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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: Feb 2018. | This topic last updated: Aug 24, 2017.

INTRODUCTION — Urinary tract infections (UTIs) are common in pregnant women. By convention, UTI is defined
either as a lower tract (acute cystitis) or upper tract (acute pyelonephritis) infection. UTIs (acute cystitis and
pyelonephritis) and asymptomatic bacteriuria in pregnant women will be reviewed here.

Issues related to urinary tract infections or asymptomatic bacteriuria in other populations are discussed in detail
elsewhere. (See "Acute uncomplicated cystitis in women" and "Acute uncomplicated 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 30 to 40 percent of pregnant women with asymptomatic bacteriuria will develop a
symptomatic urinary tract infection (UTI), including pyelonephritis, during pregnancy [7]. This risk is reduced by
70 to 80 percent if bacteriuria is eradicated (see 'Rationale for treatment' below). 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 [8].

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 [9-12]. 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 [11]. 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 [11-13]

Pregnancy outcomes — Many studies have described a relationship between maternal urinary tract infection,
particularly asymptomatic bacteriuria, and adverse pregnancy outcomes. Studies have also suggested that acute
pyelonephritis has a similar association, but there are several variables that potentially confound this association,
such as socioeconomic status and previous preterm delivery.

Untreated bacteriuria has been associated with an increased risk of preterm birth, low birth weight, and perinatal
mortality in most [1,7,14-19], but not all [8,20], 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 [19]. 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 [21].

No correlation has been clearly established between acute cystitis of pregnancy and increased risk of low birth
weight, preterm delivery, or pyelonephritis [16], 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) [12]. There were no
differences in stillbirth or neonatal death. Other complications of pyelonephritis include anemia, sepsis, and
respiratory distress [11]. Maternal morbidity and obstetric outcomes with pyelonephritis do not appear to differ
by trimester [22].

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 [23]. 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 [14,24]. (See "Maternal adaptations to pregnancy: Renal and urinary tract
physiology".)

Pressure on the bladder from the enlarging uterus may also increase the risk of progression to pyelonephritis. In
addition, the immunosuppression of pregnancy may contribute. As an example, mucosal interleukin-6 levels and
serum antibody responses to Escherichia coli antigens appear to be lower in pregnant women [25].

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 [11]. 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, even in uncomplicated
UTIs [26,27]. In India, ESBL-producing uropathogens is a particular problem, even in pregnant women [28].
Isolation of more than one species or the presence of Lactobacillus or Cutibacterium 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 [29]. Rescreening among those who did not have bacteriuria on the initial test is
generally not performed in low-risk women. It is reasonable to rescreen women at high risk for infection (eg,
history of UTI or presence of urinary tract anomalies, diabetes mellitus, hemoglobin S, or preterm labor), however
the optimal target populations for this is uncertain. (See "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 midstream sample from the first concentrated morning urine, a midstream sample, and a clean-catch
midstream sample, in that order, over the course of a day [30]. 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 [31,32].

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 lower, at ≥104 cfu/mL. (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 [33-35]. In addition, cultures are useful in guiding therapy. This can be particularly
important in pregnancy, during which the number of safe treatment alternatives is reduced.

Management — Management of asymptomatic bacteriuria in pregnant women includes antibiotic therapy


tailored to culture results and follow-up cultures to confirm sterilization of the urine. For those women with
persistent or recurrent bacteriuria, prophylactic or suppressive antibiotics may be warranted in addition to
retreatment.

Rationale for treatment — Asymptomatic bacteriuria during pregnancy increases the risk of pyelonephritis and
has been associated with adverse pregnancy outcomes, such as preterm birth and low birth weight infants (see
'Epidemiology' above). Antimicrobial treatment reduces the risk of subsequent development of pyelonephritis
and is associated with improved pregnancy outcomes [7,36-40]. 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) [8]. 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 [20].

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 [41-43]. 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 [43].

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) [44].
Follow-up — Because up to 30 percent of women fail to clear asymptomatic bacteriuria following a short
course of therapy [1], a follow-up culture should be obtained as a test of cure. We typically perform this a week
after completion of therapy. In addition, we usually repeat urine cultures monthly until completion of the
pregnancy because of the risk of persistent or recurrent bacteriuria.

There is a paucity of data and lack of consensus on the need for re-screening or the optimal re-screening interval
for women who have a negative test of cure. If re-screening is performed and persistent or recurrent
asymptomatic bacteriuria is identified, repeat treatment is warranted, as below.

Management of persistent bacteriuria — If the first follow-up culture (test of cure) is positive for bacterial
growth [≥105 cfu/mL] with the same species (persistent bacteriuria), another course of antimicrobial treatment
based on susceptibility data should be administered: either the same antimicrobial in a longer course (eg, seven
days, if a three-day regimen was used previously) or a different antimicrobial in a standard regimen. True
persistent bacteriuria implies initial therapy was inadequate and thus requires modification with a different
therapeutic approach in contrast to recurrent bacteriuria (a different species is isolated or the same species is
isolated after documented clearance of the initial bacteriuria). (See 'Management of recurrent bacteriuria' below.)

Suppressive therapy may be appropriate for women with bacteriuria that persists after two or more courses of
therapy. Nitrofurantoin (50 to 100 mg orally at bedtime) for the duration of the pregnancy may be used if the
organism is susceptible. Monthly cultures are not necessary if suppressive therapy is administered; however,
breakthrough bacteriuria can occur during suppressive therapy, so we generally perform at least one later culture,
such as at the start of the third trimester, to ensure suppression is working. If that follow-up culture is positive
[≥105 cfu/mL], another course of antimicrobial based on susceptibility data should be administered. The
suppressive regimen should be reassessed and adjusted if needed based on the susceptibility pattern.

Management of recurrent bacteriuria — If the first follow-up culture is positive with a different species or if
the first follow-up culture is not positive [<105 cfu/mL], but then a subsequent culture is positive (with the same
or different species), both scenarios imply recurrent bacteriuria. Treatment should be administered with one of
the regimens used for an initial bacteriuric episode, tailored to antimicrobial susceptibility testing (table 1).

We typically do not recommend antibiotic prophylaxis for recurrent asymptomatic bacteriuria because of the lack
of data to support this practice.

ACUTE CYSTITIS

Clinical manifestations — Cystitis is a symptomatic infection of the bladder. The typical symptoms of acute
cystitis in the pregnant woman are the same as in nonpregnant women and include the sudden onset of dysuria
and urinary urgency and frequency. Hematuria and pyuria are also frequently seen on urinalysis.

Systemic symptoms, such as fevers and chills, are generally absent in isolated cystitis.

Diagnosis — Acute cystitis should be suspected in pregnant women who complain about dysuria. Although
urinary frequency and urgency are typical findings of acute cystitis, they are also frequently a normal physiologic
change of pregnancy and reported by pregnant women without cystitis or bacteriuria [45,46]. The presence of
fever and chills, flank pain, and costovertebral angle tenderness should raise suspicion for pyelonephritis (see
'Acute pyelonephritis' below). A urinalysis and urine culture should be performed in pregnant women who have
new onset dysuria. Specimen collection is the same as for asymptomatic bacteriuria. (See 'Specimen collection'
above.)

The diagnosis of acute cystitis is confirmed by finding of bacterial growth on urine culture. Prior to confirming the
diagnosis, empiric treatment is typically initiated in a patient with consistent symptoms and pyuria on urinalysis
(see 'Management' below). As in nonpregnant women, pyuria is usually present in almost all pregnant women
with symptomatic urinary tract infection, and its absence strongly suggests an alternative diagnosis. (See
"Sampling and evaluation of voided urine in the diagnosis of urinary tract infection in adults", section on
'Interpretation of pyuria'.)

Studies defining the threshold of bacterial growth on voided urine that represents significant bacteriuria in
pregnant women have not been performed, but based on studies in nonpregnant women, relatively low colony
counts can reflect true bacteriuria in the presence of symptoms. In nonpregnant women with uncomplicated
cystitis, coliform colony counts in voided urine as low as 102 colony forming units (cfu)/mL have been noted to
reflect bladder infection [47-49]. 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 uncomplicated 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 [50].

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 [51]. 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 [27,52].
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 [>38ºC], 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 [1,50,53]. Single-dose therapy is generally limited to fosfomycin.

Follow-up — As with asymptomatic bacteriuria, a follow-up culture should be obtained as a test of cure. We
typically perform this a week after completion of therapy. In addition, we usually repeat urine cultures monthly
until completion of the pregnancy because of the risk of persistent or recurrent bacteriuria. Management of
persistent bacteriuria is discussed above. (See 'Management of persistent bacteriuria' above.)

Management of recurrent cystitis — In women who have recurrent cystitis during pregnancy, antimicrobial
prophylaxis for the duration of pregnancy is a reasonable strategy to prevent additional episodes. Prophylaxis
can be postcoital, if the cystitis is thought to be sexually related (which it commonly is) or continuous.

In the setting of other conditions that potentially increase the risk of urinary complications during episodes of
cystitis (eg, diabetes or sickle cell trait), prophylaxis following the first episode of cystitis during pregnancy is
also reasonable.

The choice of antimicrobial used for prophylaxis should be based on the susceptibility profile of the cystitis
strains. Ideally, daily or postcoital prophylaxis with low dose nitrofurantoin (50 to 100 mg PO postcoitally or at
bedtime) or cephalexin (250 to 500 mg PO postcoitally or at bedtime) can be used.

ACUTE PYELONEPHRITIS

Clinical manifestations — Acute pyelonephritis is a manifestation of infection of the upper urinary tract and
kidneys. The typical symptoms of acute pyelonephritis in the pregnant woman are the same as in nonpregnant
women and include fever (>38ºC or 100.4ºF), flank pain, nausea, vomiting, and/or costovertebral angle
tenderness. Symptoms of cystitis (eg, dysuria) are not always present. Pyuria is a typical finding. (See "Acute
uncomplicated cystitis in women".)

Most cases of pyelonephritis occur during the second and third trimesters. (See 'Incidence and risk factors'
above.)

Pregnant women may become quite ill and are at risk for both medical and obstetrical complications from
pyelonephritis. It has been estimated that as many as 20 percent of women with severe pyelonephritis develop
complications that include septic shock syndrome or its variants, such as acute respiratory distress syndrome
(ARDS) [54-56]. 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) [11]. The mechanism of anemia is not well understood, but hemolysis, perhaps
mediated by endotoxin, may be important [57]. Acute renal failure associated with microabscesses and
suppurative pyelonephritis has been described in isolated cases, independent of sepsis [58]. (See "Acute kidney
injury (acute renal failure) in pregnancy".)

Diagnosis and evaluation — Acute pyelonephritis is suggested by the presence of flank pain, nausea/vomiting,
fever (>38ºC or 100.4ºF), and/or costovertebral angle tenderness, with or without the typical symptoms of
cystitis, and is confirmed by the finding of bacteriuria in the setting of these symptoms. (See "Acute
uncomplicated cystitis in women".)
For pregnant women who present with such symptoms, we check a urinalysis and urine culture. Pyuria is present
in the majority of women with pyelonephritis, and its absence suggests an alternative diagnosis or complete
obstruction. Although many pregnant women have back or flank pain without pyelonephritis, we have a low
threshold for evaluation for bacteriuria and a diagnosis of pyelonephritis in pregnant women with these
symptoms, given the risk of complications and adverse pregnancy outcomes with untreated pyelonephritis. (See
'Pregnancy outcomes' above.)

Some investigators have questioned the value of obtaining routine blood cultures in pregnant women with
pyelonephritis [59], and data on the impact of blood cultures on outcomes are limited [60]. 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 [61].

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 of intra-amniotic infection'.)

● Placental abruption is a key differential diagnosis of acute back or abdominal pain during pregnancy. Back
pain is prominent with abruption when the placenta is on the posterior wall of the uterus. Fever is absent and
vaginal bleeding is classically present with abruption, in contrast to pyelonephritis. The uterus is often firm,
and may be rigid and tender in patients with abruption, but is usually soft in patients with pyelonephritis.
Both conditions can be associated with uterine contractions. If present, a retroplacental hematoma on
ultrasound supports the diagnosis of abruption. (See "Placental abruption: Clinical features and diagnosis".)

Management — Management of acute pyelonephritis in pregnant women includes hospital admission for


parenteral antibiotics. Antibiotic therapy can be converted to an oral regimen tailored to the susceptibility profile
of the isolated organism following clinical improvement. Following the treatment course, suppressive antibiotics
are typically used for the remainder of the pregnancy to prevent recurrence.

Site of care — Based upon the higher risk of complications in pregnant women, pyelonephritis has traditionally
been treated with hospitalization and intravenous antibiotics until the woman is afebrile for 24 to 48 hours and
symptomatically improved [62]. 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 [63,64]. 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 [63]. 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 [64]. 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 [65]. Although rates of resistance to first generation
cephalosporins have generally been less than 10 percent in surveillance studies [66-69], 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 [70]. Given these data and the
paucity of data evaluating narrow spectrum cephalosporins in the treatment of pyelonephritis [70], 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 complicated pyelonephritis,
pregnant women generally have definite improvement within 24 to 48 hours of appropriate antibiotic therapy.
Once afebrile for 48 hours, pregnant patients can be switched to oral therapy guided by culture susceptibility
results and discharged to complete 10 to 14 days of treatment [62]. 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 uncomplicated 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


[65,71,72]. As a result, low dose antimicrobial suppressive therapy with an agent to which the original organism is
susceptible is warranted for the remainder of the pregnancy; reasonable options include nitrofurantoin (50 to 100
mg orally at bedtime) or cephalexin (250 to 500 mg orally at bedtime) [62,73].

Monthly cultures are not necessary if preventive therapy is administered; however, breakthrough bacteriuria can
occur during preventive therapy, so we usually perform at least one later culture, such as at the start of the third
trimester, to ensure preventive therapy is working. If a follow-up culture is positive (≥105 colony forming
units/mL), then a course of antimicrobial therapy based on susceptibility data should be administered. In
addition, the preventive regimen should be reassessed and adjusted if needed.

PREVENTION IN WOMEN WITH HISTORY OF RECURRENT UTI — A separate issue is the management of
pregnant women with a history of recurrent urinary tract infections (UTIs) prior to pregnancy, which is often
related to sexual intercourse. We use postcoital prophylaxis in pregnant women who have recurrent UTIs that
appear to be temporally related to sexual intercourse. The preferred regimen is a single postcoital dose of either
cephalexin (250 mg) or nitrofurantoin (50 mg). (See "Recurrent urinary tract infection in women", section on
'Prevention strategies'.)

The potential efficacy of postcoital prophylaxis to prevent UTIs during pregnancy was evaluated in a report of 33
women with a history of recurrent UTIs who had 39 pregnancies [74]. 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 [75]. 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 [76,77], 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 [8]. 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 [78]. 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 [73,79].

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 [76,77]. 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 [76], but the limitations of the study discussed
above lead to uncertainty about the association.

Aminoglycosides have been associated with ototoxicity following prolonged fetal exposure [79], 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.)

● 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 cultures are performed to confirm sterilization of the urine. For those women with
persistent bacteriuria, prophylactic or suppressive antibiotics may be warranted in addition to retreatment.
(See 'Management' above.)

● Acute cystitis should be suspected in pregnant women who complain about new onset dysuria, frequency, or
urgency. The diagnosis is made by finding of bacterial growth on urine culture in this setting. Management
of acute cystitis in pregnant women includes empiric antibiotic therapy that is subsequently tailored to
culture results. Potential options for empiric and directed therapy include beta-lactams, nitrofurantoin, and
fosfomycin (table 1). As with asymptomatic bacteriuria, follow-up cultures are performed to confirm
sterilization of the urine. For those women with persistent bacteriuria or recurrent cystitis, prophylactic or
suppressive antibiotics may be warranted in addition to retreatment. (See 'Acute cystitis' above.)

● Acute pyelonephritis during pregnancy is suggested by the presence of flank pain, nausea/vomiting, fever
(>38ºC), 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, suppressive antibiotics are typically used for the remainder of the pregnancy
to prevent recurrence. (See 'Management' above.)

● It is generally accepted that penicillins (with or without beta-lactamase inhibitors), cephalosporins,


aztreonam, and fosfomycin are safe in pregnancy. Because of possible but uncertain associations with
adverse birth outcomes, we generally avoid nitrofurantoin during the first trimester and trimethoprim-
sulfamethoxazole during the first trimester and near term unless no other options are available. (See
'Antibiotic safety in pregnancy' above.)

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Topic 8065 Version 49.0


GRAPHICS

Antibiotics for asymptomatic bacteriuria and cystitis in pregnancy

Antibiotic Dose Duration Notes

Nitrofurantoin 100 mg orally every 12 hours Five to seven days Does not achieve 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 hours or Three to seven days Resistance may limit its utility
875 mg orally every 12 hours among gram-negative
pathogens.

Amoxicillin-clavulanate 500 mg orally every 8 hours or Three to seven days  


875 mg orally every 12 hours

Cephalexin 500 mg orally every 6 hours Three to seven days  

Cefpodoxime 100 mg orally every 12 hours Three to seven days  

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

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

Graphic 98083 Version 5.0


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.

Graphic 56181 Version 11.0


Contributor Disclosures
Thomas M Hooton, MD Consultant/Advisory Boards: Cubist [Complicated UTI (Ceftolozane/tazobactam)];
Danone [UTI management (Hydration therapy)]; GSK (Antimicrobial in development); Ocean Spray (Cranberry
products); Paratek Pharmaceuticals (Antimicrobial in development). Equity Ownership/Stock Options: Fimbrion
Therapeutics [UTI prevention (Development of mannosides)]. Kalpana Gupta, MD, MPH Consultant/Advisory
Boards: Paratek Pharmaceuticals; Melinta Therapeutics; Iterum Therapeutics; Tetraphase Pharmaceuticals;
Ocean Spray Inc. [UTI]. Stephen B Calderwood, MD Patent Holder: Vaccine Technologies Inc [Vaccines (Cholera
vaccines)]. Equity Ownership: Pulmatrix [Infectious diseases (Inhaled antimicrobials)]. Charles J Lockwood, MD,
MHCM Nothing to disclose Allyson Bloom, MD Nothing to disclose

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