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

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Feb 2019. | This topic last updated: Feb 25, 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 urinary tract infections 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 "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 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 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.

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 [30]. 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 [31].
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 [32,33].

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 threshold for diagnosis (and treatment) of asymptomatic
bacteriuria due to group B streptococcus during pregnancy is somewhat unique and 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 [34-36]. 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 [7,37-41]. 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] 0.30, 95% CI 0.18-0.53) 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. However, the included
studies that evaluated these outcomes were deemed to be of poor quality.

Similar effects of treatment were suggested by a subsequent prospective study of

pregnant women in the Netherlands (where screening for asymptomatic bacteriuria is not
performed routinely) [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 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 [42-44]. 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 [44].

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)
[45].

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 [46]. 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. 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 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 [47,48]. 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 [49-51]. 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'.)

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 [52].

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 [53]. 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 [28,54].

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 [>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 [1,52,55]. 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) [56-58]. 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) [12]. The
mechanism of anemia is not well understood, but hemolysis, perhaps mediated by
endotoxin, may be important [59]. Acute renal failure associated with microabscesses and
suppurative pyelonephritis has been described in isolated cases, independent of sepsis
[60]. (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 [61], and data on the impact of blood cultures on
outcomes are limited [62]. 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 [63].

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 "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 [64]. 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 [65,66]. 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 [65]. 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 [66]. 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 [67]. Although rates of resistance to first generation
cephalosporins have generally been less than 10 percent in surveillance studies [68-71],
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 [72]. Given these data and the paucity of data
evaluating narrow spectrum cephalosporins in the treatment of pyelonephritis [72], 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 oral therapy guided by culture susceptibility results and discharged to
complete 10 to 14 days of treatment [64]. 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 [67,73,74]. 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) [64,75].

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. 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".)

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 [76]. 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 [77]. 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 has been associated with birth defects in case control studies [78,79],
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
[80]. 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 [75,81].

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 [78,79]. 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 [78], but
the limitations of the study discussed above lead to uncertainty about the association.

Aminoglycosides have been associated with ototoxicity following prolonged fetal exposure
[81], 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 — 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 or, for group B Streptococcus,
≥104 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.)
●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.)
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