ࡱ>  0kbjbj 4ml_NY ####$$$XXXXXXXZ]BXQ$$$$$X##Y666$l ##X6$X66MN#$iO/NXY0NYN]1]0NNr ]YXH$$6$$$$$XX6$$$NY$$$$]$$$$$$$$$ : Recurrent urinary tract infection in women Authors Thomas M Hooton, MD Kalpana Gupta, MD, MPH Section Editor Stephen B Calderwood, MD Deputy Editor Allyson Bloom, MD All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through:Apr 2013.|This topic last updated:Mar 07, 2013. INTRODUCTION Recurrent urinary tract infection (UTI) refers to e"2 infections in six months or e"3 infections in one year. Most recurrences are thought to represent reinfection rather than relapse, although occasionally a persistent focus can produce relapsing infection. It is useful to try to distinguish clinically between relapse and reinfection, because relapsing infection warrants more extensive urologic evaluation, longer therapy, and, in some cases, surgery. However, this distinction is rarely necessary in young healthy women with recurrent UTIs. There is no evidence that recurrent UTI leads to health problems, such as hypertension or renal disease, in the absence of anatomic or functional abnormalities of the urinary tract. The epidemiology, pathogenesis, and prevention of recurrent acute uncomplicated cystitis and pyelonephritis in young, healthy non-pregnant women will be reviewed here. These infections are generally caused by the same organisms and share clinical features, diagnostic testing, and treatment regimens with sporadic uncomplicated infection. (See "Acute uncomplicated cystitis and pyelonephritis in women".) The management of asymptomatic bacteriuria, including in pregnancy, is discussed separately. (See "Approach to the adult with asymptomatic bacteriuria".) EPIDEMIOLOGYRecurrent uncomplicated UTIs are common among young, healthy women even though they generally have anatomically and physiologically normal urinary tracts. In a study of college women with their first UTI, 27 percent experienced at least one culture-confirmed recurrence within the six months following the initial infection and 2.7 percent had a second recurrence during this same time period [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f1" \t "_blank" 1]. When the first infection is caused by Escherichia coli, women appear to be more likely to develop a second UTI within six months than those with a first UTI due to another organism [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f2" \t "_blank" 2]. In a Finnish study of women ages 17 to 82 who had E. coli cystitis, 44 percent had a recurrence within one year [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f3" \t "_blank" 3]. Recurrent pyelonephritis in healthy women is very uncommon, but there are no prevalence data available. PATHOGENESISThe pathogenesis of recurrent UTI is assumed to be the same as with sporadic infection. Thus, in the normal host, most uropathogens originate in the rectal flora, colonize the periurethral area and urethra, and ascend to the bladder. Increasing evidence suggests that alteration of the normal vaginal flora, especially loss of H2O2-producing lactobacilli, may predispose women to introital colonization with E. coli and to UTI [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f4" \t "_blank" 4]. Some recurrences of UTI in women due to the same strain may be due to reinfection from a reservoir of pathogens in the epithelium of the bladder which persist following a previous UTI. Intracellular populations of bacteria have been identified in exfoliated cells in urine of women with cystitis [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f5" \t "_blank" 5]. Further studies are needed to determine whether this pathway causes same-strain recurrent UTI and if so, how it might influence treatment and prophylactic strategies. Reinfection versus relapseA recurrent UTI is classified as a reinfection if the recurrence is caused by a different strain of microorganism than the one responsible for the original infection. However, infecting pathogens frequently persist in the rectum; when a recurrence is due to the same organism, it is often impossible to distinguish between a relapse and reinfection. In clinical practice, a recurrent UTI is arbitrarily defined as a relapse if the infecting strain is the same and the recurrence occurs within two weeks of the completion of treatment for the original infection. By contrast, a recurrent UTI arising more than two weeks after treatment is considered to be a reinfection, even if the infecting pathogen is the same as the original. When a sterile urine culture is documented between the two UTIs in a patient off antibiotics, the recurrence is also classified as a reinfection. The vast majority of recurrences of cystitis appear to be reinfections. The initially infecting strain can persist in the fecal flora after elimination from the urinary tract, subsequently recolonizing the introitus and bladder and causing recurrent UTI [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f6" \t "_blank" 6]. In fact, long-term prospective studies have demonstrated that E. coli strains are capable of causing recurrent UTI one to three years later, despite appropriate treatment and disappearance of the organism in repeated urine cultures prior to the development of the next infection. However, most recurrences occur in the first three months after the initial infection [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f7%2c8" \t "_blank" 7,8]. Risk factorsSeveral host genetic, biologic, and behavioral factors appear to predispose young healthy women to uncomplicated UTI (see "Acute uncomplicated cystitis and pyelonephritis in women", section on 'Pathogenesis'). A number of factors also appear to increase the risk of recurrent UTIs. Biologic or genetic factorsWomen with recurrent UTI have been shown to have an increased susceptibility to vaginal colonization with uropathogens, even during asymptomatic periods, compared with women without a history of recurrences [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f9-13" \t "_blank" 9-13]. This difference appears to partially result from a greater propensity for uropathogenic coliforms to adhere to the uroepithelial cells of women with a history of recurrent UTIs as opposed to those without recurrent infection [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f14-18" \t "_blank" 14-18]. Genetic determinants appear to account for this underlying predisposition in some women. The nonsecretor [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f19-21" \t "_blank" 19-21] and the P1 [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f22%2c23" \t "_blank" 22,23] phenotypes are overrepresented among girls and women with recurrent UTI and recurrent pyelonephritis, respectively. (See "Bacterial adherence and other virulence factors for urinary tract infection".) In addition, uroepithelial cells from women who are nonsecretors of ABH blood group antigens show enhanced adherence of uropathogenic E. coli compared with cells from secretors [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f24" \t "_blank" 24]. The uroepithelial cells of nonsecretors selectively express unique globoseries glycolipid receptors that bind uropathogenic E. coli, which may provide a biochemical explanation for the propensity of nonsecretors to develop recurrent UTI [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f25" \t "_blank" 25]. The association between nonsecretor phenotype and recurrent UTI may be less important in women who have other strong risk factors for recurrent UTI, such as spermicide use or frequent sexual intercourse [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f4" \t "_blank" 4]. The interleukin (IL)-8 receptor, IL-8R or CXCR1, is another factor with genetic variability that may influence the development of UTI. IL-8 is an inflammatory cytokine that promotes neutrophil migration across the infected uroepithelium [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f26%2c27" \t "_blank" 26,27]. A family study of pyelonephritis-prone children found that 15 percent of 130 relatives of case children but only 3 percent of 101 relatives of controls had a UTI history [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f28" \t "_blank" 28]. CXCR1 expression was significantly lower in the pyelonephritis-prone children and their relatives than in control subjects. Behavioral risk factorsSexual intercourse, diaphragm-spermicide use, and a history of recurrent UTI are strong and independent risk factors for UTI [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f29" \t "_blank" 29]. Even spermicide-coated condom use results in an increased risk of UTI [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f30%2c31" \t "_blank" 30,31]. Recent antimicrobial use, which adversely affects vaginal flora in animals and humans [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f32" \t "_blank" 32], also is strongly associated with an increased risk of UTI [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f33" \t "_blank" 33]. However, risk factors specific for recurrent UTI have received relatively less attention. In one large case-control study of women with and without a history of recurrent UTI, the frequency of sexual intercourse was the strongest risk factor for recurrent UTI in a multivariate analysis [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f34" \t "_blank" 34]. Other risk factors identified were: Spermicide use during the past year Having a new sex partner during the past year Having a first UTI at or before 15 years of age Having a mother with a history of UTIs The latter two associations are further evidence that inherited factors may be important in some women with recurrent UTI. No associations were found in this large study or earlier studies between a history of recurrent UTI and pre- and postcoital voiding patterns, frequency of urination, delayed voiding habits, wiping patterns, douching, use of hot tubs, frequent use of pantyhose or tights, or body mass index [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f34" \t "_blank" 34]. Pelvic anatomyPelvic anatomy may predispose to recurrent UTI in some women, especially those who do not have exogenous risk factors for UTI. In one study of 213 women, 100 with a history of recurrent UTI and 113 controls without this history, perineal anatomic measurements, post-void residual urine volume, and urine voiding characteristics (eg, peak flow rate, time to peak flow) were assessed [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f35" \t "_blank" 35]. The mean distance from the urethra to anus was significantly shorter in cases than in controls (4.8 versus 5.0 cm, p = .03). This was most pronounced among non-spermicide users. However, there were no differences between cases and controls in urethral length, post-void urine residual, or urine voiding characteristics. Postmenopausal womenIn a case-control study of 149 healthy postmenopausal women with a history of recurrent UTI and 53 controls without a history of UTI, mechanical and/or physiologic factors that affect bladder emptying were found to be strongly associated with recurrent UTIs [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f36" \t "_blank" 36]. These results contrast with the predominantly behavioral risk factors described above for premenopausal women. Three urologic factors were found to be significant factors for recurrent UTI in this study: Urinary incontinence (41 versus 9 percent for cases and controls, respectively) Presence of a cystocele (19 versus 0 percent) Postvoiding residual urine (28 versus 2 percent) Multivariate analysis showed the following factors were most strongly associated with recurrent UTI (presence of a cystocele or a postvoiding residual urine were excluded because of low frequency in the controls): Urinary incontinence (OR 5.79) A history of UTI before menopause (OR 4.85) Nonsecretor status (OR 2.9) Virulence determinants of uropathogensCertain virulence determinants of uropathogens have been demonstrated to provide a selective advantage for the ability to colonize and cause infection [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f37%2c38" \t "_blank" 37,38]. Colonization with P-fimbriated strains of E. coli, for example, is a strong risk factor for acute uncomplicated pyelonephritis. However, it is not clear whether bacterial virulence determinants of strains causing recurrent UTIs differ from those causing sporadic UTIs. It is also not known whether women with recurrent UTI have a propensity for colonization with urovirulent strains compared with women who do not have recurrent UTI. PREVENTION STRATEGIESA number of strategies have been used in an attempt to prevent recurrent UTIs. Although many behavioral approaches have not been adequately tested in studies, patients and providers often hold very strong biases about their effectiveness. It is reasonable to consider such approaches for the prevention of UTI as a way of minimizing antibiotic exposure [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f39" \t "_blank" 39]. Changes in behaviorWomen with frequent recurrent UTIs can choose a different contraceptive (avoiding spermicides) or attempt other behavior modifications. However, for those who do not wish to change their method of contraception or who do not respond to other behavioral approaches, antimicrobial management should be considered. (See 'Antimicrobial prophylaxis' below.) ContraceptionWomen with recurrent UTI who are sexually active or who use spermicides (particularly in conjunction with diaphragms), should be counseled about the possible association between their infections and sexual intercourse and use of spermicides. Abstinence or a decrease or elimination of the usage of spermicide-containing products would be expected to reduce the risk of UTI. Postcoital voiding and liberal fluid intakeIt is reasonable to suggest to women that early postcoital voiding and more liberal fluid intake to increase the frequency of micturition might be helpful. These have not been shown in controlled studies to be associated with a reduced risk of recurrent UTI but are unlikely to be harmful. Cranberry juiceWe do not routinely suggest cranberry juice to reduce the incidence of recurrent UTI. Although there are plausible biological mechanisms for such an effect, clinical studies to date have not definitively demonstrated efficacy in prevention of recurrent uncomplicated cystitis [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f40-49" \t "_blank" 40-49]. However, for women with recurrent UTI who are interested in trying cranberry juice and can tolerate it, there is likely little harmful effect other than an increase in calorie and glucose intake. There may also be an increased likelihood of gastrointestinal side effects such as heartburn with cranberry juice, as suggested by some studies [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f47" \t "_blank" 47]. Laboratory studies have demonstrated that cranberry juice inhibits adherence of uropathogens to uroepithelial cells [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f50%2c51" \t "_blank" 50,51]. The mediators of this anti-adherence effect may be fructose, which could interfere with adhesion of type 1 fimbriated E. coli to uroepithelium [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f52" \t "_blank" 52], and proanthocyanidins, which can inhibit adherence of P-fimbriated E. coli [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f53" \t "_blank" 53]. The reduction in urinary P-fimbriated E. coli strains in the cranberry group of one study of 176 women, while not statistically significant, supports the biological plausibility of cranberry activity [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f47" \t "_blank" 47]. However, clinical studies on the efficacy of cranberry juice have been limited by suboptimal study design (underpowered, not blinded, or limited by other design flaws) [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f42-46%2c49" \t "_blank" 42-46,49]. In a meta-analysis of nine randomized trials, there was a decreased risk of UTI among 639 patients who used cranberry products compared with 536 control patients (RR 0.62, 95% CI 0.49-0.80) [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f48" \t "_blank" 48]. This reduction was even more marked in patients with recurrent UTI (RR, 0.53; 95% CI, 0.33-0.83). However, the meta-analysis was limited bysubstantial statistical and clinical heterogeneity, including lack of appropriate controls in several studies, extensive variability in dosing and administration of cranberry products, and variable definitions of UTI across studies. Furthermore, the meta-analysis excluded a randomized trial of 319 women presenting with an acute UTI, among whom drinking 8 ounces of 27 percent cranberry juice twice per day did not decrease the six-month incidence of recurrent UTI compared with drinking a placebo juice [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f40" \t "_blank" 40]. Of note, this study also had methodological issues including a very low event rate and lack of power [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f54" \t "_blank" 54]. An updated Cochrane meta-analysis included data from this latter study and concluded that cranberry products did not significantly reduce the occurrence of symptomatic UTI in women with recurrent UTIs (RR 0.74, 95% CI 0.42-1.31). They also concluded that cranberry juice may be unacceptable to consume over a long period [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f49" \t "_blank" 49]. Antimicrobial prophylaxisAntimicrobial prophylaxis has been demonstrated to be highly effective in reducing the risk of recurrent UTI in women [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f55%2c56" \t "_blank" 55,56]. Prophylaxis has been advocated for women who experience two or more symptomatic UTIs within six months [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f56" \t "_blank" 56] or three or more over 12 months [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f57" \t "_blank" 57]. However, the degree of discomfort experienced by the woman from these infections and concerns about antimicrobial resistance are the most important determinant of whether antimicrobial prophylaxis should be tried. Continuous prophylaxis, postcoital prophylaxis, and intermittent self-treatment (which is not really a prophylaxis method) have all been demonstrated to be effective in the management of recurrent uncomplicated cystitis. The choice of approach depends upon the frequency and pattern of recurrences and patient preference. Regimens for continuous and post-coital prophylaxis are shown in Tables 1 and 2 (table 1 and table 2). The choice of antibiotic should be based upon the susceptibility patterns of the strains causing the patient's previous UTIs and any history of drug allergies. Before any prophylaxis regimen is initiated, eradication of a previous UTI must be assured by obtaining a negative urine culture one to two weeks after treatment. ContinuousNumerous studies have demonstrated that continuous prophylaxis decreases recurrences by up to 95 percent compared with placebo or with patients' prior experience [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f56%2c58%2c59" \t "_blank" 56,58,59]. A meta-analysis from the Cochrane database evaluated 10 trials involving 430 healthy nonpregnant women with two to three or more UTIs during the previous 12 month period who were treated with continuous or postcoital prophylaxis for 6 to 12 months [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f60" \t "_blank" 60]. The following findings were noted during active prophylaxis: The range of microbiologic recurrence per patient-year was significantly reduced (0 to 0.9 in the antibiotic group versus 0.8 to 3.6 in the placebo group; relative risk of having one microbiologic recurrence 0.21, 95% CI 0.13-0.33). The number needed to treat (NNT) to prevent one recurrence in one year was 1.85. Clinical recurrence of UTI per patient-year was also significantly reduced (relative risk 0.15, 95% CI 0.08-0.28). The NNT was 2.2. Side effects, including vaginal and oral candidiasis and gastrointestinal symptoms, were significantly more common with antibiotic therapy. There was no significant difference between continuous daily and postcoital ciprofloxacin. (See 'Postcoital' below.) The review also evaluated the small number of studies that compared different antibiotics, the same antibiotic in different regimens, and antibiotics to other pharmacologic interventions. In the meta-analysis overall, no conclusions could be made with regard to the best antibiotic choice or the optimal duration of prophylaxis (the maximal duration tested was one year), schedule, or doses. Most authorities advocate a six-month trial of antibiotics administered nightly, followed by observation for further infection. The choice of six months is based upon observations that UTIs seem to cluster in some women [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f7%2c8" \t "_blank" 7,8]. However, it appears that most women revert back to the previous pattern of recurrent infections once prophylaxis is stopped (relative risk for at least one microbiologic recurrence 0.82, 95% CI 0.44 -1.53 in the above meta-analysis) [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f60" \t "_blank" 60]. Modification of other risk factors, such as sexual activity or diaphragm-spermicide use, would probably be beneficial in this regard. Some authorities advocate prophylaxis for two or more years in women who continue to have symptomatic infections [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f56" \t "_blank" 56]. Use of trimethoprim-sulfamethoxazole or other agents for as long as five years has been reported to be effective and well-tolerated [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f8%2c61" \t "_blank" 8,61]. Nitrofurantoin has also been shown to be safe and well-tolerated in long-term (12 months) prophylaxis regimens, although 16 percent of women did not benefit in one study [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f62" \t "_blank" 62]. Of note, there are concerns about toxicity with long term nitrofurantoin use, as discussed below. Data on use of fosfomycin for prophylaxis are limited. In one randomized trial of 317 nonpregnant women with a history of recurrent UTIs, administration of fosfomycin (3 g every 10 days for six months) reduced the number of UTIs per patient year (0.14 versus 2.97) [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f63" \t "_blank" 63]. The time to first infection recurrence was significantly longer in the fosfomycin group than in the placebo group (38 versus 6 days) and the drug was well tolerated. PostcoitalPostcoital prophylaxis (a single postcoital dose) may be a more efficient and acceptable method of prevention than continuous prophylaxis in women whose UTIs appear to be temporally related to sexual intercourse. Depending upon the frequency of intercourse, postcoital prophylaxis usually results in receipt of smaller amounts of antimicrobials than continuous prophylaxis. In the only placebo-controlled trial, the infection rate was lower in patients receiving postcoital trimethoprim-sulfamethoxazole (40 mg/200 mg) compared with placebo (0.3 versus 3.6 per patient-year) [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f64" \t "_blank" 64]. Uncontrolled studies suggest a comparable reduction in infection rates with postcoital trimethoprim-sulfamethoxazole, nitrofurantoin, cephalexin, and the fluoroquinolones (table 2) [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f59%2c65-68" \t "_blank" 59,65-68]. In a randomized trial, postcoital ciprofloxacin was as effective as daily ciprofloxacin in sexually active young women [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f69" \t "_blank" 69]. Postcoital prophylaxis is also effective when women with recurrent UTIs become pregnant. However, the choice of drugs is more limited. The preferred regimen is a single postcoital dose of either cephalexin (250 mg) or nitrofurantoin (50 mg) [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f70" \t "_blank" 70]. Antimicrobial resistanceThe prophylactic efficacy of any antimicrobial agent depends upon the continued susceptibility to the drug of potential uropathogens colonizing the patient's fecal, periurethral, and vaginal flora [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f8%2c58" \t "_blank" 8,58]. However, monitoring rectal or vaginal flora for the presence of resistant organisms has not been proven to be helpful in anticipating breakthrough infections [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f58" \t "_blank" 58]. The emergence of uropathogens resistant to the agent being used for prophylaxis has been increasingly reported, especially with particular antibiotics [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f57%2c69%2c71" \t "_blank" 57,69,71]. In one study comparing postcoital versus daily ciprofloxacin prophylaxis for UTIs, 5 of 62 patients receiving daily prophylaxis for three months had breakthrough UTIs, two with organisms resistant to ciprofloxacin [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f69" \t "_blank" 69]. In a study of long-term trimethoprim-sulfamethoxazole prophylaxis, breakthrough infections were due to organisms resistant to trimethoprim-sulfamethoxazole [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f61" \t "_blank" 61]. Similarly, in a randomized trial comparing daily oral trimethoprim-sulfamethoxazole to Lactobacillus for prophylaxis of recurrent UTIs, microbiologically confirmed symptomatic recurrences (76 percent caused by E. coli) were documented in 49 percent of the women taking the antibiotic. Over 90 percent of these E. coli isolates were resistant to trimethoprim-sulfamethoxazole compared with less than 30 percent of the asymptomatic bacteriuria E. coli strains isolated at baseline [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f71" \t "_blank" 71]. In contrast, fewer than 30 percent of the E. coli strains causing symptomatic recurrences during Lactobacillus prophylaxis were resistant to trimethoprim-sulfamethoxazole, which was lower than the baseline prevalence among asymptomatic bacteriuria E. coli strains. The increasing baseline prevalence of resistance among uropathogenic E. coli strains to trimethoprim or trimethoprim-sulfamethoxazole may complicate prophylaxis with these agents. Special considerationsNitrofurantoin is contraindicated for patients with renal insufficiency (creatinine clearance <60 mL/minute). In addition, long-term exposure to nitrofurantoin has been associated with pulmonary reactions, chronic hepatitis and neuropathy. These toxicities are rare but patients should be warned about them. Fluoroquinolones are contraindicated in pregnant women and children. Women on fluoroquinolones for treatment or prophylaxis should be reminded to employ effective contraception. Other adverse effects include prolonged QTc interval and tendon rupture [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f72-76" \t "_blank" 72-76]. The efficacy of oral contraceptives may be reduced by some antibiotics, as they can alter gut flora that participate in enterohepatic recycling of estrogen or induce hepatic estrogen metabolism, reducing estrogen concentrations. Rifampin has been proven to decrease serum ethinyl estradiol and progestin levels in women taking oral contraceptives [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f77" \t "_blank" 77], and women should be counseled to use a second contraceptive alternative, such as a barrier contraceptive, while on rifampin. Although some older reports describe reduced estrogen levels with other agents (penicillins, macrolides and tetracyclines), pharmacokinetic studies have not shown a significant or consistent effect [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f78%2c79" \t "_blank" 78,79]. (See "Overview of the use of estrogen-progestin contraceptives", section on 'Drug interactions'.) Antibiotics are associated with an increased risk of Clostridium difficile diarrhea (CDAD). The risk of acquiring CDAD should be discussed with patients using antibiotics for the prophylaxis of recurrent UTI. Topical estrogen for postmenopausal womenReplacement topical estrogen normalizes the vaginal flora and greatly reduces the risk of UTI in postmenopausal women. In a randomized trial of 93 postmenopausal women with a history of recurrent UTI, topically applied intravaginal estriol cream (0.5 mg estriol nightly for two weeks then twice weekly for eight months) significantly reduced the incidence of UTI compared with placebo (0.5 versus 5.9 episodes per patient year) [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f80" \t "_blank" 80]. Patients treated with estrogen cream had an increase in the prevalence of lactobacilli and decrease in E. coli vaginal colonization. The relative efficacy, safety and patient tolerability of this approach has not been directly compared with antimicrobial prophylaxis, but both strategies appear to be effective in postmenopausal women. Intravaginal estrogen may be reasonable in postmenopausal women not taking oral estrogen who have three or more recurrent UTIs per year, particularly when antimicrobial resistance to multiple drugs limits the efficacy of antimicrobial prophylaxis [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f81" \t "_blank" 81]. Other strategies ProbioticsThe use of probiotics has raised interest as a novel approach to reducing the risk of recurrent UTI. Probiotics may protect the vagina from colonization by uropathogens through a variety of mechanisms, including: Steric hindrance or blocking potential sites of attachment Production of hydrogen peroxide which is microbicidal to E. coli and other uropathogens Maintenance of a low pH Induction of anti-inflammatory cytokine responses in epithelial cells In a review of four randomized controlled trials of Lactobacillus probiotics for bacterial genitourinary infections in women, only one demonstrated a significant reduction in rates of UTI recurrence [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f82" \t "_blank" 82]. However, most of these studies did not determine whether the probiotic led to vaginal colonization with the probiotic strain. A subsequent trial, in which postmenopausal women with a history of recurrent UTI were randomly assigned to take trimethoprim-sulfamethoxazole (n = 127) or Lactobacillus tablets (n = 125) for 12 months, reported that women in the Lactobacillus group had more frequent clinical recurrences over the year (mean 3.3 versus 2.9 events) and shorter time to recurrence (three versus six months) than women in the antibiotic group [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f71" \t "_blank" 71]. Notably, a higher proportion of patients in the Lactobacillus group discontinued therapy because of adverse effects (12.2 versus 5.2 percent) and the probiotic strain of Lactobacillus tested for could not be identified by polymerase chain reaction in the vaginal flora of any women. Delivery of Lactobacillus through other methods may be more promising. Thus, a placebo-controlled trial evaluated the effect of a strain of Lactobacillus crispatus (which constitutes nearly 90 percent of the vaginal microbial flora), administered as a vaginal capsule, among premenopausal women with recurrent cystitis [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f83" \t "_blank" 83]. Vaginal Lactobacillus treatment (n = 50) was well tolerated, achieved high levels of vaginal colonization, and was associated with decreased rates of recurrent UTI (15 versus 27 percent of women in the placebo group). While the probiotic approach has a credible scientific basis, additional adequately designed clinical trials need to be performed before its routine use can be recommended. VaccinesA safe and effective vaccine to reduce the risk of recurrent UTI would be a welcome breakthrough. Whole cell vaccines, made from combinations of heat-killed uropathogenic strains delivered by injection or by a vaginal suppository, have to date had only partial success [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f84-86" \t "_blank" 84-86], and the protective effect appears to wane over several weeks. One promising approach under development is a vaccine based upon the E. coli type 1 fimbrial adhesion protein, FimH [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f87" \t "_blank" 87]. Virtually all uropathogenic strains of E. coli assemble type 1 pili that contain the FimH adhesin. (See "Bacterial adherence and other virulence factors for urinary tract infection", section on 'Adhesins'.) Avirulent bacteriaOther potential strategies include the use of a genetically engineered avirulent E. coli strain that could be instilled intravesically. This might prove useful in patients who fail to respond to conventional prophylaxis measures [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f88" \t "_blank" 88]. One preliminary report using such a strain in patients with spinal cord injury showed a 50-fold reduction in symptomatic UTI in those who were successfully colonized with the avirulent strain [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f89" \t "_blank" 89]. Compounds mimicking the host uroepithelial receptors may competitively bind to bacterial surface ligands and decrease the number of bacteria attaching to the mucosa sufficiently to alter the delicate balance of host-parasite interaction in favor of the host [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f90%2c91" \t "_blank" 90,91]. AntisepticsThe use of methenamine salts, which are converted to formaldehyde in acidified urine and thus have general antibacterial activity, has been proposed for preventing UTI, but its efficacy is unconfirmed and we do not recommend routine use of methenamine for this purpose in young healthy women. In a meta-analysis of six studies evaluating methenamine hippurate for the prevention of symptomatic UTI, significant methodologic problems and clinical heterogeneity among the studies were noted [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f92" \t "_blank" 92]. A subgroup analysis of patients from three studies did demonstrate a reduction in the incidence of UTI with the use of a short course of methenamine (one week or less) among women without renal tract abnormalities who recently underwent gynecologic surgery (RR 0.14; 95% CI 0.050.38). However, this is not a group in which we would recommend use of methenamine since such women are at low risk for UTI and are otherwise easily treated with a short course of antimicrobials. There was no benefit among patients on longer methenamine treatment courses or patients with renal tract abnormalities or neuropathic bladder. In women with recurrent UTI caused by multi-drug resistant uropathogens in whom other preventive strategies have not worked, methenamine is occasionally tried and appears to be safe and generally well tolerated, but there is only anecdotal evidence of its success. Further study of methenamine as an antimicrobial-sparing approach for the prevention of recurrent UTI, especially given the increased prevalence of multi-drug resistant uropathogens, is warranted. SELF-TREATMENTWomen who prefer to minimize their intake of antimicrobials may be candidates for self-diagnosis and self-treatment with a short course regimen of an antimicrobial, such as trimethoprim-sulfamethoxazole or a fluoroquinolone. Three studies have shown that UTI can be accurately self-diagnosed by women >85 to 95 percent of the time and that short-course antimicrobial therapy is highly effective in curing the infections [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f93-95" \t "_blank" 93-95]. Women using this approach have more symptomatic UTIs than women on continuous or postcoital prophylaxis, but their symptoms resolve quickly and the overall quantity of antimicrobials used is less with self-diagnosis and self-treatment. Use of this strategy should be restricted to those women who have clearly documented recurrent infections and who are motivated, compliant with medical instructions, and have a good relationship with a medical provider. Such women should be reminded to call their provider if the symptoms are not completely resolved by 48 hours. UROLOGIC EVALUATIONExcretory urography and cystoscopy have been shown to uncover few abnormalities to influence subsequent management of UTI in women with recurrent UTIs [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f59%2c96-99" \t "_blank" 59,96-99]. Thus, urologic evaluation of women with recurrent cystitis generally results in unnecessary expense and potential toxicity. However, further evaluation of the urinary tract is recommended if suspicion arises with any of the recurrences about complicating factors such as structural or functional abnormalities of the genitourinary tract. The isolation of Proteus spp, which is often associated with the presence of stones, and relapsing infection are examples of factors that might arouse suspicion. (See "Pathogenesis and clinical manifestations of struvite stones" and "Diagnosis and acute management of suspected nephrolithiasis in adults".) Routine urologic investigation of young women with acute pyelonephritis is also generally not cost-effective and has a low diagnostic yield [ HYPERLINK "https://mail.minapharm.net/owa/redir.aspx?C=633b7a69642146ffa92c64443d11e1b8&URL=http%3a%2f%2fwww.uptodate.com%2fcontents%2frecurrent-urinary-tract-infection-in-women%2fabstract%2f100" \t "_blank" 100] but may be indicated in those who have a delayed response to therapy. (See "Acute complicated cystitis and pyelonephritis".) Although women with recurrent acute pyelonephritis are often evaluated with excretory urography or ultrasound soon after hospitalization, in our experience with otherwise healthy college women, it is rare to find urologic abnormalities in those who respond promptly to antimicrobial therapy. We recommend such an evaluation after two recurrences of pyelonephritis or if any complicating factor is identified with any of the recurrences. (See "Acute complicated cystitis and pyelonephritis".) In those women in whom urologic evaluation is felt to be indicated, we recommend starting with computed tomography (CT) or a renal ultrasound to rule out nephrolithiasis or obstructive uropathy. Spiral CT may be superior to conventional CT. A complete urologic evaluation, including cystoscopy and excretory urography, should be performed in patients who have persistent hematuria after the infection has been eradicated. INFORMATION FOR PATIENTSUpToDate offers two types of patient education materials, The Basics and Beyond the Basics. The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on patient info and the keyword(s) of interest.) Beyond the Basics topics (see "Patient information: Urinary tract infections in adolescents and adults (Beyond the Basics)") SUMMARY AND RECOMMENDATIONS Recurrent urinary tract infection (UTI) refers to e"2 infections in six months or e"3 infections in one year. Recurrent uncomplicated UTIs are common among young, healthy women even though they generally have anatomically and physiologically normal urinary tracts. (See 'Introduction' above and 'Epidemiology' above.) Several risk factors for recurrent UTI have been identified, including the following: The frequency of sexual intercourse is a strong risk factor for recurrent UTI. Spermicide use is a strong risk factor for recurrent UTI. Women with recurrent UTI have been shown to have an increased susceptibility to vaginal colonization with uropathogens compared with women without a history of recurrences. Pelvic anatomy may predispose to recurrent UTI in some women, with a shorter distance from the urethra to the anus being associated with increased risk. Among postmenopausal women, mechanical, and/or physiological factors that affect bladder emptying are associated with recurrent UTI. (See 'Risk factors' above.) A number of strategies have been used in an attempt to prevent recurrent UTIs. Although many behavioral approaches have not been adequately studied, it is reasonable to consider such approaches for the prevention of UTI as a way of minimizing antibiotic exposure. For those who do not wish to change their method of contraception (avoiding spermicides) or who do not respond to other behavioral approaches, antimicrobial management should be considered. (See 'Changes in behavior' above.) Antimicrobial prophylaxis has been demonstrated to be highly effective in reducing the risk of recurrent UTI in women. Prophylaxis has been advocated for women who experience two or more symptomatic UTIs within six months or three or more over 12 months. However, the degree of discomfort experienced by the woman from these infections and concerns about antimicrobial resistance are the most important determinant of whether antimicrobial prophylaxis should be tried. (See 'Antimicrobial prophylaxis' above.) Continuous prophylaxis, postcoital prophylaxis, and intermittent self-treatment (which is not really a prophylaxis method) have all been demonstrated to be effective in the management of recurrent uncomplicated cystitis. The choice of approach depends upon the frequency and pattern of recurrences and patient preference. Regimens for continuous and post-coital prophylaxis are shown in Tables 1 and 2 (table 1 and table 2). The choice of antibiotic should be based upon the susceptibility patterns of the strains causing the patient's previous UTIs and any history of drug allergies. (See 'Antimicrobial prophylaxis' above.) Women who prefer to minimize their intake of antimicrobials may be candidates for self-diagnosis and self-treatment with a short course regimen of an antimicrobial, such as trimethoprim-sulfamethoxazole or a fluoroquinolone. Use of this strategy should be restricted to those women who have clearly documented recurrent infections and who are motivated, compliant with medical instructions, and have a good relationship with a medical provider. (See 'Self-treatment' above.) Excretory urography and cystoscopy have been shown to uncover few abnormalities to influence subsequent management of UTI in women with recurrent UTIs. Thus, urologic evaluation of women with recurrent cystitis generally results in unnecessary expense and potential toxicity. However, further evaluation of the urinary tract is recommended if suspicion arises with any of the recurrences about complicating factors, such as structural or functional abnormalities of the genitourinary tract. (See 'Urologic evaluation' above.) Use of UpToDate is subject to the  HYPERLINK "https://mail.minapharm.net/owa/UrlBlockedError.aspx" \t "_blank" Subscription and License Agreement. 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