Urinary tract infections and asymptomatic bacteriuria in pregnancy

Authors
Thomas M Hooton, MD
Kalpana Gupta, MD, MPH
Section Editors
Stephen B Calderwood, MD
Charles J Lockwood, MD, MHCM
Deputy Editor
Allyson Bloom, MD
All topics are updated as new evidence becomes available and our peer
review process is complete.
Literature review current through: Jan 2015. | This topic last
updated: Jan 23, 2015.

INTRODUCTION Urinary tract infections (UTIs) are common in pregnant

women. By convention, UTI is defined either as a lower tract (acute cystitis)
or upper tract (acute pyelonephritis) infection. UTIs (acute cystitis and
pyelonephritis) and asymptomatic bacteriuria in pregnant women will be
reviewed here.
Issues related to urinary tract infections or asymptomatic bacteriuria in
other populations are discussed in detail elsewhere. (See "Acute
uncomplicated cystitis and pyelonephritis in women" and "Acute
uncomplicated cystitis, pyelonephritis, and asymptomatic bacteriuria in
men" and "Acute complicated cystitis and pyelonephritis" and "Approach to
the adult with asymptomatic bacteriuria" and "Asymptomatic bacteriuria in
patients with diabetes mellitus" and "Catheter-associated urinary tract
infection in adults".)
EPIDEMIOLOGY
Incidence and risk factors The incidence of bacteriuria in pregnant
women is approximately the same as that in nonpregnant women, however,
recurrent bacteriuria is more common during pregnancy. Additionally, the
incidence of pyelonephritis is higher than in the general population, likely as
a result of physiologic changes in the urinary tract during pregnancy. (See
'Pathogenesis' below.)

Asymptomatic bacteriuria occurs in 2 to 7 percent of pregnant women [ 1,2].

It typically occurs during early pregnancy, with only approximately a
quarter of cases identified in the second and third trimesters [ 3]. Factors
that have been associated with a higher risk of bacteriuria include a history
of prior urinary tract infection, pre-existing diabetes mellitus, increased
parity, and low socioeconomic status [4-6].
Without treatment, as many as 30 to 40 percent of pregnant women with
asymptomatic bacteriuria will develop a symptomatic urinary tract infection
(UTI), including pyelonephritis, during pregnancy [ 7]. This risk is reduced by
70 to 80 percent if bacteriuria is eradicated. (See 'Rationale for treatment'
below.)
Acute cystitis occurs in approximately 1 to 2 percent of pregnant women,
and the estimated incidence of acute pyelonephritis during pregnancy is 0.5
to 2 percent [8-11]. Most cases of pyelonephritis occur during the second
and third trimesters. As an example, the incidence of acute pyelonephritis
in pregnancy in the setting of routine prenatal screening for asymptomatic
bacteriuria was examined in a prospective study of a general obstetric
population [10]. During the two year study period, 440 cases of acute
pyelonephritis were identified in 32,282 pregnant women (14 per 1000
deliveries). The majority of cases occurred in the second trimester (53
percent). In addition to prior untreated bacteriuria, other clinical
characteristics that have been associated with acute pyelonephritis during
pregnancy include age <20 years, nulliparity, smoking, late presentation to
care, sickle cell trait, and pre-existing (not gestational) diabetes [ 10-12]
Pregnancy outcomes Many studies have described a relationship
between maternal urinary tract infection, particularly asymptomatic
bacteriuria, and adverse pregnancy outcomes. Studies have also suggested
that acute pyelonephritis has a similar association, but there are several
variables that potentially confound this association, such as socioeconomic
status and previous preterm delivery.
Untreated bacteriuria has been associated with an increased risk of preterm
birth, low birth weight, and perinatal mortality [ 1,7,13-18]. As an example, in
a meta-analysis of 19 studies, among women without bacteriuria, the risks
of preterm birth and a low birth weight infant were one-half and two-thirds
the risks among women with asymptomatic bacteriuria [18]. Other
pregnancy complications have also been associated with bacteriuria. As an

example, a case control study of over 15,000 pregnant women found an

increased risk of preeclampsia with either asymptomatic bacteriuria or
symptomatic UTI [19].
No correlation has been clearly established between acute cystitis of
pregnancy and increased risk of low birth weight, preterm delivery, or
pyelonephritis [15], perhaps because pregnant women with symptomatic
lower UTI usually receive treatment.
Pyelonephritis, however, has been associated with adverse pregnancy
outcomes. In an 18-year retrospective study of over 500,000 singleton
pregnancies followed at a large health care system in the United States, the
rate of preterm birth, primarily between weeks 33 and 36, was higher
among the 2894 women who had pyelonephritis during pregnancy (10.3
versus 7.9 percent among those who did not, OR 1.3, 95% CI 1.2-1.5) [ 11].
There were no differences in stillbirth or neonatal death. Other
complications of pyelonephritis include anemia, sepsis, and respiratory
distress [10]. Maternal morbidity and obstetric outcomes with pyelonephritis
do not appear to differ by trimester [20].
PATHOGENESIS The organisms that cause bacteriuria and urinary tract
infections (UTI) in pregnant women are of the same species and have
similar virulence factors as in nonpregnant women. Thus, the basic
mechanism of entry of bacteria into the urinary tract is likely to be the same
for both groups [21]. However, the smooth muscle relaxation and
subsequent ureteral dilatation that accompany pregnancy are thought to
facilitate the ascent of bacteria from the bladder to the kidney, resulting in
the greater propensity for bacteriuria to progress to pyelonephritis during
pregnancy [7,13,22]. (See "Renal and urinary tract physiology in normal
pregnancy".)
Pressure on the bladder from the enlarging uterus may also increase the
risk of progression to pyelonephritis. In addition, the immunosuppression of
pregnancy may contribute. As an example, mucosal interleukin-6 levels and
serum antibody responses to Escherichia coli antigens appear to be lower in
pregnant women [23].
MICROBIOLOGY As in nonpregnant women, E. coli is the predominant
uropathogen found in both asymptomatic bacteriuria and urinary tract
infection (UTI) in pregnant women. As an example, in a study of over 400

cases of pyelonephritis, E. coli accounted for approximately 70 percent of

cases
[10].
Other
organisms
responsible
for
infection
included Klebsiella and Enterobacter species (3 percent each), Proteus (2
percent), and gram-positive organisms, including group B Streptococcus (10
percent). Group B Streptococcus in pregnancy is discussed in detail
elsewhere. (See "Group B streptococcal infection in pregnant women",
section on 'Urinary tract'.)
As in other community-acquired infections, antimicrobial resistance is an
increasing concern. Infections caused by extended-spectrum betalactamase (ESBL)-producing strains are increasing in number, even in
uncomplicated UTIs [24,25]. In India, ESBL-producing uropathogens is a
particular problem, even in pregnant women [26].
Isolation of more than one species or the presence of Lactobacillus
or Propionibacterium may indicate a specimen contaminated by vaginal or
skin flora. However, repeated isolation of Lactobacillus with high colony
counts and without other organisms in consecutive urine cultures may not
represent simple contamination, although the significance of this finding in
pregnancy is not known.
ASYMPTOMATIC BACTERIURIA
Diagnosis The diagnosis of asymptomatic bacteriuria is made by finding
high-level bacterial growth on urine culture in the absence of symptoms
consistent with urinary tract infection (UTI). Details on the timing of
screening, specimen collection, and diagnostic criteria are discussed below.
Screening We agree with the guidelines from the Infectious Diseases
Society of America that recommend screening all pregnant women for
asymptomatic bacteriuria at least once in early pregnancy [ 2]. The rationale
for screening is the same as for treatment of bacteriuria and is discussed
elsewhere. (See 'Rationale for treatment' below.)
Screening for asymptomatic bacteriuria is performed at 12 to 16 weeks
gestation (or the first prenatal visit, if that occurs later) with a urine culture
[27]. Rescreening among those who did not have bacteriuria on the initial
test is generally not performed in low-risk women. It is reasonable to
rescreen women at high risk for infection (eg, history of UTI or presence of
urinary tract anomalies, diabetes mellitus, hemoglobin S, or preterm labor),

however the optimal target populations for this is uncertain. (See "Initial
prenatal assessment and first trimester prenatal care".)
Specimen collection The diagnosis of asymptomatic bacteriuria should be
based on culture of a urine specimen collected in a manner that minimizes
contamination. Although the optimal method for collecting voided urine is
uncertain, instructing women to spread their labia and collect a midstream
urine (without requiring a clean-catch) seems most reasonable. Routine
catheterization to screen for bacteriuria is not warranted due to the risk of
introducing infection. (See "Sampling and evaluation of voided urine in the
diagnosis of urinary tract infection in adults".)
In order to minimize contamination of the voided specimen, it is often
recommended that the patient collect a clean-catch (after local cleansing of
the urethral meatus and surrounding mucosa) midstream (collection of the
second portion of the voided urine after discarding the initial stream)
specimen. However, it is not clear that these measures reduce
contamination. In a study of 113 asymptomatic pregnant women, each was
instructed to collect a midstream sample from the first concentrated
morning urine, a midstream sample, and a clean-catch midstream sample,
in that order, over the course of a day [ 28]. Rates of mixed growth and
growth of skin flora on culture in midstream urine were comparable with
those observed in the morning and clean-catch samples. Overall rates of
contamination were high in all three samples, and the women were tested
at a mean of 32 weeks of gestation as opposed to the recommended period
of 16 weeks. Findings from this and other studies suggest that collection of
a clean-catch voided urine specimen is of little value [ 29,30].
Proper handling and processing of the specimen is crucial to avoid falsepositive results. (See "Microbiology specimen collection and transport".)
Diagnostic criteria For asymptomatic women, bacteriuria is formally
defined as two consecutive voided urine specimens with isolation of the
same bacterial strain in quantitative counts of 10 5 colony forming
units (cfu)/mL or a single catheterized urine specimen with one bacterial
species isolated in a quantitative count of 10 2 cfu/mL [2]. In clinical
practice, however, only one voided urine specimen is typically obtained,
and diagnosis (and treatment initiation) is made in women with
105 cfu/mL without obtaining a confirmatory repeat culture. If bacteria that
are not typical uropathogens (such as lactobacillus) are isolated, treatment

should be reserved for patients in whom the organism grows as a single

isolate on consecutive cultures.
Rapid screening tests, such as dipstick, enzymatic screen, reagent strip, or
interleukin-8 testing, do not come close to urine culture in terms of
sensitivity and specificity for detecting asymptomatic bacteriuria in
pregnant women and should not be used [ 31-33]. In addition, cultures are
useful in guiding therapy. This can be particularly important in pregnancy,
during which the number of safe treatment alternatives is reduced.
Management Management of asymptomatic bacteriuria in pregnant
women includes antibiotic therapy tailored to culture results and follow-up
cultures to confirm sterilization of the urine. For those women with
persistent or recurrent bacteriuria, prophylactic or suppressive antibiotics
may be warranted in addition to retreatment.
Rationale for treatment Asymptomatic bacteriuria during pregnancy
increases the risk of pyelonephritis and has been associated with adverse
pregnancy outcomes, such as preterm birth and low birth weight infants
(see 'Epidemiology' above). Antimicrobial treatment reduces the risk of
subsequent development of pyelonephritis and is associated with improved
pregnancy outcomes [7,34-38]. This was illustrated in a meta-analysis of 14
randomized trials of antibiotic treatment versus placebo or no treatment for
pregnant women with asymptomatic bacteriuria [ 7]. Antibiotic therapy was
more likely to clear asymptomatic bacteriuria (odds ratio [OR] 0.25, 95% CI
0.14-0.48) and to lower the incidence of pyelonephritis (OR 0.23, 95% CI
0.13-0.41). There was also a reduction in the incidence of low birth weight
infants with antibiotic treatment, but the included studies that evaluated
this were deemed to be of poor quality.
Antimicrobial treatment Asymptomatic bacteriuria is treated with an
antibiotic tailored to the susceptibility pattern of the isolated organism,
which is generally available at the time of diagnosis. Potential options
include beta-lactams, nitrofurantoin, and fosfomycin (table 1). The choice of
antimicrobial agent should also take into account safety during pregnancy
(including the particular stage of pregnancy). (See 'Antibiotic safety in
pregnancy' below.)
The optimal duration of antibiotics for asymptomatic bacteruria is uncertain.
Short courses of antibiotics are preferred to minimize the antimicrobial

exposure to the fetus. Short course antibiotic therapy is usually effective in

eradicating asymptomatic bacteriuria of pregnancy, although single-dose
regimens may not be as effective as slightly longer regimens [ 39-42]. As an
example, in a meta-analysis of 13 studies comparing single-dose treatment
with four to seven day treatments, there was a trend towards lower rates of
bacteriuria clearance with the single-dose regimen.
An exception is single-dose fosfomycin, which successfully treats
bacteriuria. In three trials comparing this drug with other therapies
administered for a longer time, eradication of the organism was comparable
(77 to 94 percent versus 68 to 94 percent with other agents) [43].
Follow-up Because up to 30 percent of women fail to clear asymptomatic
bacteriuria following a short course of therapy [ 1], a follow-up culture should
be obtained as a test of cure. We typically perform this a week after
completion of therapy. In addition, we usually repeat urine cultures monthly
until completion of the pregnancy because of the risk of persistent or
recurrent bacteriuria.
Management of persistent bacteriuria If the first follow-up culture is
positive for bacterial growth [10 5 cfu/mL] with the same species
(persistent bacteriuria), another course of antimicrobial treatment based on
susceptibility data should be administered: either the same antimicrobial in
a longer course (eg, seven days, if a three-day regimen was used
previously) or a different antimicrobial in a standard regimen. True
persistent bacteriuria implies initial therapy was inadequate and thus
requires modification with a different therapeutic approach in contrast to
recurrent bacteriuria (a different species is isolated or the same species is
isolated after documented clearance of the initial bacteriuria). (See
'Management of recurrent bacteriuria' below.)
Suppressive therapy may be appropriate for women with bacteriuria that
persists after two or more courses of therapy. Nitrofurantoin (50 to 100 mg
orally at bedtime) for the duration of the pregnancy may be used if the
organism is susceptible. Monthly cultures are not necessary if suppressive
therapy is administered; however, breakthrough bacteriuria can occur
during suppressive therapy, so we generally perform at least one later
culture, such as at the start of the third trimester, to ensure suppression is
working. If that follow-up culture is positive [10 5 cfu/mL], another course
of antimicrobial based on susceptibility data should be administered. The

suppressive regimen should be reassessed and adjusted if needed based on

the susceptibility pattern.
Management of recurrent bacteriuria If the first follow-up culture is
positive with a different species or if the first follow-up culture is not
positive [<105 cfu/mL], but then a subsequent culture is positive (with the
same or different species), both scenarios imply recurrent bacteriuria.
Treatment should be administered with one of the regimens used for an
initial bacteriuric episode, tailored to antimicrobial susceptibility testing
(table 1).
We typically do not recommend antibiotic prophylaxis for recurrent
asymptomatic bacteriuria because of the lack of data to support this
practice.
ACUTE CYSTITIS
Clinical manifestations Cystitis is a symptomatic infection of the bladder.
The typical symptoms of acute cystitis in the pregnant woman are the same
as in nonpregnant women and include the sudden onset of dysuria and
urinary urgency and frequency. Hematuria and pyuria are also frequently
seen on urinalysis.
Systemic symptoms, such as fevers and chills, are generally absent in
isolated cystitis.
Diagnosis Acute cystitis should be suspected in pregnant women who
complain about dysuria. Although urinary frequency and urgency are typical
findings of acute cystitis, they are also frequently a normal physiologic
change of pregnancy and reported by pregnant women without cystitis or
bacteriuria [44]. The presence of fever and chills, flank pain, and
costovertebral angle tenderness should raise suspicion for pyelonephritis
(see 'Acute pyelonephritis' below). A urinalysis and urine culture should be
performed in pregnant women who have new onset dysuria. Specimen
collection is the same as for asymptomatic bacteriuria. (See 'Specimen
collection' above.)
The diagnosis of acute cystitis is confirmed by finding of bacterial growth on
urine culture. Prior to confirming the diagnosis, empiric treatment is
typically initiated in a patient with consistent symptoms and pyuria on

urinalysis (see 'Management' below). As in nonpregnant women, pyuria is

usually present in almost all pregnant women with symptomatic urinary
tract infection, and its absence strongly suggests an alternative diagnosis.
(See "Sampling and evaluation of voided urine in the diagnosis of urinary
tract infection in adults", section on 'Interpretation of pyuria'.)
Studies defining the threshold of bacterial growth on voided urine that
represents significant bacteriuria in pregnant women have not been
performed, but based on studies in nonpregnant women, relatively low
colony counts can reflect true bacteriuria in the presence of symptoms. In
nonpregnant women with uncomplicated cystitis, coliform colony counts in
voided urine as low as 102 colony forming units (cfu)/mL have been noted to
reflect bladder infection [45-47]. As most clinical laboratories do not
routinely quantify urine isolates to 10 2 cfu/mL, it is reasonable to use a
quantitative count 103cfu/mL in a symptomatic pregnant woman as an
indicator of symptomatic UTI. If bacteria that are not typical uropathogens
(such as lactobacillus) are isolated, the diagnosis of cystitis is typically
made only if they are isolated in high bacterial counts (10 5 cfu/mL). (See
"Sampling and evaluation of voided urine in the diagnosis of urinary tract
infection in adults", section on 'Definition of a positive culture'.)
Differential diagnosis As in nonpregnant women, dysuria in pregnant
women can be a result of other infectious and noninfectious processes, such
as vaginitis or urethritis. Similarly, urinary frequency and urgency may be
symptoms of normal pregnancy in the absence of urinary tract infection.
However, true bacteriuria is typically not present in these settings and thus
distinguishes acute cystitis. If not already performed, testing for sexually
transmitted infections (such as chlamydia and gonorrhea) is warranted for
pregnant women with dysuria without bacteriuria or women who have
persistent dysuria despite successful treatment of bacteriuria. (See "Acute
uncomplicated cystitis and pyelonephritis in women", section on
'Differential diagnosis'.)
Management Management of acute cystitis in pregnant women includes
empiric antibiotic therapy that is subsequently tailored to culture results
and follow-up cultures to confirm sterilization of the urine. For those women
with persistent or recurrent bacteriuria, prophylactic or suppressive
antibiotics may be warranted in addition to retreatment.

Antimicrobial treatment Antibiotic treatment of acute cystitis in pregnant

women is often empiric, initiated at the time of complaints of dysuria, and
then tailored to the susceptibility pattern of the isolated organism once
urine cultures return. Potential options for empiric and directed therapy
include beta-lactams, nitrofurantoin, and fosfomycin (table 1). The choice of
an antimicrobial agent should also take into account any prior
microbiological data and drug safety during pregnancy (including the
particular stage of pregnancy). (See 'Antibiotic safety in pregnancy' below.)
For empiric therapy, we typically choose between cefpodoxime, amoxicillinclavulanate, and fosfomycin, given their safety in pregnancy and the
somewhat broader spectrum of activity compared with other agents (such
as amoxicillin or cephalexin). Nitrofurantoin is another option during the
second or third trimester or if the others cannot be used for some reason
(eg, drug allergy). The choice between them should be individualized on the
basis of several factors, including patient allergy history, local practice
patterns, local community resistance prevalence, availability, and cost [48].
Although there are limited data in pregnant women, a meta-analysis
suggested that there are no large differences in outcomes between different
antibiotic regimens in terms of cure rates, recurrent infection, incidence of
preterm delivery, and the need for a change of antibiotics [ 49]. All of the
antibiotics studied were very effective and complications were rare. There
was not enough evidence to recommend a particular treatment scheme.
For women who are thought to be at risk for or have documented infection
with
extended-spectrum
beta-lactamase
(ESBL)-producing
Enterobacteriaceae, nitrofurantoin and fosfomycin are active in vitro against
many such strains and are potential oral options [25,50].
The optimal duration of treatment of acute cystitis during pregnancy is
uncertain. As with asymptomatic bacteriuria, short courses of antibiotics are
preferred, to minimize the antimicrobial exposure to the fetus. We treat
acute cystitis with a three to seven day course of antibiotics as long as
there are no symptoms suggestive of pyelonephritis (eg, flank
pain,nausea/vomiting, fever
[>38C], and/or costovertebral
angle
tenderness). Based on data among nonpregnant individuals, there appear
to be no differences between short antibiotic courses (three to seven days)
and longer ones [1,48,51]. Single-dose therapy is generally limited to
fosfomycin.

Follow-up As with asymptomatic bacteriuria, a follow-up culture should be

obtained as a test of cure. We typically perform this a week after
completion of therapy. In addition, we usually repeat urine cultures monthly
until completion of the pregnancy because of the risk of persistent or
recurrent bacteriuria. Management of persistent bacteriuria is discussed
above. (See 'Management of persistent bacteriuria' above.)
Management of recurrent cystitis In women who have recurrent cystitis
during pregnancy, antimicrobial prophylaxis for the duration of pregnancy is
a reasonable strategy to prevent additional episodes. Prophylaxis can be
postcoital, if the cystitis is thought to be sexually related, which it
commonly is, or continuous
In the setting of other conditions that potentially increase the risk of urinary
complications during episodes of cystitis (eg, diabetes or sickle cell trait),
prophylaxis following the first episode of cystitis during pregnancy is also
reasonable.
The choice of antimicrobial used for prophylaxis should be based on the
susceptibility profile of the cystitis strains. Ideally, daily or postcoital
prophylaxis with low dose nitrofurantoin (50 to 100 mg PO postcoitally or at
bedtime) or cephalexin (250 to 500 mg PO postcoitally or at bedtime) can
be used.
ACUTE PYELONEPHRITIS
Clinical manifestations Acute pyelonephritis is a manifestation of
infection of the upper urinary tract and kidneys. The typical symptoms of
acute pyelonephritis in the pregnant woman are the same as in
nonpregnant women and include fever (>38C or 100.4F), flank pain,
nausea, vomiting, and/or costovertebral angle tenderness. Symptoms of
cystitis (eg, dysuria) are not always present. Pyuria is a typical finding. (See
"Acute uncomplicated cystitis and pyelonephritis in women".)
Most cases of pyelonephritis occur during the second and third trimesters.
(See 'Incidence and risk factors' above.)
Pregnant women may become quite ill and are at risk for both medical and
obstetrical complications from pyelonephritis. It has been estimated that as
many as 20 percent of women with severe pyelonephritis develop

complications that include septic shock syndrome or its variants, such as

acute respiratory distress syndrome (ARDS) [52-54]. As an example, in a
prospective study of 440 cases of acute pyelonephritis identified among
32,282 pregnant women in a general obstetric population, complications
included anemia (23 percent), bacteremia (17 percent in the minority of
patients who were tested), respiratory insufficiency (7 percent), and renal
dysfunction (2 percent) [10]. The mechanism of anemia is not well
understood, but hemolysis, perhaps mediated by endotoxin, may be
important [55]. Acute renal failure associated with microabscesses and
suppurative pyelonephritis has been described in isolated cases,
independent of sepsis [56]. (See "Acute kidney injury (acute renal failure) in
pregnancy".)
Diagnosis and evaluation Acute pyelonephritis is suggested by the
presence
of
flank
pain, nausea/vomiting, fever
(>38C
or
100.4F), and/or costovertebral angle tenderness, with or without the
typical symptoms of cystitis, and is confirmed by the finding of bacteriuria
in the setting of these symptoms. (See "Acute uncomplicated cystitis and
pyelonephritis in women".)
For pregnant women who present with such symptoms, we check a
urinalysis and urine culture. Pyuria is present in the majority of women with
pyelonephritis, and its absence suggests an alternative diagnosis or
complete obstruction. Although many pregnant women have back or flank
pain without pyelonephritis, we have a low threshold for evaluation for
bacteriuria and a diagnosis of pyelonephritis in pregnant women with these
symptoms, given the risk of complications and adverse pregnancy
outcomes with untreated pyelonephritis. (See 'Pregnancy outcomes' above.)
Some investigators have questioned the value of obtaining routine blood
cultures in pregnant women with pyelonephritis [ 57]. Although there is no
evidence that bacteremia portends a worse prognosis or requires longer
therapy in an otherwise healthy pregnant woman with pyelonephritis, it is
reasonable to obtain blood cultures in those with signs of sepsis or serious
underlying medical conditions such as diabetes.
Imaging is not routinely used to diagnose pyelonephritis. However, in
patients with pyelonephritis who are severely ill or who also have symptoms
of renal colic or history of renal stones, diabetes, history of prior urologic
surgery, immunosuppression, repeated episodes of pyelonephritis, or

urosepsis, imaging of the kidneys can be helpful to evaluate for

complications. In pregnant women, renal ultrasound is the preferred
imaging modality in order to avoid contrast or radiation exposure.
Differential diagnosis Nephrolithiasis can present with significant flank or
back pain and abnormal findings on the urinalysis, but fever is uncommon
with uncomplicated stone disease. This can also be distinguished from
pyelonephritis by visualization of the stones on renal ultrasound. (See
"Diagnosis and acute management of suspected nephrolithiasis in adults".)
For pregnant women presenting with fever and/or flank or back pain, certain
obstetric complications are important to consider in the differential:
Intraamniotic infection, with or without preterm labor, is an important
diagnostic consideration in pregnant women who have fever and abdominal
pain. The following features suggest intraamniotic infection over
pyelonephritis: presentation with premature rupture of membranes, uterine
tenderness and/or foul odor of the amniotic fluid, and the absence of
bacteriuria. Other potential causes of fever and back or flank pain in the
absence of bacteriuria include other infections (eg, influenza, pneumonia,
appendicitis). (See "Intraamniotic infection (chorioamnionitis)", section on
'Diagnosis of clinical chorioamnionitis'.)
Placental abruption is a key differential diagnosis of acute back or
abdominal pain during pregnancy. Back pain is prominent with abruption
when the placenta is on the posterior wall of the uterus. Fever is absent and
vaginal bleeding is classically present with abruption, in contrast to
pyelonephritis. The uterus is often firm, and may be rigid and tender in
patients with abruption, but is usually soft in patients with pyelonephritis.
Both conditions can be associated with uterine contractions. If present, a
retroplacental hematoma on ultrasound supports the diagnosis of
abruption. (See "Placental abruption: Clinical features and diagnosis".)
Management Management of acute pyelonephritis in pregnant women
includes hospital admission for parenteral antibiotics. Antibiotic therapy can
be converted to an oral regimen tailored to the susceptibility profile of the
isolated organism following clinical improvement. Following the treatment
course, suppressive antibiotics are typically used for the remainder of the
pregnancy to prevent recurrence.

Site of care Based upon the higher risk of complications in pregnant

women, pyelonephritis has traditionally been treated with hospitalization
and intravenous antibiotics until the woman is afebrile for 24 to 48 hours
and symptomatically improved [58]. Initial outpatient therapy of pregnant
women with pyelonephritis has been attempted in carefully selected
populations (eg, no underlying serious medical conditions, renal or urologic
abnormalities, pregnancy complications, signs of sepsis, or recent antibiotic
use). However, we suggest not initiating therapy of pyelonephritis in
pregnant women in the outpatient setting given the limited data evaluating
its safety and the need for close monitoring of the patient.
Evidence on the safety of outpatient initiation of pyelonephritis treatment
during pregnancy is limited to two trials by the same group [ 59,60]. Although
the studies suggested that outpatient treatment resulted in similar
outcomes as inpatient management, several limitations of the studies
create uncertainty about the safety and practicality of outpatient
management:
In the first trial, 120 pregnant women with pyelonephritis prior to 24
weeks gestation were randomly assigned to receive an outpatient regimen
consisting of intramuscular ceftriaxone for 2 days followed by oral
cephalexin for 10 days or an inpatient regimen consisting of IV cefazolin
followed at discharge by oral cephalexin for 10 days [ 59]. Clinical responses
to therapy and birth outcomes were similar for both outpatients and
inpatients. However, six patients initially treated with ceftriaxone were
ultimately admitted to the hospital for intravenous therapy, and one woman
developed septic shock during the emergency department observation
period. Of note, the outpatient regimen included initial parenteral
antibiotics, and home health nurses monitored patients assigned to the
outpatient strategy.
In the second trial, 92 women who presented after 24 weeks gestation
were hospitalized for intramuscular ceftriaxone for 24 hours and then
randomly assigned to early discharge on oral cephalexin or continued
hospitalization until afebrile for 48 hours [ 60]. Clinical response and birth
outcomes were similar for those who completed the assigned strategy.
However, 51 percent of patients either did not qualify for outpatient
management based upon study criteria or developed complications, which
precluded early discharge from the hospital.

Empiric antibiotics Parenteral, broad spectrum beta-lactams are the

preferred antibiotics for initial empiric therapy of pyelonephritis (table 2).
The choice between them should be guided by local microbiology and
susceptibility data as well as expected patient tolerance. Fluoroquinolones
and aminoglycosides, which are often used for pyelonephritis in
nonpregnant individuals, should be avoided in pregnancy if possible. (See
'Antibiotic safety in pregnancy' below.)
The efficacy of beta-lactams was demonstrated in a randomized trial of 179
pregnant women with acute pyelonephritis before the 24th week of
gestation: intravenous cefazolin or intramuscular ceftriaxone had equivalent
efficacy to intravenous ampicillin plus gentamicin [ 61]. Although rates of
resistance to first generation cephalosporins have generally been less than
10 percent in surveillance studies [ 62-65], beta-lactams (including first
generation cephalosporins) have been less effective than trimethoprimsulfamethoxazole or the fluoroquinolones for treatment of cystitis in studies
of nonpregnant individuals [66]. Given these data and the paucity of data
evaluating narrow spectrum cephalosporins in the treatment of
pyelonephritis [66], we favor third generation cephalosporins over first or
second generation cephalosporins, such as cefazolin, for the empiric
treatment of acute pyelonephritis.
For women with a history of infections with extended-spectrum betalactamase (ESBL)-producing Enterobacteriaceae (or other risk factors), a
carbapenem is an appropriate choice for empiric therapy. Of note, some
animal studies have shown adverse fetal effects with imipenem-cilastatin,
so meropenem, ertapenem, or doripenem are the preferred carbapenems
for use during pregnancy. (See 'Antibiotic safety in pregnancy' below.)
Directed antibiotic therapy and follow-up As with nonpregnant patients
with complicated pyelonephritis, pregnant women generally have definite
improvement within 24 to 48 hours of appropriate antibiotic therapy. Once
afebrile for 48 hours, pregnant patients can be switched to oral therapy
guided by culture susceptibility results and discharged to complete 10 to 14
days of treatment [58]. Oral options are mainly limited to beta-lactams or, if
in the second trimester, trimethoprim-sulfamethoxazole. Nitrofurantoin and
fosfomycin are not appropriate for treatment of pyelonephritis due to
inadequate tissue levels. General principles regarding the safety of
antibiotics in pregnancy are discussed elsewhere. (See 'Antibiotic safety in
pregnancy' below.)

If symptoms and fever persist beyond the first 24 to 48 hours of treatment,

a repeat urine culture and renal ultrasound should be performed to rule out
persistent infection and urinary tract pathology.
For women who do not use antimicrobial prophylaxis for the duration of
pregnancy following an episode of pyelonephritis (see 'Preventing
recurrence' below), we generally check monthly urine cultures to evaluate
for recurrent bacteriuria and treat as indicated because of the risk of
recurrent pyelonephritis. (See 'Asymptomatic bacteriuria' above.)
Obstetric management Pyelonephritis is not itself an indication for
delivery. If induction of labor or cesarean delivery for standard obstetrical
indications is planned in a patient on treatment for pyelonephritis, we favor
waiting until the patient is afebrile, as long as delaying the delivery is
relatively safe for the mother and fetus.
Since pyelonephritis is associated with preterm birth, an important obstetric
consideration is whether tocolysis should be used when pyelonephritis
triggers preterm labor at various gestational ages. Detailed discussion of
the benefits and risks of tocolysis for acute preterm labor are found
elsewhere. (See "Inhibition of acute preterm labor", section on 'Patient
selection and treatment goals'.)
Preventing recurrence Recurrent pyelonephritis during pregnancy occurs
in 6 to 8 percent of women [61,67,68]. As a result, low dose antimicrobial
suppressive therapy with an agent to which the original organism is
susceptible is warranted for the remainder of the pregnancy; reasonable
options include nitrofurantoin (50 to 100 mg orally at bedtime) or
cephalexin (250 to 500 mg orally at bedtime) [58,69].
Monthly cultures are not necessary if preventive therapy is administered;
however, breakthrough bacteriuria can occur during preventive therapy, so
we usually perform at least one later culture, such as at the start of the
third trimester, to ensure preventive therapy is working. If a follow-up
culture is positive (105 colony forming units/mL), then a course of
antimicrobial therapy based on susceptibility data should be administered.
In addition, the preventive regimen should be reassessed and adjusted if
needed.

PREVENTION IN WOMEN WITH HISTORY OF RECURRENT UTI A separate

issue is the management of pregnant women with a history of recurrent
urinary tract infections (UTIs) prior to pregnancy, which is often related to
sexual intercourse. We use postcoital prophylaxis in pregnant women who
have recurrent UTIs that appear to be temporally related to sexual
intercourse. The preferred regimen is a single postcoital dose of either
cephalexin (250 mg) or nitrofurantoin (50 mg). (See "Recurrent urinary tract
infection in women", section on 'Prevention strategies'.)
The potential efficacy of postcoital prophylaxis to prevent UTIs during
pregnancy was evaluated in a report of 33 women with a history of
recurrent UTIs who had 39 pregnancies [ 70]. The women were treated with a
single postcoital dose of either cephalexin (250 mg) or nitrofurantoin (50
mg). Only one UTI occurred during pregnancy; this was in sharp contrast to
130 UTIs during a mean observation period of seven months before
prophylaxis.
ANTIBIOTIC SAFETY IN PREGNANCY Much of the information regarding the
safe use of antibiotics during pregnancy was obtained decades ago, before
pregnant women were excluded from drug studies because of concerns
about risk to the fetus. Thus, there is little direct information about the
safety of many newer antibiotics in pregnancy, and concern about the use
of certain antibiotics generally derives from indirect evidence (eg, animal
studies) or observational studies that may have numerous confounders.
Overall, the safest course is to use the antibiotics that have well-established
safety profiles in pregnancy and limit the use of antibiotics of potential
concern to cases in which no safer alternative exists. (See "Initial prenatal
assessment and first trimester prenatal care", section on 'Antibiotic
therapy'.)
It is generally accepted that penicillins (with or without beta-lactamase
inhibitors), cephalosporins, and aztreonam are safe in pregnancy. However,
drugs with very high protein binding, such as ceftriaxone, may be
inappropriate the day before parturition because of the possibility of
bilirubin displacement and subsequent kernicterus. Of the carbapenems,
some animal studies have shown adverse fetal effects with imipenemcilastatin, so meropenem, ertapenem, or doripenem are the preferred
carbapenems for use during pregnancy.

Fosfomycin is also generally considered safe in pregnancy [ 71]. In several

studies of single-dose fosfomycin during pregnancy, it was well-tolerated,
and adverse fetal effects were not observed.
Nitrofurantoin is frequently used during pregnancy, although some potential
concerns exist. Nitrofurantoin was associated with birth defects in a case
control study [72], but this finding should be interpreted with caution as
multiple comparisons involving small numbers of affected exposed infants
may have led by chance to the observed association. The safest course is to
avoid using nitrofurantoin in the first trimester if another antibiotic that is
safe and effective is available. Nitrofurantoin has also been reported to
cause hemolytic anemia in the mother and fetus with G-6PD deficiency [ 73].
The risk of hemolytic anemia is estimated to be only 0.0004 percent of
cases, but its use should be avoided near term for this reason [ 69,74].
Use of trimethoprim-sulfamethoxazole is typically limited to mid-pregnancy,
avoiding the first trimester and near term. Trimethoprim is generally
avoided in the first trimester because it is a folic acid antagonist, has
caused abnormal embryo development in experimental animals, and some
case control studies have reported a possible association with a variety of
birth defects [72]. However, it is not a proven teratogen in humans. Women
are routinely prescribed folic acid supplementation during pregnancy; this
may be particularly important in those who are taking trimethoprim.
Sulfonamides should be avoided in the last days before delivery because
they can displace bilirubin from plasma binding sites in the newborn, with
the theoretical increased risk for kernicterus, although kernicterus related
solely to in utero sulfonamide exposure has never been reported.
Sulfonamides have also been associated with birth defects in a case control
study [72], but the limitations of the study discussed above lead to
uncertainty about the association.
Aminoglycosides have been associated with ototoxicity following prolonged
fetal exposure [74], and therefore should be avoided unless intolerance or
resistance prohibits the use of less toxic agents.
Fluoroquinolones and tetracyclines are contraindicated during pregnancy.
INFORMATION FOR PATIENTS UpToDate offers two types of patient
education materials, "The Basics" and "Beyond the Basics." The Basics
patient education pieces are written in plain language, at the 5 th to 6th grade

reading level, and they answer the four or five key questions a patient
might have about a given condition. These articles are best for patients who
want a general overview and who prefer short, easy-to-read materials.
Beyond the Basics patient education pieces are longer, more sophisticated,
and more detailed. These articles are written at the 10 th to 12th grade
reading level and are best for patients who want in-depth information and
are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We
encourage you to print or e-mail these topics to your patients. (You can also
locate patient education articles on a variety of subjects by searching on
"patient info" and the keyword(s) of interest.)
Beyond the Basics topics (see "Patient information: Urinary tract infections
in adolescents and adults (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
Bacteriuria occurs commonly in pregnancy, typically during early
pregnancy. Without treatment, as many as 30 to 40 percent of pregnant
women with asymptomatic bacteriuria will develop a symptomatic urinary
tract infection (UTI). The smooth muscle relaxation and subsequent ureteral
dilatation that occurs in pregnancy are thought to facilitate the ascent of
bacteria from the bladder to the kidney, accounting for the greater risk of
pyelonephritis. Additionally, untreated bacteriuria is associated with an
increased risk of preterm birth, low birth weight, and perinatal mortality.
(See 'Epidemiology' above and 'Pathogenesis' above.)
As in nonpregnant women, Escherichia coli is the predominant
uropathogen found in both asymptomatic bacteriuria and UTI in pregnant
women. (See 'Microbiology' above.)
We screen all pregnant women at least once for asymptomatic bacteriuria.
Screening for asymptomatic bacteriuria is performed at 12 to 16 weeks
gestation with a midstream urine for culture. The diagnosis is made by
finding high-level bacterial growth (10 5 colony forming units [cfu]/mL) on
urine culture in the absence of symptoms consistent with UTI. (See
'Diagnosis' above.)

Management of asymptomatic bacteriuria in pregnant women includes

antibiotic therapy tailored to culture results, which reduces the risk of
subsequent pyelonephritis and is associated with improved pregnancy
outcomes. Potential options include beta-lactams, nitrofurantoin, and
fosfomycin (table 1). Following treatment, follow-up cultures are performed
to confirm sterilization of the urine. For those women with persistent
bacteriuria, prophylactic or suppressive antibiotics may be warranted in
addition to retreatment. (See 'Management' above.)
Acute cystitis should be suspected in pregnant women who complain
about new onset dysuria, frequency, or urgency. The diagnosis is made by
finding of bacterial growth on urine culture in this setting. Management of
acute cystitis in pregnant women includes empiric antibiotic therapy that is
subsequently tailored to culture results. Potential options for empiric and
directed therapy include beta-lactams, nitrofurantoin, and fosfomycin (table
1). As with asymptomatic bacteriuria, follow-up cultures are performed to
confirm sterilization of the urine. For those women with persistent
bacteriuria or recurrent cystitis, prophylactic or suppressive antibiotics may
be warranted in addition to retreatment. (See 'Acute cystitis' above.)
Acute pyelonephritis during pregnancy is suggested by the presence of
flank pain, nausea/vomiting, fever (>38C), and/orcostovertebral angle
tenderness, with or without the typical symptoms of cystitis, and is
confirmed by the finding of bacteriuria in the setting of these symptoms.
Pregnant women may become quite ill and are at risk for both medical (eg,
sepsis,
respiratory
failure)
and
obstetrical
complications
from
pyelonephritis. (See 'Clinical manifestations' above and 'Diagnosis and
evaluation' above.)
Management of acute pyelonephritis in pregnant women includes hospital
admission for parenteral antibiotics, preferably broad spectrum betalactams (table 2). Antibiotic therapy can be converted to an oral regimen
tailored to the susceptibility profile of the isolated organism following
clinical improvement. Oral options are generally limited to beta-lactams or,
if in the second trimester, trimethoprim-sulfamethoxazole. Following the
treatment course, suppressive antibiotics are typically used for the
remainder of the pregnancy to prevent recurrence. (See 'Management'
above.)

It is generally accepted that penicillins (with or without beta-lactamase

inhibitors), cephalosporins, aztreonam, and fosfomycin are safe in
pregnancy. Because of possible but uncertain associations with adverse
birth outcomes, we generally avoid nitrofurantoin during the first trimester
and trimethoprim-sulfamethoxazole during the first trimester and near term
unless no other options are available. (See 'Antibiotic safety in pregnancy'
above.)
Use of UpToDate is subject to the
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Disclosures
Disclosures: Thomas M Hooton, MD Consultant/Advisory Boards: Cubist
[Complicated UTI (Ceftolozane/tazobactam)]; Vifor Pharma [Uncomplicated UTI
(Immunostimulant uro-vaxom)]. Equity Ownership/Stock Options: Fimbrion
Therapeutics [Prevention of UTI (Developing mannosides that may eventually be
useful in prevention of UTI)]. Kalpana Gupta, MD, MPH Consultant/Advisory Boards:
Boehringer Ingelheim GmbH [UTI (Empagliflozin)]; Paratek [UTI (Omadacycline)];

Melinta Pharmaceuticals [UTI]. Stephen B Calderwood, MD Consultant/Advisory

Boards: Pulmatrix [Inhaled antimicrobial products (Not currently released)]. Patent
Holder: Vaccine Technologies [Cholera (Cholera vaccines)]. Equity Ownership/Stock
Options: PharmAthene [Biodefense (Anthrax)]. Charles J Lockwood, MD,
MHCM Nothing to disclose. Allyson Bloom, MD Employee of UpToDate, Inc.
Contributor disclosures are reviewed for conflicts of interest by the editorial group.
When found, these are addressed by vetting through a multi-level review process, and
through requirements for references to be provided to support the content.
Appropriately referenced content is required of all authors and must conform to
UpToDate standards of evidence.
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