Expert Reviews ajog.

org

Diagnosis and treatment of urinary tract

infections across age groups
Christine M. Chu, MD; Jerry L. Lowder, MD

each year.1,2 Complications of UTI

Urinary tract infections are the most common outpatient infections, but predicting the include pyelonephritis requiring hospi-
probability of urinary tract infections through symptoms and test results can be complex. talization and can result in permanent
The most diagnostic symptoms of urinary tract infections include change in frequency, renal damage. UTI is most commonly
dysuria, urgency, and presence or absence of vaginal discharge, but urinary tract infections caused by uropathogens from fecal flora
may present differently in older women. Dipstick urinalysis is popular for its availability and (predominantly Escherichia coli) that
usefulness, but results must be interpreted in context of the patient’s pretest probability ascend the urethra to infect the bladder.3
based on symptoms and characteristics. In patients with a high probability of urinary tract Normal defense mechanisms against
infection based on symptoms, negative dipstick urinalysis does not rule out urinary tract UTIs include complete voiding, which
infection. Nitrites are likely more sensitive and specific than other dipstick components for removes bacteria from the bladder; uri-
urinary tract infection, particularly in the elderly. Positive dipstick testing is likely specific for nary acidification from concentrated
asymptomatic bacteriuria in pregnancy, but urine culture is still the test of choice. urea and other excreted organic acids;
Microscopic urinalysis is likely comparable to dipstick urinalysis as a screening test. vesicoureteral valves, which prevent
Bacteriuria is more specific and sensitive than pyuria for detecting urinary tract infection, reflux of the bacteria to the upper uri-
even in older women and during pregnancy. Pyuria is commonly found in the absence of nary tract; leukocyte phagocystosis; and
infection, particularly in older adults with lower urinary tract symptoms such as inconti- IgA production.4 Women are especially
nence. Positive testing may increase the probability of urinary tract infection, but initiation of prone to UTIs because of their shorter
treatment should take into account risk of urinary tract infection based on symptoms as urethral length, frequent vaginal colo-
well. In cases in which the probability of urinary tract infection is moderate or unclear, urine nization, and interference of urine flow
culture should be performed. Urine culture is the gold standard for detection of urinary tract and complete bladder emptying from
infection. However, asymptomatic bacteriuria is common, particularly in older women, and prolapse and urinary retention. Other
should not be treated with antibiotics. Conversely, in symptomatic women, even growth as risk factors include anatomic and func-
low as 102 colony-forming unit/mL could reflect infection. Resistance is increasing to tional urologic abnormalities, sexual
fluoroquinolones, beta-lactams, and trimethoprim-sulfamethoxazole. Most uropathogens activity, history of UTIs (especially age
still display good sensitivity to nitrofurantoin. First-line treatments for urinary tract infection <15 years), urinary incontinence, and
include nitrofurantoin, fosfomycin, and trimethoprim-sulfamethoxazole (when resistance physical limitations.5,6
levels are <20%). These antibiotics have minimal collateral damage and resistance. In An estimated 11% of women report at
pregnancy, beta-lactams, nitrofurantoin, fosfomycin, and trimethoprim-sulfamethoxazole least 1 physician-diagnosed UTI per
can be appropriate treatments. Interpreting the probability of urinary tract infection year, and 20-30% report multiple re-
based on symptoms and testing allows for greater accuracy in diagnosis of urinary tract currences.7,8 UTIs are a common
infection, decreasing overtreatment and encouraging antimicrobial stewardship. concern throughout the lifespan. Young
women who are sexually active are
Key words: antibiotic resistance, asymptomatic bacteriuria, diagnostic performance, particularly vulnerable. In pregnancy,
dipstick urinalysis, likelihood ratio, microscopic urinalysis, symptoms, urinary tract bacteriuria can lead to complications
infection, urine culture, women such as pyelonephritis, urosepsis, and
increased risk of preterm birth.9 Addi-
tionally, the prevalence of UTI increases
Introduction encountered in the United states.1 UTIs with age, such that prevalence increases
Urinary tract infections (UTI) are the result in 8.6 million health care visits and to 20% in women age of >65 years.10
most common outpatient infections an estimated cost of 1.6 billion dollars This makes UTI an important issue in
our increasingly aging population.
UTIs can be difficult to diagnose
From the Department of Obstetrics and Gynecology, Washington University in St Louis, St Louis, because they may present differently in
MO. different subgroups, and commonly
Received Sept. 9, 2017; revised Dec. 18, 2017; accepted Dec. 27, 2017. used office and laboratory testing may
The authors report no conflict of interest. further confuse the picture. In this
Corresponding author: Christine M. Chu, MD. cchu23@wustl.edu review, we explore the evidence behind
0002-9378/$36.00
ª 2018 Elsevier Inc. All rights reserved.
https://doi.org/10.1016/j.ajog.2017.12.231 the use of signs, symptoms, and uri-
nary testing in prediction of UTI in

40 American Journal of Obstetrics & Gynecology JULY 2018

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TABLE 1
Summary of diagnostic performance of symptoms
Study Test or symptom Sensitivity Specificity LRD LRe
11
Bent et al, 2002 Self-diagnosis 4 0
Dysuria 1.5 0.5
Frequency 1.8 0.6
Hematuria 2.0 0.9
Lower abdominal pain 1.1 0.9
Fever 1.6 0.9
Vaginal discharge 0.3 (self-reported); 3.1 (self-reported);
0.7 (on examination) 1.1 (on examination)
Dysuria þ frequency and 24.6
no vaginal discharge
No dysuria and þ vaginal 0.3
discharge
Giesen et al,12 2010 Dysuria 80% 38% 1.3 0.51
Frequency 88% 20% 1.1 0.6
Hematuria 25% 85% 1.72 0.88
Nocturia 59% 55% 1.3 0.75
Urgency 67% 45% 1.22 0.73
Vaginal discharge 15% 77% 0.65 1.1
Medina-Bombardó and Dysuria 1.09 0.8
Jover-Palmer,13 2011
Frequency 1.03 0.83
Vaginal discharge 0.63 1.18
Nocturia 1.28 0.72
Urgency 1.18 0.75
Sexual activity 1.14 0.66
Urgency and dysuria 1.53 0.44
Older population
Woodford and George,15 2009 Any UTI symptom 48.7% 89.6%
LR, likelihood ratio; UTI, urinary tract infection.
Chu. UTI across age groups. Am J Obstet Gynecol 2018.

women across age groups. We also empiric treatment. Pretest probability
discuss treatment guidelines, with takes into account the probability of UTI
special focus on older women and based on presenting symptoms, and is
pregnancy. calculated by dividing the sum of true
positives and false negatives by the total
Clinical manifestations sample size. Pretest probability can
Although the probability of UTI can be significantly influence the probability of
estimated from laboratory testing, UTI after diagnostic testing is performed
accurate diagnosis requires careful (posttest probability); for instance, a
consideration of the individual’s symp- patient with a high risk of UTI based on
toms alongside test results. Pretest and symptoms still has a significant chance of
posttest probability play important roles having a UTI even if testing is negative,
in decisions for additional testing or while the risk of UTI in a patient with
low risk of UTI based on symptoms is
only moderately elevated in the presence
of positive testing. The most common
UTI symptoms are urgency, frequency,
and dysuria. Other symptoms include
suprapubic, vaginal, and urethral
tenderness, as well as hematuria. It is
important to note that systemic symp-
toms, such as nausea, vomiting, flank
pain, upper back pain, and fevers may
indicate ascension of infection to the
upper urinary tract and should not be
treated as uncomplicated UTI.

JULY 2018 American Journal of Obstetrics & Gynecology 41

Expert Reviews
FIGURE 1
Interpretation of likelihood
ratios (LR)
LR and their effect on posttest probability.
Chu. UTI across age groups. Am J Obstet Gynecol 2018.
The predictive value of symptoms in
the diagnosis of UTI has been frequently
studied (Table 1). In a comprehensive
systematic review by Bent et al11 in 2002,
the positive predictive value (PPV) of
self-diagnosis in women with recurrent
UTIs was 84%. The likelihood ratio
(LR)þ (that is, the true-positive rate of
self-diagnosis of UTI divided by the
false-positive rate; for further explana-
tion, see Figure 1) was 4, meaning that
the pretest probability of UTI increases
approximately 25%. These data support
the practice of empirical treatment in
uncomplicated females with clear
symptoms of UTI. LRþ for common
symptoms including dysuria, frequency,
hematuria, lower abdominal pain, and
fever were 1.5, 1.8, 2, 1.1, and 1.6,
respectively.11 Importantly, the presence
of vaginal discharge resulted in a lower
LR of 0.3 (self-reported) to 0.7 (if found
on examination).11 This suggests that
the presence of vaginal discharge de-
creases the probability of UTI by about
25%. In this study, the combination of
dysuria and frequency without vaginal
discharge resulted in a very high LR of
24.6, or a pretest probability of about
90%.11 This suggests that empirical
treatment in women with this set of
symptoms is reasonable. Moreover, a
woman simply presenting with 1
42 American Journal of Obstetrics & Gynecology JULY 2018
symptom of UTI to the office has a
pretest probability of approximately
50%. In a 2010 review, 5 symptoms
significantly predicted the diagnosis of
UTI (at threshold of 102 colony-
forming units [CFU]/mL): dysuria,
frequency, hematuria, nocturia, and ur-
gency.12 Vaginal discharge was again
found to decrease the risk of UTI.
Hematuria was the most useful symp-
tom in ruling in UTI (with LRþ of 1.72,
specificity of 85%, sensitivity of 25%),
whereas absence of dysuria, frequency,
and urgency were the most useful
symptoms for ruling out UTI.12
Conversely, a meta-analysis found that
dysuria, urgency, nocturia, sexual activ-
ity, and combined presence of urgency
and dysuria were weakly predictive of
UTI.13 Though few studies noted the
severity of symptoms, in a study by Little
et al,14 only dysuria defined as moder-
ately severe or greater was significantly
associated with positive culture. Thus, in
the general female population, the most
diagnostic symptoms are likely
frequency, dysuria, urgency, and pres-
ence (UTI less likely) or absence (UTI
more likely) of vaginal discharge.
In older adults, typical UTI symptoms
may be less diagnostic for UTI. Although
the probability of UTI is greater with age,
older women without UTIs tend to
present with higher rates of lower uri-
nary tract symptoms that may be
confused with UTI, such as urgency and
frequency. In a study examining women
75 years old who were discharged from
the hospital with a UTI diagnosis, the
sensitivity and specificity of any pre-
senting UTI symptoms were noted to be
48.7% and 89.6%, respectively.15 This
study also found that dysuria, frequency,
suprapubic and flank pain, discolored
urine, and upper urinary tract symp-
toms such as costovertebral tenderness,
rigors, and fever were significantly
associated with positive urine cultures.
In the study, urinary retention was also
significantly associated with positive
cultures, but atypical symptoms that are
commonly assumed to be associated
with UTI in the elderly, such as falls,
worsening incontinence, functional and
cognitive decline, and malodorous
urine, were not associated with positive
ajog.org
cultures. This may indicate that signs
and symptoms can present differently in
older adults than in younger women. In a
study that compared the clinical pre-
sentation of UTI in premenopausal and
postmenopausal women, premeno-
pausal women displayed more typical
symptoms such as frequency and
dysuria, whereas postmenopausal
women displayed symptoms related to
urinary storage (urgency, frequency, in-
continence, difficulty emptying
bladder).16 Although nursing home
residents often differ from community-
dwelling older women with regards to
UTI characteristics, 1 study noted that
dysuria, change in urine (color, odor,
hematuria), and mental status were
significantly associated with positive
urine culture.17 Among institutionalized
women with dysuria and at least 1
additional symptom, probability of UTI
was 63%, but among those with only 1
clinical feature, probability decreased to
39%.17 Symptoms in the elderly, espe-
cially in those who are institutionalized,
may therefore be unreliable in ruling in
infection.
Symptoms and signs of UTI in preg-
nancy are not well studied, as the inci-
dence of symptomatic UTI is around
1-2%.9 Additionally, symptoms are not
needed in pregnant women before
treating bacteriuria. This is because
asymptomatic bacteriuria often pro-
gresses to pyelonephritis in pregnancy,
likely as a result of ureteric dilation due
to elevated progesterone. In a small case
series, the majority of pregnant women
with symptoms of UTI presented with
urinary frequency (82%), suprapubic
pain (73.1%), and dysuria (55.1%).18
However, only 26.9% of these women
had positive cultures, indicating a high
rate of false positives based on urinary
symptoms alone in this population.
Indeed, lower urinary tract symptoms
are common in pregnant women, and
frequency, urgency, and nocturia are
frequently reported in the absence of
UTI.19-22
Urine testing
Laboratory analysis for UTIs includes 3
main tests: dipstick urinalysis, micro-
scopic urinalysis, and urine culture.
ajog.org
FIGURE 2
Using pretest and posttest probability for prediction of urinary tract infection (UTI)
Probability of UTI changes based on patient’s symptoms and results of urine testing. Likelihood ratios based on data published by Bent et al.11
Chu. UTI across age groups. Am J Obstet Gynecol 2018.
Urine dipstick and microscopic urinal-
ysis results may increase or decrease the
pretest probability of UTI, allowing cli-
nicians to more accurately diagnose
UTIs (Figure 2). Women with high
posttest probability and significant
urinary symptoms will most likely
benefit from empiric treatment and may
not need confirmation by culture. In
those with moderate probability of UTI,
a culture may be beneficial to confirm
diagnosis and allow for more precise
selection of antibiotics. In those with low
posttest probability of UTI, further
testing and treatment may not be
needed.
Dipstick urinalysis
Urine testing often begins with dipstick
urinalysis, which is easily available in the
office and takes minutes for interpreta-
tion. The most common type of dipstick
urinalysis permits analysis of multiple
urine components, the most important
being leukocyte esterase (LE), nitrite,
and red blood cells.
LE is expressed in white blood cells
(WBCs), which are elevated in urine
during infection. Dipstick testing is fairly
sensitive to LE in the urine and turns
positive in the presence of >5-15 WBC/
high-power field (hpf). Nitrite is indic-
ative of the presence of bacteria, as some
uropathogens contain bacterial enzymes
that convert nitrates into nitrites. Urine
dipsticks are able to detect nitrites in the
presence of bacteria >105 CFU/mL.
Urine dipsticks can detect very low levels
of blood in the urine (correlates with
>1-4 red blood cells/hpf). Although
blood may be associated with other pa-
thology, in the presence of symptoms or
positive nitrite and LE testing, its pres-
ence may increase the probability of UTI.
Several conditions can influence the
interpretation of dipstick urinalysis.
Uropathogens such as enterococci and
Staphylococcus saprophyticus do not
reduce nitrates and would result in false
negatives. Although testing for nitrites
and red blood cells requires only 1
minute before interpretation, LE re-
quires 2 minutes for accurate interpre-
tation.23 Urine that is too dilute may
result in lysis of cells, increasing the risk
of false-negative results. Lastly, urine
dipsticks cannot distinguish between
myoglobin and hemoglobin, so hema-
turia based on dipstick urinalysis should
always be checked with microscopic
urinalysis.23
Dipstick urinalysis testing can be
useful for rapidly screening urine for the
possibility of UTI but is not foolproof
(Table 2). The approximate sensitivity of
a urine dipstick showing positive nitrites
with or without LE, with small blood or
greater, was 75%.11 Specificity, or those
JULY 2018 American Journal of Obstetrics & Gynecology
Expert Reviews
without UTI who test negative, was
82%.11 PPV and negative predictive
value (NPV) were approximately 79%
and 76%, respectively.11 The LRþ is 4.2
(posttest probability of a UTI increases
approximately 25% from the pretest
probability with a positive test).
Conversely, the LRe decreases pretest
probability by approximately 25% (LRe
of 0.3).11 Accuracy of urine dipstick
testing is thus based on pretest proba-
bility: in a patient with high pretest
probability of UTI based on symptoms, a
negative dipstick does not rule out the
possibility of UTI, and a culture should
be performed. Although the presence of
nitrites or LE are both useful, nitrite is
more useful as a diagnostic indicator of
UTI (pooled diagnostic odds ratio
[DOR] of 11.3; 95% confidence interval,
6.95e18.35).13 Another systematic re-
view also found that positive nitrites had
higher LRþ than LE and blood, whereas
absence of LE and blood had the lowest
LRe.24
Population-specific dipstick urinalysis
performance. In older women, who tend
to have higher rates of asymptomatic
bacteriuria, urine dipstick testing is
likely less specific and sensitive than in
the general population. Sensitivity
ranges from 64.3-100%, with specificity
around 70% (20-76.7%). PPV is low in
43
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TABLE 2
Summary of diagnostic performance of dipstick urinalysis and microscopic urinalysis
Study Test Sensitivity Specificity PPV NPV LRD LRe DOR
Testing
Dipstick urinalysis
Bent et al11 Nitrite  LE 75% 82% 79% 76% 4.2 0.3
24
Meister et al Nitrite 34e42% 94e98% 7.5e24.6 0.6e0.7
LE (>0) 75e91% 41e87% 1.5e5.6 0.2e0.4
LE (>0) or nitrite 91e92% 39e41% 1.5e1.6 0.2
Medina-Bombardó and Nitrite 6.51 0.58 11.3
Jover-Palmer13
LE 1.42 0.44 3.58
Population specific
Older population
Ducharme et al,25 Deville et al,26 Nitrite  LE (except 64.3e100% 20e76.7% 31e45% 92e100%
Juthani-Mehta et al27 for Juthani-Mehta
et al27: nitrite þ LE)
Pregnancyeasymptomatic bacteriuria
Rogozinska et al30 Nitrite 55% 99% 54.08 0.46
Nitrite  LE 73% 89% 6.36 0.31
26
Deville et al Nitrite 46% 98% 165
Nitrite  LE 68% 87% 17
Microscopic urinalysis
Kayalp et al31 Pyuria 68.2% 87.8% 11.7% 99.2% 5.6 0.36 15.5
Bacteriuria 78.8% 97.8% 45.4% 99.5% 35.3 0.22 162.6
32
Lammers et al Pyuria (5 WBC) 90e92% 43e47% 58e59% 83e85%
Pyuria (3 WBC) 99% 17% 50% 93%
Population specific
Older population
Kupelian et al37 Pyuria 42% 73% 40% 75%
31
Kayalp et al Bacteriuria 86.4% 84.4% 65.4% 94.8% 5.5 0.16 34.4
Pyuria 84.4% 72e76% 54.6% 93.5% 3.5 0.21 17.7
Pregnancyeasymptomatic bacteriuria
Rogozinska et al30 Bacteriuria 78% 92% 9.4 2.4
39
Bachman et al Bacteriuria 75% 59.7% 4.2%
Pyuria (>10 WBC) 25% 99% 37.5%
Bacteriuria  pyuria 83.3% 58.9% 4.5%
DOR, diagnostic odds ratio; LE, leukocyte esterase; LR, likelihood ratio; NPV, negative predictive value; PPV, positive predictive value; WBC, white blood cell.
Chu. UTI across age groups. Am J Obstet Gynecol 2018.

the elderly (31-45%), but NPV is high
(92-100%), indicating that a negative
urine dipstick can be useful in ruling out
UTI in older women.25-27 Dipstick
urinalysis testing does not distinguish
well between symptomatic and
asymptomatic UTI. One study that
examined difference in dipstick testing
for symptomatic and asymptomatic pa-
tients age >65 years showed similar
specificity (76.7% vs 70.4%), PPV (37%
vs 31%), and NPV (92% and 93%)
between the groups, although sensitivity
was slightly better for symptomatic than
asymptomatic patients (73.7% vs
64.3%). Additionally, 61% of patients
who had positive dipstick testing had
negative cultures.25 Treatment based

44 American Journal of Obstetrics & Gynecology JULY 2018

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solely on dipstick testing would have
resulted in overdiagnosis of UTI and
inappropriate antibiotic treatment. Data
are likewise mixed for those with base-
line lower urinary tract symptoms, most
of whom tend to be older women. One
study found poor sensitivity of dipstick
urinalysis for cultures of 102-105 CFU/
mL (nitrite, 10%; LE, 56%),28 whereas
another study found moderate sensi-
tivity (nitrite, 73.7%; LE, 84.2%).29 In
this study, among those with lower uri-
nary tract symptoms, age <65 years or
65 years did not affect sensitivity of LE
or specificity of the dipstick.
Nitrites have a high PPV in the elderly.
In a subgroup analysis of dipstick accu-
racy, the DOR of nitrites was 108, indi-
cating high discriminative power. Data
are mixed for those with baseline lower
urinary tract symptoms; in 1 study, ni-
trite was poorly sensitive,28 but in
another study, nitrite had higher sensi-
tivity, specificity, NPV, and PPV than LE
and LE þ nitrite.29 Of note, both nitrite
alone and combination of LE þ nitrite
were more sensitive in those age 65
years than those age <65 years.29
During pregnancy, urine dipstick
testing can be useful to detect asymp-
tomatic bacteriuria. In a subgroup
analysis, Deville et al26 found that nitrites
had a DOR of 165 (with sensitivity and
specificity of 46% and 98%, respec-
tively), indicating high accuracy for
diagnosis of UTI. A recent systematic
review of 9 studies reported pooled
sensitivity of 73% for either positive ni-
trites or LE, with a specificity of 89%.30
Nitrites alone were more specific (99%)
but less sensitive (55%) for asymptom-
atic bacteriuria than nitrites  LE.30 The
LRþ for nitrites alone was also higher
than nitrites  LE (54.08 vs 6.36).
Overall, positive dipstick urinalysis is
likely specific for bacteriuria, but nega-
tive results do not rule out significant
bacteriuria in pregnancy.
Microscopic urinalysis
Microscopic urinalysis is performed with
manual or automated light microscopy.
The presence of leukocytes (pyuria,
defined as >5-10 leukocytes/hpf) or
bacteria (bacteriuria, 15 bacteria/hpf)
in the urine can be helpful in diagnosing
UTI. Occasionally, hematuria in the
presence of bacteriuria or pyuria may also
indicate UTI. The presence of squamous
epithelial cells may occasionally indicate
contamination, and WBC casts may
indicate upper urinary tract inflamma-
tion or infection.
Pyuria and bacteriuria can both be
helpful in establishing presence of
infection, but sensitivity and specificity
vary with cut-off definitions (Table 2). In
1 study that used the classic cut-off value
of 5 WBC/hpf, with a positive culture
definition of >105 CFU/mL, sensitivity
and specificity of pyuria was 68.3% and
87.8%, respectively, with LRþ of 5.6 and
LRe of 0.36. Bacteriuria was more sen-
sitive and specific (78.8% and 97.8%,
respectively), with LRþ of 35.3 and LRe
of 0.22.31 If the definition of positive
culture decreased to >104 CFU/mL,
sensitivity decreased, but specificity
increased.32 Conversely, if the definition
of pyuria is changed to 3 WBC/hpf,
sensitivity increases, but specificity de-
creases, resulting in a possible greater
overtreatment rate.32 Thus, it is impor-
tant to consider culture and urinalysis
cut-offs when interpreting results.
Absence of pyuria with bacteriuria
could suggest colonization or contami-
nation rather than active infection.33
However, bacteriuria consistently shows
higher sensitivity and specificity than
pyuria, and in the context of clinical
symptoms and dipstick urinalysis
results, may be more accurate in the
diagnosis of UTI. In women with
symptoms of UTI, dipstick analysis is
likely comparable to microscopic uri-
nalysis.32 Microscopic urinalysis,
particularly bacteriuria, is helpful for
ruling out and diagnosing UTI in the
context of the patient’s clinical presen-
tation, but not through test results
alone.31-34
Population-specific microscopic urinalysis
. In older adults, microscopic urinalysis
should be interpreted with care. Both
bacteriuria and pyuria may be found in
older patients in the absence of symp-
tomatic infection.35,36 In those with
lower urinary tract symptoms, pyuria
was a poor indicator of UTI, with poor
to moderate sensitivity (42-84.4%),
JULY 2018 American Journal of Obstetrics & Gynecology
Expert Reviews
moderate specificity (72-76%), and rela-
tively poor PPV (0.4) and NPV
(0.75).31,37 Pyuria is also misleading in
chronic incontinence, as up to 45% of
women with chronic incontinence and
asymptomatic bacteriuria were found to
have pyuria.38 When Kayalp et al31
examined the diagnostic performance of
urine microscopy in various age groups,
sensitivity was higher and specificity
lower for both bacteriuria and pyuria in
adults >70 years old than in the general
population. In this study, bacteriuria was
more sensitive and specific than pyuria,
with LRþ of 5.5 (vs 3.5) and LRe of
0.16 (vs 0.21).31 Thus, the absence of
bacteriuria on urinalysis may decrease
probability of UTI but cannot rule in
infection.
Few studies have examined the use of
microscopic urinalysis for detection of
asymptomatic bacteriuria in pregnancy.
In a meta-analysis examining onsite test
accuracy, bacteriuria of >20 WBC/hpf
was found to have sensitivity and speci-
ficity of 0.78 and 0.92, respectively. LRþ
was 9.4 and LRe was 2.4.30 One study
also found that bacteriuria had better
sensitivity, though less specificity, than
pyuria.39 Overall, this study found that
urine dipstick testing was superior to
urinalysis. However, both tests have low
to moderate sensitivity for asymptom-
atic bacteriuria in pregnancy.
Urine culture
Urine culture is the gold standard for
diagnosis of UTI and is considered the
most appropriate screening test for
asymptomatic bacteriuria in preg-
nancy. Urine specimens are most
commonly collected through clean
catch of midstream urine, though
catheterized specimens are sometimes
obtained. There is likely no difference
in contamination between cleansing
and no cleansing before midstream
urine collection.40 Although evidence
is limited, clean-catch midstream is as
accurate as catheterized urine for
diagnosis of UTI.40 The traditional
definition of significant bacteriuria is
105 CFU/mL, but this standard results
in a high rate of false negatives (94%
sensitivity, 50-70% sensitivity).41
Studies have shown that between
45
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TABLE 3
Treatment recommendations for uncomplicated urinary tract infections in nonpregnant women
First-line antibiotic
Antibiotic name Dose Duration Clinical efficacy61-77 Side effects Comments
Nitrofurantoin 100 mg Twice daily, 90e95% (5e7 d Common: nausea, headache, Avoid if suspicion for
monohydrate/macrocrystals for 5 d regimen) flatulence, diarrhea pyelonephritis; likely safe in mild
Rare: pulmonary fibrosis, renal impairment (creatinine
hepatitis, pancreatitis clearance 30 mL/min)
Trimethoprim- 160/800 mg Twice daily, 86e100% Common: nausea, vomiting, Avoid if prevalence of
sulfamethoxazole (double-strength for 3 d anorexia, rash, urticarial, resistance >20%;
tablet) photosensitivity, trimethoprim 100 mg alone for
hematologic complications 3 d may be equivalent in some
Rare: Stevens-Johnson areas
syndrome, toxic epidermal
necrolysis, hepatitis
Fosfomycin trometamol 3g Once, may 91% (1 RCT), likely Common: diarrhea, nausea, Avoid if suspicion for
be repeated less effective than headache, vaginitis pyelonephritis
48 h later other first-line Rare: dizziness, rash,
medications and abdominal pain, weakness,
fluoroquinolones elevated liver enzymes
Pivmecillinam 400 mg Twice daily, 55e82% Common: nausea, vomiting, Not available in United States;
for 3e7 d diarrhea avoid if suspicion for
pyelonephritis
Second-line antibiotics
Fluoroquinolones
Ciprofloxacin 250 mg Twice daily, 85e98% Common: Nausea, vomiting, Increased resistance limits its
Levofloxacin 250 or 500 mg for 3 d abdominal discomfort, usefulness; should be reserved
Once daily, headache, dizziness, for pyelonephritis if possible;
for 3 d insomnia higher risk of tendon rupture in
Rare: Peripheral neuropathy, older adults or
tendinopathy, tendon immunosuppressed patients
rupture, QT interval
prolongation, hepatotoxicity
Beta-lactams Varies 3e7 d, 7 79e98% (3e5 Common: diarrhea, nausea, Avoid ampicillin or amoxicillin
(amoxicillin-clavulanate, d likely more d regimen) vomiting, rash, urticarial due to high resistance and poor
cefdinir, cefaclor, effective Rare: encephalopathy, efficacy; narrow spectrum
cefpodoxime) seizures, glomerulonephritis cephalosporins such as
cephalexin may be used, but
has less efficacy data; durations
<7 d may result in less efficacy
compared to ciprofloxacin5
RCT, randomized controlled trial.
Chu. UTI across age groups. Am J Obstet Gynecol 2018.

30-50% of women with symptomatic
UTIs have counts as low as 102 CFU/
mL.42 Another study found that a
threshold of 102 CFU/mL resulted in a
93% PPV for Escherichia coli UTI.43
Lower bacterial counts reflecting
infection may also be seen in women
who have already taken antibiotics, as
well as those infected with uropath-
ogens such as Pseudomonas, Klebsiella,
Enterobacter, Serratia, and Moraxella.
However, many laboratories only bacteriuria occurs in about 5% of
report values >104, which may result healthy, premenopausal women33; up to
in undertreatment in symptomatic 30-50% of institutionalized older
women. Cultures showing a significant women38; 10.8-15% of community-
growth of a single uropathogen are dwelling older women; and 2-10% of
considered positive, and cultures with pregnant women.36 Bacteriuria can
mixed flora are considered fluctuate significantly in both premeno-
contaminated. pausal and postmenopausal women,
However, a culture that shows signif- with spontaneous development and
icant bacterial growth may not reflect an resolution over the course of several
active infection. Asymptomatic months.5,44,45 With the exception of

46 American Journal of Obstetrics & Gynecology JULY 2018

ajog.org
pregnant women, women undergoing
invasive genitourinary procedures, and
patients in the early posttransplantation
period, asymptomatic bacteriuria does
not increase adverse outcomes and
should not precipitate routine screening
or treatment.36
The most important information ob-
tained from culture results is confirma-
tion of the causative bacteria and
antimicrobial sensitivity. The most
common cause of UTI is Escherichia coli
regardless of age group, constituting at
least 70% of isolates.3 Other common
uropathogens include Enterobacteri-
aceae, Proteus, Klebsiella, and Staphylo-
coccus saprophyticus. Staphylococcus
saprophyticus and Streptococcus aga-
lactiae are more commonly isolated in
UTIs in younger women than in older
women.46,47 In pregnancy, group B
streptococcus is isolated frequently and
may be more common than Escherichia
coli, particularly in the third trimester.48
Uropathogens such as Gardnerella vagi-
nalis and Ureaplasma, though rare, may
be more frequently isolated in pregnant
women, particularly those with under-
lying renal disease.49 In older women,
Klebsiella, Pseudomonas, and Proteus UTI
may become more prevalent with age,
though Escherichia coli remains the
most common cause of UTI.50-52
Organisms normally considered
contaminants, such as lactobacilli,
enterococci, group B streptococcus, and
other coagulase-negative staphylococci,
may be treated in symptomatic UTI if
isolated individually with significant
growth.5,53
Resistance to all antibiotics is
increasing, both in the United States and
worldwide. From 2010 through 2014, the
rates of extended-spectrum beta-lacta-
mase (ESBL)-positive Escherichia coli
isolated in urinary specimens from across
the United States increased from 7.9-
18.3% (P < .001). ESBL bacteria
contain an enzyme that hydrolyzes
certain antibiotics and thus confers
resistance to many beta-lactam antibi-
otics such as penicillins, cephalosporins,
and aztreonam, and are concerning
as they are often associated with
multidrug resistance. Overall, suscepti-
bility to fluoroquinolones is low, but
remained stable (64.8-64.7% susceptibil-
ity from 2010 through 2014), while sus-
ceptibility to cephalosporins significantly
decreased.54 Resistance to ampicillin and
trimethoprim-sulfamethoxazole (TMP-
SMX) has also increased, though resis-
tance to nitrofurantoin remains low.55
However, among ESBL-positive Escher-
ichia coli, resistance to nitrofurantoin may
be higher.56 In adults age >80 years,
resistance to fluoroquinolones and
TMP-SMX significantly increased from
2005 through 2009.55,57 Resistance to
beta-lactams has also been increasing in
the obstetric population.58
Treatment
Guidelines for UTI treatment have been
published, but adherence to guidelines
with regards to antibiotic preference,
dose, and duration is poor.59 Non-
adherence can result in decreased effec-
tiveness of antibiotic (due to
development of resistance) and
increased health care costs.59,60 For
treatment of acute, uncomplicated UTI,
first-line antibiotics include nitro-
furantoin monohydrate/macrocrystals,
TMP-SMX, and fosfomycin trometa-
mol61 (Table 3). These have low collat-
eral damage (selection for drug-resistant
organisms), high efficacy, and good
resistance profiles. Because of higher
resistance in certain populations, TMP-
SMX is only first line if local resistance
rates are not >20%. Second-line medi-
cations include fluoroquinolones and
beta-lactam agents (Table 3). Compared
to the first-line drugs, these have higher
risk of collateral damage, higher risk of
subsequent infections such as clos-
tridium difficile, and worse effects on
normal fecal flora.
Efficacy is high for first-line antibi-
otics. A 5- to 7-day regimen of nitro-
furantoin has an estimated 93%
(84-95%) clinical efficacy,62-66 as does a
3-day regimen of TMP-SMX (90-100%)
in regions with <20% resis-
tance.62,63,67,68 Fosfomycin has an
estimated clinical efficacy of 91%.64
Second-line antibiotics like fluo-
roquinolones have estimated efficacy of
90% (85-98%),63,67,69-76 whereas beta-
lactam agents have an estimated clinical
efficacy of 89% (79-98%).68,74,77 Efficacy
JULY 2018 American Journal of Obstetrics & Gynecology
Expert Reviews
depends on bacterial resistance rates, as
higher resistance leads to decreased
effectiveness of treatment. Local anti-
biograms, generally available at hospitals
and other institutions, are useful in
determining resistance patterns in the
area and can help guide antibiotic se-
lection. However, even though expected
bacterial eradication rates decrease with
increasing resistance, this does not
necessarily translate into therapeutic
failure. In a study by Gupta and Traut-
ner,53 even as resistance increased in the
population, clinical outcomes outpaced
expected eradication rates.
When selecting an antibiotic for older
adults, adverse effects must be consid-
ered. Fluoroquinolones should be used
with caution in the elderly and the
immunocompromised, as there is an
increased risk of tendinitis and tendon
rupture.78 Additionally, as noted above,
resistance to fluoroquinolones is likely
higher in older adults. Nitrofurantoin,
though previously contraindicated for
use on patients with creatinine clearance
of <60 mL/min, has now been shown to
be safe in patients with creatinine clear-
ance of 30 mL/min.79-82 Creatinine
clearance of <30 mL/min is primarily
associated with decreased efficacy of
nitrofurantoin and not toxicity. Toxicity,
such as pulmonary fibrosis, is rare but
has been reported, and any new symp-
toms should be immediately investi-
gated. A Cochrane review examining 15
randomized controlled trials concluded
that efficacy did not significantly differ
between short (3-6 days) and long (7-14
days) courses of treatment in older
women.83
In pregnancy, antibiotic selection
includes amoxicillin (500 mg, twice
daily for 5-7 days), amoxicillin-
clavulanate (500/125 mg, twice daily,
3-7 days), and cephalexin (500 mg,
twice daily, 3-7 days) (Table 4).9
Nitrofurantoin is frequently used (100
mg, twice daily, 5-7 days).9 Though its
use in the first trimester has been pre-
viously associated with possible fetal
defects, prospective studies have not
shown any association with fetal de-
fects.84-86 Fosfomycin can also be used,
as it is a category-B drug (Table 4).9
TMP-SMX may be used, though it
47
Expert Reviews ajog.org

TABLE 4
Treatment recommendations for uncomplicated urinary tract infections in pregnant women
First-line antibiotic
Pregnancy-specific concerns
Antibiotic name Dose Duration Comments
Nitrofurantoin 100 mg Twice daily, for 5 d Avoid if suspicion for pyelonephritis; avoid in first trimester
monohydrate/macrocrystals (due to rare association with birth defects in case-control
studies, though prospective studies have shown no
association)84-86; can cause hemolytic anemia in G6PD
deficiency at term
Amoxicillin 500 or 875 mg Every 8 h (500 mg) or 12 h Resistance is increasing in population
(875 mg), for 3e7 d
Amoxicillin-clavulanate 500 or 875 mg Every 8 h (500 mg) or 12 h Resistance is increasing in population
(875 mg), for 3e7 d
Cephalexin 500 mg Every 6 h, for 3e7 d
Cefpodoxime 100 mg Twice daily, for 3e7 d
Fosfomycin trometamol 3g Once, may be repeated Avoid if suspicion for pyelonephritis
48 h later
Trimethoprim-sulfamethoxazole 160/800 mg Twice daily, for 3 d Avoid during first trimester due to action as folic acid
(double-strength antagonist; association with birth defects, though not proven
tablet) in human beings84,85; theoretical risk for kernicterus at term87
G6PD, glucose-6-phosphate dehydrogenase.
Chu. UTI across age groups. Am J Obstet Gynecol 2018.

should be avoided in the first trimester
because it acts as a folic acid antagonist,
and near term because of the theoretical
risk for kernicterus.87 Duration of
treatment varies from 3-7 days, but
literature is not sufficient to determine
optimal length of treatment.88
Comment
UTIs are common, but interpretation of
symptoms and test results can be com-
plex. Overtreatment with antibiotics
leading to increased uropathogen resis-
tance necessitates careful diagnosis of
UTI. The most diagnostic symptoms of
UTI include change in frequency,
dysuria, urgency, and presence or
absence of vaginal discharge, but UTIs
may present differently in older women.
In young women with clear UTI symp-
toms and without vaginal discharge,
treatment can be started immediately,
and further testing may not be needed
except in the context of recurrent UTIs.
Among laboratory analyses, dipstick
urinalysis is popular for its availability
and ease of use, but results should be
interpreted in context of the patient’s
pretest probability based on symptoms
and characteristics. In patients with a
high pretest probability of UTI, negative
testing does not rule out UTI (Figure 2).
Nitrites are likely more sensitive and
specific than other dipstick tests for UTI,
particularly in the elderly. Positive
dipstick testing is likely specific for
asymptomatic bacteriuria in pregnancy,
but dipstick urinalysis is not the test of
choice. Positive testing may increase the
probability of UTI, but initiation of
treatment should be based on posttest
probability (Figure 2). In cases in which
the probability of UTI is unclear, further
testing should be done.
Microscopic urinalysis is likely com-
parable to dipstick urinalysis as a
screening test but may occasionally be
helpful in further confirming or ruling
out UTI. Bacteriuria is more specific and
sensitive than pyuria for detecting UTI,
even in older women and during preg-
nancy. Pyuria is often found in the
absence of infection, particularly in older
women with lower urinary tract symp-
toms and incontinence.
Urine culture is the gold standard for
detection of UTI, but significant bacte-
rial growth in culture may not indicate
active infection. Bacteriuria is prevalent
in women without symptoms, particu-
larly in women with lower urinary tract
symptoms and older women.
Conversely, in symptomatic women,
growth as low as 102 CFU/mL could
reflect infection. Escherichia coli is the
most common uropathogen isolated in
urine cultures, regardless of age. Resis-
tance is increasing to fluoroquinolones,
beta-lactams, and TMP-SMX, though
nitrofurantoin still has good efficacy.
First-line treatments for UTI include
nitrofurantoin, fosfomycin, and TMP-
SMX (when resistance levels are <20%
for TMP-SMX). These antibiotics have
minimal collateral damage and resis-
tance. In pregnancy, beta-lactams and
nitrofurantoin are first-line treatments.
Future improvements in diagnostic
testing would help to better distinguish
active infection from colonization and to
detect infection in patients with baseline
urinary symptoms. -
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