Two common medical problems in women are urinary tract infections (UTIs) and vaginal yeast infections or vulvovaginal candidiasis (VVC).
UTI is a common infection in any part of the urinary tract, including the urethra (urethritis), bladder (cystitis), ureters, and kidneys (pyelonephritis), although it is most common in the bladder.1 Unresolved cases of lower UTIs can spread, causing pyelonephritis, male genital infections, or progression to more severe life-threatening urosepsis.2 The risk of UTI can be as much as 14 times greater in women than in men.3 The disproportionate infection rates are primarily due to anatomical differences in the length of the female urethra and proximity to the rectum, making bacterial entry into the urinary tract easier.4 Other risk factors include previous UTIs, pregnancy, age, vaginal flora changes, and menopause.4 Common UTI symptoms include urge and urinary incontinence, burning sensation while urinating, cloudy urine, and pelvic pain, while more serious symptoms can include fever and chills.1
The most common uropathogen responsible for UTI is Escherichia coli (E. coli), a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium that commonly resides in the lower intestine.5 The most well-known Shiga toxin-producing E. coli (STEC) is E. coli O157:H728, which can cause “severe stomach cramps, bloody diarrhea, and vomiting.”6 Healthy adults typically recover from E. coli O157:H7 infections within a week. Young children and older adults are at greater risk of developing a life-threatening form of kidney failure.6
While E. coli is the predominant uropathogen in UTIs, other bacteria, such as Klebsiella spp., Enterococcus spp. and Pseudomonas aeruginosa, are also common in healthcare-associated UTIs, complicated UTIs, pyelonephritis, and urosepsis.2,3Candida spp. are the most common organisms among fungal urinary tract infections referred to as candiduria.7 While only accounting for 1% of positive urine cultures in hospital laboratories, candiduria represents a disproportionately large proportion of ICU-acquired positive urine cultures and catheter-associated UTIs.7
Antibiotics are often the first-line treatment for bacteria that cause tract infections. Health status and the type of bacteria found in urine determine which medicine is used and how long a person needs to take it; however, antibiotics can cause side effects such as “rash, dizziness, nausea, diarrhea, and yeast infections.”7 The increasing prevalence of uropathogenic antimicrobial resistance poses a significant threat to public health.2,3 As these pathogens become increasingly resistant to commonly prescribed antibiotics8–10 and antifungals7, the treatment of urinary tract infections (UTIs) has become more challenging. Along with novel antimicrobial developments, the exploration of nonantimicrobial prevention and treatment methods that do not increase bacterial and fungal resistant pathogens is crucial.
Candida albicans (C. albicans), a gram-positive fungus that can take on a unicellular (yeast) or multicellular form, is an opportunistic pathogenic yeast that is a common member of the human gut flora. It is detected in the gastrointestinal tract and mouth of 40–60% of healthy adults.11,12C. albicans is the most common Candida species that causes candidiasis in humans, resulting from overgrowth of the fungus.13,14
Candidiasis is a broad term that clinically refers to a spectrum ranging from nonlife-threatening superficial mucocutaneous infections to life-threatening deep-seated organ infections caused by the fungi Candida genus.15 Invasive candidiasis (IC) occurs when superficial infections invade the bloodstream and disseminate to different organs in the body, often causing severe complications.15,16 Risk factors for IC include but are not limited to immunosuppressive agents, surgery, prolonged stay in an intensive care unit, prior administration of broad-spectrum antibiotics, and catheter use.15,16
The most common term for candidiasis in the vagina is vaginal yeast infection.15 Other names for this infection include vaginal candidiasis, vulvovaginal candidiasis (VVC), and candida vaginitis.17 According to the CDC, “Candida normally lives on skin and inside the body such as in the mouth, throat, gut, and vagina, without causing any problems. Scientists have estimated that approximately 20% of women normally have Candida in the vagina without any symptoms. Candida can cause infection if the conditions inside the vagina change to encourage growth. Factors such as hormones, medicines, or changes in the immune system can increase the likelihood of infection.”17
It is estimated that approximately 75% of women will experience an episode of VVC in their lifetime, and over 50% will experience two or more episodes in their lifetime.12 The estimated prevalence of recurrent vulvovaginal candidiasis (RVVC) (characterized by four or more VVC episodes per year) is 5–10% of all women.12,18
Symptoms of VVC are often mild and include but are not limited to itching, burning, pain, vaginal discharge, and bad odor.18 Some of these symptoms overlap with other common vaginal infections, such as bacterial vaginosis (which results from an overgrowth of the bacteria naturally found in the vagina) and trichomoniasis (which is caused by a parasite and is often sexually transmitted).12,18,19
The treatment of candidiasis varies based on the location and severity of the infection as well as the patient’s previous exposure to antifungal agents and other comorbidities.15,16 Of the three major classes of antifungal agents generally recognized for use against Candida spp., echinocandins are typically considered the first line of defense for the treatment of adult patients with IC.15,16,20 Azoles such as fluconazole and certain polyenes such as nystatin can be administered orally or topically and are the most common antifungal drugs used to treat and prevent VVC, RVVC, and oral candidiasis.12,16,18,21
Recent studies suggest that the increased prevalence of Candida spp. antifungal drug resistance will likely persist because of the limited number of antifungal treatment options, diversification of Candida spp. infections, increased reported cases of candidiasis, and the emergence of intrinsically resistant Candida spp.20,22,23
The currently accepted definition of probiotics is “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host.”24 This means that if the microorganisms are not “live,” they cannot be considered probiotic, and if their amount is not adequate to confer a health benefit, they cannot be considered probiotic either.
Probiotics have remained an area of interest for the nonantimicrobial prevention and treatment of UTIs and VVC. A healthy microbiome imbalance, such as decreased levels of Lactobacillus, has been associated with an increased risk of recurrent UTIs.3,25 Mechanistically, probiotics, especially those belonging to the Lactobacillus genus, may help prevent and treat UTIs and VVC by inhibiting pathogen biofilm formation, preventing hyphae formation, and interfering with virulence gene expression.25–27 However, the efficacy of probiotics in the prevention and treatment of UTIs3,28–31 and VVC32–35 has shown mixed results and varies depending on the type of pathogen, specific strains of probiotics used, dosage, duration of treatment, and individual patient factors. Probiotics have shown no concern in developing resistant pathogenic strains of bacteria and yeasts.34
Cranberry (Vaccinium macrocarpon) is an evergreen shrub that has historically been used for bladder, stomach, and liver disorders.36 Today, cranberry is often promoted for urinary tract infections (UTIs).36 Some research has shown that cranberry use reduces the risk of UTIs by approximately one-third in people who are at increased risk for UTIs or have had recurrent UTIs.36 However, according to the U.S. National Center for Complementary and Integrative Health, there is still some uncertainty about the effectiveness of cranberry because some of the research has not been of high quality.”36 It is noteworthy that cranberry alone has not been shown to be effective as a treatment for an existing UTI37–39 as far as safety is concerned, and “cranberry products are generally thought to be safe”.36 However, cranberries consumed in large amounts can cause upset stomach and diarrhea.36 Little is known about the safety of cranberry consumption for health reasons during pregnancy or while breastfeeding. There is conflicting evidence about cranberry interactions with the anticoagulant warfarin.36 It is not recommended to use cranberry products in place of proven treatment for a UTI.36 On July 21, 2020, the U.S. Food and Drug Administration announced in a letter of enforcement discretion that it “does not intend to object to the use of certain qualified health claims regarding consuming certain cranberry products and a reduced risk of recurrent urinary tract infection (UTI) in healthy women.”40 Specifically, “the FDA intends to exercise its enforcement discretion regarding claims for the association between the consumption of cranberry juice beverages containing at least 27 percent cranberry juice (most commercially available cranberry cocktails contain this amount) and cranberry dietary supplements containing at least 500 milligrams (mg) of cranberry fruit powder (100% fruit) and a reduced risk of recurrent UTI.
The claims do not include other conventional foods or food products made from or containing cranberries, such as dried cranberries or cranberry sauce.”40
The following qualified health claims for cranberry dietary supplements are included in the FDA’s letter of enforcement discretion.
-
“Limited scientific evidence shows that by consuming 500 mg each day of cranberry dietary supplement, healthy women who have had a urinary tract infection (UTI) may reduce their risk of recurrent UTI.”40
-
“Consuming 500 mg of cranberry dietary supplement may help reduce the risk of recurrent urinary tract infection (UTI) in healthy women. The FDA concluded that there is limited scientific evidence to support this claim.”40
-
“Consuming 500 mg [X capsules/tablets/soft gels] each day of [this identified cranberry dietary supplement] may help reduce the risk of recurrent urinary tract infection (UTI) in healthy women. The FDA concluded that there is limited scientific evidence to support this claim.”40
On the one hand, the diverse observations and inconsistent results of various probiotic strains on E. coli and C. albicans, as well as the National Center for Complementary and Integrative Health, as well as the FDA’s cautious approach for the use of cranberry powder for UTI, suggest that neither probiotics alone nor cranberry powder alone can effectively inhibit both E. coli and C. albicans.
Consequently, we envisioned that the combination of an optimum probiotic blend and organic cranberry powder in an optimum carrier (liquid organic fruit/vegetable juice) should effectively inhibit both E. coli and C. albicans (as the microorganisms responsible for urinary tract infection and vulvovaginal candidiasis).
Therefore, the specific objective of this research project was to prove that our dietary women’s health formulation (containing probiotics and organic cranberry powder in a mixture of organic juices) can effectively inhibit E. coli and C. albicans, thus reducing the need for antimicrobial usage, which in turn would contribute to the reduction of overall antimicrobial resistance by these pathogens.