Learning Objectives:After participating in this continuing education activity, the provider should be better able to:

1. Identify at-risk patients for recurrent urinary tract infection, according to the current guidelines.

2. Formulate a treatment plan, including appropriate antibiotic selection, and/or integrative medicine.

Urinary tract infection (UTI) is the most common type of bacterial infection, affecting more than 50% to 60% of women of all racial and socioeconomic backgrounds. Of those women experiencing UTI, 30% will have recurrent episodes causing significant morbidity, reduced quality of life, and health care costs totaling billions of dollars.¹ Accurate diagnosis continues to evolve based on emerging information of the intravesical microbiome. The American Urologic Association has current recommendations for the diagnosis of recurrent UTI (rUTI). Urinalysis (UA) and culture are not always necessary for simple cystitis, but UA and culture with sensitivities before initiating antibiotic therapy are indicated in cases of recurrent infection. Adjustment of therapy is based on culture results to ensure appropriate treatment of resistant bacteria.² A repeat urine culture 1 to 2 weeks after therapy may be indicated as a test of cure (TOC), as it may be beneficial to define therapy and differentiate between symptoms and the presence of bacteriuria.³ Although antibiotic therapy is the mainstay of treatment, antimicrobial resistance, sensitivities, and allergies necessitate continued assessment of therapeutic options. For this reason, providers must become knowledgeable in the diagnosis and consider both conventional and integrative regimens for prevention and treatment. Proper diagnosis of rUTI and potential therapies are reviewed in this article.

Epidemiology

UTIs impact a large number of women regardless of age, race, or socioeconomic level. UTIs are responsible for approximately 3.6 million office visits per year, and cost nearly $2 billion in health care.¹

Over 50% of women are diagnosed with a UTI in their lifetime. Infections are based on the presence of a lower and/or upper urinary tract pathogen without underlying functional or structural abnormalities of the genitourinary tract. Over 30% to 40% of those women with a UTI will experience recurrent episodes. rUTI is defined as the presence of 2 or more culture-proven infections in 6 months or 3 in 1 year.⁴

Although there is a high prevalence of UTI in women older than 18 years, there are few data describing the association and impact of rUTI on socioeconomic and racial disparities.^3,5 Those studies that have addressed the socioeconomic impact of rUTI have been performed in Europe and Asia, and do not address these differences in the United States.²

One survey of 5506 male and female adults of different ethnicities, aged 30 to 79 (2301 males, 3205 females, 1770 African Americans, 1877 Hispanics, and 1859 Whites), was performed. The overall prevalence of lower urinary tract symptoms was 18.7% and increased with age but did not differ by sex or race. The study also demonstrated that lower urinary tract symptoms had a negative impact on quality of life across all ages regardless of background.⁶

Pathophysiology

The pathophysiology contributing to UTI may occur when a shift in the normal vaginal bacterial flora predisposes women to colonization from colonic or other vaginal organisms. Alteration of normal vaginal flora, especially loss of lactobacilli, can predispose to colonization of Escherichia coli at the introitus and increase the risk of cystitis.¹ Abnormal bacterial colonization can lead to ascent of bacteria from the urethra into the bladder. Several additional factors can increase the risk of rUTI in women including sexual intercourse, spermicide use, catheterization, and the changes in vaginal pH associated with menopause.^1,3,5

Uncomplicated cystitis is caused most commonly by E. coli (70%-95%), with other pathogens such as Staphylococcus saprophyticus, Proteus mirabilis, Klebsiella pneumonia, and Enterococcus less frequently implicated.⁴ In cases of recurring infection, the etiology may be due to one of several factors including persistence of the initiating organism occurring within 2 weeks of treating the original infection, reinfection with the original organism after 2 weeks of initial treatment, or reinfection at any time with a different organism.⁵

Diagnosis

Presenting symptoms for uncomplicated UTIs can include dysuria, urinary frequency, urgency, suprapubic pain, and hematuria. These symptoms may be present in acute or recurrent infection.¹ For adequate diagnosis, a history and physical examination should be performed. An abdominal and suprapubic examination and detailed pelvic examination can evaluate structural or functional abnormalities such as vaginal atrophy, pelvic organ prolapse, masses, foreign bodies, and fistulas. Hygiene and costovertebral, flank tenderness should also be evaluated.^2,4

The urine dipstick test for nitrite and leukocyte esterase can be unreliable in diagnosis of UTI given poor sensitivity and specificity.² Instead, UA and culture on a proper clean catch or straight catheter specimen showing 10⁵ colony-forming units are commonly performed for diagnosis of UTI. In patients with symptoms of straightforward UTIs, antibiotic treatment can be started without waiting for the results of the urine culture. Adjustment of therapy may be indicated based on culture results to ensure appropriate treatment of resistant bacteria.² Of note, different laboratories and society guidelines may use a different threshold for diagnosis.⁴

Due to the emerging understanding of the intravesical microbiome, there is growing concern that standard urine culture may have limitations in the diagnosis of UTI. Testing such as 16S rRNA rapid next-generation gene sequencing and expanded quantitative urine culture has been developed to cultivate up to 92% of the microorganisms not routinely grown in urine culture assays.⁶ However, due to limitations of these methods such as availability and longer processing time, their clinical utility is not yet clear.⁶

Cystoscopy and imaging studies are not routinely indicated in patients with rUTI.^2,4

Studies in patients with uncomplicated rUTI report that there is a low probability of anatomical abnormalities; therefore, cystoscopy is not warranted.⁵ Imaging studies are reserved for patients who do not respond appropriately to therapy, have anatomical or structural abnormalities, previous pelvic surgery, hematuria outside of the presence of infection, or complicated cases of rUTI. Renal ultrasound or CT can rule out nephrolithiasis, renal masses or cysts, hydronephrosis, and/or obstruction.

Conventional Treatment

Antibiotic Selection

Data obtained evaluating treatment of acute uncomplicated UTI have been extrapolated to those with recurrent infection.⁴ Antibiotic choices are based on efficacy in achieving clinical/biological cure with consideration given to prevalence of resistance and adverse effects.

First-line agents include nitrofurantoin, trimethoprim/sulfamethoxazole, and fosfomycin (Table 1).⁴ The dosage of nitrofurantoin monohydrate macrocrystals is 100 mg twice daily for 5 to 7 days. Nitrofurantoin is generally well tolerated and bacteriostatic for gram-negative organisms, such as E. coli, but is ineffective for Proteus, Klebsiella, and Enterobacter.⁵ Adverse effects associated with nitrofurantoin are pulmonary and hepatotoxicity and peripheral neuropathy. These are of particular concern in the elderly.

Table 1. Antibiotic Regimens for UTI

Therapy with trimethoprim-sulfamethoxazole is appropriate for susceptible organisms such as most gram-negative and gram-positive bacteria and methicillin-resistant Staphylococcus aureus. It is not effective against Pseudomonas. Treatment for 5 to 14 days has been used. Three-, 5-, or 10-day regimens have been shown to have similar efficacy.⁴ This antibiotic is highly effective in treatment of bacterial cystitis if local resistance rates for the uropathogen(s) do not exceed 20%, or if antibiotic susceptibility is known. Cure rates range from 90% to 100%. Adverse effects can include rash, urticaria, nausea, vomiting, neutropenia, thrombocytopenia, Stevens-Johnson syndrome, and toxic epidermal necrosis.

Fosfomycin is another first-line agent for treatment. The single-dose administration as well as its use for multidrug resistant organisms makes it useful for treating UTIs. Adverse effects can include diarrhea, nausea, headache, and hypersensitivity. Rates of fosfomycin resistance are lower in comparison to other antimicrobials.⁴

Fluoroquinolones are very effective in treatment of UTIs with an efficacy of 85% to 90%. Levofloxacin 250 twice a day or 500 mg extended-release daily for 3 days is appropriate dosing. Multiple, serious adverse events include rash, confusion, seizures, restlessness, headache, severe hypersensitivity, QTc prolongation, hypoglycemia, hyperglycemia, and Achilles tendon rupture over age 60, and potential risk for aortic dissection or aneurysm. Therefore, levofloxacin should be used cautiously. Fluoroquinolones have high rates of resistance and are more expensive; therefore, they are not recommended as a first-line therapy.^4,5

Nonantibiotic Treatments

Due to the risks of adverse antibiotic reactions and bacterial resistance, investigations have been made into the impact of nonantibiotic management of rUTI and the rate of pyelonephritis after 1 to 6 months of treatment. Bleidorn et al⁷ performed a retrospective study that evaluated the long-term effect of ibuprofen therapy versus fosfomycin for treatment of UTI. In 386 patients (189 ibuprofen and 197 fosfomycin), 6-month follow-up was performed with no negative impact on rUTI rates or pyelonephritis from 28 days up to 6 months.

Self-Start Treatment

The option to self-treat with previously prescribed antibiotics may be indicated for certain patients who are able to accurately diagnose UTI based on symptoms.^2,4,5 The ability to self-treat lessens patient anxiety and decreases health care costs and clinic load. Self-start antibiotics recommended can include nitrofurantoin 100 mg twice a day x 5 days, trimethoprim/sulfamethoxazole 160/800 mg twice a day x 3 days, or fosfomycin 3 g 1 dose.⁴

Monitoring Resolution of Infection

A repeat urine culture 1 to 2 weeks after therapy may be performed as a TOC. Although a TOC is not well supported in the literature or by current guidelines for routine evaluation after antibiotic therapy, in select cases of rUTI, it may be beneficial to define therapy and differentiate between symptoms and the presence of bacteriuria.³ Another consideration for TOC is that in those whose symptoms have resolved, a negative TOC (ie, positive culture) may prompt unnecessary treatment of asymptomatic bacteriuria and also promote subsequent antibiotic resistance. Resolution of the patient's symptoms is usually a sufficient marker of treatment efficacy.

Prevention of Recurrence: Conventional Approaches

Continuous Antibiotic Prophylaxis

Women with rUTI may effectively prevent future infections with a 6- to 12-month course of antibiotic prophylaxis.^2-4 Antibiotic choices include nitrofurantoin 50 or 100 mg daily; trimethoprim-sulfamethoxazole 40/200 mg daily or 3 times weekly; trimethoprim 100 mg once daily; cephalexin 125 or 250 mg once daily; and fosfomycin 3 g every 10 days.⁴ There are, however, adverse effects such as candidiasis and nausea with use of continuous antibiotic therapy.^1,3,4

Postcoital Antibiotic Prophylaxis

In patients who experience rUTI temporally related to sexual intercourse, postcoital prophylaxis allows for much less antimicrobial use than continuous daily dosing. Postcoital prophylaxis seems to be as effective as a daily administration. Antibiotic options include a single dose of nitrofurantoin 50 or 100 mg, trimethoprim/sulfamethoxazole 40/200 mg or 80/400 mg, trimethoprim 100 mg, and cephalexin 250 mg.⁴ The decision should be based on reported community resistance, adverse effects, and cost.

Intravesical Antibiotic Instillations

Intravesical antibiotics have been shown to be safe and effective with little systemic absorption. Gentamicin has been most frequently studied, with regimens including instillation of 30 to 60 mL of gentamicin solution (gentamicin 40-80 mg in 50 mL of normal saline).⁴

Intravesical Instillations With Hyaluronic Acid

In patients with rUTI, damage may occur to the urothelium affecting the glycosaminoglycan (GAG) layer. Hyaluronic acid replenishes the GAG layer, thereby theoretically preventing bacterial adherence to the urothelium.⁸ Small studies have been performed examining the role of hyaluronic acid (alone or in combination with chondroitin sulfate) in prevention of rUTI. A randomized, placebo-controlled trial of women with rUTI (n = 57) demonstrated a statistically significant reduction in UTI incidence among those treated with intravesical instillations of hyaluronic acid-chondroitin sulfate solution when compared with placebo.⁸

Intravesical Chitosan Plus Antibiotics

Chitosan is a type of fiber derived from chitin that comes from the shells of crustaceans. It stimulates exfoliation of urothelial cells, promoting clearance of uropathogenic E. coli that has colonized these urothelial cells in persistent bacterial reservoirs.⁹ A future therapy that shows promise for treatment of rUTI involves chitosan instillations in combination with antibiotics. Although initial studies in mice of a single dose of chitosan and subsequent doses of ciprofloxacin alone did not prevent relapsing infection, a subsequent mouse study of 4 doses of chitosan combined with ciprofloxacin shows promise for treating rUTI.⁹

Fulguration

Women with rUTI who experience trigonitis may benefit from fulguration of the trigone during a cystoscopy. Trigonitis is inflammation seen at the trigone and may be due to colonization at the trigone.¹⁰ In 1 study, 33 patients underwent cystoscopic fulguration. The primary outcome measure was complete resolution of trigonitis on subsequent cystoscopy at 6 months. Of the 76% with negative cystoscopic evaluation, 32% were completely cured with negative urine cultures and no antibiotic courses or symptoms suggestive of UTI at a mean of 48 months after fulguration. Seventy-six percent (n = 25) of patients with a follow-up of 50 +/- 19 months had a resolution of trigonitis. Eight patients experienced failure.¹⁰ Fulguration may be a potential treatment option for patients with antibiotic resistance, allergies, or recurrence despite completion of antibiotic therapy.

Prevention of rUTI: Integrative Approaches

Postcoital Nonantibiotic Prophylaxis

Postcoital prophylaxis in the form of an oral preparation of hyaluronic acid, chondroitin sulfate, curcumin, and quercetin was studied as a preventative strategy. In the study, the mixture was given daily for 1 month, then once monthly for 5 additional months. In the 98 women studied, episodes of dysuria and number of voids decreased, and only 7.1% of women reported positive urine cultures. Although promising, further studies into the efficacy of oral hyaluronic acid in prevention of rUTI are needed.¹¹

Hydration

Fluid intake dilutes the urine and clears intravesical bacteria preventing them from cellular adhesion. In patients with rUTI whose hydration is less than that recommended, increasing water intake may decrease risk for recurrence. Hooton et al¹² performed a randomized controlled trial (RCT) in 140 women who drank less than 1.5-L fluid per day. Patients were randomized to a control group that received no additional water and a study group that received 1.5 L of water additionally. At 1 year, the mean number of UTIs/antibiotic courses in the control group was 3.2/3.6 and in the water group 1.7/1.9 (P < 0.001). In patients with rUTI whose hydration is less than that recommended, increasing water intake may decrease risk for recurrence.

Cranberry

The active ingredient in cranberry, proanthocyanidins, inhibits the binding of E. coli to urothelial cells by affecting pili binding. A systematic review of the literature investigating the efficacy of cranberry in preventing UTIs in 4473 patients was equivocal.¹³ Initial studies demonstrated that cranberry juice may decrease the number of UTIs, but subsequent small studies showed only small benefit that did not reach statistical significance.^4,13,14

A more recent review of the literature included 7 RCTs and a meta-analysis and showed a reduction of risk of UTI by 26%. The studies were small with high loss to follow-up.¹⁵ Future larger, RCTs are necessary before one can definitively recommend cranberry for the prevention of rUTI.

D-mannose

The sugar monomer D-mannose is thought to glycosylate proteins and affect bacterial pili, thereby inhibiting binding to urothelial cells. Few trials have been performed to assess its effectiveness. In 1 randomized clinical trial, 103 women received D-mannose powder in 200 mL of water daily for 6 months and 103 women received nitrofurantoin 50 mg daily. A control group of 102 women had no intervention. Ninety-eight patients (31.8%) had rUTI with 14.6% in the D-mannose group, 20.4% in the nitrofurantoin group, and 60.8% with no prophylaxis. D-mannose and nitrofurantoin significantly decreased the risk of rUTI (P < 0.0001) and were well tolerated.¹⁶

A recent systematic review and meta-analysis demonstrated that D-mannose is more effective than placebo and potentially as effective as antibiotics in the prevention of rUTIs.¹⁷ D-mannose has good tolerability, with diarrhea as the most frequently reported adverse effect (<8%).¹⁷

Methenamine

Methenamine was first used to treat UTIs in 1899. In the acidic bladder environment, it converts to formaldehyde and ammonia. It comes as a salt form, hippurate or mandelate, which aids in forming the acidic environment necessary for it to work. Formaldehyde then prevents the formation of DNA bases in bacteria. Methenamine may be effective in preventing UTI in patients with normal renal tracts. It appears to be a safe and effective preventative strategy for older patients.¹⁸

A retrospective study in renal transplant patients followed over a median of 300 days pre- and post-methenamine therapy showed a 45% reduction in UTI frequency.¹⁹ This study addresses patients with a complicated history of rUTI. Further studies are necessary to extrapolate the data to uncomplicated patents.

Urinary Alkalization

Medications that reduce the acidity of the urine to improve the symptoms associated with UTIs have been used in some countries. The most common alkalinizers have been potassium citrate, sodium citrate, and sodium bicarbonate. They raise urinary pH, which might provide symptomatic relief. However, it is not known whether there is a correlation between urine pH and dysuria. There is also conflicting information as to whether or not alkalization is bactericidal, promoting symptom relief. Conversely, some studies show urine pH in the acidic versus alkaline range is more favorable leading to an inhibitory environment for bacterial growth. A 2016 Cochrane review examined the benefits and harms of the use of urinary alkalinizers for treatment of uncomplicated UTIs in women. However, of the studies reviewed, no RCTs investigating urinary alkalinizers exist, nor did the studies show the correlation between reported UTI symptoms and urine pH. Therefore, there is insufficient evidence to support the use of alkalinizers for eradication or symptom improvement in uncomplicated UTI.²⁰

Topical Estrogen in Postmenopausal Women

It is understood that changes in the hormonal status of postmenopausal women promote changes in the vaginal bacterial flora due to loss of lactobacilli, changes in vaginal pH, and colonization of the vagina by enteric bacteria. Application of vaginal estrogen helps to restore the vaginal environment, and studies have been performed to determine whether treatment with vaginal estrogen decreases the incidence of rUTI. Results have shown a reduction in rUTI; however, not all demonstrate clinical significance. A 2008 Cochrane review states that vaginal estrogen is helpful in the prevention of rUTI.²¹ Regarding the optimal dose of topical estrogen, a recent RCT of postmenopausal women (n = 26) demonstrated that formulations of vaginal estrogen (cream or ring) that are commonly prescribed in the United States for treatment of vaginal atrophy were effective in preventing UTI.²² Of note, these authors noted improved adherence in patients who used the vaginal estrogen ring.²²

Additionally, 93 postmenopausal women with a history of rUTI were randomized in a double-blind placebo-controlled trial to receive topical estriol. Monthly urine cultures were performed in symptomatic patients along with assessment of vaginal pH and evaluation of vaginal microflora for a total of 8 months. There was a reduction in the incidence of rUTI in the estriol group versus the placebo group with a total of 0.5 versus 5.9 UTIs per patient year, respectively. Additionally, the estriol group had a reduction in the vaginal pH, reduced E. coli colonization of the vagina, and normalized lactobacilli-dominant vaginal flora. Although the doses of estriol studied are not recommended in the United States, the results suggest that restoration of bacterial flora may play a role in prevention of rUTI.²³

Probiotics

The presence of normal vaginal flora is protective against UTI. The predominating Lactobacillus species produce lactic acid, which lowers the vaginal pH, preventing bacterial overgrowth, and are known to prevent uropathogens from adhering to the bladder urothelium.

Additionally, there is mounting evidence that the gut microbiome plays a role in the pathogenesis of UTI, considering that many uropathogens (such as E. coli) are originally bacteria found in the gut.²⁴ Furthermore, there is a growing body of research characterizing normal urinary tract flora and examining the role that alterations in this urinary microbiome plays in rUTI.²⁴

The mainstay of treatment for rUTI involves antibiotic therapy, which can affect the microbial flora of the vagina and urinary tract. Such disruptions can predispose to further infections as well as promote antibacterial resistance. There are only small studies available evaluating the benefit of probiotics in treating UTI. Weekly administration of Lactobacilli to restore the normal bacterial flora has been investigated in small studies and found some recolonization of the epithelium and reduction of UTIs.²⁵ In one trial, postmenopausal women were randomized to receive oral Lactobacillus twice daily or trimethoprim/sulfamethoxazole 480 mg daily. After 12 months, patients receiving Lactobacilli did not meet noninferiority criteria in the prevention of rUTI. However, there was no antibiotic resistance associated with use in comparison to the antibiotic arm.²⁶

A Cochrane review of 9 studies showed no significant reduction in the risk of recurrent symptomatic UTIs between patients treated with probiotics and placebo [6 studies, n = 352: relative risk (RR), 0.82; 95% confidence interval (CI), 0.60-1.12]. Additionally, there was no significant reduction in the risk of recurrent symptomatic UTI found in patients treated with probiotics versus antibiotics (1 study, n = 223: RR, 1.12; 95% CI, 0.95-1.33).²⁷ Further investigation into the role and ideal regimen of probiotics for rUTI prevention is warranted.

Vitamin C

Vitamin C (ascorbic acid) has been theorized to prevent UTI by acidifying urine. There are 2 small studies that have investigated the role of vitamin C in UTI prevention with conflicting results. A study of 13 male and female patients with spinal cord injury demonstrated no difference in urine pH or prophylactic benefit of vitamin C compared with placebo.²⁸ However, a randomized trial of pregnant women (n = 110) demonstrated that daily vitamin C supplementation for 3 months reduced risk of UTI.²⁹ Both trials studied specific susceptible populations, thereby limiting the generalizability of these studies. Furthermore, these studies did not control for dietary factors that may confound the acidifying property of vitamin C. Thus, larger clinical trials evaluating the role of vitamin C in healthy nonpregnant women are needed.

Vitamin D

Vitamin D may have a role in preventing rUTI. A randomized placebo-controlled trial of 511 participants demonstrated that those who received 20,000 IU of vitamin D weekly for 5 years had significantly fewer UTI compared with placebo.³⁰ In a mouse model, vitamin D-deficient mice had higher levels of uropathogenic bacteria compared with those that were supplemented with vitamin D.³¹ Vitamin D has also been shown in ex vivo studies of bladder epithelium to increase tight junction proteins thereby protecting against E. coli infection by strengthening the bladder epithelial integrity.³²

Herbal Medicine

Herbal medicine has historically been used across cultures for treatment of UTI, and potentially represents an accessible treatment option in the setting of increasing antibiotic resistance. Several herbs in the form of essential oils such as oregano, thyme, and cinnamon have been reported to have antioxidant properties and may function as antifungals or antibacterials.³³ Essential oils such as cinnamon, clove, geranium, lemon, lime, orange, and rosemary have been reported to have an antiseptic, inhibitory effect on gram-positive and gram-negative bacteria.

Biofilm-forming bacteria (including E. coli) have been implicated in rUTI and may be resistant to antibiotic treatment. A study examining the inhibitory effect of several essential oils demonstrated significant antibiofilm activity for R. officinalis (rosemary), T. zygis (thyme), and O. majorana (oregano).³³R. officinalis was found to inhibit biofilm formation in over 85% of E. coli isolates.³³

Leaf extract from Arctostaphylos uva-ursi (bearberry) has reported antimicrobial and anti-inflammatory properties.³⁴ It has historically been used for treatment of UTI,³⁴ and some studies have been undertaken. In a double-blind RCT, uva-ursi extract combined with dandelion root (UVA-E) was more effective than placebo in preventing rUTI.³⁵ Additionally, a recent double-blind, placebo-controlled, randomized trial (n = 382) demonstrated a reduction in antibiotic use for women given uva-ursi compared with placebo, although this reduction was not statistically significant.³⁶ Adverse effects include insomnia, nausea, and vomiting. It is contraindicated in pregnancy and breastfeeding, and also possibly unsafe when taken orally in high doses or on a long-term basis. Possible complications include hepatotoxicity, eye problems, respiratory distress, convulsions, and even death. The limited data regarding its role in UTI prophylaxis are promising, but adverse effects are concerning.

Chinese Herbal Medicine

Chinese herbal medicine (CHM) refers to use of various herbal formulations used in traditional Chinese medicine and has been used for over 2000 years in the treatment of UTI symptoms.³⁷ A systematic review that examined the use of CHM on rUTI in women included 7 RCTs (n = 542) and demonstrated that CHM alone or when combined with antibiotics may be helpful for acute treatment of UTI as well as reducing the risk of recurrence for at least 6 months.³⁷

Vaccines

Vaccination for rUTI is a method under investigation that reinforces natural mechanisms of defense. Uromune, a bacterial vaccine containing E. coli, Klebsiella pneumoniae, Proteus vulgaris, and Enterococcus faecalis, was studied in women with rUTI. Uromune was given to 159 patients for 3 months and sulfamethoxazole/trimethoprim 200/40 mg was given to 160 patients for 6 months. At 3 months, the mean number of infections was 0.36 and 1.6, respectively. At 3, 9, and 15 months, the number of patients with no UTI was 101, 90, and 55 in the vaccinated group and 9, 4, and 0 in those receiving antibiotic prophylaxis (P < 0.0001).³⁸

In Europe, an immunoactive agent, OM-89, a preparation of membrane proteins from 18 different uropathogenic E. coli strains, is recommended for UTI prophylaxis. Its safety and efficacy are well documented, and it is included in the European Association of Urology guidelines on urological infections. In a randomized, single-blinded, placebo-controlled phase 1b trial, ExPEC4V, a tetravalent bioconjugate vaccine against extraintestinal pathogenic E. coli, was evaluated for safety, immunogenicity, and clinical efficacy. Initial data in patients with rUTI showed that the vaccine was well tolerated, elicited a robust antibody response, and reduced the frequency of UTIs. These data suggest that bacterial immunosensitization may be a future therapy for the prevention of rUTI. Future RCTs are necessary to determine the clinical value of this approach.³⁹

Acupuncture

Acupuncture has been used in the treatment and prevention of many clinical conditions. However, there is little scientific documentation on the clinical use related to urological systems, including rUTI. In 1 study, 67 women were randomized to acupuncture, sham acupuncture, or no treatment. In a 6-month period, the acupuncture group experienced half as many episodes of UTIs as the sham group. There were one-third fewer infections than in the control group. Eighty-five percent of the acupuncture group, 58% of the sham group, and 36% of the control group were UTI free in a 6-month interval. Acupuncture was highly effective in reducing the reinfection rate among women with rUTI.⁴⁰

Conclusion

Despite our advances in the understanding of the pathogenesis and epidemiology of rUTI, these infections continue to demand significant health care resources and represent an important cause of morbidity and even mortality. Although a number of preventative and treatment modalities are available, weak evidence is available to support their use in all patients. Treatments are generally individualized based on patient choice, treatment tolerability, and success in decreasing frequency of rUTI. Integrative medicine approaches may have the potential to represent a cost-effective approach to avoiding antibiotics, which in turn could result in lower rates of antibiotic resistance and adverse effects. Our algorithm for treatment is illustrated in Figure 1.

Figure 1. Integrative approach to recurrent UTI prevention algorithm.

References