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Recurrent Urinary Tract Infections in Women

Article in International Urogynecology Journal · June 2015

DOI: 10.1007/s00192-014-2569-5

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Int Urogynecol J
DOI 10.1007/s00192-014-2569-5
REVIEW ARTICLE
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
Abstract
Introduction 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 the
last 12 months. In a primary care setting, 53 % of women
above the age of 55 years and 36 % of younger women report
a recurrence within 1 year. Thus, management and prevention
of recurrent UTI is of utmost significance. This review aims to
highlight the latest research in prevention strategies and sug-
gest a management pathway.
Methods A search was conducted on MEDLINE, Embase and
the Cochrane Database of Systematic Reviews databases for
the latest systematic reviews and high-quality randomized
controlled trials. Special emphasis was placed on the remit
“recurrent” and strongly adhered to. Furthermore, a Google
search was conducted for current guidelines on the manage-
ment of UTIs.
Results Current prevention strategies include eliminating risk
factors that increase the risk of acquiring recurrent UTI and
continuous, post-coital and self-initiated antimicrobial pro-
phylaxis. Other prospective preventative strategies, currently
under trial, include use of vaccinations, D-mannose and lacto-
bacillus (probiotics).
Conclusion Although risk factors should be identified and
addressed accordingly, individualized antibiotic prophylaxis
remains the most effective method of management. Non-
antibiotic prevention strategies such as cranberry, vitamin C
and methenamine salts lack strong evidence to be introduced
as routine management options and as alternatives to antibi-
otics. Based on current evidence and guidelines, a
A. Aydin : K. Ahmed (*) : I. Zaman : M. S. Khan : P. Dasgupta
Department of Urology, Guy’s and St. Thomas’ NHS Foundation
Trust, King’s Health Partners, MRC Centre for Transplantation,
King’s College London, London, UK
e-mail: kamran.ahmed@kcl.ac.uk
management pathway is recommended. Emerging therapies
require 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 of
women acquiring a UTI in their lifetime has been estimated to
be over 50 % [1, 2], with about 25 % having a recurrence [3,
4]. Recurrent UTIs are symptomatic infections that follow
complete resolution of a previous UTI [5]. In a primary care
setting, 53 % of women above the age of 55 years and 36 % of
younger women report a recurrence within 1 year [6]. Hence,
its management and prevention is of utmost significance for
all 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 the
latest information from systematic reviews, randomized con-
trolled trials and current clinical guidelines. We recommend a
pathway for the management of recurrent UTIs, based on
current 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 with
a structural or functional urinary tract abnormality or an un-
derlying pathology, both of which can subsequently increase

risks of acquiring an infection or failure of therapy (see
Table 1). Uncomplicated UTIs are sporadic, community-
acquired episodes of cystitis and pyelonephritis in otherwise
healthy individuals, but could lead to more serious outcomes
and thus require additional attention. A recurrent UTI is
widely defined as more than two episodes of uncomplicated
UTI in the last 6 months or more than three in the last
12 months, documented by culture [8, 9].
Pathophysiology
Responsible uropathogens
Escherichia coli is the predominant uropathogen responsible
for both sporadic and recurrent UTI, seen in 70–95 % of cases.
Other causative organisms include Staphylococcus
saprophyticus (10–15 % of cases) [9], Klebsiella pneumoniae
and Proteus mirabilis [7].
Following the resolution of a UTI, small numbers of the
original strain of uropathogens may persist in the host and lead
to infection stones (e.g. P. mirabilis). Although rare, it is
important that bacterial persistence is identified as it is the
only surgically curable cause of recurrent UTIs [9, 10].
Relapse vs reinfection
Recurrent UTI can either be a relapse or reinfection. A relapse
UTI is caused by the same bacterial strain implicated in a
previous UTI within 2 weeks of the completion of treatment
for the original infection [11–13]. By contrast, a recurrent UTI
arising more than 2 weeks after treatment or after sterile
intervening culture is considered to be a reinfection, even if
the infecting pathogen is the same as the original [11–13].
They are most commonly seen in women and girls and are
associated with ascending colonization from the faecal flora.
Infection occurs through bacterial colonization of the vagina
and distal urethra, which subsequently ascends into the blad-
der [8, 10]. Reservoirs of bacteria may remain in the vagina
and gastrointestinal tract of susceptible patients. It has been
Table 1 Predisposing factors for
complicated UTIs Factors
Urinary tract anatomic abnormality
Urinary tract obstruction
Voiding dysfunction
Iatrogenic
Other
Int Urogynecol J
suggested that household contacts may also act as reservoirs
for the recolonization of these UTI-susceptible patients [14].
Risk factors
The risk factors for recurrent UTI in women vary between
premenopausal and postmenopausal women (Fig. 1). In pre-
menopausal women, behavioural risk factors such as frequen-
cy of sexual intercourse [1], new partners, use of spermicide
and diaphragm use [7, 8, 11] predominate. All of these risk
factors have been found to increase vaginal and urethral
colonization with E. coli [11]. In a well-powered case-control
study [4], women aged 18–30 years, with recurrent UTI were
compared with women who had no history of UTIs. The
former 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, previous
case of UTI before 15 years of age [8] and a shorter distance
between the urethra and anus [15] suggest that genetics and
pelvic 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-hydroxy
vitamin D, suggesting a deficiency [16].
For postmenopausal women, the risk factors are markedly
different and include oestrogen deficiency, cystocoele, uro-
genital surgery, high post-void residual volume and a previous
UTI [11]. These women also have a relative depletion of
vaginal lactobacilli and an increase in vaginal E. coli com-
pared with premenopausal women. This age-related alteration
of the normal vaginal flora, especially loss of hydrogen per-
oxide producing lactobacilli, may predispose women to
introital 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 recurrent
UTIs. Some studies suggest that non-secretors of histo-blood
group antigens are more susceptible to recurrent UTIs, although
Polycystic kidneys, cystocoele, diverticulum, fistula
Bladder outflow obstruction, congenital abnormality,
ureteral/urethral stricture, urolithiasis
Vesicoureteric reflux, neurological disease, i.e. multiple sclerosis,
hHigh post-void residual volume, incontinence
Indwelling catheter, ureteral stent, nosocomial infections, surgery
Immunosuppressive medications, diabetes, pregnancy, renal failure
Int Urogynecol J
Fig. 1 Risk factors for recurrent
UTIs in women
this has not been the case in every study [19]. Another factor
with genetic variability is the interleukin (IL)-8 receptor, IL-8R
or CXCR1, which is expressed to a significantly lower extent in
pyelonephritis-prone children and their relatives [20].
Furthermore, UTIs have been seen to be more prevalent in
female relatives of women with recurrent UTIs, suggesting a
familial genetic predisposition [19].
Urological evaluation
Clinical presentation
The clinical presentation of recurrent UTI is similar to sporadic
UTI. Most patients present with classic symptoms of cystitis
which include frequency, polyuria, dysuria, suprapubic tender-
ness and haematuria. On the basis of prospective cohort studies,
the Health Protection Agency and British Infection Association
recommend that UTIs be diagnosed when at least three of these
symptoms are present [21]. Fever and flank pain may also be
evident with an episode of acute pyelonephritis [22].
Investigations
Diagnostic evaluation for recurrent UTIs should begin with a
detailed history and physical examination (Fig. 2). This is vital
for 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 nitrite
positive urine dipstick has been considered a highly sensitive
test in predicting a UTI [23]. However, since some bacteria,
such as S. saprophyticus, lack the enzymes to reduce nitrates
into nitrites, false-positive results are fairly common [8]. Thus,
history, physical examination or urine dipstick analysis are not
sufficient to reliably rule out UTIs.
Urine microscopy and culture of midstream urine sample is
the gold standard test for a definitive diagnosis [11]. Although
sporadic UTIs are often treated empirically with a urine cul-
ture obtained when the diagnosis is unclear or the symptoms
persist despite antibiotic treatment, urine culture is necessary
in patients with recurrent UTIs to confirm the diagnosis and to
guide antibiotic therapy for any future recurrences.
Historically, UTI has been defined as >105 colony units of
bacteria/ml on culture [8]; however, according to European
Association of Urology (EAU) guidelines a count of >103
cells/ml in symptomatic patients is sufficient to diagnose
suspected cystitis or >104 cells/ml for suspected pyelonephri-
tis [22]. In order to assess for bacterial persistence, the urine
sample 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 of
no benefit but may in fact cause harm [25, 26], the diagnosis
of UTI in this group of patients should not be based on urine
culture alone but in light of symptoms and any evidence of a
systemic inflammatory response [27].

Fig. 2 History and assessment of women with suspected recurrent UTI
Conventional urine culture requires up to 72 h from sample
collection to pathogen identification. Recently, Bonkat et al.
[28] attempted to determine the quantity of bacteria and
leucocytes using a combination of matrix-assisted laser
desorption/ionization time of flight and urine flow cytometry
in order to try to shorten the time of microbiological identifi-
cation and initiation of adequate antibiotic treatment. The
authors compared this method against the standard and auto-
mated culture methods and reported an almost 60 % early
identification success rate. However, these are preliminary
results and this method requires further evaluation but may
lead to targeted adjustment of antibiotic treatment at early
stages of UTI.
Although there are no guidelines for imaging studies in
women with uncomplicated recurrent UTIs [7], patients who
present with atypical symptoms of either acute uncomplicated
cystitis or acute uncomplicated pyelonephritis, as well as those
who fail to respond to appropriate antimicrobial therapy and
remain febrile after 72 h of treatment, should be considered for
additional diagnostic investigations such as unenhanced heli-
cal computed tomography (CT), excretory urography or
dimercaptosuccinic acid (DMSA) scanning [22, 24]. They
also need to be screened for any predisposing factors for
complicated UTIs and may need a specialist referral.
Preventative measures
Lifestyle modifications
Patients should be informed and educated about behavioural
risk factors, such as sexual activity [29]. Likewise, premeno-
pausal women on spermicides or vaginal diaphragms should
be offered alternative forms of contraception [12]. It should be
noted that a number of studies have failed to identify any
Int Urogynecol J
association between recurrent UTIs and pre- or post-coital
voiding patterns, frequency of urination, delayed voiding
habits, wiping patterns, douching, use of hot tubs, bubble
baths, body mass index (BMI), use of tight clothing, type of
clothing, 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 women with recurrent UTI, continuous antibiotic prophylaxis
(once daily) has been recommended for prevention of any future
episodes. Public Health England [29] recommends low-dose
antibacterial prophylaxis (trimethoprim 100 mg or
nitrofurantoin 50–100 mg) nightly for women with frequent
symptomatic recurrent infections. Other antibiotics that have
been 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 by
inhibiting the recovery rate of uropathogens (especially E. coli)
from the faecal reservoir [30], while nitrofurantoin plays a role
in sterilizing the urine and inhibiting bacterial attachment [31].
The latter is effective in terms of bacterial sensitivity with less
than 5 % resistance to strains of E. coli [32].
Prior to prophylactic treatment, patients should have the
elimination of a previous UTI confirmed by a negative urine
culture 1–2 weeks post-treatment [12]. As per EAU guide-
lines, antibiotic prophylaxis should be considered only after
counselling and where appropriate behavioural modifications
have failed to prevent the recurrences [24].
The efficacy of continuous prophylaxis was demonstrated
by a Cochrane review [33], which concluded that continuous
antibiotic 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 prophylaxis
with 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, but
also the most expensive. Studies have compared
nitrofurantoin, trimethoprim, cinoxacin and TMP-SMX [33],
where one trial showed superiority of nitrofurantoin 100 mg
daily over trimethoprim 100 mg daily. However, no antibiotic
class has been clearly favoured for prophylaxis on the basis of
randomized controlled trials and meta-analyses [33].
Although certain dose regimens have been suggested
(Table 2), the choice and the dose of the drug can vary
based on physician preference and patient health-related
factors such as allergies, comorbidities as well as sen-
sitivities of previously cultured organisms. There are no
specific guidelines on the duration of continuous
Int Urogynecol J
Fig. 3 Recommended pathway for the management of recurrent UTIs
antibiotic prophylaxis; however, 6 months of treatment
followed by observation for reinfection remains the em-
piric recommendation [5, 35]. In those with a greater
frequency of recurrence following cessation of prophy-
lactic therapy, longer duration on prophylaxis can be
considered. Tables 2 and 3 outline the typical antibiotics
used for continuous prophylaxis.
Continuous antibiotic prophylaxis has been associated with
a number of side effects, the most common of which are
nausea and candidiasis [18]. Although rare, trimethoprim,
especially in combination with sulphamethoxazole, can lead
to 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
 Int Urogynecol J

Table 2 Continuous antibiotic

prophylaxis for recurrent UTIs [5, Antimicrobial Dose Frequency Expected UTI/year
33, 36, 39]
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
a
High recurrence rates observed Ofloxacin 100 mg Daily –
with trimethoprim associated with Fosfomycin 3 g every 10 days 3 g every 10 days –
trimethoprim resistance

for hepatotoxicity and pneumonitis, which is associated with
long-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 antibiotics
following 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-coital
prophylaxis is required in smaller amounts than continuous
prophylaxis and ia associated with fewer side effects [39].
patient satisfaction with self-start therapy is high, resolution
prompt and side-effects few [41–43], it is advised that the use
of this method be restricted to patients who have documented
previous infections and are motivated and compliant with
given medical instructions [40]. The Infectious Diseases
Society of America and the European Society for
Microbiology and Infectious Diseases recommends
nitrofurantoin monohydrate/macrocrystals (100 mg, twice
daily for 5 days), TMP-SMX [160/800 mg (one double-
strength tablet), twice daily for 3 days], fosfomycin
trometamol (3 g, single dose) or pivmecillinam (400 mg, twice
daily for 5 days) [44].
Non-antibiotic prevention strategies
Oestrogen therapy

Patient-initiated therapy Oestrogen has been associated with colonization of vagina

with lactobacilli, which has been found to be protective
This is also referred to as self-start therapy and is ideal for against UTIs. With menopause, there is a change in the
women who are not suitable candidates for long-term prophy- vaginal pH and flora, increasing the risk of UTI. A 2008
laxis or for those who do not wish to take the long-term Cochrane review [40] demonstrated vaginal oestrogen to be
therapy [40]. Through this method, patients can identify epi- an effective prophylaxis in the prevention of recurrent UTIs.
sodes of infection on the basis of symptoms, perform their Similarly, Stamm and Raz et al. [45] reported a significant
own culture and begin a standard 3-day course of antibiotics. decrease in UTIs amongst postmenopausal women, who used
However, it has been associated with a higher rate of infection 0.5 mg of vaginal oestriol cream every night for 2 weeks and
compared with continuous prophylaxis (2.2 episodes per pa- then twice a week for 8 months, compared with those using a
tient year vs 0.2 episodes per patient year) [41]. Although placebo. However, oral oestrogen tablets have been found to
be ineffective in prevention of recurrent UTIs, whilst also
Table 3 Post-coital antibiotic prophylaxis for recurrent UTIs [5, 33, 36,
being associated with a number of adverse effects including
39]
breast tenderness and vaginal bleeding [40, 46]. Furthermore,
Antimicrobial Dose Expected UTI/year an epidemiological case-control study by Weiderpass et al.
[47] showed that oral treatment with oestriol increased the
TMP-SMX 40 mg/200 mg 0.3
relative risk of endometrial proliferation and carcinoma.
80 mg/400 mg 0
Nitrofurantoin 50–100 mg 0.1
Cephalexin 250 mg 0.03 Cranberry juice and tablets
Ciprofloxacin 125 mg 0
Norfloxacin 200 mg 0
Although laboratory studies have demonstrated that cranberry
Ofloxacin 100 mg 0.06
juice inhibits adherence of uropathogens to uroepithelial cells
[48, 49], the clinical use of cranberry juice as a prophylactic in
Int Urogynecol J
prevention of recurrent UTIs remains debated. A Cochrane
review [50] of 24 studies, with a total of 4,473 subjects,
revealed that cranberry products were of no benefit compared
to placebo in most populations, whereas another meta-
analysis found that the number of events halved [51]. A recent
retrospective review concluded that clinical studies on cran-
berry products strongly support their prophylactic use in
young and middle-aged women but that evidence among other
patients remains controversial [52]. A 2011 clinical trial [53]
with 221 premenopausal women showed that continuous
antibiotics were more effective in preventing recurrent UTIs
than 500 mg cranberry capsules taken twice daily, at the
expense of emerging antibiotic resistance. Thus, the potential
benefit of cranberry in terms of product type (solid/liquid),
dosing and optimal patient population therefore remains to be
elucidated and is not routinely recommended. However, for
women 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 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 the
urine [36]. In vitro studies suggest that it has a bacteriostatic
effect in the urine, mediated by the reduction of urinary nitrites
to reactive nitrogen oxides rather than by lowering urinary pH
[55, 56]. However, convincing clinical evidence to support
this is lacking.
Foxman and Chi [57] found a weak association between
dietary vitamin C and decreased incidence in a total of 110
pregnant women, who were randomized to receive either
ferrous sulphate (200 mg/day), folic acid (5 mg/day) and
ascorbic acid (100 mg/day) or daily ferrous sulphate and folic
acid only. At 3 months, UTIs in the former group were
significantly lower than in the latter.
Methenamine salts
Methenamine is hydrolysed to ammonia and formaldehyde
when in acidic urine, which act as a bactericide to some strains
of bacteria [58]. They are well tolerated and have mild adverse
effects, such as gastrointestinal upsets, rashes, anorexia and
stomatitis. These features make it an attractive agent for
recurrent UTI prophylaxis. A number of small studies have
compared methenamine hippurate with placebo in healthy
pre- and postmenopausal women. Although the evidence is
weak, they suggest that methenamine hippurate may be more
effective in reducing recurrences at 12 months [59–61]. A
Cochrane 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 metabolism
and has an important role. It is thought that its mechanism of
action is through inhibition of bacterial adherence to urothelial
cells [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 the
epithelium of the urinary tract [64, 65]. So far, Kranjčec et al.
[66] have conducted the only randomized clinical trial to
determine the effect of regular D-mannose intake on reducing
the rate of recurrent UTIs. It was conducted amongst 308
women >18 years of age with acute UTI and a history of
recurrent UTIs. The first group received daily D-mannose
prophylaxis for 6 months, the second received continuous
antibiotic prophylaxis with nitrofurantoin and the third did
not receive any prophylaxis. The rate of recurrent UTI was
significantly 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 to
have episodes of diarrhoea as the only side effect, but they did
not require discontinuation of the prophylaxis. Although these
initial 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 novel
approach to reducing the risk of recurrent UTIs. A recent
phase 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 history
of at least one UTI in the last 12 months and found a signif-
icant reduction in the incidence of recurrent UTIs in women
receiving intravaginal lactobacillus as compared to those in
the placebo group [67]. Similar findings have been presented
by several other studies. However, a subsequent trial, in which
postmenopausal women with a history of recurrent UTIs were
randomly assigned to TMP-SMX or lactobacillus tablets for
12 months, reported that the latter group had more frequent
recurrences over the year and shorter time to recurrence [68].
Thus, while having a credible scientific basis, further research
must be conducted before probiotics can be recommended as a
preventative measure.

Vaccination
Another alternative prophylactic measure that has been a
subject of extensive research is use of systemic or mucosal
vaccines. Several types of vaccines have been studied so far.
Uro-Vaxom is an oral capsular vaccine comprising 18 heat
killed E. coli strains. It has been found to be an effective
prophylaxis for prevention of UTI. A meta-analysis of four
studies comprising 891 patients demonstrated that Uro-
Vaxom significantly reduced the risk for development of
UTI, as the mean number of UTI were halved in the partici-
pants taking Uro-Vaxom capsule daily in comparison to those
on 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 and
Enterococcus faecalis). Currently this vaccine has suc-
cessfully completed a phase 2 trial, where it has been
demonstrated that administration of this vaccine as prima-
ry immunization plus its booster vaccination is effective
in prolonging the time until first recurrence of UTI as
compared to those participants who were administered
primary immunization or placebo only. This trial further
demonstrated that mean number of UTIs were significant-
ly lower in women receiving primary immunization and
vaccination boosters in comparison to those who received
either primary immunization or vaccination only. The trial
showed that primary immunization by its own was not
effective in preventing recurrence of UTI as compared to
the placebo [72, 75]. Urovac is yet to be included in a
large phase 3 trial.
Conclusion
Recurrent UTIs are common phenomena amongst pre- and
postmenopausal women. It is important that patients with
recurrences are recognized through thorough history and ex-
amination. Although risk factors should be identified and
addressed accordingly, antibiotics remain the most effective
method of management. The type and regimen of antibiotic
agent should be individualized to each patient. Non-antibiotic
prevention strategies such as cranberry, vitamin C and methe-
namine salts lack strong evidence to be introduced as routine
management options and as alternatives to antibiotics.
However, they may be used as adjuvant measures, where the
patient is able to tolerate them. Figure 3 shows our recom-
mended management pathway at all stages of care. There are
also a number of emerging therapies including D-mannose,
probiotics and vaccination. However, further basic science
Int Urogynecol J
and randomized controlled trials are necessary before they
can be recommended.
Conflicts of interest None.
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