Prevention of Urinary Tract Infection (UTI)

Approximately 25% of women with acute cystitis develop recurrent urinary tract infections (UTIs). (See Urinary Tract Infections in Females.) The rate per woman ranges from 0.3-7.6 episodes per year; frequently, they are clustered in time. The causative organism arise from those colonizing the fecal or periurethral areas. ^[1]

Women who develop a UTI within 2 weeks of a treated UTI may have a new infection or a relapse of the infection caused by the original uropathogen. The latter is supported by cultures that grow the same species, especially if it is biotyped or shares the same antimicrobial sensitivities. Looking for a source of persistent infection, such as a structural abnormality (eg, calculus, abscess, cystic disease), is prudent.

Prevention of UTIs has become even more important because of the recognition of what has been described a "stealth pandemic" of Escherichia coli sequence type 131 (ST131) that is resistant to both fluoroquinolones and extended spectrum beta-lactamases. Across the board, E coli is responsible for at least 80% of the 7 million uncomplicated outpatient UTIs that occur yearly in the United States. ^{[2, 3, 4]}

The 3 main risk factors for recurrent urinary tract infection (UTI) in healthy women are frequent sexual intercourse, the loss of the protective effect of lactobacilli from the vagina and periurethra due to menopause or use of spermicidal jelly or diaphragm, and menopausal loss of estrogen’s effect in the vagina and periurethral structures. Perhaps the most established method of preventing recurrent UTI in postmenopausal women is vaginal estrogen therapy administered either via vaginal ring or cream application. ^[5] Because spermicidal jelly disrupts the normal vaginal flora, women with recurrent UTI should consider other methods of contraception.

Women with 2 or 3 recurrent UTIs yearly may benefit from behavioral modification. Behavioral modifications generally are easy, low-risk, and low-cost maneuvers.

A study of 140 women with recurrent UTIs showed that increased fluid intake reduces the risk for repeat infections. The study participants were otherwise healthy premenopausal women who had experienced 3 or more UTIs in the preceding year and who self-reported low fluid intake (< 1.5 liters/day). The intervention group was instructed to increase their water intake by an additional 1.5 liters per day, whereas the control group was instructed to continue with their usual intake. At 1 year, the intervention group had experienced 48% fewer UTIs than the control group. The only fluid involved in the study was water, although other fluids would probably provide similar results, and the benefits would probably also apply to postmenopausal women. In addition, the intervention group used 47% fewer courses of antibiotics than the control group (1.8 vs 3.5; P< 0.0001). ^[6] Despite the results of this and similar studies, the only randomized controlled trial that showed statistically significant effects of increased fluid intake for UTI was conducted in healthy premenopausal women cared for in primary care clinics. ^[7]

Menopausal women appear to benefit from estrogen replacement administered systemically or applied locally. A randomized, double-blind, placebo-controlled trial in 93 postmenopausal women documented that estriol vaginal cream (0.5 mg nightly for 2 weeks, then twice weekly for 8 months) significantly lowered the frequency of recurrent UTI, ^{[5, 8]}  probably because of its ability to restore the premenopausal flora of lactobacilli. This, in turn, suppresses gram-negative flora by decreasing the vaginal pH.

Sexually active women may attempt voiding immediately after intercourse to lessen the risk for coitus-related introduction of bacteria into the bladder. Some authors recommend large urinary flow volumes as a measure that will reduce the risk for UTI.

Drinking cranberry juice (10 oz/day) or taking cranberry tablets may offer some benefit in reducing recurrent UTI and does not appear to be harmful. The positive effect appears mainly to women with recurrent UTIs. ^[9]

One study found lower rates of UTI recurrence in women who drank 50 mL of cranberry-lingonberry concentrate daily for 6 months. ^[10] The mechanism of action of cranberry juice has not been fully clarified. ^[11] The juice is bacteriostatic perhaps due to hippuric acid. Another mechanism may involve suppression of Escherichia coli fimbriae by proanthocyanidins (tannins). This theoretically should be under the attachment of urinary pathogens to the bladder mucosal cells. The studies conducted have generally been flawed because of small numbers, unknown amounts of active ingredients, and a high rate of nonadherence to drinking adequate amounts of cranberry juice. ^[12]  At best, cranberry juice/tablets can be regarded as a safe complementary therapy in women with recurrent UTI. ^[13]

 The claimed preventative effect of its urinary acidification by ascorbic acid (vitamin C) remains unproven. It simply does not cause significant urinary acidification.

Self-initiated antibiotic therapy has been an acceptable alternative for women with recurrent UTIs. The clinician should educate the patient about the warning signs of a persistent or worsening infection despite therapy. With the marked rise in uropathogenic resistance especially among gram negative organisms, this approach needs to be reassesed. 

In 1 study, women with a history of at least 2 urinary tract infections (UTIs) in the past year proved capable of self-diagnosing and treating UTIs. ^[14] Uropathogens were isolated in 84% of 172 UTIs and sterile pyuria in 11%; clinical and microbiologic cures were achieved in about 95% of episodes. Self-treatment consisted of ofloxacin tablets, 200-mg tablets taken twice daily for 3 days if UTI symptoms developed, or levofloxacin, 250-mg tablets taken once daily for 3 days.

A study from China evaluated patient-initiated single-dose antibiotic prophylaxis and continuous long-term low-dose daily antibiotic use for the prevention of recurrent UTI in 68 postmenopausal women, finding that the former was as effective as the latter and was associated with fewer gastrointestinal adverse events. ^[15]

Women with more than 3 recurrent UTIs yearly should be considered for more aggressive prophylactic regimens in addition to behavioral modification. Women whose recurrent UTIs are associated with sexual intercourse should be offered postcoital prophylaxis. This involves taking a single dose of an effective antimicrobial (eg, nitrofurantoin 50 mg, trimethoprim-sulfamethoxazole [TMP-SMX] 40/200 mg, or cephalexin 500 mg) after sexual intercourse.

A double-blind, double-dummy noninferiority trial found that TMP-SMX (480 mg once daily) is more effective than cranberry capsules (500 mg twice daily) in preventing recurrent UTIs. However, after 1 month, patients in the TMP-SMX group showed increased resistance to the antibiotic as well as to trimethoprim, amoxicillin, and ciprofloxacin. This resistance reached baseline levels 3 months after discontinuance. ^[16]

Continuous antimicrobial prophylaxis may be required for women in whom a postcoital regimen fails; women who do not associate frequent UTIs with a modifiable cause; or those who are at risk for recurrent complicated UTIs. Regimens include the following:

• TMP-SMX - 40/200 mg at bedtime or 3 times weekly

• Nitrofurantoin - 50-100 mg at bedtime or 3 times weekly

• Norfloxacin - 200 mg at bedtime or 3 times weekly

• Trimethoprim - 100 mg at bedtime or 3 times weekly

These regimens have been shown to be safe and effective, even after 5 years of use. However, after 6-12 months, a trial without the medication is warranted, because as many as 30% of women experience a prolonged UTI-free period. Prophylaxis may be reinstituted if the patient again develops recurrent UTIs. ^[17]

Patients with spinal cord injury

For patients with spinal cord injury, the efficacy of prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX) or nitrofurantoin has been demonstrated. The possibility of developing resistant organisms is a concern, especially in an institutional setting. One option includes the use of methenamine (1 g 3 times daily), alternating every 2 months with nitrofurantoin (50-100 mg twice daily). Methenamine is converted into formic acid, which is bactericidal.

Risk can also be decreased by the use of intermittent catheterization. (See Urinary Tract Infections in Spinal Cord Injury Patients and Urethral Catheterization in Women.) ^{[18, 19]}

Catheterized patients

Many steps can be taken to prevent catheter-associated urinary tract infections (UTIs). ^[20] These steps can postpone the development of a UTI for weeks but are not likely to be successful in chronically catheterized patients. One to 3 days of antibiotic prophylaxis at the time of catheter removal results in a decrease of symptomatic UTIs. This should probably be considered in patients who are severely immunosuppressed, not as a general practice, which may result in a significant increase in the use of antibiotics in hospitalized patients. ^[21] (See Catheter-Related Urinary Tract Infections and Urethral Catheterization in Women.)

Renal transplant recipients

UTI is an important complication after renal transplantation, especially in the initial months after the procedure, and can result in graft failure and patient mortality. Prophylaxis with TMP-SMX (1 tablet/day orally), beginning 2-4 days after surgery and continuing for 4-8 months, can reduce the incidence of UTIs (especially after catheter removal), febrile hospital days, bacterial infections (during and after hospitalization), and graft rejection.

For a variety of reasons, usage guidelines and controls are failing to prevent the development of widespread antibiotic resistance. Uropathogenic E coli (UPEC) have long been recognized as the leading causes of UTIs. The properties underlying these properties have only begun to be recognized. One example of such is that the UPEC strains survive in the GI tract despite high concentrations of antibiotic to which they are sensitive, because they can develop mutations in a gene that promotes the production of a polysaccharide capsule and a type of O antigen that fosters the bacterial ability to invade and survive within human colonocytes. When antibiotic luminal concentrations decline, intestinal invasion of the gut epithelium accelerates. ^[22]  The urobiome has been less studied than that of the GI tract but may provide equally promising diagnostic and therapeutic options. ^[23]

The development of antimicrobial nanoparticles and low-risk liposomal carriers of drug delivery systems offer hope for our fading antimicrobial options. ^[24]  Indeed, these technologies may finally settle the role of various natural substances, such as cranberry juice, in the prevention and treatment of UTIs.