Urinary tract infections and asymptomatic bacteriuria in
pregnancyAuthorsThomas M Hooton, MDKalpana Gupta, MD, MPHSection
EditorsStephen B Calderwood, MDCharles J Lockwood, MD, MHCMDeputy
EditorAllyson Bloom, MDAll topics are updated as new evidence
becomes available and our peer review process is
complete.Literature review current through:Jan 2015.|This topic
last updated:Jan 23, 2015.
INTRODUCTIONUrinary tract infections (UTIs) are common in
pregnant women. By convention, UTI is defined either as a lower
tract (acute cystitis) or upper tract (acute pyelonephritis)
infection. UTIs (acute cystitis and pyelonephritis) and
asymptomatic bacteriuria in pregnant women will be reviewed
here.Issues related to urinary tract infections or asymptomatic
bacteriuria in other populations are discussed in detail elsewhere.
(See "Acute uncomplicated cystitis and pyelonephritis in women" and
"Acute uncomplicated cystitis, pyelonephritis, and asymptomatic
bacteriuria in men" and "Acute complicated cystitis and
pyelonephritis" and "Approach to the adult with asymptomatic
bacteriuria" and "Asymptomatic bacteriuria in patients with
diabetes mellitus" and "Catheter-associated urinary tract infection
in adults".)EPIDEMIOLOGYIncidence and risk factorsThe incidence of
bacteriuria in pregnant women is approximately the same as that in
nonpregnant women, however, recurrent bacteriuria is more common
during pregnancy. Additionally, the incidence of pyelonephritis is
higher than in the general population, likely as a result of
physiologic changes in the urinary tract during pregnancy. (See
'Pathogenesis' below.)Asymptomatic bacteriuria occurs in 2 to 7
percent of pregnant women [1,2]. It typically occurs during early
pregnancy, with only approximately a quarter of cases identified in
the second and third trimesters [3]. Factors that have been
associated with a higher risk of bacteriuria include a history of
prior urinary tract infection, pre-existing diabetes mellitus,
increased parity, and low socioeconomic status [4-6].Without
treatment, as many as 30 to 40 percent of pregnant women with
asymptomatic bacteriuria will develop a symptomatic urinary tract
infection (UTI), including pyelonephritis, during pregnancy [7].
This risk is reduced by 70 to 80 percent if bacteriuria is
eradicated. (See 'Rationale for treatment' below.)Acute cystitis
occurs in approximately 1 to 2 percent of pregnant women, and the
estimated incidence of acute pyelonephritis during pregnancy is 0.5
to 2 percent [8-11]. Most cases of pyelonephritis occur during the
second and third trimesters. As an example, the incidence of acute
pyelonephritis in pregnancy in the setting of routine prenatal
screening for asymptomatic bacteriuria was examined in a
prospective study of a general obstetric population [10]. During
the two year study period, 440 cases of acute pyelonephritis were
identified in 32,282 pregnant women (14 per 1000 deliveries). The
majority of cases occurred in the second trimester (53 percent). In
addition to prior untreated bacteriuria, other clinical
characteristics that have been associated with acute pyelonephritis
during pregnancy include age 38C or 100.4F), flank pain, nausea,
vomiting,and/orcostovertebral angle tenderness. Symptoms of
cystitis (eg, dysuria) are not always present. Pyuria is a typical
finding. (See "Acute uncomplicated cystitis and pyelonephritis in
women".)Most cases of pyelonephritis occur during the second and
third trimesters. (See 'Incidence and risk factors' above.)Pregnant
women may become quite ill and are at risk for both medical and
obstetrical complications from pyelonephritis. It has been
estimated that as many as 20 percent of women with severe
pyelonephritis develop complications that include septic shock
syndrome or its variants, such as acute respiratory distress
syndrome (ARDS) [52-54]. As an example, in a prospective study of
440 cases of acute pyelonephritis identified among 32,282 pregnant
women in a general obstetric population, complications included
anemia (23 percent), bacteremia (17 percent in the minority of
patients who were tested), respiratory insufficiency (7 percent),
and renal dysfunction (2 percent) [10]. The mechanism of anemia is
not well understood, but hemolysis, perhaps mediated by endotoxin,
may be important [55]. Acute renal failure associated with
microabscesses and suppurative pyelonephritis has been described in
isolated cases, independent of sepsis [56]. (See "Acute kidney
injury (acute renal failure) in pregnancy".)Diagnosis and
evaluationAcute pyelonephritis is suggested by the presence of
flank pain,nausea/vomiting,fever (>38C or
100.4F),and/orcostovertebral angle tenderness, with or without the
typical symptoms of cystitis, and is confirmed by the finding of
bacteriuria in the setting of these symptoms. (See "Acute
uncomplicated cystitis and pyelonephritis in women".)For pregnant
women who present with such symptoms, we check a urinalysis and
urine culture. Pyuria is present in the majority of women with
pyelonephritis, and its absence suggests an alternative diagnosis
or complete obstruction. Although many pregnant women have back or
flank pain without pyelonephritis, we have a low threshold for
evaluation for bacteriuria and a diagnosis of pyelonephritis in
pregnant women with these symptoms, given the risk of complications
and adverse pregnancy outcomes with untreated pyelonephritis. (See
'Pregnancy outcomes' above.)Some investigators have questioned the
value of obtaining routine blood cultures in pregnant women with
pyelonephritis [57]. Although there is no evidence that bacteremia
portends a worse prognosis or requires longer therapy in an
otherwise healthy pregnant woman with pyelonephritis, it is
reasonable to obtain blood cultures in those with signs of sepsis
or serious underlying medical conditions such as diabetes.Imaging
is not routinely used to diagnose pyelonephritis. However, in
patients with pyelonephritis who are severely ill or who also have
symptoms of renal colic or history of renal stones, diabetes,
history of prior urologic surgery, immunosuppression, repeated
episodes of pyelonephritis, or urosepsis, imaging of the kidneys
can be helpful to evaluate for complications. In pregnant women,
renal ultrasound is the preferred imaging modality in order to
avoid contrast or radiation exposure.Differential
diagnosisNephrolithiasis 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
feverand/orflank 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 tendernessand/orfoul odor of the amniotic fluid, and the
absence of bacteriuria. Other potential causes of fever and back or
flank pain in the absence of bacteriuria include other infections
(eg, influenza, pneumonia, appendicitis). (See "Intraamniotic
infection (chorioamnionitis)", section on 'Diagnosis of clinical
chorioamnionitis'.)Placental abruption is a key differential
diagnosis of acute back or abdominal pain during pregnancy. Back
pain is prominent with abruption when the placenta is on the
posterior wall of the uterus. Fever is absent and vaginal bleeding
is classically present with abruption, in contrast to
pyelonephritis. The uterus is often firm, and may be rigid and
tender in patients with abruption, but is usually soft in patients
with pyelonephritis. Both conditions can be associated with uterine
contractions. If present, a retroplacental hematoma on ultrasound
supports the diagnosis of abruption. (See "Placental abruption:
Clinical features and diagnosis".)ManagementManagement 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 careBased
upon the higher risk of complications in pregnant women,
pyelonephritis has traditionally been treated with hospitalization
and intravenous antibiotics until the woman is afebrile for 24 to
48 hours and symptomatically improved [58]. Initial outpatient
therapy of pregnant women with pyelonephritis has been attempted in
carefully selected populations (eg, no underlying serious medical
conditions, renal or urologic abnormalities, pregnancy
complications, signs of sepsis, or recent antibiotic use). However,
we suggest not initiating therapy of pyelonephritis in pregnant
women in the outpatient setting given the limited data evaluating
its safety and the need for close monitoring of the
patient.Evidence on the safety of outpatient initiation of
pyelonephritis treatment during pregnancy is limited to two trials
by the same group [59,60]. Although the studies suggested that
outpatient treatment resulted in similar outcomes as inpatient
management, several limitations of the studies create uncertainty
about the safety and practicality of outpatient management:In the
first trial, 120 pregnant women with pyelonephritis prior to 24
weeks gestation were randomly assigned to receive an outpatient
regimen consisting of intramuscular ceftriaxone for 2 days followed
by oral cephalexin for 10 days or an inpatient regimen consisting
of IV cefazolin followed at discharge by oral cephalexin for 10
days [59]. Clinical responses to therapy and birth outcomes were
similar for both outpatients and inpatients. However, six patients
initially treated with ceftriaxone were ultimately admitted to the
hospital for intravenous therapy, and one woman developed septic
shock during the emergency department observation period. Of note,
the outpatient regimen included initial parenteral antibiotics, and
home health nurses monitored patients assigned to the outpatient
strategy.In the second trial, 92 women who presented after 24 weeks
gestation were hospitalized for intramuscular ceftriaxone for 24
hours and then randomly assigned to early discharge on oral
cephalexin or continued hospitalization until afebrile for 48 hours
[60]. Clinical response and birth outcomes were similar for those
who completed the assigned strategy. However, 51 percent of
patients either did not qualify for outpatient management based
upon study criteria or developed complications, which precluded
early discharge from the hospital.Empiric antibioticsParenteral,
broad spectrum beta-lactams are the preferred antibiotics for
initial empiric therapy of pyelonephritis (table 2). The choice
between them should be guided by local microbiology and
susceptibility data as well as expected patient tolerance.
Fluoroquinolones and aminoglycosides, which are often used for
pyelonephritis in nonpregnant individuals, should be avoided in
pregnancy if possible. (See 'Antibiotic safety in pregnancy'
below.)The efficacy of beta-lactams was demonstrated in a
randomized trial of 179 pregnant women with acute pyelonephritis
before the 24th week of gestation: intravenous cefazolin or
intramuscular ceftriaxone had equivalent efficacy to intravenous
ampicillin plus gentamicin [61]. Although rates of resistance to
first generation cephalosporins have generally been less than 10
percent in surveillance studies [62-65], beta-lactams (including
first generation cephalosporins) have been less effective than
trimethoprim-sulfamethoxazole or the fluoroquinolones for treatment
of cystitis in studies of nonpregnant individuals [66]. Given these
data and the paucity of data evaluating narrow spectrum
cephalosporins in the treatment of pyelonephritis [66], we favor
third generation cephalosporins over first or second generation
cephalosporins, such as cefazolin, for the empiric treatment of
acute pyelonephritis.For women with a history of infections with
extended-spectrum 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-upAs with nonpregnant
patients with complicated pyelonephritis, pregnant women generally
have definite improvement within 24 to 48 hours of appropriate
antibiotic therapy. Once afebrile for 48 hours, pregnant patients
can be switched to oral therapy guided by culture susceptibility
results and discharged to complete 10 to 14 days of treatment [58].
Oral options are mainly limited to beta-lactams or, if in the
second trimester, trimethoprim-sulfamethoxazole. Nitrofurantoin and
fosfomycin are not appropriate for treatment of pyelonephritis due
to inadequate tissue levels. General principles regarding the
safety of antibiotics in pregnancy are discussed elsewhere. (See
'Antibiotic safety in pregnancy' below.)If symptoms and fever
persist beyond the first 24 to 48 hours of treatment, a repeat
urine culture and renal ultrasound should be performed to rule out
persistent infection and urinary tract pathology.For women who do
not use antimicrobial prophylaxis for the duration of pregnancy
following an episode of pyelonephritis (see 'Preventing recurrence'
below), we generally check monthly urine cultures to evaluate for
recurrent bacteriuria and treat as indicated because of the risk of
recurrent pyelonephritis. (See 'Asymptomatic bacteriuria'
above.)Obstetric managementPyelonephritis is not itself an
indication for delivery. If induction of labor or cesarean delivery
for standard obstetrical indications is planned in a patient on
treatment for pyelonephritis, we favor waiting until the patient is
afebrile, as long as delaying the delivery is relatively safe for
the mother and fetus.Since pyelonephritis is associated with
preterm birth, an important obstetric consideration is whether
tocolysis should be used when pyelonephritis triggers preterm labor
at various gestational ages. Detailed discussion of the benefits
and risks of tocolysis for acute preterm labor are found elsewhere.
(See "Inhibition of acute preterm labor", section on 'Patient
selection and treatment goals'.)Preventing recurrenceRecurrent
pyelonephritis during pregnancy occurs in 6 to 8 percent of women
[61,67,68]. As a result, low dose antimicrobial suppressive therapy
with an agent to which the original organism is susceptible is
warranted for the remainder of the pregnancy; reasonable options
include nitrofurantoin (50 to 100 mg orally at bedtime) or
cephalexin (250 to 500 mg orally at bedtime) [58,69].Monthly
cultures are not necessary if preventive therapy is administered;
however, breakthrough bacteriuria can occur during preventive
therapy, so we usually perform at least one later culture, such as
at the start of the third trimester, to ensure preventive therapy
is working. If a follow-up culture is positive (105colony
formingunits/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 UTIA separate
issue is the management of pregnant women with a history of
recurrent urinary tract infections (UTIs) prior to pregnancy, which
is often related to sexual intercourse. We use postcoital
prophylaxis in pregnant women who have recurrent UTIs that appear
to be temporally related to sexual intercourse. The preferred
regimen is a single postcoital dose of either cephalexin (250 mg)
or nitrofurantoin (50 mg). (See "Recurrent urinary tract infection
in women", section on 'Prevention strategies'.)The potential
efficacy of postcoital prophylaxis to prevent UTIs during pregnancy
was evaluated in a report of 33 women with a history of recurrent
UTIs who had 39 pregnancies [70]. The women were treated with a
single postcoital dose of either cephalexin (250 mg) or
nitrofurantoin (50 mg). Only one UTI occurred during pregnancy;
this was in sharp contrast to 130 UTIs during a mean observation
period of seven months before prophylaxis.ANTIBIOTIC SAFETY IN
PREGNANCYMuch of the information regarding the safe use of
antibiotics during pregnancy was obtained decades ago, before
pregnant women were excluded from drug studies because of concerns
about risk to the fetus. Thus, there is little direct information
about the safety of many newer antibiotics in pregnancy, and
concern about the use of certain antibiotics generally derives from
indirect evidence (eg, animal studies) or observational studies
that may have numerous confounders. Overall, the safest course is
to use the antibiotics that have well-established safety profiles
in pregnancy and limit the use of antibiotics of potential concern
to cases in which no safer alternative exists. (See "Initial
prenatal assessment and first trimester prenatal care", section on
'Antibiotic therapy'.)It is generally accepted that penicillins
(with or without beta-lactamase inhibitors), cephalosporins, and
aztreonam are safe in pregnancy. However, drugs with very high
protein binding, such as ceftriaxone, may be inappropriate the day
before parturition because of the possibility of bilirubin
displacement and subsequent kernicterus. Of the carbapenems, some
animal studies have shown adverse fetal effects with
imipenem-cilastatin, so meropenem, ertapenem, or doripenem are the
preferred carbapenems for use during pregnancy.Fosfomycin is also
generally considered safe in pregnancy [71]. In several studies of
single-dose fosfomycin during pregnancy, it was well-tolerated, and
adverse fetal effects were not observed.Nitrofurantoin is
frequently used during pregnancy, although some potential concerns
exist. Nitrofurantoin was associated with birth defects in a case
control study [72], but this finding should be interpreted with
caution as multiple comparisons involving small numbers of affected
exposed infants may have led by chance to the observed association.
The safest course is to avoid using nitrofurantoin in the first
trimester if another antibiotic that is safe and effective is
available. Nitrofurantoin has also been reported to cause hemolytic
anemia in the mother and fetus with G-6PD deficiency [73]. The risk
of hemolytic anemia is estimated to be only 0.0004 percent of
cases, but its use should be avoided near term for this reason
[69,74].Use of trimethoprim-sulfamethoxazole is typically limited
to mid-pregnancy, avoiding the first trimester and near term.
Trimethoprim is generally avoided in the first trimester because it
is a folic acid antagonist, has caused abnormal embryo development
in experimental animals, and some case control studies have
reported a possible association with a variety of birth defects
[72]. However, it is not a proven teratogen in humans. Women are
routinely prescribed folic acid supplementation during pregnancy;
this may be particularly important in those who are taking
trimethoprim. Sulfonamides should be avoided in the last days
before delivery because they can displace bilirubin from plasma
binding sites in the newborn, with the theoretical increased risk
for kernicterus, although kernicterus related solely to in utero
sulfonamide exposure has never been reported. Sulfonamides have
also been associated with birth defects in a case control study
[72], but the limitations of the study discussed above lead to
uncertainty about the association.Aminoglycosides have been
associated with ototoxicity following prolonged fetal exposure
[74], and therefore should be avoided unless intolerance or
resistance prohibits the use of less toxic agents.Fluoroquinolones
and tetracyclines are contraindicated during pregnancy.INFORMATION
FOR PATIENTSUpToDate 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 5thto
6thgrade 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 10thto 12thgrade reading level
and are best for patients who want in-depth information and are
comfortable with some medical jargon.Here are the patient education
articles that are relevant to this topic. We encourage you to print
or e-mail these topics to your patients. (You can also locate
patient education articles on a variety of subjects by searching on
"patient info" and the keyword(s) of interest.)Beyond the Basics
topics (see "Patient information: Urinary tract infections in
adolescents and adults (Beyond the Basics)")SUMMARY AND
RECOMMENDATIONSBacteriuria occurs commonly in pregnancy, typically
during early pregnancy. Without treatment, as many as 30 to 40
percent of pregnant women with asymptomatic bacteriuria will
develop a symptomatic urinary tract infection (UTI). The smooth
muscle relaxation and subsequent ureteral dilatation that occurs in
pregnancy are thought to facilitate the ascent of bacteria from the
bladder to the kidney, accounting for the greater risk of
pyelonephritis. Additionally, untreated bacteriuria is associated
with an increased risk of preterm birth, low birth weight, and
perinatal mortality. (See 'Epidemiology' above and 'Pathogenesis'
above.)As in nonpregnant women,Escherichia coliis 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 (105colony forming
units[cfu]/mL)on urine culture in the absence of symptoms
consistent with UTI. (See 'Diagnosis' above.)Management of
asymptomatic bacteriuria in pregnant women includes antibiotic
therapy tailored to culture results, which reduces the risk of
subsequent pyelonephritis and is associated with improved pregnancy
outcomes. Potential options include beta-lactams, nitrofurantoin,
and fosfomycin (table 1). Following treatment, follow-up cultures
are performed to confirm sterilization of the urine. For those
women with persistent bacteriuria, prophylactic or suppressive
antibiotics may be warranted in addition to retreatment. (See
'Management' above.)Acute cystitis should be suspected in pregnant
women who complain about new onset dysuria, frequency, or urgency.
The diagnosis is made by finding of bacterial growth on urine
culture in this setting. Management of acute cystitis in pregnant
women includes empiric antibiotic therapy that is subsequently
tailored to culture results. Potential options for empiric and
directed therapy include beta-lactams, nitrofurantoin, and
fosfomycin (table 1). As with asymptomatic bacteriuria, follow-up
cultures are performed to confirm sterilization of the urine. For
those women with persistent bacteriuria or recurrent cystitis,
prophylactic or suppressive antibiotics may be warranted in
addition to retreatment. (See 'Acute cystitis' above.)Acute
pyelonephritis during pregnancy is suggested by the presence of
flank pain,nausea/vomiting,fever (>38C),and/orcostovertebral
angle tenderness, with or without the typical symptoms of cystitis,
and is confirmed by the finding of bacteriuria in the setting of
these symptoms. Pregnant women may become quite ill and are at risk
for both medical (eg, sepsis, respiratory failure) and obstetrical
complications from pyelonephritis. (See 'Clinical manifestations'
above and 'Diagnosis and evaluation' above.)Management of acute
pyelonephritis in pregnant women includes hospital admission for
parenteral antibiotics, preferably broad spectrum 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.)Use of
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Topic 8065 Version 27.0All rights reserved.2015UpToDate,
Inc.Disclosures
Disclosures:Thomas M Hooton, MDConsultant/Advisory Boards:
Cubist [Complicated UTI (Ceftolozane/tazobactam)]; Vifor Pharma
[Uncomplicated UTI (Immunostimulant uro-vaxom)]. Equity
Ownership/Stock Options: Fimbrion Therapeutics [Prevention of UTI
(Developing mannosides that may eventually be useful in prevention
of UTI)].Kalpana Gupta, MD, MPHConsultant/Advisory Boards:
Boehringer Ingelheim GmbH [UTI (Empagliflozin)]; Paratek [UTI
(Omadacycline)]; Melinta Pharmaceuticals [UTI].Stephen B
Calderwood, MDConsultant/Advisory Boards: Pulmatrix [Inhaled
antimicrobial products (Not currently released)]. Patent Holder:
Vaccine Technologies [Cholera (Cholera vaccines)]. Equity
Ownership/Stock Options: PharmAthene [Biodefense (Anthrax)].Charles
J Lockwood, MD, MHCMNothing to disclose.Allyson Bloom, MDEmployee
of UpToDate, Inc.Contributor disclosures are reviewed for conflicts
of interest by the editorial group. When found, these are addressed
by vetting through a multi-level review process, and through
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