European Journal of Obstetrics & Gynecology and Reproductive Biology 156 (2011) 131–136

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European Journal of Obstetrics & Gynecology and

Reproductive Biology
journal homepage: www.elsevier.com/locate/ejogrb

Review

Urinary tract infections in women

Stefano Salvatore a,*, Silvia Salvatore b, Elena Cattoni a, Gabriele Siesto c, Maurizio Serati a,
Paola Sorice a, Marco Torella d
a
Department of Obstetrics and Gynecology, University of Insubria, Varese, Italy
b
Department of Pediatrics, University of Insubria, Varese, Italy
c
Department of Gynecology, IRCCS, Humanitas Clinical Institute, Rozzano, Milano, Italy
d
Department of Obstetrics and Gynecology, 2nd Faculty, Naples, Italy

A R T I C L E I N F O A B S T R A C T

Article history: Urinary tract infections (UTIs) are conditions frequently complained by women both in the general
Received 28 October 2010 population and in the hospital setting. Indeed it has been estimated that one woman out of three will
Received in revised form 5 January 2011 experience at least an episode of UTI during lifetime. A comprehensive literature review of published
Accepted 26 January 2011
experimental and clinical studies of UTI was carried out at the University of Insubria electronic library
(SFX Bicocca-Insubria) with cross-search of seven different medical databases (AMED, BIOSIS Previews
Keywords: on Web of Knowledge, Cochrane Library, Embase and Medline on Web of Knowledge, OvidSP and
Urine infections
PubMed). We aimed to draw a clinical guideline addressed to the management of UTI, based on the most
Bacteriuria
recent evidence.
Cystitis
Management ß 2011 Elsevier Ireland Ltd. All rights reserved.
Review

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ............................. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132

2. Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ............................. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132
2.1. Review criteria . . . . . . . . . . . . . . . . . . . . . . . . . . ............................. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132
3. Definition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ............................. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132
4. Prevalence, epidemiology and costs . . . . . . . . . . . . . . . ............................. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132
5. Pathophysiology and microbiology . . . . . . . . . . . . . . . . ............................. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132
6. Risk factors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ............................. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
7. Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ............................. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
7.1. Laboratory evaluation . . . . . . . . . . . . . . . . . . . . . ............................. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
8. Treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ............................. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
8.1. Specific groups of treatment . . . . . . . . . . . . . . . ............................. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
8.1.1. Children . . . . . . . . . . . . . . . . . . . . . . . . ............................. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
8.1.2. Pregnancy and breastfeeding . . . . . . . ............................. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
8.1.3. Diabetes . . . . . . . . . . . . . . . . . . . . . . . . ............................. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134
8.1.4. Spinal cord injury (SCI), quadriplegics and high-level spinal cord injuries. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134
8.1.5. Intermittent catheterization . . . . . . . . ............................. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134
9. Prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ............................. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134
9.1. Sexual intercourse . . . . . . . . . . . . . . . . . . . . . . . ............................. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134
9.2. Low-dose antibiotic treatment . . . . . . . . . . . . . . ............................. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134
9.3. Probiotics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ............................. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134
9.4. Dietary factors, cranberry and lingonberry . . . . ............................. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134
9.5. Oestrogen deficiency. . . . . . . . . . . . . . . . . . . . . . ............................. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135
9.6. Immunoactive prophylaxis . . . . . . . . . . . . . . . . . ............................. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ............................. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135

* Corresponding author at: Department of Obstetrics and Gynaecology, University of Insubria, ‘‘Del Ponte’’ Hospital, Piazza Biroldi 1, 21100 Varese, Italy.
Tel.: +39 0332 299 309; fax: +39 0332 299 307.
E-mail address: stefanosalvatore@hotmail.com (S. Salvatore).

0301-2115/$ – see front matter ß 2011 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.ejogrb.2011.01.028
132 S. Salvatore et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 156 (2011) 131–136
1. Introduction
In routine gynecological practice it is very common to be
consulted for symptoms suggestive of urinary tract infection (UTI).
Indeed UTI is the first and the second infection recorded in the
hospital setting and in the social community, respectively. It has
been estimated that over one third of the female population
experiences at least one episode of UTI during their lifetime.
Therefore we decided to review the available international
literature in order to provide a practical clinical guideline for
the management of UTI. For this purpose we decided to track the
contents of this document through a schematic academic division.
2. Methods
2.1. Review criteria
A comprehensive literature review of published experimental
and clinical studies on UTI was carried out at the University of
Insubria with cross-search of seven different medical databases
(Allied and Complementary Medicine Database (AMED), BIOSIS
Previews on Web of Knowledge, Cochrane Library, Embase and
Medline on Web of Knowledge, OvidSP and PubMed). Search
temporal limits included papers published between January 1999
and October 2010 with the purpose of providing the most recent
evidence regarding this issue. Studies were queried using the
following keywords in various combinations: ‘‘urinary/urinary
tract/urine’’; ‘‘infection/infections/bacteriuria/cystitis’’; and
‘‘treatment/recurrence/recurrent/children/female/women/preg-
nant/pregnancy/elderly/menopause/asymptomatic’’.
Among the thousands of articles identified, we retrieved those
manuscripts that were more relevant for the purpose of this review
and provided results from case series and/or conceptual findings. If
manuscripts were comparable for aim, their clinical relevance was
scaled according to: originality, study design (meta-analyses vs.
randomized vs. prospective vs. retrospective studies), the method
used, the evidence level and the sample size. The journal relevance
based on the actual impact factor score was used as ultimate
criterion of choice, if needed. When the same authors published
more than one paper on the same population only one study was
included (the first or the most specific).
A further manual cross-search of the references of each selected
article was finally performed in order to further identify studies not
captured by the online search but potentially relevant for this
review. Only articles published in English language were considered.
3. Definition
UTI are among the most common bacterial infections in
women: it is estimated that the lifetime possibility of each woman
developing a UTI is above 40–60%. UTI can involve the lower and/or
the upper urinary tract [1]. UTI can be schematically divided into
different groups according to their characteristics, as follows:
 Asymptomatic bacteriuria: the presence of 100,000 colony-form-
ing units (CFU)/mL in a woman without symptoms; if the patient
is symptomatic, the presence of 100 CFU/mL is enough to
diagnose bacteriuria.
 Acute urethral syndrome: symptoms of dysuria, frequency and/or
pyuria without evidence of significant bacteriuria, often in
association with vaginitis or urethritis.
 Cystitis: symptoms of dysuria, frequency and urgency and,
sometimes, supraubic tenderness.
 Acute pyelonephritis: infection of renal parenchyma and pelvi-
calyceal system with bacteriuria, usually accompanied by fever
and flank pain.
 Recurrent UTI (RUTI): symptomatic UTI that follows the resolu-
tion of a previous one. Also if the same bacteria of the first
infection are isolated after adequate antibiotic therapy, it can be
defined as relapse and is usually drug resistant. Otherwise a
reinfection is diagnosed when a second infection is found after
effective antibiotic therapy with a subsequent negative urine
culture; it can be caused by the same bacteria during the first two
weeks after treatment or by a different one [1] and is usually
drug-susceptible. Most recurring episodes of cystourethritis are
due to reinfection.
UTI is considered complicated when it is associated with
symptoms of upper urinary tract infection or if it affects patients
with compromised general conditions (including structural abnor-
malities of the urinary tract, previous pyelonephritis, symptoms
lasting more than 14 days, diabetes, pregnancy, or immunosup-
pression). Episodes may be refractory to therapy, often resulting in
relapses and occasionally leading to significant sequelae such as
sepsis, metastatic abscesses and rarely acute renal failure.
4. Prevalence, epidemiology and costs
The prevalence of UTI is higher in women than in men: about
81% of UTI occurs in women, with a peak between 16 and 35 years.
Approximately 27% of women with a first episode of UTI record a
recurrence within 6 months, and 48% within the first year. Such
infection causes about 6 days of disability per episode, with an
increasing morbidity in the USA. UTI is responsible for about 15% of
all antibiotic prescriptions in the community with more than 1.6
billion dollars spent every year. UTI results in nearly 7 million
office visits, with additional 1 million visits to emergency rooms
which result in over 100,000 hospitalizations every year in the USA
alone [2,3].
5. Pathophysiology and microbiology
UTI usually arises from ascending infection from the urethra to
the bladder, but occasionally it develops with haematogenous or
lymphatic spread. Evidence suggests a sort of genetic predisposi-
tion to develop UTI; non-secretors of ABH blood-group antigens,
especially in premenopausal women, are genetically determined
factors which may predispose to the development of UTI [4,5].
Similarly, a study conducted on mice evidenced the role of innate
immunity which is modulated by variable expression of the
chemokine receptor CXCR1, involved in the activation of neu-
trophils [6].
About 80–90% of UTI is caused by Escherichia coli. A randomized
control trial showed that 77% of patients with RUTI had a relapse
with the primary infecting E. coli strain and 23% had a reinfection
with a different E. coli strain; a burgeoning opinion suggests that E.
coli strains originate from a reservoir in the gastrointestinal flora
with the hypothesis of a faecal–vaginal–periurethral route of
infection; the phylogenetic groups B2 and D of E. coli derive
predominantly from faecal strain and the virulence of B2 group is
closely associated with faecal abundance, dominance and pauci-
clonality [7]. The main mechanism of invasion of the uroepithe-
lium seems to be related to the adhesion process mediated by the
bacterial fimbria which allows E. coli to penetrate into the bladder
epithelium cells. During the replication phase, bacteria produce
intracellular niches, known as bacterial factories, that constitute a
stable reservoir for bladder colonization. In this particular
condition bacteria produce also a bio-film which provides an
effective protection against the surrounding inflammatory agents
[8,9]. Experiments in vitro and in mice confirmed that treatment
with mecillinam can eradicate E. coli in the urine without affecting
the bladder reservoir, which can re-start the infection [10].
 S. Salvatore et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 156 (2011) 131–136
About 5–10% of UTI are caused by Staphylococcus saprophyticus,
while long-lasting cases are caused by Proteus, Pseudomonas,
Klebsiella and Enterobacter: these infections are quite uncommon
and are associated with structural abnormalities of the urinary
tract, indwelling catheters and renal calculi, whereas Streptococ-
cus of group B is generally associated with fungal infection in
hospitalized women [3,5].
6. Risk factors
Anatomic congenital abnormalities, urinary tract calculi, neuro-
logical disorders, diabetes, medical conditions determining indwell-
ing or recurrent bladder catheterizations are the most frequent risk
factors. Traumas to the pelvic floor also contribute to the
development of UTI, as do multiparity and pelvic organ prolapse.
In addition, in young women a number of other important risk
factors for recurrent acute cystitis have been recognized, including
recent history of UTI, young age at first UTI, frequent or recent sexual
intercourse and spermicidal use, especially if in combination with
diaphragm. Infrequent voiding, poor fluid intake and functional
stool retention are also identified as behavioural abnormalities that
facilitate UTI in younger women [11,12].
7. Diagnosis
Lower UTI generally presents with dysuria, frequent and urgent
micturition, sometimes associated with suprapubical pain or
pressure and rarely with haematuria. Fever is uncommon and it is
usually associated with complicated forms of UTI, as previously
mentioned. The likelihood that the underlying condition of a
woman presenting with these symptoms is a UTI is about 50% in
primary care settings. This possibility rises to 84–92% when
women complaining these symptoms have a history of RUTI.
Upper UTI occurs with flank pain radiating to the groin,
associated with fever and chills. Upper UTI can be frequently found
in association with lower UTI symptoms.
Elderly women with UTI are frequently asymptomatic, com-
plaining only urinary incontinence. Septic shock (urosepsis) is
unusual, but it may arise as the onset in the most neglected
conditions. In postmenopausal women UTI can increase the urine
loss occurrence in the immediate 3-day time period post-UTI [13].
Imaging studies and/or cystoscopy are mandatory if haematuria
persists. However, the diagnosis of UTI, from simple cystitis to
complicated pyelonephritis with sepsis, can be established with
absolute certainty only by quantitative cultures of urine.
7.1. Laboratory evaluation
Bacteriuria is defined as the presence of 100,000 single isolate
bacteria/mL collected by a clean-voided midstream urine sample.
In young women with symptoms of cystitis the threshold for a
positive urine culture can be lowered to 1000 bacteria/mL, raising
the sensitivity and reducing the specificity.
Urine dipstick testing for leukocyte esterase, blood or nitrite is
rapid and economic, with a sensitivity of 77% and specificity of
70%; its positive predictive value is 81% and its negative predictive
value is 65%. Diagnosis is predicted by three variables indepen-
dently: nitrite is more predictive for UTI, followed by leucocytes
and presence of blood [14].
8. Treatment
The gold standard for symptomatic treatment of uncomplicated
acute cystitis is a three-day treatment [15] with trimethoprim–
sulfamethoxazole, with a percentage of eradication rate of 90%.
Ciprofloxacin, levofloxacin, norfloxacin and gatifloxacin give
133
comparable eradication rates after 3 days of administration [16].
This short-term treatment option achieves similar results to those
obtained by prolonged therapies, and it reduces the number of
adverse events and costs. Fosfomycin tromethamine can be used in
a single dose, while nitrofurantoin monohydrate macrocrystals are
given at seven-day treatment, twice daily.
A one-day therapy cures the 80–100% of young women with
acute uncomplicated cystitis in the short-term period, but it results
in a higher rate of RUTI in the long term: these data suggest that a
single dose in not enough to eradicate completely the vaginal and
periurethral reservoir of the infection. A seven-day antibiotic
regimen might be used in a minority of women suffering with
immunosuppressive conditions or planning pregnancy, prolonged
symptoms (more than seven days), recent UTI and age above 65
years in order to achieve a complete bacterial eradication.
The management of acute pyelonephritis requires a 14-day
treatment scheme of oral or parental antibiotics, with a percentage
of eradication that rises up to 100%. Amoxicillin or amoxicillin
combined with clavulanic acid might be useful. Patients who
require admission to the hospital, however, should be treated
initially with a third-generation cephalosporin or a fluoroquino-
lone and gentamicin. If no complications ensue, the remaining
two-week course can be completed with oral therapy.
During treatment of RUTI, a 3-day therapy allows the relief of
symptoms, but prolonged administration (five days or more) is
suggested to achieve the complete eradication of the infection. For
this reason bacteriological eradication with 7-day antibiotic
administration should be considered as the gold standard for
the management of RUTI in women [17].
In postmenopausal women a 3-day regimen has been suggested
[18], as well as a local hormone supplementation.
More than 90% of women have symptom relief within 72 h after
the beginning of antibiotic therapy. Resistance rate ranges are
based on patient’s age: younger women record higher rates of
resistance of E. coli toward ampicillin and trimethoprim–sulfa-
methoxazole than the elderly (namely 45–31% vs. 39–14%). On the
contrary the resistance rate for nitrofurantoin and fluoroquino-
lones is higher in the elderly than in adolescents (1,8–1.7% vs. 16–
10%) [19,20]. A resistance rate higher than 15–20% requires the
choice of a different antibiotic class [21]. Therefore, assessment of
local resistance patterns is needed to guide empirical therapy.
8.1. Specific groups of treatment
8.1.1. Children
UTI affects up to 10% of the childhood population. Compared with
adults, young children are more likely to have anatomic abnormali-
ties and/or vesicoureteral reflux predisposing them to have upper
UTI. Otherwise, UTI are often identified in preverbal children, who
are unable to distinguish and refer symptoms of infections. For these
reasons the American Academy of Pediatrics recommended that
infants and young children receive a 7- to 14-day antimicrobial
course [22]. These data have been also confirmed by a meta-analysis
that compared short and long courses of antibiotic therapy for UTI in
children, showing that a 7- to 14-day regimen allowed fewer
treatment failures without a concomitant increase in reinfections
[23]. Moreover, asymptomatic bacteriuria in preschool and school-
aged girls may signify underlying vesicoureteral reflux. Therefore,
asymptomatic bacteriuria should routinely be detected and treated
with follow-up urologic evaluation after six weeks.
8.1.2. Pregnancy and breastfeeding
Bacteriuria in early pregnancy should be regarded as uncom-
plicated UTI. Later in pregnancy hormonal effects lead to decreased
autonomic muscle tone and stasis of the genitourinary tract, and
therefore bacteriuria must be considered as complicated UTI.
134 S. Salvatore et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 156 (2011) 131–136
During pregnancy asymptomatic bacteriuria must be treated to
reduce the risk of pyelonephritis and preterm delivery. Nitrofur-
antoin, b-lactam antimicrobials, including both penicillin and
cephalosporins, and fosfomycin trometamol are considered safe
also during pregnancy [24].
During breastfeeding trimethoprim and sulfamethoxazole can
be used, but with caution in infants with known deficit of G6PD;
nitrofurantoin, ciprofloxacin and ofloxacin are allowed during
breastfeeding, even though available data in humans are still
limited [25].
8.1.3. Diabetes
Women with diabetes record higher frequency of symptomatic
UTI than the general population. Similarly, complicated UTI also
with bilateral renal involvement are more frequently reported.
Moreover, in diabetic patients under insulin regimen the risk of
asymptomatic bacteriuria and UTI is three- and fourfold higher
than the healthy counterpart, respectively.
A prospective randomized trial compared antimicrobial thera-
py with no antimicrobial therapy in women with diabetes and
asymptomatic bacteriuria: no benefits were identified in the
continuing screening vs. treatment strategy of asymptomatic
bacteriuria; specific diabetes variables associated with symptom-
atic infections are neuropathy and glycosuria [26]. Previous
antimicrobial treatment and macrovascular complications are
other reported risk factors [27].
8.1.4. Spinal cord injury (SCI), quadriplegics and high-level spinal cord
injuries
Approximately 40% of patients with SCIs die as a consequence of
renal-related conditions. E. coli remains a common uropathogen
among SCI patients, in addition to Enterococci, Pseudomonas and
Proteus mirabilis, which are frequently represented in the retrieved
flora. Factors that increase susceptibility to UTI include: over-
distension of the bladder, impaired voiding and increased incidence
of renal stones. Similarly, quadriplegics and patients with high-level
SCI are at higher risk of developing UTI because of the autonomic
dysreflexia and the need for indwelling catheterization. Current
evidence suggests 14-day of therapy for management of UTI.
UTIs are the most common nosocomial infection in the Intensive
Care Unit settings, where patients predominantly need indwelling
catheterization. In this particular condition it is extremely difficult
differentiate asymptomatic bacteriuria from symptomatic UTIs that
require catheter removal and specific antibiotic therapy, since
multidrug resistance represents a significant problem. Targeted
strategies for preventing catheter-associated UTI include limiting
the use and duration of catheterization with particular attention to
respecting aseptic technique for insertion [28]. The empiric therapy
of these infections is similar to complicated UTIs and patients who
rapidly respond to the therapy may be treated only for seven days.
8.1.5. Intermittent catheterization
Intermittent catheterization is a crucial issue for healthcare of
individuals with incomplete bladder emptying and it is a well-
known cause of UTI. Catheterization is the most common source of
nosocomial infection with a risk that proportionally increases with
the number and duration of the procedures. Currently, evidence
that catheter type, technique or strategy could prevent UTI is still
lacking [29,30].
9. Prevention
9.1. Sexual intercourse
For women who describe a clear relationship between sexual
intercourse and subsequent cystitis, the use of post-coital
prophylaxis can be worthwhile. Postcoital voiding does not
prevent cystitis. In sexually active women who use vaginal
spermicide or diaphragms with history of RUTI, alternative
methods of contraception should be suggested.
9.2. Low-dose antibiotic treatment
In women complaining of 2 UTI during a 6-month period or
3 infections over a 12-month period, prophylaxis with low-dose
antibiotics once a day can be used, reducing 95% of recurrences.
Suggested antimicrobial agents are nitrofurantoin, norfloxacin,
ciprofloxacin, trimethoprim and trimethoprim–sulfamethoxazole,
continued for 6–12 months. Low dose trimethoprim–sulfameth-
oxazole, as little as half a tablet (trimethoprim 40 mg, sulfameth-
oxazole 200 mg) three times weekly at bed-time, is associated with
an infection frequency of less than 0.2 per patient year [3,5].
9.3. Probiotics
Lactobacilli are probiotics, which are defined as living micro-
organisms that confer a health benefit to the host. Probiotics seem
to prevent the colonization of pathogens of the vagina and bladder.
Lactobacilli produce antimicrobial compounds such as lactic acid,
bacteriocins and hydrogen peroxide that are toxic to many
microorganisms at vaginal concentrations. In addition lactobacilli
produce a bio surfactant that inhibits the adhesion of uropatho-
gens to the surface of cells and seems to contribute to a non-
specific augmentation of the innate immune response [31,32].
The use of Lactobacillus in vaginal suppositories has been tested
in the prevention of RUTI. A pilot study carried out with
suppositories containing Lactobacillus crispatus GAI 98332 demon-
strates a significant reduction of RUTI after a 12-month treatment
[33]. Otherwise the vaginal instillation of Lactobacilli induces a
mild inflammatory response in the bladder and vaginal mucosa,
sometimes causing vaginal discharge followed by external genital
irritation and vaginal candidiasis [34]. The role of lactobacilli for
the prophylaxis of UTI needs further investigations, however, as
stated in a recent review [35].
9.4. Dietary factors, cranberry and lingonberry
Berries such as cranberry and lingonberry contain proantho-
cyanidins, tannins able to prevent the expression of the P fimbriae
of E. coli, inhibiting bacterial cell wall synthesis and cellular
expression of adhesion molecules. The block of the E. coli’s fimbriae
has a key-role for the prevention of colonization although these
effects are dose-dependent [36]. A randomized trial concluded that
a daily dose of 50 mL of cranberry/lingonberry juice concentrate
for six months can significantly reduce the risk of RUTI [37].
Similarly another randomized controlled pilot study compared the
effects of daily cranberry juice to those of placebo in pregnant
women over 16 weeks of gestation, suggesting a protective effect
of cranberry administration against symptomatic UTI and bacteri-
uria, although the therapy compliance of pregnant women could in
part limit these findings [38].
A Cochrane review of 2008 identified 10 studies on the use of
cranberries to prevent UTI and highlighted that cranberries are
effective for the prevention of RUTI, especially in young sexually
active women [39].
A randomized control trial including women aged >45 years
compared the use of 100 mg of trimethoprim vs. 500 mg of
cranberry extract, concluding that antibiotic treatment provided
only limited advantages over cranberry extract with more adverse
events [40]. Dietary factors can contribute to prevent UTI in fertile
women: the consumption of fresh juice, especially berry juice, and
fermented milk products containing probiotic bacteria can
 S. Salvatore et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 156 (2011) 131–136
decrease RUTI. On the contrary neither association was demon-
strated with the consumption of coffee, tea or soft drinks nor with
vitamins implementation or volume of daily fluid intake [41].
9.5. Oestrogen deficiency
Oestrogen therapy has been shown to increase vaginal pH and
to reverse the microbiological changes that occur in the vaginal
environment during the menopausal period. After the menopause
oestrogen deficiency causes atrophic changes within the urogeni-
tal tract that are usually associated with urinary symptoms, such as
frequency, urgency, nocturia, urinary incontinence and RUTI. In a
randomized trial, 72 postmenopausal women with RUTI were
assigned to oral oestriol vs. placebo; after six months of treatment
no differences were found between the groups in terms of
frequency of RUTI. Another randomized trial, which included 2763
women, compared the effect of a 4-year treatment with conjugated
oestrogens plus medroxypregesterone acetate vs. placebo: this
study concluded that hormonal replacement therapy did not affect
outcomes in terms of frequency of UTI [42]. On the contrary, a
different randomized placebo-controlled trial showed that an
estradiol-releasing silicone vaginal ring in postmenopausal wom-
en with history of RUTI is an effective option since it decreased the
number of annual recurrences of UTI and prolonged intervals
between infections episodes [43]. These findings have been
confirmed by other papers that recorded reduction of RUTI after
the vaginal administration of oestrogen [44–46].
9.6. Immunoactive prophylaxis
An increasing number of papers are currently highlighting the
advantages offered by bacterial lysates. The biologic rationale of
these therapies is that the administration of bacterial lysates
should diminish susceptibility toward infections (including RUTI),
enhancing the host’s defences. A meta-analysis on this subject
showed that the administration of an oral immunostimulant (OM-
89) reduces the rate of RUTI by 36% [47]. These data have been also
confirmed by a double blind randomized study reporting the
efficacy of a multivalent bacterial vaccine of mucosal immunogens
in women (from late teens to early 70s) in reducing RUTI [48].
Many other vaccines are currently being tested on animals.
Conflicts of interest
None.
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