http://www.nlm.nih.gov/medlineplus/ency/article/000521.htm. Last updated Sep. 13, 2011a. Accessed December 13, 2012.

Mikes V, Dadak V. Berberine derivatives as cationic fluorescent probes for the investigation of the energized state of mitochondria. Biochimica et biophysica acta. 1983;723(2):231-239.

Mikes V, Yaguzhinskij LS. Interaction of fluorescent berberine alkyl derivatives with respiratory chain of rat liver mitochondria. Journal of bioenergetics and biomembranes. 1985;17(1):23-32.

Miller LA, Gardner A. Interstitial cystitis: A current guide to diagnosis and treatment. JAAPA : official journal of the American Academy of Physician Assistants. Jun 2012;25(6):28-32: quiz 55.

Mounnissamy VM, Kavimani S, Gunasegaran R. Antibacterial activity of gossypetin isolated from hibiscus sabdariffa. The Antiseptic. 2002 Mar; 99(3): 81-2.

Moutzouris DA, Falagas ME. Interstitial cystitis: an unsolved enigma. Clinical journal of the American Society of Nephrology : CJASN. Nov 2009;4(11):1844-1857.

Mulvey MA, Scholling JD, Hultgren SJ. Establishment of a persistent Escherichica coli reservoir during the acute phase of a bladder infection. Infection and Immunity. 2001;69(7):4572-4579.

Mulvey MA. Adhesion and entry of uropathogenic Escherichia coli. Cellular Microbiology. 2002;4(5):257-271.

National Kidney and Urologic Diseases Information Chearinghouse (NKUDIC). Pyelonephritis: Kidney Infection. Available at: http://kidney.niddk.nih.gov/kudiseases/pubs/pyelonephritis/#1. Last updated June 11, 2012b. Accessed December 14, 2012.

National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC). Urinary Tract Infections in Adults. http://kidney.niddk.nih.gov/kudiseases/pubs/utiadult/ Updated May 24, 2012a. Assessed Nov. 14 2012.

Nicolle LE. Uncomplicated urinary tract infection in adults including uncomplicated pyelonephritis. Urologic Clinics of North America. 2008;35:1-12.

Ochoa-Brust GJ, Fernandez AR, Villanueva-Ruiz GJ, Velasco R, Trujillo-Hernandez B, Vasquez C. Daily intake of 100 mg ascorbic acid as urinary tract infection prophylactic agent during pregnancy. Acta Obsetetrica et Gynecologica. 2007;86:783-787.

Ofek I, Goldhar J, Zafrir D, Lis H, Adar R, Sharon N. Anti-Escherichia Coli adhesin activity of cranberry and blueberry juices. The New England Journal of Medicine. 1991;324(22):1599.

Ohlsen K, Oelschlaeger TA, Hacker J, Khan S. Carbohydrate receptors of bacterial adhesins: implications and reflections. Topics in Current Chemistry. 2009;288:109-120.Ramakrishnan K and Scheid DC. Diagnosis and management of acute pyelonephritis in adults. American Family Physician. 2005;71(5):933-942.

Parsons CL, Koprowski PF. Interstitial cystitis: successful management by increasing urinary voiding intervals. Urology. Mar 1991;37(3):207-212.

Quillin RB, Erickson DR. Management of interstitial cystitis/bladder pain syndrome: a urology perspective. The Urologic clinics of North America. Aug 2012;39(3):389-396.

Raz R and Stamm WE. A controlled trial of intravaginal estriol in postmenopausal women with recurrent urinary tract infections. New England Journal of Medicine. 1993;329:753-756.

Raz R. Urinary tract infection in postmenopausal women. Korean Journal of Urology. 2011;52:801-808.

Reid G, Bruce AW. Probiotics to prevent urinary tract infections: the rationale and evidence. World journal of urology. Feb 2006;24(1):28-32.

Reid G, van der Mei HC, Tieszer C, Busscher HJ. Uropathogenic Escherichia coli adhere to urinary catheters without using fimbriae. FEMS Immunology and Medical Microbiology. 1996;16:159-162.

Roberts JA. Bacterial adherence and urinary tract infection. Southern Medical Journal. 1987;80(3):347-351.

Ronald A. The etiology of urinary tract infection: traditional and emerging pathogens. The American Journal of Medicine. 2002;113(1A):14S-19S.

Rudaitis S, Pundziene B, Jievaltas M, Uktveris R, Kevelaitis E. Recurrent urinary tract infection in girls: do urodynamic, behavioral and functional abnormalities play a role? Journal of Nephrology. 2009;22(6):766-773.

Sanchez GV, Master RN, Karlowsky JA, Bordon JM. In vitro antimicrobial resistance of urinary Escherichia coli isolates among U.S. outpatients from 2000 to 2010. Antimicrobial Agents and Chemotherapy. 2012:2181-2183.

Schaeffer AJ and Schaeffer EM. Infections of the Urinary Tract. In: Wein: Campbell-Walsh Urology, 10th ed. Copyright © 2011. MD Consult website. Available at: http://www.mdconsult.com/books/page.do?eid=4-u1.0-B978-1-4160-6911-9..00010-4--s0015&isbn=978-1-4160-6911-9&uniqId=389328419-2#4-u1.0-B978-1-4160-6911-9..00010-4--s0015. Accessed December 14, 2012.

Schaeffer AJ, Amundsen SK, Jones JM. Effects of carbohydrates on adherence of Escherichia coli to human urinary tract epithelial cells. Infection and Immunity. 1980;30(2):531-536.

Schaeffer AJ, Rajan N, Cao Q, et al. Host pathogenesis in urinary tract infections. Int J Antimicrob Agents. 2001;17(4):245-51.

Scholes D, Hooton TM, Roberts PL, Gupta K, Stapleton AE, Stamm WE. Risk factors associated with acute pyelonephritis in healthy women. Annals of Internal Medicine. 2005;142:20-27.

Schollum JB, Walker RJ. Adult urinary tract infection. British journal of hospital medicine. Apr 2012;73(4):218-223.

Schoolnik GK. How Escherichia coli infects the urinary tract. The New England Journal of Medicine. 1989;320(12):804-805.

Sogabe H, Terado T. Open clinical study of effects of pumpkin seed extract/soybean germ extract mixture containing processed foods on nocturia. Jpn J Med Pharm Sci. 2001;46(5):727-37.

Stapleton A and Stamm WE. Prevention of urinary tract infection. Infectious Disease Clinics of North America. 1997;11(3):719-733.

Stapleton AE, Au-Yeung M, Hooton TM, et al. randomized, placebo-controlled phase 2 trial of a Lactobacillus crispatus probiotic given intravaginally for prevention of recurrent urinary tract infection. CID. 2011;52:1212-1217.

Stauffer CM, van der Weg B, Donadini R, Ramelli GP, Marchand S, Bianchetti MG. Family history and behavioral abnormalities in girls with recurrent urinary tract infections: a controlled study. The Journal of Urology. 2004;171:1663-1665.

Stothers L. A randomized trial to evaluate effectiveness and cost effectiveness of naturopathic cranberry products as prophylaxis against urinary tract infection in women. The Canadian Journal of Urology. 2002;9(3):1558-1562.

Sun D, Abraham SN, Beachey EH. Influence of berberine sulfate on synthesis and expression of pap fimbrial adhesin in uropathogenic Escherichia coli. Antimicrobial Agents and Chemotherapy. 1988;32(8):1274-1278.

Teichman JM. The role of pentosan polysulfate in treatment approaches for interstitial cystitis. Reviews in urology. 2002;4 Suppl 1:S21-27.

Terado T et al. Clinical study of mixed processed food containing pumpkin seed extract and soybean germ extract on pollakiuria in night in elderly men. Jpn J Med Pharm Sci. 2004;52(4):551-61.

University Health Service. Urinary Tract Infections in Women. http://www.uhs.umich.edu/uti Updated 2012. Assessed Nov. 15 2012.

University of Maryland Medical Center. Urinary Tract Infection. http://www.umm.edu/patiented/articles/urinary_tract_infection_000036.htm Updated 2011. Assessed Nov. 15 2012.

Vij M, Srikrishna S, Cardozo L. Interstitial cystitis: diagnosis and management. European journal of obstetrics, gynecology, and reproductive biology. Mar 2012;161(1):1-7.

Weiss EI, Lev-Dor R, Sharon N, Ofek I. Inhibitory effect of a high-molecular-weight constituent of cranberry on adhesion of oral bacteria. Critical Reviews in Food Science and Nutrition. 2002;42:285-292.Reid G. Probiotic agents to protect the urogenital tract against infection. The American Journal of Clinical Nutrition. 2001;733:437S-443S.

Wildenfels P, Opal S, and Hessen MT. Urinary tract infection. MD Consult Website. Available at: http://www.mdconsult.com/das/pdxmd/body/388879023-2/0?type=med&eid=9-u1.0-_1_mt_1014619. Last updated February 19, 2010. Accessed December 12, 2012.

Wilson ML and Gaido L. Laboratory diagnosis of urinary tract infections in adult patients. Clinical Infectious Diseases. 2004;38:1150-1158.

Wing DA, Rumney PJ, Preslicka C, Chung JH. Daily cranberry juice for the prevention of asymptomatic bacteriruia in pregnancy: a randomized, controlled pilot study. Journal of Urology. 2008;180(4):1367-1372.

Womenshealth.gov. Urinary Tract Infection Fact Sheet. http://womenshealth.gov/publications/our-publications/fact-sheet/urinary-tract-infection.cfm Updated May 1, 2008. Assessed Nov. 14 2012.