Clinical Presentations

and Epidemiology of
Urinary Tract Infections
SUZANNE E. GEERLINGS1
1
Department of Internal Medicine, Division of Infectious Diseases, Center for Infection and
Immunity Amsterdam (CINIMA), Academic Medical Center, 1105 AZ Amsterdam, The Netherlands

ABSTRACT Urinary tract infection (UTI) is one of the most opening in women is close to the rectum. Urogenital
common bacterial infections, and the incidence in women is manipulations associated with daily living or medical
much higher than in men. The diagnosis of a UTI can be made
interventions facilitate the movement of bacteria to the
based on a combination of symptoms and a positive urine
urethra (1).

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analysis or culture. Most UTIs are uncomplicated UTIs,
defined as cystitis in a woman who is not pregnant, The diagnosis of a UTI can be made by a combination
is not immunocompromised, has no anatomical and functional of symptoms and a positive urine analysis or culture.
abnormalities of the urogenital tract, and does not exhibit signs In most patient groups, the threshold for bacteriuria is
of tissue invasion and systemic infection. All UTIs that are not considered to be 1,000 colony-forming units (cfu)/ml,
uncomplicated are considered to be complicated UTIs. based on studies correlating midstream-urine specimens
Differentiation between uncomplicated and complicated UTIs with catheterized collection to demonstrate bladder
has implications for therapy because the risks of complications
bacteriuria. However, up to 20% of women with clas-
or treatment failure are increased for patients with a
complicated UTI. Asymptomatic bacteriuria (ASB) is defined as sical urinary symptoms can have negative cultures,
the presence of a positive urine culture collected from a depending on the cut-off value used (1).
patient without symptoms of a UTI. Concerning the The differentiation between uncomplicated and com-
complicated UTI, it is possible to make a differentiation between plicated UTIs has implications for therapy because the
UTI with systemic symptoms (febrile UTI) and UTI in a host, risks of complications or treatment failure are increased
which carries an increased risk to develop complications of this for patients with a complicated UTI. In general, the
UTI. Febrile UTIs are urosepsis, pyelonephritis, and prostatitis.
following definitions are used: an uncomplicated UTI is
A complicated host is defined as one that has an increased
risk for complications, to which the following groups belong:
an episode of cystitis in a woman who is not pregnant, is
men, pregnant women, immunocompromised patients, not immunocompromised, has no anatomical and func-
or those who have an anatomical or functional abnormality tional abnormalities of the urogenital tract, and does not
of the urogenital tract (e.g., spinal cord-injury patients, exhibit signs of tissue invasion and systemic infection.
renal stones, urinary catheter).

Received: 29 June 2012, Accepted: 1 April 2016,

Published: 9 September 2016
CLINICAL SYNDROMES AND DEFINITIONS Editors: Matthew A. Mulvey, University of Utah, Salt Lake City, UT;
Urinary tract infection (UTI) is one of the most common Ann E. Stapleton, University of Washington, Seattle, WA; and
David J. Klumpp, Northwestern University, Chicago, IL
bacterial infections. Bacteria live around the urethra and Citation: Geerlings SE. 2016. Clinical presentations and
colonize the bladder, but are washed out during mictu- epidemiology of urinary tract infections. Microbiol Spectrum
rition. The shorter distance to the bladder in women (as 4(5):UTI-0002-2012. doi:10.1128/microbiolspec.UTI-0002-2012.
Correspondence: Suzanne E. Geerlings, S.E.Geerlings@amc.uva.nl
compared to men) makes it easier for bacterial colo-
© 2016 American Society for Microbiology. All rights reserved.
nizers to reach the bladder. Furthermore, the urethral

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Geerlings

All UTIs that are not uncomplicated are considered to be able to an earlier UTI. A 3-year follow-up of these 116
complicated UTIs (2). Therefore, episodes of acute cys- schoolgirls with ASB (treated or untreated) showed that
titis occurring in healthy nonpregnant women with the risk of developing renal damage as a result of ASB in
no history suggestive of an abnormal urinary tract are a schoolgirl with a roentgenographically normal urinary
generally classified as uncomplicated, whereas all others tract seemed to be small (7).
are classified as complicated (3). This distinction has Long-term follow-up studies have shown that ASB
been used to guide the choice and duration of antimi- with E. coli is not associated with a decline in renal
crobial treatment, with broader-spectrum agents and function or the development of end-stage renal failure in
longer courses of treatment often recommended for a population of generally healthy adult women (8). Al-
persons with complicated UTIs. However, this classifi- though E. coli bacteriuria may increase the risk of future
cation scheme does not account for the diversity of hypertension, the pathogenesis is not fully understood
complicated UTIs (3). A classification scheme that strat- (8, 9).
ifies patients with UTI into multiple, homogeneous cat- Following the guidelines, screening and treatment is
egories has been proposed but is not (yet) routinely used only recommended for pregnant women, or for patients
in practice (2, 3). prior to selected invasive genitourinary procedures (6).
Another differentiation of UTIs is between community- Clinical trials in spinal cord-injury patients, diabetic
and hospital-acquired UTIs. UTIs in patients acquired women (10), patients with indwelling urethral catheters,
within the hospital or hospitalized for treatment are and elderly nursing-home residents have consistently
generally complicated UTIs. More often uropathogens found no benefits with treatment of ASB. Negative out-
other than Escherichia coli are the causative microorga- comes with antimicrobial treatment do occur, including
nisms. Furthermore, more-resistant pathogens are cul- adverse drug effects and reinfection with organisms of
tured compared to community-acquired UTI. Earlier increasing resistance (11).
antimicrobial treatment remains the strongest predictor In renal-transplant patients, no differences in renal-
for resistant causative microorganisms (4). Epidemics function prognosis between patients with and without

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of nosocomial UTI have been described by recognizing ASB following kidney transplantation could be demon-
unusual antibiotic-resistance profiles. Most are caused strated. However, the incidence of pyelonephritis was
by transmission of outbreak strains between patients on much higher in the group of patients with ASB. There-
the hands of hospital staff. An estimated 80% of the fore, screening protocols may be beneficial in this patient
hospital-acquired UTIs are associated with catheters (1). group (12).
In a recent study, patients with healthcare-associated (not Since nearly all studies on ASB are performed in
hospital) UTI were older, had more co-morbidities, and women, it is not possible to draw conclusions about
had received previous antimicrobial treatment more fre- the association between ASB, the incidence of UTIs, or
quently compared to patients with community-acquired the development of renal-function decline in men.
UTI. Extended-spectrum beta-lactamase (ESBL) E. coli
and Pseudomonas aeruginosa infections were also more Uncomplicated Urinary Tract Infection/Cystitis
frequently cultured (5). Therefore, patients from nursing Cystitis (infection of the bladder or lower UTI) has the
homes can be considered as having hospital-acquired following symptoms: dysuria with or without frequency,
UTIs. urgency, suprapubic pain, or hematuria. Women with a
suspected uncomplicated UTI mostly present to primary
Asymptomatic Bacteriuria care. The most-common symptom is urinary frequency.
Asymptomatic bacteriuria (ASB), which is defined as Dysuria is also common with urethritis or vaginitis, but
the presence of a positive urine culture with at least cystitis is more likely when symptoms include frequency,
105 cfu/ml collected from a patient without symptoms urgency, or hematuria and when the onset of symptoms
of a UTI, is a common, but usually benign, phenomenon, is sudden or severe, without the presence of vaginal ir-
especially in women (6). Both host and bacterial factors ritation and discharge (13, 14). Many women also feel
influence the probability that ASB will resolve sponta- extremely unwell and have restricted physical activity.
neously or progress to symptomatic UTI. Patients without adequate treatment, in other words,
A Swedish study among 116 schoolgirls with ASB those not given antibiotics, and those with antibiotic-
showed that at baseline renal parenchymal reduction resistant organisms, complain of at least one symptom
was found in 10.3%, while reflux was found in 20.7%, that is moderately severe or worse lasting for five days
but only 30% of the 116 patients had a history refer- (15).

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 Clinical Presentations and Epidemiology of Urinary Tract Infections

The probability of cystitis is greater than 50% in Urinary Tract Infections with Systemic
women with any symptoms of UTI and greater than 90% Symptoms or Febrile UTI
in women who have dysuria and frequency without vag- Acute pyelonephritis
inal discharge or irritation (3, 13). Therefore, additional Typical clinical manifestations suggestive of pyelone-
urine analysis is not always needed in this patient group. phritis (infections of the kidney or upper UTI) are fever
Acute uncomplicated cystitis rarely progresses to (temperature >38°C) and chills, mental confusion as a
severe disease, even if untreated. A trial with nitrofu- sign of delirium, flank pain, costovertebral-angle ten-
rantoin and placebo showed that the result for combined derness, and nausea or vomiting (13, 14). The two routes
symptomatic improvement and cure after three days was by which bacteria can invade and spread within the
present in 27 of the 35 women in the nitrofurantoin urinary tract are the ascending route and the hematog-
group, but also in 19 of the 35 patients in the placebo enous route. There is no clear evidence for a lymphatic
group. In the same study, only one case in the placebo route. In practice, nearly all upper UTIs are caused by
group (1/38 = 12.6%) progressed to pyelonephritis (16). the ascending route from the bladder to the kidney. Al-
Therefore, the primary goal of treatment is to ameliorate though some patients can remember recent symptoms
symptoms. After start of treatment, the symptoms of a of cystitis or these symptoms are still present, this is often
lower UTI resolved quickly; the mean duration of uri- not the case. It should be recognized that symptoms
nary frequency was 3.46 days, for hematuria 1.88 days, may vary greatly. Flank tenderness may be more intense
and for urgency 3.6 days (15). when an obstructive disease is present. Normal kidney
In 2011, the Infectious Diseases Society of America function can be present, but progressive destruction of
(IDSA) updated its guidelines for antimicrobial treat- the kidney may give rise to clinical manifestations of
ment in acute uncomplicated cystitis in women. It is renal insufficiency.
interesting, in view of the worldwide problem of in-
creasing antimicrobial resistance, that these guidelines Prostatitis
recommend that ecological adverse effects of an anti-

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Prostatitis ranges from a straightforward clinical entity
microbial agent (selection for antimicrobial-resistant in its acute form to a complex, debilitating condition
organisms) must also be considered together with effi- when chronic. Diagnosis of acute and chronic bacte-
cacy in selecting the choice of the antimicrobial agent rial prostatitis is primarily based on history, physical
and duration of therapy (17). examination, urine culture, and urine-specimen test-
ing. Patients with acute prostatitis complain of symp-
Complicated Urinary Tract Infections toms associated with lower UTI, such as frequency and
It is possible to differentiate between UTI with systemic dysuria. They may also experience lower urinary-tract
symptoms and UTI in a host, which has an increased risk obstruction due to prostatic edema. Therefore, the dif-
to develop complications (complicated host). Systemic ferential diagnosis of prostatitis includes (amongst others):
symptoms can be noticed by signs of tissue invasion, like acute cystitis, benign prostatic hyperplasia, urinary-tract
fever, flank pain, and delirium. These UTIs can be called stones, and bladder cancer. On physical examination,
febrile UTI, because it is difficult to differentiate between patients may have a high temperature and lower abdom-
urosepsis, pyelonephritis, and prostatitis (18). However, inal or suprapubic discomfort due to bladder infection.
all of these syndromes require a therapeutic antibiotic The rectal examination shows an exquisitely tender
drug level in both tissue and urine. prostate on palpation (19, 20), but a normal rectal ex-
A complicated host is defined as one that has an in- amination cannot exclude this diagnosis (21).
creased risk for complications of the UTI, to which
the following groups belong: men, pregnant women, Urosepsis
immunocompromised patients, or those who have an Urosepsis is defined as sepsis caused by infection of the
anatomical or functional abnormality of the urogenital urinary tract. In urosepsis (as in other types of sepsis), the
tract (e.g., renal stones, urinary catheter, neurogenic severity of sepsis mainly depends on the host response.
bladder, spinal cord injury, renal transplant). Treatment The underlying UTI is almost exclusively a complicated
of a UTI (cystitis) in a complicated host requires a one with involvement of parenchymatous urogenital
therapeutic antibiotic drug level in the urine only, but organs (e.g., kidneys, prostate). The leading cause for
generally a longer treatment duration is recommended. developing an uroseptic shock in urological patients is
These different ‘complicated’ hosts are described below urinary obstruction. It is reported that 17% of patients
in the section Special patient groups. develop urosepsis after urological interventions (22).

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SPECIAL PATIENT GROUPS mended as first choice because these drugs are more
Children effective than trimethoprim/sulfamethoxazole (28,
UTI is one of the most common bacterial infections in 29). Since it is not an acute illness, the results of the
children. UTI in young children and infants are often culture (urine, if necessary, after massage of the
presented with nonspecific clinical signs, such as fever, prostate or semen) can be awaited before therapy is
irritability, and vomiting, making the diagnosis diffi- initiated.
cult. Urine collection and interpretation of urine tests
in children is not easy and does not always lead to un-
equivocal confirmation of the diagnosis. Failure to di- Pregnant Women
agnose UTI or delaying treatment of a UTI may result in ASB occurs in 2 to 10% of pregnant women (6). ASB
a clinical deterioration with additional long-term renal during pregnancy can lead to serious complications for
damage. Renal anatomical abnormalities that are fre- both mother and child. The incidence of ASB is similar in
quently associated with UTIs are vesicoureteric reflux, both pregnant and nonpregnant women (30). However,
double systems, hydronephrosis, hydroureter, and ure- pregnant women with ASB more often develop pyelo-
thral obstructions (23, 24). nephritis, probably due to the anatomic and physiologic
In a cohort study, encopresis was found to be signif- changes that occur during pregnancy, which may facil-
icantly associated with recurrent UTI (25). Therefore, itate bacterial growth and the ascent of bacteria to the
dysfunctional elimination syndromes and constipation kidneys (31). If left untreated, 20 to 40% of pregnant
should be treated in infants and children who have had a women with ASB will develop pyelonephritis (30, 32,
UTI. 33). Furthermore, during pregnancy there is an elevated
Concerning treatment duration, in 10 randomized risk of a more severe course of a UTI with adverse
controlled trials with 625 children with cystitis (aged consequences for mother and child (34).
3 months to 18 years), no significant differences were Other possible adverse effects, such as preterm de-
livery and delivering a low-birth-weight infant, are less

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found in persistence of clinical symptoms or bacteriuria,
recurrent UTI, compliance with medication, or devel- well established. Although preterm delivery is the main
opment of bacterial resistance between short duration cause of neonatal mortality and morbidity worldwide,
(2–4 days) oral antibiotic treatment and the earlier- the causal mechanisms remain unknown. One of the
recommended treatment duration of 7–14 days (26). hypotheses is that endotoxins released by bacteria cause
uterine contractions leading to preterm delivery.
Men Antibiotics are effective again ASB during pregnancy
As a rule, a UTI in a man is considered to be a compli- and lower the incidence of pyelonephritis as well as
cated UTI because the prostate is often involved (21). prematurity and dysmaturity (35, 36).
However, in general, men with a bacterial UTI can be In view of the lack of reported teratogenic effects
separated into three groups, each with its own therapy: and the resistance percentages of the causative mi-
croorganisms, the beta-lactam antibiotics are a good
1. Young men with a UTI without systemic symp- choice for the treatment of a UTI during pregnancy.
toms, where the patient’s medical history and phys- Amoxicillin-clavulanic acid or nitrofurantoin are first-
ical examination do not suggest a causative factor. choice drugs for the treatment of cystitis during preg-
The UTIs in this group can be considered uncom- nancy (however, nitrofurantoin must not be used just
plicated UTIs, but are very uncommon (27). before delivery). In view of the high resistance percent-
2. Men with a UTI and systemic symptoms or with a age of the uropathogens for amoxicillin, this drug is not
medical history and physical examination that suitable for empirical treatment. A 2nd or 3rd genera-
suggest a causative factor. These UTIs must be tion cephalosporin is the drug of first choice and
considered complicated UTIs. The systemic symp- amoxicillin-clavulanic acid is second choice for treat-
toms indicate invasion of the tissue in the prostate ment of a pyelonephritis during pregnancy (34).
(acute bacterial prostatitis) or the kidney (pyelo- It is a sign of maternal colonization with group B
nephritis) (28). streptococcus (GBS) whenever a GBS is found in the
3. Men with complaints that fit a chronic bacterial urine culture. Intravenous-antibiotic treatment of the
prostatitis. In these cases, it is advised to wait for mother during delivery reduces the number of neonatal
the results of the culture. For men with a chronic infections with GBS (37). Based on the literature, it is
bacterial prostatitis, a fluoroquinolone is recom- recommended that pregnant and nonpregnant women

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 Clinical Presentations and Epidemiology of Urinary Tract Infections

with cystitis should be treated for 3–7 days (36). In gen- In addition to bacteriuria and CA-UTI, long-term
eral, it is recommended to hospitalize a pregnant woman catheterization can also lead to the following complica-
with a pyelonephritis and to administer antibiotics in- tions: bacteremia, catheter obstruction, renal and blad-
travenously. After a fever-free period of 24–48 hours, der stone formation, incontinence, and, with prolonged
oral antibiotics can be given; the total duration of ther- use, bladder cancer (39, 45).
apy must be at least 10 days (38). The insertion of an indwelling catheter increases the
susceptibility of a patient to UTIs, as it provides easier
Patients with a Urinary Catheter access of microorganisms to the urinary tract. Most of
Catheter-associated (CA) infection refers to infection these uropathogens are fecal or skin bacteria from a
occurring in a person whose urinary tract is currently patient’s own native or transitory microflora. Bacteria
catheterized or has been catheterized within the past can enter the bladder at the time of catheter inser-
48 hours. UTI refers to significant bacteriuria in a pa- tion, through the catheter lumen, or along the catheter-
tient with symptoms or signs attributable to the urinary urethral interface. Most microorganisms that cause
tract and no alternative source. Bacteriuria is a non- CA-UTI enter the bladder extraluminally by ascending
specific term that refers to UTI and ASB combined. In along the catheter-mucosa interface and are primarily
the urinary-catheter literature, CA-bacteriuria is mainly endogenous. Microorganisms can also enter the bladder
comprised of CA-ASB (39). intraluminally, by contamination of the collecting tube
Indwelling urinary catheters are widely used in hos- or drainage bag. These organisms are often exogenous,
pitalized patients for patients with urinary retention and derived from cross-contamination of organisms on the
for frequent monitoring of urine output in critically ill hands of healthcare personnel (39, 40, 46).
patients. Most patients are catheterized for 2–4 days, but Indwelling catheters facilitate colonization of uro-
many have a catheter inserted for a longer duration as, pathogens by enhancing microbial adhesion. The cathe-
for example, spinal cord-injury patients. Unfortunately, ter provides an attachment surface for bacterial adhesins
the use of indwelling catheters is not without risks. that recognize host-cell receptors on the surfaces of the

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Many catheterized patients develop bacteriuria, with host cell or catheter. In addition, urinary catheters may
an incidence of 3 to 10% per day (40). Duration of damage the uroepithelial mucosa, which leads to expo-
catheterization is the most important risk factor for sure of new binding sites for bacterial adhesins. Once
the development of CA-bacteriuria; almost all patients attached to the catheter surface or uroepithelium, bac-
with long-term catheterization (>1 month) will have teria undergo phenotypical changes, replicate, and form
bacteriuria. Although most patients with bacteriuria microcolonies that eventually mature into biofilms. These
are asymptomatic, symptoms of UTI will develop in biofilms protect uropathogens from antimicrobials and
some patients. UTI is one of the most common hospital- the host-immune response, and migrate over the cathe-
acquired infections, and 80% of these are associated ter surface to the bladder within 1–3 days. Bacteriuria
with the use of indwelling catheters (41). A surveillance in patients with short-term catheterization is commonly
study in the Netherlands found that 1.2% of all hospi- caused by a single organism, mostly E. coli, while infec-
talized patients had a catheter-associated UTI (42). In a tions in long-term catheterization are polymicrobial (39,
prospective study, the incidence of UTI was 15.6% in 40, 46). Bacteriuria contains a large reservoir of antimi-
about 1,500 patients catheterized for at least 24 hours crobial-resistant organisms and can be a source of cross-
(43). The proportion of patients with catheter-related infection. The most effective way to reduce CA-UTI is to
bacteriuria in whom symptomatic UTI and bacteremia avoid urinary catheterization (39).
will develop was estimated through quantitative synthe- The guidelines of the IDSA define CA-UTI as the pres-
sis of previous reports. Of patients who had indwelling ence of symptoms: new-onset or worsening of fever, rigors,
catheters for 2–10 days, bacteriuria was expected to altered mental status, malaise, or lethargy of no other iden-
develop in 26%, bacteriuria and symptoms of a UTI tified cause; flank pain; costovertebral angle tenderness;
would develop in 24%, and bacteremia from a urinary- acute hematuria; or pelvic discomfort, and more than
tract source would develop in 3.6%. Each episode of 1,000 cfu/ml of one or more bacterial species (39).
symptomatic UTI infection was expected to cost an ad- Results of studies included in a Cochrane review on
ditional $676 US, and catheter-related bacteremia was short-term urinary-catheter use in female patients with
at least $2,836 US. Given the clinical and economic abdominal surgery and a urethral catheter for 24 hours,
burden of catheter-related UTI, all health care workers show weak evidence that antibiotic prophylaxis, com-
should try to reduce this common complication (44). pared to giving antibiotics when clinically indicated,

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reduced the rate of symptomatic UTI [relative risk (RR) It is desirable to limit the duration of treatment, es-
0.20 (95% confidence interval [CI] 0.06–0.66)]. There pecially for milder infections and infections that respond
was also limited evidence that prophylactic antibiotics promptly to treatment, to reduce the selection pressure
reduced bacteriuria in nonsurgical patients (47). for drug-resistant flora, especially in patients on long-
Regarding the question as to whether antibiotic pro- term catheterization. Therefore, 5–7 days is the recom-
phylaxis is better than giving antibiotics when clinically mended duration of antimicrobial treatment for patients
indicated (i.e., having a symptomatic UTI), the available with CA-UTI who have prompt resolution of symptoms,
evidence is too limited to be a basis for clinical practice and 10–14 days is recommended in those with a delayed
(39). For patients using intermittent catheterization the response, irrespective of whether or not the patient
data were inconclusive. For patients using indwelling remains catheterized (39).
urethral catheterization, only a single crossover trial
with 34 elderly inpatients investigated this issue and re- Diabetes mellitus
sults showed fewer episodes of symptomatic UTI in the Diabetic patients have an increased risk for UTI (49,
prophylaxis (norfloxacin) group (48). For patients using 50). A recent study in primary care patients from the
intermittent catheterization, the limited evidence sug- Netherlands demonstrated that relapses and reinfec-
gested that antibiotic prophylaxis reduces the number tions were reported in 7.1% and 15.9%, respectively,
of episodes of bacteriuria (asymptomatic and symp- of women with diabetes mellitus (DM) versus 2.0%
tomatic). For patients using urethral catheterization, no and 4.1%, respectively, of women without DM. There
data were available (47). Based on these observations, was a higher risk of recurrent UTI in women with DM
the contradictory results, and the concerns about rising compared to women without DM (odds ratio [OR]
antimicrobial resistance, prophylactic antimicrobials 2.0; 95% CI 1.4–2.9). Women who had had DM for at
are not routinely recommended for catheter placement, least 5 years (OR 2.9; 95% CI 1.9–4.4) or who had
removal, or replacement. This recommendation is also retinopathy (OR 4.1; 95% CI 1.9–9.1) were at risk of
supported by the low rate of serious complications in recurrent UTI (51). This increased recurrence rate was

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the large number of patients undergoing long-term in- confirmed in one study (52) but not in another (53).
termittent catheterization with a clean technique in the In an American study in women with DM type 1 it was
setting of chronic bacteriuria (39). found that sexual activity, rather than measures of dia-
CA-UTIs are often polymicrobial and caused by betes control and complications, was the main risk fac-
multiple-drug-resistant uropathogens. Urine cultures are tor for UTI (54).
recommended prior to treatment in order to confirm that Diabetic patients more often develop complications,
an empiric regimen provides appropriate coverage and such as bacteremia (55) and a longer hospitalization (50,
to allow tailoring of the regimen based on antimicrobial 56), of their UTI compared to nondiabetic patients. For
susceptibility data (39). this reason, cystitis in a patient with DM is considered a
Only a few small studies have investigated which complicated UTI.
causative uropathogens are present in patients with CA- No prospective trial has investigated the optimal
UTIs. The numbers are too small to translate the results treatment (agent and duration) in these patients.
into a strong recommendation for empirical treatment. Concerning the recurrence rate of UTI in diabetic com-
In patients on long-term catheterization, empirical treat- pared to nondiabetic women, two studies using Dutch
ment with fluoroquinolones or gentamicin may be war- registration databases containing pharmacy-dispensing
ranted to cover less-common microorganisms such as data from two different time periods show contradic-
Serratia, Providencia, and Acinetobacter. However, a tory results (57, 58). In the largest study (58), the pre-
study from the Netherlands demonstrated that patients scriptions of 10,366 women with diabetes and 200,258
with a urinary catheter are at increased risk to have women without diabetes were compared. Women with
a fluoroquinolone-resistant microorganism (4), which diabetes more often received a long treatment, but still
only leaves the toxic aminoglycosides for empirical had a higher recurrence rate of UTI, compared with
treatment in this patient group. Earlier antimicrobial those without diabetes.
treatment remains the strongest predictor for resistant It is reported that ASB in women with DM is benign
causative microorganisms (4). Therefore, in a patient and that 20% of diabetic subjects with ASB remained
with a catheter who has only local symptoms and ex- bacteriuric with the original infecting organism through-
hibits no signs of a systemic infection, we recommend to out the period of observation. Women infected with
wait for the results of the cultures. gram-negative organisms were more likely to have per-

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 Clinical Presentations and Epidemiology of Urinary Tract Infections

sistent bacteriuria. Many women with resolution of ini- mon in the family members of children with a history of
tial bacteriuria, with or without antibiotics, became acute pyelonephritis (15%) than in relatives of control
bacteriuric again during follow-up. Furthermore, ASB subjects (3%) (68).
in women with DM does not result in renal function
decline (59). However, more women with ASB will de-
velop a symptomatic UTI compared to those without RECURRENT URINARY TRACT INFECTIONS
(60). Also, in another study with male and female Recurrent UTI is a common health care problem and
patients with DM type 1 and 2, the presence of ASB was is defined in the literature by three episodes of UTI in
associated with an increased risk of hospitalization for the last 12 months or two episodes in the last 6 months.
urosepsis (61). About 20 to 30% of women who have a UTI will have
In the above-mentioned prospective study (59), be- a recurrent UTI (69, 70).
cause no evidence was found that ASB alone can lead Looking at the causative microorganism, it was re-
to a decline in renal function (in women with type 1 and cently demonstrated that uropathogenic E. coli adhere,
type 2 DM), it is unlikely that treatment of ASB will lead invade, and replicate within the murine bladder uro-
to a decrease in the incidence of diabetic nephropathy. thelium to form intracellular bacterial communities. The
This is in accordance with a study on women with presence of exfoliated intracellular bacterial communi-
DM and with ASB, in which a comparison was made ties and filamentous bacteria in the urine of women with
between women who received antibiotic therapy and acute cystitis suggests that this pathogenic pathway,
women who received placebo. In that study, no differ- characterized in the murine model, may occur in hu-
ence was seen in serum creatinine levels after a mean mans. The findings support the occurrence of an intra-
follow-up of 2 years (10). cellular bacterial niche in some women with cystitis that
Treatment of ASB in patients with DM is not needed, may have important implications for UTI recurrence and
because in these women ASB does not result in renal treatment (71).
function decline, and most of these women do not de- In general, in men and postmenopausal women, it is

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velop a symptomatic UTI. Therefore, screening for ASB recommended to exclude anatomical or functional ab-
is not indicated in these patients. This is in accordance normalities of the urogenital tract as a cause of recurrent
with the IDSA guideline for the diagnosis and treatment UTI. In premenopausal women the yield of most diag-
of ASB in adults (6). nostic procedures is low (72).
There are four patterns of response of bacteriuria to
therapy: cure, bacteriologic persistence, bacteriologic
RISK FACTORS relapse, or reinfection. Bacteriologic persistence is the
Risk factors for uncomplicated and recurrent cases of persistence of bacteriuria with the same microorganism
lower and upper UTI include sexual intercourse, use of after 48 hours of treatment. Relapse is an infection with
spermicides, previous UTI, a new sex partner, and a the same microorganism that caused initial infection and
history of UTI in a first-degree female relative (3, 62–65). usually occurs within 1–2 weeks after the cessation of
Case-control studies have shown no significant asso- treatment. A relapse indicates that the infecting organ-
ciations between recurrent UTI and precoital- or post- ism has persisted in the urinary tract. Reinfection is
coital-voiding patterns, daily beverage consumption, an infection after sterilization of the urine. Most of the
frequency of urination, delayed-voiding habits, wiping time there is a change in bacterial species. Reinfection
patterns, tampon use, douching, use of hot tubs, type can be defined as a ‘true’ recurrence. Both persistence
of underwear, or body-mass index (65); however, at and relapse may be related to inadequate treatment. It is
least some of this absence of findings might reflect a very important to determine whether recurrent UTIs are
misclassification of behaviors (3, 66). relapses or reinfections and to make a differentiation
A genetic predisposition to recurrent UTI is suggested between these patterns, since this has treatment con-
by the strong association between a history of UTI in one sequences. In a persistent UTI the cause must be evalu-
or more first-degree female relatives and an increased ated. In a relapse of the UTI, the treatment can be given
risk of recurrent UTIs (63). Certain toll-like-receptor for a longer period.
polymorphisms and other genetic variations, particu- The first consideration in prevention is to address
larly those affecting the immune response, are associated modifiable behavioral practices. Other effective strate-
with an increased risk for UTI (66, 67). Other studies gies are generally considered as antimicrobial or non-
have shown that acute pyelonephritis was more com- antimicrobial. Low-dose antimicrobial therapy remains

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Geerlings

an effective intervention to manage frequent, recurrent,

acute, and uncomplicated UTI. The antimicrobial may
be given as continuous daily or every-other-day therapy,
usually at bedtime, or as postcoital prophylaxis (69).
Topical vaginal estrogen is a potential intervention
to decrease the number of recurrent episodes for post-
menopausal women (73).

EPIDEMIOLOGY
The self-reported annual incidence of UTI in women is
12%, and by the age of 32 years, 50% of all women
report having had at least one UTI (3, 74). In a study of
young college women, the incidence of cystitis (lower
UTI) was 0.70 episodes per person-year (62). Among
young healthy women with cystitis, the infection recurs
in 25% of women within 6 months after the first UTI.
Although the risk of second UTI is strongly influenced
by sexual behavior, women with a first UTI caused by FIGURE 1 Overview of the incidence of symptomatic UTI and
E. coli are more likely than those with a non-E. coli the prevalence of asymptomatic bacteriuria according to age
and sex (curves, females; hatched areas, males) (79).
first UTI to have a second UTI within 6 months (75).
In a population-based study with 1,017 postmenopausal
women, the incidence of cystitis was 0.07 episodes per ASB was higher in both women (14.2% DM vs 5.1%

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person-year (76). controls) and men (2.3 % DM vs 0.8% controls) (78).
In general, about 50 to 70% of women will have a The high incidence of UTI results in considerable
UTI sometime during their lifetime, and 20 to 30% of health care costs. The estimated annual direct and indi-
women who have a UTI will have a recurrent UTI (69, rect cost of UTI in the USA in 1995 was $1.6 billion
70). In certain periods of life (childhood, honeymoon, (equivalent to $2.3 billion in 2010) (1). A nosocomial
pregnancy, elderly), an increased incidence of UTI has UTI necessitates one extra hospital day per patient,
been described (Fig. 1). resulting in almost 1 million extra hospital days each
Acute pyelonephritis (upper UTI) is much less com- year in the USA (1).
mon than cystitis. Incidence of pyelonephritis is highest
among young women, followed by infants and the el-
derly population. The annual rates of outpatient pyelo- SUMMARY
nephritis in women and men were 12–13 and 2–3 cases UTI is one of the most common bacterial infections and
per 10,000, respectively (77). UTIs account for approxi- the incidence in women is much higher than in men. The
mately 5 to 7% of all cases of severe sepsis (22). diagnosis of a UTI can be made based on a combination
The prevalence of complaints compatible with chronic of symptoms and a positive urine analysis or culture.
prostatitis/chronic pelvic pain syndrome (CP/CPPS) is high Most UTIs are uncomplicated UTIs, defined as cystitis
with an overall rate of 8.2%, with prevalence ranging in a woman who is not pregnant, is not immunocom-
from 2.2 to 9.7%. Two studies suggest that about one- promised, has no anatomical and functional abnormal-
third of men reporting prostatitis symptoms had resolu- ities of the urogenital tract, and does not exhibit signs
tion after 1 year (19). of tissue invasion and systemic infection. All UTIs that
The prevalence of ASB depends on the patient group. are not uncomplicated are considered to be complicated
Different studies report a prevalence of approximately UTIs. Differentiation between uncomplicated and com-
1 to 5% among healthy young women, increasing to plicated UTIs has implications for therapy, because the
over 20% in the elderly and 12 to 26% in women with risks of complications or treatment failure are increased
DM. In a systematic review and meta-analysis, in which for patients with a complicated UTI. ASB is defined as
22 studies were included, ASB was present in 439 of the presence of a positive urine culture collected from a
3,579 (12.2%) patients with DM and in 121 of 2,702 patient without symptoms of a UTI. Concerning com-
(4.5%) healthy control subjects. The point prevalence of plicated UTI, it is possible to make a differentiation

8 ASMscience.org/MicrobiolSpectrum
 Clinical Presentations and Epidemiology of Urinary Tract Infections

between UTI with systemic symptoms (febrile UTI) and 15. Little P, Merriman R, Turner S, Rumsby K, Warner G, Lowes JA,
UTI in a host, who has risk factors to carry resistant Smith H, Hawke C, Leydon G, Mullee M, Moore MV. 2010. Presenta-
tion, pattern, and natural course of severe symptoms, and role of anti-
microorganisms and/or with difficulty in successfully biotics and antibiotic resistance among patients presenting with suspected
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S, De Maeseneer JM. 2002. Randomised controlled trial of nitrofurantoin
including: men, pregnant women, immunocompromised versus placebo in the treatment of uncomplicated urinary tract infection in
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