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RecurrentUrinaryTractInfectionsinWomen

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DOI:10.1007/s00192-014-2569-5

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REVIEWARTICLE

Recurrent urinary tract infections in women

Abdullatif Aydin & Kamran Ahmed & Iftikhar Zaman &

Muhammad Shamim Khan & Prokar Dasgupta

Received: 16 August 2014 /Accepted: 4 November 2014# The International Urogynecological Association 2014

AbstractIntroduction and hypothesis Recurrent urinary tract infections(UTIs) are more common in women and are frequently de-fined as ≥2 episodes in the last 6 months or ≥3 episodes in thelast 12 months. In a primary care setting, 53 % of womenabove the age of 55 years and 36 % of younger women reporta recurrence within 1 year. Thus, management and preventionof recurrent UTI is of utmost significance. This review aims tohighlight the latest research in prevention strategies and sug-gest a management pathway.Methods A searchwas conducted onMEDLINE, Embase andthe Cochrane Database of Systematic Reviews databases forthe latest systematic reviews and high-quality randomizedcontrolled trials. Special emphasis was placed on the remit“recurrent” and strongly adhered to. Furthermore, a Googlesearch was conducted for current guidelines on the manage-ment of UTIs.Results Current prevention strategies include eliminating riskfactors that increase the risk of acquiring recurrent UTI andcontinuous, post-coital and self-initiated antimicrobial pro-phylaxis. Other prospective preventative strategies, currentlyunder trial, include use of vaccinations, D-mannose and lacto-bacillus (probiotics).Conclusion Although risk factors should be identified andaddressed accordingly, individualized antibiotic prophylaxisremains the most effective method of management. Non-antibiotic prevention strategies such as cranberry, vitamin Cand methenamine salts lack strong evidence to be introducedas routine management options and as alternatives to antibi-otics. Based on current evidence and guidelines, a

management pathway is recommended. Emerging therapiesrequire further evaluation before they can be recommended.

Keywords Recurrent urinary tract infection . Recurrent UTI .

Women .Management . Prevention . Pathway

Introduction

Urinary tract infection (UTI) is one of the commonest bacte-rial infections globally encountered by women. The risk ofwomen acquiring a UTI in their lifetime has been estimated tobe over 50 % [1, 2], with about 25 % having a recurrence [3,4]. Recurrent UTIs are symptomatic infections that followcomplete resolution of a previous UTI [5]. In a primary caresetting, 53% of women above the age of 55 years and 36% ofyounger women report a recurrence within 1 year [6]. Hence,its management and prevention is of utmost significance forall clinicians including non-specialists and those in the prima-ry care setting.

In this article, we attempt to provide an overview of recur-rent urinary tract infections and their management, using thelatest information from systematic reviews, randomized con-trolled trials and current clinical guidelines. We recommend apathway for the management of recurrent UTIs, based oncurrent evidence.

Definitions

UTI can manifest as either cystitis (lower UTI) or pyelone-phritis (upper UTI) [7] and may also be classified as compli-cated or uncomplicated. A complicated UTI is associated witha structural or functional urinary tract abnormality or an un-derlying pathology, both of which can subsequently increase

A. Aydin :K. Ahmed (*) : I. Zaman :M. S. Khan : P. DasguptaDepartment of Urology, Guy’s and St. Thomas’ NHS FoundationTrust, King’s Health Partners, MRC Centre for Transplantation,King’s College London, London, UKe-mail: kamran.ahmed@kcl.ac.uk

Int Urogynecol JDOI 10.1007/s00192-014-2569-5

risks of acquiring an infection or failure of therapy (seeTable 1). Uncomplicated UTIs are sporadic, community-acquired episodes of cystitis and pyelonephritis in otherwisehealthy individuals, but could lead to more serious outcomesand thus require additional attention. A recurrent UTI iswidely defined as more than two episodes of uncomplicatedUTI in the last 6 months or more than three in the last12 months, documented by culture [8, 9].

Pathophysiology

Responsible uropathogens

Escherichia coli is the predominant uropathogen responsiblefor both sporadic and recurrent UTI, seen in 70–95% of cases.Other causative organisms include Staphylococcussaprophyticus (10–15 % of cases) [9], Klebsiella pneumoniaeand Proteus mirabilis [7].

Following the resolution of a UTI, small numbers of theoriginal strain of uropathogensmay persist in the host and leadto infection stones (e.g. P. mirabilis). Although rare, it isimportant that bacterial persistence is identified as it is theonly surgically curable cause of recurrent UTIs [9, 10].

Relapse vs reinfection

Recurrent UTI can either be a relapse or reinfection. A relapseUTI is caused by the same bacterial strain implicated in aprevious UTI within 2 weeks of the completion of treatmentfor the original infection [11–13]. By contrast, a recurrent UTIarising more than 2 weeks after treatment or after sterileintervening culture is considered to be a reinfection, even ifthe infecting pathogen is the same as the original [11–13].They are most commonly seen in women and girls and areassociated with ascending colonization from the faecal flora.Infection occurs through bacterial colonization of the vaginaand distal urethra, which subsequently ascends into the blad-der [8, 10]. Reservoirs of bacteria may remain in the vaginaand gastrointestinal tract of susceptible patients. It has been

suggested that household contacts may also act as reservoirsfor the recolonization of these UTI-susceptible patients [14].

Risk factors

The risk factors for recurrent UTI in women vary betweenpremenopausal and postmenopausal women (Fig. 1). In pre-menopausal women, behavioural risk factors such as frequen-cy of sexual intercourse [1], new partners, use of spermicideand diaphragm use [7, 8, 11] predominate. All of these riskfactors have been found to increase vaginal and urethralcolonization with E. coli [11]. In a well-powered case-controlstudy [4], women aged 18–30 years, with recurrent UTI werecompared with women who had no history of UTIs. Theformer were ten times more likely to have had sexual inter-course more than nine times a month in the previous year,almost twice as likely to have used a spermicide in the previ-ous year and reported higher number of sexual partners. Non-behavioural risk factors such as maternal history, previouscase of UTI before 15 years of age [8] and a shorter distancebetween the urethra and anus [15] suggest that genetics andpelvic anatomy also play a role. Furthermore, a recent retro-spective study found that premenopausal women with recur-rent UTIs also had significantly lower levels of 25-hydroxyvitamin D, suggesting a deficiency [16].

For postmenopausal women, the risk factors are markedlydifferent and include oestrogen deficiency, cystocoele, uro-genital surgery, high post-void residual volume and a previousUTI [11]. These women also have a relative depletion ofvaginal lactobacilli and an increase in vaginal E. coli com-pared with premenopausal women. This age-related alterationof the normal vaginal flora, especially loss of hydrogen per-oxide producing lactobacilli, may predispose women tointroital colonization with E. coli and also to UTI [17, 18].

Genetics and family history

There is also evidence to indicate that genetic involvement,associated with an alteration in the patient’s host response,may predispose some individuals to developing recurrentUTIs. Some studies suggest that non-secretors of histo-bloodgroup antigens are more susceptible to recurrent UTIs, although

Table 1 Predisposing factors forcomplicated UTIs Factors

Urinary tract anatomic abnormality Polycystic kidneys, cystocoele, diverticulum, fistula

Urinary tract obstruction Bladder outflow obstruction, congenital abnormality,ureteral/urethral stricture, urolithiasis

Voiding dysfunction Vesicoureteric reflux, neurological disease, i.e. multiple sclerosis,hHigh post-void residual volume, incontinence

Iatrogenic Indwelling catheter, ureteral stent, nosocomial infections, surgery

Other Immunosuppressive medications, diabetes, pregnancy, renal failure

Int Urogynecol J

this has not been the case in every study [19]. Another factorwith genetic variability is the interleukin (IL)-8 receptor, IL-8Ror CXCR1, which is expressed to a significantly lower extent inpyelonephritis-prone children and their relatives [20].Furthermore, UTIs have been seen to be more prevalent infemale relatives of women with recurrent UTIs, suggesting afamilial genetic predisposition [19].

Urological evaluation

Clinical presentation

The clinical presentation of recurrent UTI is similar to sporadicUTI. Most patients present with classic symptoms of cystitiswhich include frequency, polyuria, dysuria, suprapubic tender-ness and haematuria. On the basis of prospective cohort studies,the Health Protection Agency and British Infection Associationrecommend that UTIs be diagnosed when at least three of thesesymptoms are present [21]. Fever and flank pain may also beevident with an episode of acute pyelonephritis [22].

Investigations

Diagnostic evaluation for recurrent UTIs should begin with adetailed history and physical examination (Fig. 2). This is vitalfor assessment as it enables identification of any risk factors

associated with acquisition of a complicated UTI (Table 1)and therefore guides the subsequent management (Fig. 3).

Urinalysis is usually the next step. A leucocyte and nitritepositive urine dipstick has been considered a highly sensitivetest in predicting a UTI [23]. However, since some bacteria,such as S. saprophyticus, lack the enzymes to reduce nitratesinto nitrites, false-positive results are fairly common [8]. Thus,history, physical examination or urine dipstick analysis are notsufficient to reliably rule out UTIs.

Urine microscopy and culture of midstream urine sample isthe gold standard test for a definitive diagnosis [11]. Althoughsporadic UTIs are often treated empirically with a urine cul-ture obtained when the diagnosis is unclear or the symptomspersist despite antibiotic treatment, urine culture is necessaryin patients with recurrent UTIs to confirm the diagnosis and toguide antibiotic therapy for any future recurrences.Historically, UTI has been defined as >105 colony units ofbacteria/ml on culture [8]; however, according to EuropeanAssociation of Urology (EAU) guidelines a count of >103

cells/ml in symptomatic patients is sufficient to diagnosesuspected cystitis or >104 cells/ml for suspected pyelonephri-tis [22]. In order to assess for bacterial persistence, the urinesample should be re-cultured 2 weeks after initiating therapy[24]. However, since the prevalence of asymptomatic bacteri-uria is very high in the elderly and its treatment shown to be ofno benefit but may in fact cause harm [25, 26], the diagnosisof UTI in this group of patients should not be based on urineculture alone but in light of symptoms and any evidence of asystemic inflammatory response [27].

Fig. 1 Risk factors for recurrentUTIs in women

Int Urogynecol J

Conventional urine culture requires up to 72 h from samplecollection to pathogen identification. Recently, Bonkat et al.[28] attempted to determine the quantity of bacteria andleucocytes using a combination of matrix-assisted laserdesorption/ionization time of flight and urine flow cytometryin order to try to shorten the time of microbiological identifi-cation and initiation of adequate antibiotic treatment. Theauthors compared this method against the standard and auto-mated culture methods and reported an almost 60 % earlyidentification success rate. However, these are preliminaryresults and this method requires further evaluation but maylead to targeted adjustment of antibiotic treatment at earlystages of UTI.

Although there are no guidelines for imaging studies inwomen with uncomplicated recurrent UTIs [7], patients whopresent with atypical symptoms of either acute uncomplicatedcystitis or acute uncomplicated pyelonephritis, as well as thosewho fail to respond to appropriate antimicrobial therapy andremain febrile after 72 h of treatment, should be considered foradditional diagnostic investigations such as unenhanced heli-cal computed tomography (CT), excretory urography ordimercaptosuccinic acid (DMSA) scanning [22, 24]. Theyalso need to be screened for any predisposing factors forcomplicated UTIs and may need a specialist referral.

Preventative measures

Lifestyle modifications

Patients should be informed and educated about behaviouralrisk factors, such as sexual activity [29]. Likewise, premeno-pausal women on spermicides or vaginal diaphragms shouldbe offered alternative forms of contraception [12]. It should benoted that a number of studies have failed to identify any

association between recurrent UTIs and pre- or post-coitalvoiding patterns, frequency of urination, delayed voidinghabits, wiping patterns, douching, use of hot tubs, bubblebaths, body mass index (BMI), use of tight clothing, type ofclothing, bicycle riding and the volume of fluid consumed [4,8]. Hence, such myths should be cleared up with patients.

Antibiotic therapy

Continuous antibiotic prophylaxis

In womenwith recurrent UTI, continuous antibiotic prophylaxis(once daily) has been recommended for prevention of any futureepisodes. Public Health England [29] recommends low-doseantibacterial prophylaxis (trimethoprim 100 mg ornitrofurantoin 50–100 mg) nightly for women with frequentsymptomatic recurrent infections. Other antibiotics that havebeen suggested include cephalexin and norfloxacin (Table 2).Trimethoprim and nitrofurantoin are commonly used prophy-lactic antimicrobial agents. Trimethoprim/sulfamethoxazole(TMP-SMX) and fluoroquinolones prevent recurrent UTIs byinhibiting the recovery rate of uropathogens (especially E. coli)from the faecal reservoir [30], while nitrofurantoin plays a rolein sterilizing the urine and inhibiting bacterial attachment [31].The latter is effective in terms of bacterial sensitivity with lessthan 5 % resistance to strains of E. coli [32].

Prior to prophylactic treatment, patients should have theelimination of a previous UTI confirmed by a negative urineculture 1–2 weeks post-treatment [12]. As per EAU guide-lines, antibiotic prophylaxis should be considered only aftercounselling and where appropriate behavioural modificationshave failed to prevent the recurrences [24].

The efficacy of continuous prophylaxis was demonstratedby a Cochrane review [33], which concluded that continuousantibiotic prophylaxis reduces the rate of recurrent uncompli-cated UTIs in pre- and postmenopausal women when com-pared with placebo. Furthermore, a recent systematic review[34] also demonstrated that continuous antibiotic prophylaxiswith nitrofurantoin was the most effective mode of prophy-laxis compared to acupuncture, cranberry, oestrogen and self-initiated therapy, reducing the UTI rate to 0.4 UTIs/year, butalso the most expensive. Studies have comparednitrofurantoin, trimethoprim, cinoxacin and TMP-SMX [33],where one trial showed superiority of nitrofurantoin 100 mgdaily over trimethoprim 100 mg daily. However, no antibioticclass has been clearly favoured for prophylaxis on the basis ofrandomized controlled trials and meta-analyses [33].Although certain dose regimens have been suggested(Table 2), the choice and the dose of the drug can varybased on physician preference and patient health-relatedfactors such as allergies, comorbidities as well as sen-sitivities of previously cultured organisms. There are nospecific guidelines on the duration of continuous

Fig. 2 History and assessment of women with suspected recurrent UTI

Int Urogynecol J

antibiotic prophylaxis; however, 6 months of treatmentfollowed by observation for reinfection remains the em-piric recommendation [5, 35]. In those with a greaterfrequency of recurrence following cessation of prophy-lactic therapy, longer duration on prophylaxis can beconsidered. Tables 2 and 3 outline the typical antibioticsused for continuous prophylaxis.

Continuous antibiotic prophylaxis has been associated witha number of side effects, the most common of which arenausea and candidiasis [18]. Although rare, trimethoprim,especially in combination with sulphamethoxazole, can leadto Lyell’s syndrome, Stevens-Johnson syndrome and pancy-topenia [22]. For those requiring >6 months of nitrofurantoin,it is recommended to perform liver function tests to monitor

Fig. 3 Recommended pathway for the management of recurrent UTIs

Int Urogynecol J

for hepatotoxicity and pneumonitis, which is associated withlong-term use, even at the lower doses [36]. Fortunately,reports suggest that pulmonary toxicity reverses upon discon-tinuation [37, 38].

Post-coital prophylaxis

Post-coital therapy consists of a single dose of antibioticsfollowing sexual activity and may be a more acceptable meth-od of prevention in women where frequency of sexual inter-course is a risk factor. A Cochrane review [5] found that post-coital prophylaxis was equally effective as low-dose continu-ous antibiotic prophylaxis in prevention of a recurrent UTI.Depending upon the frequency of sexual activity, post-coitalprophylaxis is required in smaller amounts than continuousprophylaxis and ia associated with fewer side effects [39].

Patient-initiated therapy

This is also referred to as self-start therapy and is ideal forwomen who are not suitable candidates for long-term prophy-laxis or for those who do not wish to take the long-termtherapy [40]. Through this method, patients can identify epi-sodes of infection on the basis of symptoms, perform theirown culture and begin a standard 3-day course of antibiotics.However, it has been associated with a higher rate of infectioncompared with continuous prophylaxis (2.2 episodes per pa-tient year vs 0.2 episodes per patient year) [41]. Although

patient satisfaction with self-start therapy is high, resolutionprompt and side-effects few [41–43], it is advised that the useof this method be restricted to patients who have documentedprevious infections and are motivated and compliant withgiven medical instructions [40]. The Infectious DiseasesSociety of America and the European Society forMicrobiology and Infectious Diseases recommendsnitrofurantoin monohydrate/macrocrystals (100 mg, twicedaily for 5 days), TMP-SMX [160/800 mg (one double-strength tablet), twice daily for 3 days], fosfomycintrometamol (3 g, single dose) or pivmecillinam (400mg, twicedaily for 5 days) [44].

Non-antibiotic prevention strategies

Oestrogen therapy

Oestrogen has been associated with colonization of vaginawith lactobacilli, which has been found to be protectiveagainst UTIs. With menopause, there is a change in thevaginal pH and flora, increasing the risk of UTI. A 2008Cochrane review [40] demonstrated vaginal oestrogen to bean effective prophylaxis in the prevention of recurrent UTIs.Similarly, Stamm and Raz et al. [45] reported a significantdecrease in UTIs amongst postmenopausal women, who used0.5 mg of vaginal oestriol cream every night for 2 weeks andthen twice a week for 8 months, compared with those using aplacebo. However, oral oestrogen tablets have been found tobe ineffective in prevention of recurrent UTIs, whilst alsobeing associated with a number of adverse effects includingbreast tenderness and vaginal bleeding [40, 46]. Furthermore,an epidemiological case-control study by Weiderpass et al.[47] showed that oral treatment with oestriol increased therelative risk of endometrial proliferation and carcinoma.

Cranberry juice and tablets

Although laboratory studies have demonstrated that cranberryjuice inhibits adherence of uropathogens to uroepithelial cells[48, 49], the clinical use of cranberry juice as a prophylactic in

Table 2 Continuous antibioticprophylaxis for recurrent UTIs [5,33, 36, 39]

a High recurrence rates observedwith trimethoprim associated withtrimethoprim resistance

Antimicrobial Dose Frequency Expected UTI/year

TMP-SMX 40 mg/200 mg Daily or 3×week 0–0.2

Trimethoprim 100 mg Daily 0–0.15a

Nitrofurantoin 50–100 mg Daily 0–0.7

Cephalexin 125–250 mg Daily 0.1–0.2

Ciprofloxacin 125 mg Daily 0

Norfloxacin 200 mg Daily 0

Ofloxacin 100 mg Daily –

Fosfomycin 3 g every 10 days 3 g every 10 days –

Table 3 Post-coital antibiotic prophylaxis for recurrent UTIs [5, 33, 36,39]

Antimicrobial Dose Expected UTI/year

TMP-SMX 40 mg/200 mg 0.3

80 mg/400 mg 0

Nitrofurantoin 50–100 mg 0.1

Cephalexin 250 mg 0.03

Ciprofloxacin 125 mg 0

Norfloxacin 200 mg 0

Ofloxacin 100 mg 0.06

Int Urogynecol J

prevention of recurrent UTIs remains debated. A Cochranereview [50] of 24 studies, with a total of 4,473 subjects,revealed that cranberry products were of no benefit comparedto placebo in most populations, whereas another meta-analysis found that the number of events halved [51]. A recentretrospective review concluded that clinical studies on cran-berry products strongly support their prophylactic use inyoung andmiddle-aged women but that evidence among otherpatients remains controversial [52]. A 2011 clinical trial [53]with 221 premenopausal women showed that continuousantibiotics were more effective in preventing recurrent UTIsthan 500 mg cranberry capsules taken twice daily, at theexpense of emerging antibiotic resistance. Thus, the potentialbenefit of cranberry in terms of product type (solid/liquid),dosing and optimal patient population therefore remains to beelucidated and is not routinely recommended. However, forwomen who are interested in trying cranberry juice and cantolerate it, there is likely little harmful effect other than anincrease in calorie and glucose intake and an increased likeli-hood of heartburn, as suggested by some studies [54].

Ascorbic acid

Ascorbic acid (vitamin C) is often recommended as a supple-ment that can prevent recurrent UTIs by acidification of theurine [36]. In vitro studies suggest that it has a bacteriostaticeffect in the urine, mediated by the reduction of urinary nitritesto reactive nitrogen oxides rather than by lowering urinary pH[55, 56]. However, convincing clinical evidence to supportthis is lacking.

Foxman and Chi [57] found a weak association betweendietary vitamin C and decreased incidence in a total of 110pregnant women, who were randomized to receive eitherferrous sulphate (200 mg/day), folic acid (5 mg/day) andascorbic acid (100 mg/day) or daily ferrous sulphate and folicacid only. At 3 months, UTIs in the former group weresignificantly lower than in the latter.

Methenamine salts

Methenamine is hydrolysed to ammonia and formaldehydewhen in acidic urine, which act as a bactericide to some strainsof bacteria [58]. They are well tolerated and havemild adverseeffects, such as gastrointestinal upsets, rashes, anorexia andstomatitis. These features make it an attractive agent forrecurrent UTI prophylaxis. A number of small studies havecompared methenamine hippurate with placebo in healthypre- and postmenopausal women. Although the evidence isweak, they suggest that methenamine hippurate may be moreeffective in reducing recurrences at 12 months [59–61]. ACochrane review on the use of methenamine hippurate con-cluded that short-term use is effective in preventing recurrent

UTIs in women without urinary tract abnormalities or a neu-ropathic bladder [62].

Emerging therapies

D-Mannose

D-Mannose is a sugar normally present in human metabolismand has an important role. It is thought that its mechanism ofaction is through inhibition of bacterial adherence to urothelialcells [63]. In vitro and in vivo studies have shown that D-mannose causes saturation of FimH adhesin, which is posi-tioned at the tip of the type 1 fimbria of enteric bacteria on theepithelium of the urinary tract [64, 65]. So far, Kranjčec et al.[66] have conducted the only randomized clinical trial todetermine the effect of regular D-mannose intake on reducingthe rate of recurrent UTIs. It was conducted amongst 308women >18 years of age with acute UTI and a history ofrecurrent UTIs. The first group received daily D-mannoseprophylaxis for 6 months, the second received continuousantibiotic prophylaxis with nitrofurantoin and the third didnot receive any prophylaxis. The rate of recurrent UTI wassignificantly higher in the group that did not receive prophy-laxis (60 %) in contrast with those receiving D-mannose(15 %) and nitrofurantoin (20 %), which did not differ signif-icantly. Of the patients taking D-mannose, 8 % were noted tohave episodes of diarrhoea as the only side effect, but they didnot require discontinuation of the prophylaxis. Although theseinitial findings show D-mannose may be useful for UTI pre-vention, the authors concluded further clinical trials are need-ed to validate the results of their study.

Lactobacillus (probiotics)

The use of probiotics has been suggested and trialed as a novelapproach to reducing the risk of recurrent UTIs. A recentphase 2 trial has found that treatment with probiotics follow-ing cystitis is associated with a decrease in recurrent UTIs.This trial involved 100 premenopausal women with a historyof at least one UTI in the last 12 months and found a signif-icant reduction in the incidence of recurrent UTIs in womenreceiving intravaginal lactobacillus as compared to those inthe placebo group [67]. Similar findings have been presentedby several other studies. However, a subsequent trial, in whichpostmenopausal women with a history of recurrent UTIs wererandomly assigned to TMP-SMX or lactobacillus tablets for12 months, reported that the latter group had more frequentrecurrences over the year and shorter time to recurrence [68].Thus, while having a credible scientific basis, further researchmust be conducted before probiotics can be recommended as apreventative measure.

Int Urogynecol J

Vaccination

Another alternative prophylactic measure that has been asubject of extensive research is use of systemic or mucosalvaccines. Several types of vaccines have been studied so far.Uro-Vaxom is an oral capsular vaccine comprising 18 heatkilled E. coli strains. It has been found to be an effectiveprophylaxis for prevention of UTI. A meta-analysis of fourstudies comprising 891 patients demonstrated that Uro-Vaxom significantly reduced the risk for development ofUTI, as the mean number of UTI were halved in the partici-pants taking Uro-Vaxom capsule daily in comparison to thoseon a placebo capsule daily [53, 69–72].

Research in use of Urovac, which is a vaginal suppos-itory vaccine, has yielded positive results so far [73, 74].Urovac comprises ten uropathogenic strains of bacteria(six E. coli strains and one strain each of Proteus,Mirabilis, Morganella morganii, K. pneumoniae andEnterococcus faecalis). Currently this vaccine has suc-cessfully completed a phase 2 trial, where it has beendemonstrated that administration of this vaccine as prima-ry immunization plus its booster vaccination is effectivein prolonging the time until first recurrence of UTI ascompared to those participants who were administeredprimary immunization or placebo only. This trial furtherdemonstrated that mean number of UTIs were significant-ly lower in women receiving primary immunization andvaccination boosters in comparison to those who receivedeither primary immunization or vaccination only. The trialshowed that primary immunization by its own was noteffective in preventing recurrence of UTI as compared tothe placebo [72, 75]. Urovac is yet to be included in alarge phase 3 trial.

Conclusion

Recurrent UTIs are common phenomena amongst pre- andpostmenopausal women. It is important that patients withrecurrences are recognized through thorough history and ex-amination. Although risk factors should be identified andaddressed accordingly, antibiotics remain the most effectivemethod of management. The type and regimen of antibioticagent should be individualized to each patient. Non-antibioticprevention strategies such as cranberry, vitamin C and methe-namine salts lack strong evidence to be introduced as routinemanagement options and as alternatives to antibiotics.However, they may be used as adjuvant measures, where thepatient is able to tolerate them. Figure 3 shows our recom-mended management pathway at all stages of care. There arealso a number of emerging therapies including D-mannose,probiotics and vaccination. However, further basic science

and randomized controlled trials are necessary before theycan be recommended.

Conflicts of interest None.

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