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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: Dec 2019. | This topic last updated: Dec 17, 2019.

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 UTIs or asymptomatic bacteriuria in other populations are discussed in detail
elsewhere. (See "Acute simple cystitis in women" and "Acute simple cystitis in men" and "Acute
complicated urinary tract infection (including pyelonephritis) in adults" and "Asymptomatic
bacteriuria in adults" 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].

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Without treatment, as many as 20 to 35 percent of pregnant women with asymptomatic bacteriuria


will develop a symptomatic urinary tract infection (UTI), including pyelonephritis, during pregnancy
[7,8]. This risk is reduced by 70 to 80 percent if bacteriuria is eradicated (see 'Rationale for
treatment' below). Although a study from the Netherlands suggested a low rate of pyelonephritis
among 208 women with untreated asymptomatic bacteriuria (2.4 percent versus 0.6 percent
among 4035 women without bacteriuria), this study included only low-risk women with
uncomplicated singleton pregnancies without diabetes mellitus or urinary tract abnormalities, and
it is uncertain whether these results are generalizable [9].

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 [10-13]. 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 [12]. 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 [12-14]

Pregnancy outcomes — Many studies have described a correlation 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 in most [1,7,15-20], but not all [9,21], studies. 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
[20]. 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 [22].

No correlation has been clearly established between acute cystitis of pregnancy and increased
risk of low birth weight, preterm delivery, or pyelonephritis [17], 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

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among those who did not, OR 1.3, 95% CI 1.2-1.5) [13]. There were no differences in stillbirth or
neonatal death. Other complications of pyelonephritis include anemia, sepsis, and respiratory
distress [12]. Maternal morbidity and obstetric outcomes with pyelonephritis do not appear to differ
by trimester [23].

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 [24].
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 [15,25].
(See "Maternal adaptations to pregnancy: Renal and urinary tract physiology".)

Pressure on the bladder and ureters 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 [26].

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 [12]. 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 beta-lactamase (ESBL)-producing strains are increasing
in number [27,28]. In India, ESBL-producing uropathogens is a particular problem, even in
pregnant women [29].

Isolation of more than one species or the presence of Lactobacillus or Cutibacterium (formerly
Propionibacterium) acnes 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.

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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]. Other expert groups make a similar recommendation [30,31]. 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 [32]. 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. There is minimal evidence informing the benefits and harms of repeat screening
following an initial negative culture.(See "Prenatal care: Initial assessment".)

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 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 [33]. 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 [34,35].

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Proper handling and processing of the specimen is crucial to avoid false-positive 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 ≥105 colony-forming units (cfu)/mL or a single catheterized urine specimen with one
bacterial species isolated in a quantitative count of ≥102 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. The diagnosis
(and treatment) of asymptomatic bacteriuria due to group B streptococcus during pregnancy is
discussed in detail elsewhere. (See "Group B streptococcal infection in pregnant women", section
on 'Asymptomatic bacteriuria'.)

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 [36-38]. 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.

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
[7,39-44]. This was illustrated in a meta-analysis of 15 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] 0.30, 95% CI 0.18-
0.53) and to lower the incidence of pyelonephritis (OR 0.24, 95% CI 0.13-0.41). There was also a
reduction in the incidence of low birth weight infants with antibiotic treatment. However, the
included studies that evaluated these outcomes were deemed to be of poor quality.

This meta-analysis included a trial of pregnant women in the Netherlands (where screening for
asymptomatic bacteriuria is not performed routinely), which suggested generally similar effects of
treatment [9]. Women with asymptomatic bacteriuria between 16 and 22 weeks gestation who
were not treated or received placebo treatment had a higher rate of pyelonephritis (2.4 percent of
208 women) compared with both those who received nitrofurantoin treatment for asymptomatic
bacteriuria (0 percent of 40 women) and those who did not have asymptomatic bacteriuria (0.6

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percent of 4035 women). Likewise, low birth weight occurred in 17 of 208 untreated or placebo-
treated women with asymptomatic bacteriuria (8 percent) compared with 1 of 40 of nitrofurantoin-
treated women (2.5 percent). While this difference was not statistically significant, the study was
under-powered for this outcome. Preterm birth did not differ between these two groups. Notably,
the study included only women who were at low risk for UTI, pre-term birth, or other complications,
and the pyelonephritis rate was lower than in previous studies of pregnant women with
asymptomatic bacteriuria [21].

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 [45-47]. 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 [47].

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) [48].

Follow-up — Up to 30 percent of women fail to clear asymptomatic bacteriuria following a


short course of therapy [1]. Thus, a repeat culture is generally recommended as a test of cure,
which can be performed a week after completion of therapy for asymptomatic bacteriuria [49].
However, there are insufficient data informing the utility of repeat testing following an initial
episode of asymptomatic bacteriuria, and it is not known whether retreatment of recurrent or
persistent bacteriuria improves outcomes [2]. Thus, our approach is based primarily on expert
opinion:

● If repeat culture has no growth, there is no indication for further testing for bacteriuria in the
absence of symptoms suggestive of urinary tract infection.

● If repeat culture is positive for bacterial growth (≥105 cfu/mL), optimal management is
uncertain. We generally repeat antibiotic treatment tailored to antimicrobial susceptibility
testing (table 1); if the repeat culture yielded the same species as the first culture, we give
either the same antimicrobial as administered the first time for a longer course (eg, seven
days, if a three-day regimen was used previously) or a different antimicrobial for a typical

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duration. However, we do not continue testing for asymptomatic bacteriuria following this
second treatment course.

There are insufficient data to support the use of suppressive or prophylactic antibiotics for
persistent or recurrent asymptomatic bacteriuria, and we do not do this.

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 absent in simple 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 [50,51]. 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 acute simple cystitis, coliform colony counts in voided urine as low as
102 colony-forming units (cfu)/mL have been noted to reflect bladder infection [52-54]. As most
clinical laboratories do not routinely quantify urine isolates to 102 cfu/mL, it is reasonable to use a
quantitative count ≥103 cfu/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 (≥105 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'.)
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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
simple cystitis 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, amoxicillin-clavulanate, 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 [55].

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 [56]. 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 [28,57].

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

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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
[>38°C], 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 [1,55,58]. 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. As above, if the patient
is asymptomatic but has bacteriuria on test of cure, the optimal management is uncertain. (See
'Follow-up' above.)

Management of recurrent cystitis — In women who have three or more episodes of 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. However, there are no data to guide
whether treatment of isolated recurrent episodes or prophylaxis is a better approach in terms of
risks versus benefits.

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
pathogens causing the cystitis. Ideally, daily or postcoital prophylaxis with low-dose nitrofurantoin
(50 to 100 mg orally postcoitally or at bedtime) or cephalexin (250 to 500 mg orally 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 (>38°C or 100.4°F), flank pain, nausea,
vomiting, and/or costovertebral angle tenderness. Symptoms of cystitis (eg, dysuria) are not
always present. Pyuria is a typical finding.

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) [59-61]. As an example, in a

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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) [12]. The mechanism of anemia is not well understood, but hemolysis,
perhaps mediated by endotoxin, may be important [62]. Acute renal failure associated with
microabscesses and suppurative pyelonephritis has been described in isolated cases,
independent of sepsis [63]. (See "Acute kidney injury in pregnancy".)

Diagnosis and evaluation — Acute pyelonephritis is suggested by the presence of flank pain,
nausea/vomiting, fever (>38°C or 100.4°F), 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 simple cystitis 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 should prompt
consideration of an alternative diagnosis or complete obstruction. However, absence of pyuria
does not rule out UTI if symptoms and urine culture are consistent with the diagnosis. 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 [64], and data on the impact of blood cultures on outcomes are limited
[65]. 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. Other tests, such as a serum lactate level, can also be useful in women with suspected
sepsis to inform the severity of disease [66].

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".)

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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 "Intra-
amniotic infection (clinical chorioamnionitis or triple I)", section on 'Diagnosis'.)

● 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: Pathophysiology, clinical
features, diagnosis, and consequences".)

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 [67]. 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 [68,69]. 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

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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 [68]. 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 [69]. 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 [70]. Although rates of
resistance to first generation cephalosporins have generally been less than 10 percent in
surveillance studies [71-74], beta-lactams (including first generation cephalosporins) have been
less effective than trimethoprim-sulfamethoxazole or the fluoroquinolones for treatment of cystitis
in studies of nonpregnant individuals [75]. Given these data and the paucity of data evaluating
narrow spectrum cephalosporins in the treatment of pyelonephritis [75], 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 beta-lactamase (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


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

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oral therapy guided by culture susceptibility results and discharged to complete 10 to 14 days of
treatment [67]. 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. Tocolysis is typically not administered after 34 weeks gestation. If a woman with
pyelonephritis prior to that gestational age experiences preterm labor, administration of tocolysis
and steroids is reasonable to attempt to prolong the pregnancy. However, if the patient is septic,
tocolysis is generally avoided. Pregnant women with pyelonephritis are at increased risk of
pulmonary edema and acute respiratory distress syndrome (ARDS), which may be exacerbated
by administration of tocolysis with or without corticosteroids. 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'.)

Preventing recurrence — Recurrent pyelonephritis during pregnancy occurs in 6 to 8 percent


of women [70,76,77]. As a result, after an initial episode of pyelonephritis, low-dose antimicrobial
preventive therapy with an agent to which the original organism is susceptible for the remainder of
the pregnancy is a reasonable strategy; but there are no randomized trials to inform the optimal
approach. If preventive therapy is utilized, reasonable options include nitrofurantoin (50 to 100 mg
orally at bedtime) or cephalexin (250 to 500 mg orally at bedtime) [67,78].

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

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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. It is reasonable to
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 simple cystitis in women", section
on 'Initial approach to prevention'.)

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 [79]. 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 "Prenatal care: Patient education, health promotion, and safety of
commonly used drugs", section on 'Antibiotics'.)

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 imipenem-cilastatin, so meropenem, ertapenem, or doripenem are the
preferred carbapenems for use during pregnancy.

Fosfomycin is also generally considered safe in pregnancy [80]. In several studies of single-dose
fosfomycin during pregnancy, it was well-tolerated, and adverse fetal effects were not observed.

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Nitrofurantoin is frequently used during pregnancy, although some potential concerns exist.
Nitrofurantoin has been associated with birth defects in case control studies [81,82], but these
findings should be interpreted with caution as multiple comparisons involving small numbers of
affected exposed infants may have led by chance to the observed associations. In a prospective
study of pregnant women with asymptomatic bacteriuria, there were no congenital birth
abnormalities reported among the 40 women who received nitrofurantoin compared with 2 among
the 208 women who received placebo or no antimicrobial treatment [9]. 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 [83]. 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 [78,84].

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 [81,82].
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 [81],
but the limitations of the study discussed above lead to uncertainty about the association.

Aminoglycosides have been associated with ototoxicity following prolonged fetal exposure [84],
and therefore should be avoided unless intolerance or resistance prohibits the use of less toxic
agents.

Tetracyclines should not be used, and fluoroquinolones are generally not used during pregnancy.
(See "Prenatal care: Patient education, health promotion, and safety of commonly used drugs",
section on 'Antibiotics'.)

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: Urinary tract infections in
adults" and "Society guideline links: Asymptomatic bacteriuria in adults".)

INFORMATION FOR PATIENTS

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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 5th 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 10th 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.)

● Basics topics (see "Patient education: Urinary tract infections in pregnancy (The Basics)")

● Beyond the Basics topics (see "Patient education: 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 may be 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 (≥105 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 culture is performed to
confirm sterilization of the urine. (See 'Management' above.)

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● 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 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 (>38°C), 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. 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 beta-lactams (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, preventive
antibiotics are a reasonable strategy 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 Subscription and License Agreement.

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GRAPHICS

Antibiotics for asymptomatic bacteriuria and cystitis in pregnancy

Antibiotic Dose Duration Notes

Nitrofurantoin 100 mg orally every 12 Five to seven days Does not achieve
hours therapeutic levels in the
kidneys so should not be
used if pyelonephritis is
suspected.
Avoid use during the first
trimester and at term if
other options are
available.

Amoxicillin 500 mg orally every 8 Five to seven days Resistance may limit its
hours or utility among gram-
875 mg orally every 12 negative pathogens.
hours

Amoxicillin-clavulanate 500 mg orally every 8 Five to seven days


hours or
875 mg orally every 12
hours

Cephalexin 250 to 500 mg orally every Five to seven days


6 hours

Cefpodoxime 100 mg orally every 12 Five to seven days


hours

Fosfomycin 3 g orally as single dose Does not achieve


therapeutic levels in the
kidneys so should not be
used if pyelonephritis is
suspected.

Trimethoprim- 800/160 mg (one double Three days Avoid during the first
sulfamethoxazole strength tablet) every 12 trimester and at term.
hours

The durations listed in the table are based on data from studies conducted in both nonpregnant and pregnant
women.

Graphic 98083 Version 7.0

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Parenteral regimens for empiric treatment of pyelonephritis in pregnancy

Antibiotic Dose, interval

Mild to moderate pyelonephritis

Ceftriaxone 1 g every 24 hours

Cefepime 1 g every 12 hours

Aztreonam* 1 g every 8 hours

Ampicillin 1-2 g every 6 hours


PLUS
Gentamicin ¶ 1.5 mg/kg every 8 hours

Severe pyelonephritis with an impaired immune system and/or incomplete urinary drainage

Piperacillin-tazobactam 3.375 g every 6 hours

Meropenem 1 g every 8 hours

Ertapenem 1 g every 24 hours

Doripenem 500 mg every 8 hours

Doses are for patients with normal renal function.


If methicillin-resistant S. aureus (MRSA) is known or suspected, see treatment regimens outlined separately in
topics addressing MRSA management.

* Alternative in the setting of beta lactam allergy.


¶ Aminoglycosides have been associated with fetal ototoxicity; this regimen should be used only if intolerance precludes
the use of less toxic agents.

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Contributor Disclosures
Thomas M Hooton, MD Consultant/Advisory Boards: Danone [UTI management (Hydration therapy)]; GSK
(Antimicrobial in development); Ocean Spray (Cranberry products). Equity Ownership/Stock Options:
Fimbrion Therapeutics [UTI prevention (Development of mannosides)]. Kalpana Gupta, MD,
MPH Grant/Research/Clinical Trial Support: Pfizer [Staphylococcus aureus post-surgical infections].
Consultant/Advisory Boards: Paratek Pharmaceuticals [UTI]; Ocean Spray [UTI]; Nabriva [UTI]; Shionogi
[UTI]; First Light Diagnostics [UTI]. Equity Ownership/Stock Options: First Light Diagnostics [Rapid detection
and antimicrobial testing of infections]. Stephen B Calderwood, MD Equity Ownership: Pulmatrix [Infectious
diseases (Inhaled antimicrobials)]. Consultant/Advisory Boards: Day Zero Diagnostics [Whole genome
sequencing for microbial identification and determination of antimicrobial susceptibility]. Charles J
Lockwood, MD, MHCM Nothing to disclose Allyson Bloom, MD Nothing to disclose

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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