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Practice Essentials
Pregnancy causes numerous changes in the woman’s body that
increase the likelihood of urinary tract infections (UTIs). Hormonal
and mechanical changes can promote urinary stasis
and vesicoureteral reflux. These changes, along with an already
short urethra (approximately 3-4 cm in females) and difficulty with
hygiene due to a distended pregnant belly, help make UTIs the most
common bacterial infections during pregnancy.
Untreated bacteruria  during pregnancy is associated with risks to
both the fetus and the mother, including pyelonephritis, preterm birth,
low birth weight, and increased perinatal mortality.

In general, pregnant patients are considered immunocompromised

UTI hosts because of the physiologic changes associated with
pregnancy (see Pathophysiology). These changes increase the risk
of serious infectious complications from symptomatic and
asymptomatic urinary infections even in healthy pregnant women.
(See Urinary Tract Infection in Females.)

Oral antibiotics are the treatment of choice for asymptomatic

bacteriuria and cystitis. The standard course of treatment for
pyelonephritis is hospital admission and intravenous antibiotics.
Antibiotic prophylaxis is indicated in some cases (see Treatment).
Patients treated for three or more episodes of cystitis or one
episodes of pyelonephritis during pregnancy should be continued on
daily prophylactic antibiotics for the duration of their pregnancy.

Annual health costs for UTI exceed $1 billion. screening for these
conditions in pregnant women is cost-effective, compared with
treating UTI and pyelonephritis without screening.

Definitions of key terms

Urinary tract infection
UTI is defined as the presence of at least 100,000 organisms per
milliliter of urine in an asymptomatic patient, or as more than 100
organisms/mL of urine with accompanying pyuria (> 7 white blood
cells [WBCs]/mL) in a symptomatic patient. A diagnosis of UTI should
be supported by a positive culture for a uropathogen, particularly in
patients with vague symptoms. [1]

Asymptomatic bacteriuria
Asymptomatic bacteriuria is commonly defined as the presence of
more than 100,000 organisms/mL in 2 consecutive urine samples in
the absence of declared symptoms. Untreated asymptomatic
bacteriuria is a risk factor for acute cystitis (40%) and pyelonephritis
(25-30%) in pregnancy. This usually occurs in early pregnancy. Risk
factors include prior UTIs, pre-existing diabetes, increased parity, and
low socioeconomic status. 

Cystitis

Acute cystitis involves only the lower urinary tract; it is characterized

by inflammation of the bladder as a result of bacterial or nonbacterial
causes (eg, radiation or viral infection). Acute cystitis develops in
approximately 1- 2% of pregnant patients, of whom 60% have a
negative result on initial screening. Signs and symptoms include
hematuria, dysuria, suprapubic discomfort, frequency, urgency, and
nocturia. These symptoms are often difficult to distinguish from those
due to pregnancy itself.
Acute cystitis is complicated by upper urinary tract disease (ie,
pyelonephritis) in 15-50% of cases.

Acute pyelonephritis
Pyelonephritis is the most common urinary tract complication in
pregnant women, occurring in approximately 0.5-2% of all
pregnancies. Acute pyelonephritis is characterized by fever, flank
pain, and tenderness in addition to significant bacteriuria. Other
symptoms may include nausea, vomiting, frequency, urgency, and
dysuria. Most cases of pyelonephritis occur in the second and third
trimester. 
Additional risk factors for complicated UTI in pregnancy include the
following [2] :
 Immunosuppression
 Pre-existing diabetes
 Sickle cell anemia
 Neurogenic bladder
 Recurrent or persistent UTIs before pregnancy
 Tobacco use
 Age < 20 years
 Late presentation for prenatal care

Next: Pathophysiology
Pathophysiology
Infections result from ascending colonization of the urinary tract,
primarily by existing vaginal, perineal, and fecal flora. Various
maternal physiologic and anatomic factors predispose to ascending
infection. Such factors include urinary retention caused by the weight
of the enlarging uterus on the bladder; urinary stasis due to
progesterone-induced ureteral smooth muscle relaxation; and blood-
volume expansion, which increases the glomerular filtration rate and
urinary output.

Loss of ureteral tone combined with increased urinary tract volume

results in urinary stasis, which can lead to dilatation of the ureters,
renal pelvis, and calyces.
Urinary stasis can serve as a reservoir for bacteria. Urinary stasis
and the presence of vesicoureteral reflux predispose some women
to acute pyelonephritis. [3]
Calyceal and ureteral dilatation are more common on the right side;
in up to 80% of cases, the dilatation is localized to the right. The
degree of calyceal dilatation is also more pronounced on the right
than the left (average 15 mm vs 5 mm). This dilatation appears to
begin by about 10 weeks’ gestation and increases throughout
pregnancy, resolving approximately 6-12 weeks postpartum. This is
underscored by the distribution of cases of pyelonephritis during
pregnancy: 2% during the first trimester, 52% during the second
trimester, and 46% in the third trimester.
Glucosuria and an increase in levels of urinary amino acids
(aminoaciduria) during pregnancy are additional factors that lead to
UTI. In many cases, glucose excretion increases during pregnancy
over nonpregnant values of 100 mg/day. Glycosuria is due to
impaired glucose reabsorption by the proximal collecting tubule and
loop of Henle.
The fractional excretion of alanine, glycine, histidine, serine, and
threonine is increased throughout pregnancy. Levels of cystine,
leucine, lysine, phenylalanine, taurine, and tyrosine are elevated in
the first half of pregnancy but return to reference range levels by the
second half. The mechanism of selective aminoaciduria is unknown,
although its presence has been postulated to affect the adherence
of Escherichia coli to the urothelium.

Next: Etiology
Etiology
Pathogens
E coli is the most common cause of UTI, accounting for
approximately 70-80% of cases in pregnancy. It originates from fecal
flora colonizing the periurethral area, causing an ascending infection.
Other pathogens include the following [4] :
 Klebsiella pneumoniae (5%)
 Proteus mirabilis (5%)
 Enterobacter species (3%)
 Staphylococcus saprophyticus (3%)
 Group B beta-hemolytic  Streptococcus (GBS; 2-5%)
 Proteus species (2%)
Gram-positive organisms, particularly Enterococcus faecalis and
GBS, are clinically important pathogens. They cause up to 10% of
UTIs in pregnant women.

Infection with S saprophyticus,an aggressive community-acquired

organism, can cause upper urinary tract disease, and this infection is
more likely to be persistent or recurrent.

Urea-splitting bacteria, including Proteus, Klebsiella,

Pseudomonas, and coagulase-negative Staphylococcus,alkalinize
the urine and may be associated with struvite stones. Chlamydial
infections are associated with sterile pyuria and account for more
than 30% of atypical pathogens.
GBS colonization has important implications during pregnancy.
Intrapartum transmission that leads to neonatal GBS infection can
cause pneumonia, meningitis, sepsis, and death.

Current guidelines recommend universal vaginal and rectal screening

in all pregnant women at 35-37 weeks’ gestation rather than
treatment based on risk factors.

Incidental documentation of GBS bacteriuria suggests a higher

colonization count than is revealed by a screening vaginal or rectal
culture.
Beta-streptococcal colonization in the urine warrants immediate
treatment and antibiotic prophylaxis when the patient presents in
labor.
Whether beta streptococci are associated with preterm labor is
controversial.  A systemic review and meta-analysis found no
association between GBS colonization and preterm delivery. In cases
where preterm delivery occurred, however, there was an increased
risk of subsequent GBS colonization. [5]
Patient factors
Several patient-level factors are associated with an increased
frequency of bacteriuria during pregnancy. Compared with
nonindigent patients, indigent patients have a 5-fold increased
incidence of bacteriuria. The risk is doubled in women with sickle cell
trait. Other risk factors for bacteriuria include the following:
 Pre-existing  diabetes mellitus [6]
 Neurogenic bladder retention 
 History of  vesicoureteral reflux (treated or untreated) [7]
 Kidney transplantation [8]
 Increased parity
 History of previous UTIs
A study that compared pregnant women with and without a positive
urine culture found that the following factors were associated with
increased odds of UTI [9] :
 Intercourse ≥3x/week (odds ratio [OR] 5.62)
 Recent UTI (OR = 3.27)
 Not washing genitals precoitus (OR = 2.16)
 Not washing genitals postcoitus (OR = 2.89)
 Not urinating postcoitus (OR = 8.62)
 Washing genitals from back to front (OR = 2.96)
Cesarean delivery
Cesarean delivery is associated with UTI (increasing the likelihood
2.7-fold), but this association may be confounded by bladder
catheterization or prolonged rupture of membranes (PROM). The
incidence of symptomatic UTI is 9.3%, and that of asymptomatic
bacteriuria is 7.6%.
Orthotopic continent urinary diversion
In orthotopic continent diversion (OCD), an ileal-ascending colon
conduit is made (OCD, Kock pouch) and reattached to the in situ
urethra (OCD) or a continent abdominal stoma (Kock pouch).
Typical candidates are patients born with congenital exstrophy of the
bladder in whom primary reconstruction has failed. Recurrent UTI
and hydronephrosis are common because of outflow obstruction of
the orthotopic stoma secondary to uterine compression or uterine
prolapse. Indwelling catheterization of the urethra or continent stoma
may be necessary, particularly during the later stages of pregnancy.
In rare cases, a percutaneous nephrostomy tube or antegrade
passage of a ureteral stent may be indicated.
Next: Epidemiology

Epidemiology
United States statistics
The frequency of urinary tract infection (UTI) in pregnant women (0.3-
1.3%) is similar to that in non-pregnant women. [10] However, recurrent
bacteruria is more common in pregnant women than non-pregnant
women. Changes in coital patterns (eg, position, frequency,
postcoital antibiotics) can offset recurrence in at-risk individuals. 
Overall, UTIs are 14 times more frequent in women than in men. This
difference is attributed to the following factors:
 The urethra is shorter in women, so perineal and fecal flora
have a shorter distance to travel.
 In women, the lower third of the urethra is continually
contaminated with pathogens from the vagina and the rectum.
 Women tend not to empty their bladders as completely as men
do.
 female urogenital system is exposed to bacteria during
intercourse.
A difference between pregnant and nonpregnant women is that the
prevalence of asymptomatic bacteriuria in pregnant women is 2.5-
11%, as opposed to 3-8% in nonpregnant women. In as many as
35% of these cases, bacteriuria may progress to symptomatic upper
UTI or pyelonephritis; this rate is significantly higher than that seen in
nonpregnant women [11]

International statistics
Versi et al described a higher prevalence of bacteriuria in pregnant
white women (6.3%) than in pregnant Bangladeshi women
(2%). [12] Pregnancies that resulted in preterm deliveries were strongly
associated with bacteriuria in white women; this association was not
observed in Bangladeshi women. The authors hypothesized that the
difference could be due to variation in hygiene practices and clothing.

A large population-based study of nearly 200,000 pregnant Israeli

women demonstrated a 2.5% rate of asymptomatic bacteriuria [13] and
a 2.3% rate of symptomatic UTI. [14] In this population, asymptomatic
bacteriuria was found to have an association with multiple pregnancy
complications, including hypertension, diabetes, intrauterine growth
retardation, prolonged hospitalization, and preterm labor.
The authors suggested that these findings may be a marker for
intensity of prenatal care rather than a specific causal effect of the
urinary infection. [13] Additionally, their follow-up study examining
women with symptomatic UTI showed a clear association between
UTI and low birth weight and preterm delivery, a finding consistent
with those of multiple previous investigations. [14]
Age- and race-related demographics
The prevalence of UTI during pregnancy increases with maternal
age.
A retrospective analysis of 24,000 births found the prevalence of UTI
during pregnancy to be 28.7% in whites and Asians, 30.1% in blacks,
and 41.1% in Hispanics. When socioeconomic status is controlled
for, no significant interracial differences seem to exist. A survey-
based analysis of self-reported UTI found similar trends. This study
also considered Native American women and found the highest
prevalence of UTI in this population (24.2%) as compared with Asian
(10.3%), white (16.6%), Hispanic (18.3%), and black (20.3%)
women. [15]
UTI is associated with preterm delivery in persons of all races. The
adjusted odds ratio in infants with very low birth weight is 2.8 in
blacks and 5.6 in whites, adjusted for parity, body mass index,
maternal age, marital status, cigarette smoking, education, and
prenatal care. The overall relative risk of bacteriuria in blacks or
whites is estimated at 1.5-5, and the relative risk of preterm birth in
women with bacteriuria is 1.8-2.3.

Next: Prognosis

Prognosis
In most cases of bacteriuria and urinary tract infection (UTI) in
pregnancy, the prognosis is excellent. The majority of long-term
sequelae are due to complications associated with septic shock,
respiratory failure, and hypotensive hypoxia (ie, extremity gangrene).
Maternal UTI has few direct fetal sequelae because fetal bloodstream
infection is rare; however, uterine hypoperfusion due to maternal
dehydration, maternal anemia, and direct bacterial endotoxin damage
to the placental vasculature may cause fetal cerebral hypoperfusion.

Untreated upper UTIs are associated with low birth weight,

prematurity, premature labor, hypertension, preeclampsia, maternal
anemia, and amnionitis. [16, 17] A retrospective population-based study
by Mazor-Dray et al showed that UTI during pregnancy is
independently associated with intrauterine growth restriction,
preeclampsia, preterm delivery, and cesarean delivery. [13]  
Preeclampsia
 A meta-analysis of 19 studies demonstrated an increased odds
(1.31-fold) of preeclampsia in women with any UTI during pregnancy
versus those without UTI. [17]  A multicenter retrospective study found
that UTI in pregnancy, particularly in the third trimester, is strongly
associated with preeclampsia. Rates of preeclampsia in patients with
UTI compared with those without reported UTI were 31.1% vs 7.8%,
respectively (P < 0.001). The authors hypothesize that the increased
maternal inflammatory burden from UTI enhances the risk of
preeclampsia. [18]
 

Clinical Presentation

History
The presentation varies according to whether the patient has
asymptomatic bacteriuria, a lower urinary tract infection (UTI; ie,
cystitis) or an upper UTI (ie, pyelonephritis).
Burning with urination (dysuria) is the most significant symptom in
pregnant women with symptomatic cystitis. Other symptoms include
frequency, urgency, suprapubic pain, hematuria, and pyuria in the
absence of systemic symptoms.
The usual complaints of increased frequency, nocturia, and
suprapubic pressure are not particularly helpful, because most
pregnant women experience these as a result of increased pressure
from the growing uterus, expanding blood volume, increased
glomerular filtration rate, and increased renal blood flow.

Pyelonephritis signs and symptoms often include fever (> 38°C),

shaking chills, anorexia, nausea, vomiting, and costovertebral angle
tenderness. Right-side flank pain is more common than left-side or
bilateral flank pain. Pyuria is a common finding. Patients may also
present with hypothermia (as low as 34°C). Symptoms of simple
cystitis are not always present.

Next: Physical Examin
Physical Examination
Physical examination findings should be considered in relation to the
duration of pregnancy. The differential diagnoses may change from
one trimester to the next, and the increasing size of the gravid uterus
may mask or mimic disease findings. A thorough physical
examination is recommended, with particular attention to the
abdomen. Suprapubic or costovertebral tenderness may be present.
In asymptomatic bacteriuria, no physical findings are typically
present. Symptoms may arise intermittently, only to be overlooked
because of lack of persistence or severity.
Pelvic examination is recommended in all symptomatic patients (with
the exception of third-trimester patients with bleeding) to rule
out vaginitis or cervicitis. In patients with cystitis, tenderness can
often be elicited with isolation of the bladder on pelvic examination.
Patients with pyelonephritis have fever (usually > 38°C), flank
tenderness upon palpation, and an ill appearance. Flank tenderness
occurs on the right side more frequently, and is present in more than
half of patients. Pain may also be found suprapubically with
palpation.
Assessment of the fetal heart rate on the basis of gestational age
should be included as part of the evaluation. Often, owing to maternal
fever, the fetal heart rate is elevated to more than 160 beats/min.

Next: Complications

Complications
The primary complication of bacteriuria during pregnancy is cystitis,
though the primary morbidity is due to pyelonephritis.
Complications may include the following:
 Perinephric cellulitis and abscess
 Septic shock
 Renal dysfunction (usually transient, but as many as 25% of
pregnant women with pyelonephritis have a decreased
glomerular filtration rate)
 Hematologic dysfunction, including anemia or
thrombocytopenia 
 Hypoxic fetal events due to maternal complications of infection
that lead to hypoperfusion of the placenta
 Preeclampsia [18]
 Preterm labor, and possible subsequent preterm delivery,
leading to increased infant morbidity and mortality
Pregnant women with pyelonephritis can become critically ill very
quickly. It has been estimated that approximately 20% of pregnant
women with severe pyelonephritis develop complications that include
septic shock variants. [19] In a prospective study of cases of pregnant
women with acute pyelonephritis, complications included anemia
(23%), bacteremia (17%), respiratory insufficiency (7%), and renal
dysfunction (2%). [16]
Pulmonary injury may also complicate UTI in pregnancy.
Approximately 2% of women with severe pyelonephritis during
pregnancy have evidence of pulmonary injury due to systemic
inflammatory response syndrome and respiratory insufficiency.
Endotoxins that alter alveolar-capillary membrane permeability are
produced; subsequently, pulmonary edema and acute respiratory
distress syndrome develop.

Differential Diagnoses

Diagnostic Considerations
The differential diagnosis of urinary tract infection (UTI) in pregnancy includes
the following:
 Cervicitis
 Chlamydial Genitourinary Infections
 Nonbacterial and Noninfectious Cystitis
 Ectopic Pregnancy
 Interstitial Cystitis
 Nephrolithiasis
 Trichomoniasis
 Trigonitis
 Urethritis
 Vaginitis
Other disorders to consider include the following:
 Glomerulonephritis
 Group B streptococcal colonization
 Sexually transmitted infection (eg, gonorrhea, nongonococcal urethritis)
 Threatened or incomplete miscarriage
 Urge incontinence
Common symptoms of a UTI, including urgency and frequency, can also be
normal symptoms of pregnancy.
Vaginal infections can cause or mimic UTIs, which are common in women of
reproductive age, affecting 25-35% of women aged 20-40 years.
Discriminating between the 2 depends on the results of vaginal and urinary
cultures (see Urine Studies).
Workup

Approach Considerations
Laboratory studies can include blood studies and urine studies,
including culture, urinalysis, dipstick testing, and other tests (eg, urine
cytology, sulfosalicylic acid [SSA] testing).
Imaging tests can include ultrasonography and intravenous
pyelography.

Next: Blood Studies

Blood Studies
The following blood tests should be ordered at the physician’s
discretion, though the results do not aid in the diagnosis or change
treatment unless they are markedly abnormal:
 Complete blood count (CBC)
 Serum electrolytes
 Blood urea nitrogen (BUN)
 Serum creatinine
 In pregnant women who are showing signs of sepsis, it is reasonable
to obtain blood cultures and a lactic acid assay.  Although there is no
evidence that positive blood cultures are associated with worse
prognosis, elevated lactic acid levels have been associated with
adverse maternal outcomes in presumed sepsis. [20]

Next: Urine Studies

Urine Studies
Urine specimen collection
Universal screening is recommended for  all pregnant patients. A
urine specimen should be carefully collected for urinalysis and
culturing at 12-16 weeks’ gestation, or the first prenatal appointment,
whichever comes first. [21] These tests help to identify patients with
asymptomatic bacteriuria, as well as those with other concerning
findings such as glucosuria.
For urine collection, a midstream clean catch is adequate, provided
that the patient is given careful instructions. The technique is as
follows:
   With one hand, spread the labia
 With the other hand, use a castile soap–moistened towelette to
wipe the urethral meatus downward toward the rectum, then
discard the towelette.
 Void the initial portion of the bladder contents into the toilet
 Catch the middle portion of the bladder contents in the sterile
collection container, while keeping the labia spread with the first
hand
Unfortunately, a study looking at different methods of specimen
collection by pregnant women suggests that the cleansing process
does not completely prevent contamination by skin flora. The data
showed minimal difference in rates of contamination whether a clean
catch was performed or not. [22] Therefore, it may be reasonable to
obtain a midstream (not clean catch) urine sample.

If the patient is unable to void, too ill, extremely obese, or bedridden,

a catheterized specimen should be collected. Routine catheterization
is not recommended, because of the risks of introducing bacteria into
the urinary tract.

The specimen should be sent for evaluation as soon as possible.

Specimens that are allowed to sit at room temperature may have
falsely elevated colony counts, as bacteria will continue to proliferate
in warm urine. Refrigerate the specimen at 4°C if it cannot be
transported immediately as this will stop further growth of the bacteria
Urine culture
Urine culture is the standard method for evaluating for urinary tract
infection (UTI) during pregnancy. Indications for performing a urine
culture include the following:
 New onset of symptoms of cystitis with positive urinalysis or
dipstick testing
 Recurrent UTI
 Pyelonephritis
 Failure to respond to initial treatment regimens
 History of recent instrumentation
 Hospital admission
A voided specimen with a bacterial growth of 100,000 colony-forming
units (CFUs) per milliliter or higher is the standard definition of a
positive urine culture. [4] Counts lower than 100,000 CFU/mL usually
indicate specimen contamination rather than infection. Patients with
pyelonephritis often have white blood cell (WBC) casts.
Culture results can be used to identify specific organisms and
antibiotic sensitivities, but results are often unavailable at the time of
treatment.

Urinalysis by microscopy
Positive results for nitrites, leukocyte esterase, WBCs (pyuria), red
blood cells (RBCs), and protein suggest UTI. Pyuria is present in
almost all women with cystitis. Bacteria found in the specimen can
help with the diagnosis. The presence of bacteria without pyuria
usually represents contamination of the urine.
Urinalysis has a specificity of 97-100%, but it has a sensitivity of only
25-67% when compared with culture in the diagnosis of
asymptomatic bacteriuria.
Clumping WBCs and WBC casts are indicative of kidney
inflammation and are consistent with upper tract infection or
pyelonephritis. RBC casts are characteristic of acute
glomerulonephritis, which should be suspected after a recent or
concurrent streptococcal infection.
Renal involvement usually leads to proteinuria. Nephrotic syndrome
includes high proteinuria (> 3.5 g/24 h), edema,
hypercholesterolemia, and hypoalbuminemia; however, this can be
confused with preeclampsia. Oval fat bodies and fatty casts can
suggest membranous glomerulonephritis.
Dipstick testing
Several reports describe the use of urine dip for nitrites and leukocyte
esterase in the evaluation of asymptomatic bacteriuria. In comparison
with culture, sensitivity ranges from 50% to 92% and specificity from
86% to 97%.
In the evaluation of symptomatic patients, dipstick testing is useful
and inexpensive. However, the leukocyte esterase test may be
unreliable in patients with low-level pyuria (5-20 WBCs/HPF). The
addition of protein and blood increases the sensitivity and specificity
of the test in the evaluation of UTI.
A positive nitrite test is reliable for bacteriuria, but a negative test
does not exclude bacteriuria. The reason for this is that bacteria
converts the dietary metabolite nitrate to nitrite in the urine. As
suggested by Kodikara et al, nitrite dipstick testing may be a
reasonable and cost-effective screening strategy for women who
otherwise may not undergo screening for bacteriuria, as is often the
case in developing countries. [23]
Next: Renal Ultrasono

Renal Ultrasonography and Intravenous

Pyelography
Unless an anatomic abnormality or renal disease is suspected, initial
routine imaging studies are not necessary. Patients with suspected
pyelonephritis who are not responsive to appropriate antibiotic
therapy after 48-72 hours should undergo imaging. In pregnant
patients, the recommended imaging study to perform first is a renal
ultrasound, to avoid contrast and radiation unless necessary.
Renal ultrasound is helpful to visualize kidney or ureteral stones,
renal abscess formation, or hydronephrosis. Renal ultrasonography
(or limited intravenous pyelography [IVP] if the benefits of a definitive
diagnosis outweigh the minor risk of radiation) may be helpful in
patients with recurrent urinary tract infection (UTI) or symptoms that
suggest nephrolithiasis (see the images below). Confusion about the
diagnosis of urolithiasis, pyelonephritis, or both is an indication for
obtaining imaging studies.

Twenty-nine-year-old pregnant woman with history of reflux uropathy

and ureteral reimplantation at age 21 months presents with right-side
flank pain and proteinuria. Renal cortical thinning suggests chronic
hydronephrosis.
View Media Gallery
 Color-flow Doppler
highlights normal flow in right kidney of 29-year-old pregnant woman
with history of reflux uropathy and ureteral reimplantation at age 21
months who presents with right-side flank pain and proteinuria.
View Media Gallery

25-year-old pregnant woman

with right lower quadrant pain and hematuria has proximal ureteral
obstruction consistent with urolithiasis. After 25 minutes, intravenous
pyelography reveals dense right nephrogram and no filling of right
collecting system. Left side shows unremarkable nonhydronephrotic
collecting system. This is consistent with right ureteral lithiasis.
View Media Gallery

Urolithiasis and pyelonephritis have many symptoms in common (eg,

hematuria, flank pain, shaking chills, anorexia). Urolithiasis is usually
not associated with fever, except in patiens with concomitant
pyelonephritis.
Urolithiasis presents a unique problem in pregnant women. Kidney
stones should initially be treated conservatively because 50-67% of
stones diagnosed during pregnancy pass spontaneously.
Conservative therapy includes appropriate antibiotic coverage,
adequate hydration, and systemic analgesics (usually narcotics,
which are class C agents in pregnancy). Anti-inflammatory
medications may cause oligohydramnios, premature closure of the
patent ductus arteriosus, or both and should therefore be avoided if
possible.
If ultrasonography reveals a stone, ultrasound-guided cystoscopic
passage of a ureteral stent may relieve ureteral colic. In some cases
(eg, pyonephrosis with an obstructing stone), percutaneous
nephrostomy can be useful. Cystoscopic extraction of a distal
ureteral stone (with fluoroscopic guidance) should be used sparingly
because of the risk of ionizing radiation to the fetus.
The total dosage of ionizing radiation should not exceed 3-5 cGy
during the course of pregnancy. Of particular concern is radiation
delivered during the first trimester, during organogenesis (especially
days 11-56). A limited IVP can deliver 0.4-1 cGy. Radiation doses
greater than 5 cGy have been associated with an increased
likelihood of benign and malignant tumors in the child after birth. No
patient should receive more than 10-14 cGy.
Renal ultrasonography is often performed initially, but the findings are
often inconclusive. A limited IVP (ie, kidneys-ureters-bladder [KUB]
with a 30-minute shot after contrast injection) can be helpful in
delineating the site of the obstruction.

Next: Histologic Findin

Histologic Findings
On urine cytology, clumping white blood cells (WBCs) and WBC
casts are consistent with pyelonephritis. Red blood cell (RBC) casts
are characteristic of acute glomerulonephritis, which should be
suspected in patients with a recent or concurrent streptococcal
infection.
Renal involvement usually leads to proteinuria. Nephrotic syndrome
includes high proteinuria (> 3.5 g/24 h), edema,
hypercholesterolemia, and hypoalbuminemia; however, this can be
confused with preeclampsia. Oval fat bodies and fatty casts can
suggest membranous glomerulonephritis.
Treatment & Manage

Approach Considerations
Treatment of bacteriuria and cystitis
Because of the dangers of maternal and fetal complications, acute care
should focus on identifying and treating asymptomatic and symptomatic
bacteriuria, along with ensuring that an alternate process is not the cause of
the symptoms.
Treatment of asymptomatic bacteriuria in pregnant patients is important
because of the increased risk of urinary tract infection (UTI) and its associated
sequelae, including increased risk of pyelnonephritis, preterm delivery, and
low birth weight. [24]  

Behavioral methods
Any discussion of treatment should be prefaced with a discussion of
behavioral methods that may be used to ensure good hygiene and reduce
bacterial contamination of the urethral meatus, thereby preventing inadequate
treatment and recurrent infection. Behavioral methods include the following:
 Avoid baths
 Wipe front-to-back after urinating or defecating
 Wash hands before using the toilet
 Use washcloths to clean the perineum
 Use liquid soap to prevent colonization from bar soap
 Clean the urethral meatus first when bathing

Antibiotic therapy
Oral antibiotics are the treatment of choice for asymptomatic bacteriuria and
cystitis. Treatment is most commonly initiated empirically before culture and
susceptibility results return. A meta-analysis concluded that although antibiotic
treatment is effective in patients with UTIs, the data are insufficient to
recommend any specific regimen for treatment of symptomatic UTIs during
pregnancy. [25, 26] All of the antibiotics studied were effective in terms of both
increasing cure rates of UTI in pregnancy and decreasing the incidence of
associated adverse outcomes. Current oral regimens are summarized in
Table 1 below.

Table.

Table 1. Treatment Regimens for Pregnant Women with

Asymptomatic Bacteruria or UTI

  Nitrofurantoin monohydrate/macrocrystals 100 mg orally twice

daily for 5-7 days  or
  Amoxicillin 875 mg orally twice daily (alternative: 500 mg
 Table 1. Treatment Regimens for Pregnant Women with
Asymptomatic Bacteruria or UTI

orally three times daily) for 5-7 days  or

  Amoxicillin-clavulanate 500/125 mg orally three times daily for
5-7 days (alternative: 875/125 mg orally two times daily for 5-7
days)  or
  Cephalexin 500 mg orally four times daily for 5-7 days or
  Fosfomycin 3 g orally as a single dose with 3-4 oz. of water

Antibiotics most commonly given as empiric therapy are cephalexin,

amoxicillin-clavulanate, or fosfomycin, due to their broader spectrum
of coverage than the other antibiotic options. The resistance
of Escherichia coli to ampicillin and amoxicillin is 20-40%;
accordingly, these agents are no longer considered optimal for
treatment of UTIs caused by this organism.
Although 1-, 3-, and 7-day antibiotic courses have been evaluated,
10-14 days of treatment is usually recommended to eradicate the
offending bacteria. For example, studies with cephalexin,
trimethoprim-sulfamethoxazole, and amoxicillin have indicated that a
single dose is as effective as a 3- to 7-day course of therapy, but the
cure rate is only 70%. A systematic review that compared single-
dose antibiotic treatment with 4- to 7-day treatments concluded that
single-dose regimens may be less effective than a short-course
regimen, but until more data become available from large trials,
pregnant women with asymptomatic bacteriuria should be treated
with the standard regimen. [26]
Treatment success depends on eradication of the bacteria rather
than on the duration of therapy. A test-for-cure urine culture should
show negative findings 1-2 weeks after completion of  therapy. A
nonnegative culture result is an indication for a 10- to 14-day course
of a different antibiotic.
Recurrent Cystitis
Pregnant women who have three or more episodes of cystitis or
bacteruria should be started on daily antibiotic prophylaxis for the
remainder of pregnancy.
Daily antibiotics should also be considered in pregnant women after
one episode of pyelonephritis. Regimens for daily prophylaxis
includes nitrofurantion 100 mg nightly, or cephalexin 250-500 mg
nightly. A Cochrane review in 2015 noted that the rates of recurrent
UTI were no different with a daily dose of nitrofurantoin and close
surveillance versus close surveillance alone. More research needs to
be done to evaluate this, especially due to the increasing prevalence
of antibiotic resistance. 
In patients who are immunosuppressed or have medical conditions
that would increase the risk of complications from cystitis, it is
reasonable to consider antibiotic prophylaxis after one episode of
cystitis.
Treatment of pyelonephritis
The standard course of treatment for pyelonephritis consists of
hospital admission and intravenous (IV) administration of antibiotics
until the patient has been afebrile for 48 hours. The recommended IV
antibiotic would be a broad spectrum beta-lactam, such as
ceftriaxone. Once culture results with susceptibilities become
available and the patient is clinically improved, treatment can be
transitioned to an oral antibiotic regimen.
For women with a history of extended-spectrum beta-lactamase
(ESBL) Enterobacter, carbapenem is recommended. Patients should
be discharged with 10-14 days of antibiotic treatment, and then will
need daily prophylactic antibiotics for the remainder of pregnancy.  
IV fluids must be administered with caution. Patients with
pyelonephritis can become dehydrated because of nausea and
vomiting and need IV hydration. However, they are at high risk for the
development of pulmonary edema and acute respiratory distress
syndrome (ARDS).
Fever should be managed with antipyretics (preferably,
acetaminophen) and nausea and vomiting with antiemetics. If fever
persists beyond 24 hours, urine and blood cultures should be
repeated and a renal ultrasound should be performed.
Preterm labor and delivery are additional risks associated with
pyelonephritis. These risks must be evaluated and treated early in
the course of admission with tocolysis as necessary per the preterm
labor guidelines. If the patient is septic, tocolysis is not
recommended.

Inpatient versus outpatient treatment

The prevailing view is that pregnant patients with pyelonephritis
require aggressive inpatient hydration and parenteral antibiotics.
Pyelonephritis places the patient at risk for spontaneous abortion in
early pregnancy and for preterm labor after 24 weeks’ gestation.
However, a randomized, controlled trial of outpatient treatment of
pyelonephritis in pregnancy by Millar et al concluded that outpatient
therapy is as safe and effective as inpatient care in the treatment of
pyelonephritis before 24 weeks’ gestation. [27] Benefits of outpatient
care include cost savings and the psychosocial benefits for the
patient. Risks include septic shock and respiratory insufficiency.
Consideration of outpatient therapy should be limited to selected
patients in their second trimester. More study is necessary before a
change in the physician’s practice pattern is considered. 
Antibiotic selection
Antibiotic selection should be based on urine culture sensitivities, if
known. Often, therapy must be initiated on an empirical basis, before
culture results are available. This requires clinical knowledge of the
most common organisms and their practice-specific or hospital-
specific sensitivities to medications.
Institution-specific drug resistances should also be considered before
a treatment antibiotic is chosen. For instance, with E coli infection
alone, resistance to ampicillin can be as high as 28-39%. Resistance
to trimethoprim-sulfamethoxazole has been described as 31%, and
resistance to first-generation cephalosporins may be as high as 9-
19%.
Maternal physiologic changes that influence pharmacokinetics
include increased glomerular filtration rate (GFR) and renal plasma
flow, increased volume of distribution, decreased gastric motility and
emptying, and decreased albumin levels. Serum levels of antibiotics
are lower in pregnancy because of the gross increase in blood
volume and the increased GFR.
Some antibiotics should not be used during pregnancy, because of
their effects on the fetus. These include the following:
  Tetracyclines (adverse effects on fetal teeth and bones)
  Aminoglycosides (ototoxicity following prolonged fetal
exposure)
 Fluoroquinolones; avoid during pregnancy and lactation (toxic
to developing cartilage)
 Trimethoprim-sulfamethoxazole; avoid during first and third
trimester
Fosfomycin does not achieve therapeutic levels in the kidneys and
therefore should not be used in cases of pyelonephritis. 

Nitrofurantoin is safe and effective; however, poor tissue penetration

has limited its use in pyelonephritis. Use near delivery can cause
hemolytic anemia in the fetus or neonate as a consequence of their
immature erythrocyte enzyme systems (glutathione instability).
Nitrofurantoin has also been associated with cardiac birth defects
when taken in the first trimester. [28]  Given this risk profile, use of
nitrofurantoin is best limited to the second trimester. However,
nitrofurantoin is also safe and effective for once-daily prophylactic
therapy during pregnancy. [29]
Macrolides are not first-line agents for UTI in pregnancy. However,
they are well tolerated by mother and fetus
Trimethoprim-sulfamethoxazole is a safe medication to treat UTIs
during the second trimester. Trimethoprim is a folic acid antagonist
and has been associated with an increased risk of birth defects when
taken in the first trimester during organogenesis. [28]  Sulfonamides are
avoided at term because they displace the bilirubin from its binding
site in the newborn, which give a theoretical risk of kernicterus. 
Surgical treatment
Surgical care is rarely indicated. Cystoscopy may aid in establishing
the diagnosis of urethral or bladder diverticulum, bladder stones,
urethral syndrome, lower urinary tract trauma, interstitial cystitis, or
bladder cancer.
A retrograde stent or a percutaneous nephrostomy tube should be
placed to relieve ureteral colic or decompress an obstructed infected
collecting system. More invasive procedures, such as ureteroscopic
stone extraction, [30]  are rarely indicated. Extracorporeal shock wave
lithotripsy (ESWL) is contraindicated in pregnancy.
In the rare patient for whom invasive surgical therapy is indicated, the
operation should be planned for the second trimester. Surgical
intervention during the first trimester is associated with increased risk
of miscarriage; surgery in the third trimester is associated with
increased risk of preterm labor. Urgent surgical intervention in the
third trimester should coincide with delivery of the fetus.

Medication

Medication Summary
The goals of pharmacotherapy are to eradicate the infection, reduce
morbidity, and prevent complications. Agents used include antibiotics
and analgesics.

Next: Antibiotics

Antibiotics

Nitrofurantoin (Furadantin, Macrobid, Macrodantin)

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Nitrofurantoin is a synthetic nitrofuran that interferes with bacterial
carbohydrate metabolism by inhibiting acetylcoenzyme A. It is
bacteriostatic at low concentrations (5-10 mcg/mL) and bactericidal at
higher concentrations. It is bactericidal against uropathogens such as
Staphylococcus saprophyticus, Enterococcus faecalis, and
Escherichia coli; it possesses no activity against Proteus, Serratia, or
Pseudomonas species. It received a “A-I”  rating in the 2011 IDSA
guidelines for treating UTIs.
It is manufactured in different forms to facilitate durable urine
concentrations: macrocrystals (Macrodantin), microcrystal
suspension (Furadantin), and a combined preparation (Macrobid).
This agent achieves no appreciable concentrations in the prostate,
kidney, or blood. Administer 100 mg orally twice daily for 5-7 days.

Cephalexin (Keflex)
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This is a first-generation cephalosporin that inhibits bacterial growth
by inhibiting bacterial cell wall synthesis. It is bactericidal and
effective against rapidly growing organisms forming cell walls.
Administer 500 mg orally every six hours for 5-7 days. 

Amoxicillin and clavulanate (Augmentin, Amoclan)

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Amoxicillin interferes with the synthesis of cell wall mucopeptides
during active multiplication, resulting in bactericidal activity against
susceptible bacteria. This drug combination treats bacteria normally
resistant to beta-lactam antibiotics. Administer 500/125 mg orally
every 8 hours for 5-7 days. An alternative dosing is 875/125 mg twice
daily for 5-7 days.

Amoxicillin (Moxatag)
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Amoxicillin interferes with synthesis of cell wall mucopeptides during
active multiplication, resulting in bactericidal activity against
susceptible bacteria. Administer 500 mg orally every eight hours for
5-7 days. This should not be used for empiric treatment given its poor
efficacy.
Cefuroxime (Ceftin, Zinacef)
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Cefuroxime is a second-generation cephalosporin that maintains the
gram-positive activity of first-generation cephalosporins; it adds
activity against Proteus mirabilis, Haemophilus influenzae,
Escherichia coli, Klebsiella pneumoniae, and Moraxella catarrhalis.
Administer 250 mg orally twice daily for 3-7 days

Fosfomycin (Monurol)
 View full drug information
Fosfomycin was given a "B, I" rating in the 1999 IDSA guidelines for
treating UTIs. Phosphonic acid is a bactericidal agent active against
most UTI pathogens, including Escherichia coli and Enterobacter,
Klebsiella, and Enterococcus species. Little cross-resistance
between fosfomycin and other antibacterial agents exists. It is
primarily excreted unchanged in the urine, and concentrations remain
high for 24-48 hours after a single dose. It is unique but quite
expensive. Administer 3 g orally as single dose with 3-4 oz of water

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