Urinary Tract Infections in Pregnancy 

Updated: Oct 27, 2018
Author: Emilie Katherine Johnson, MD, MPH; Chief Editor: Edward David Kim, MD, FACS 

Overview

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.

UTIs during pregnancy are 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 symptomatic UTI during pregnancy should be continued on daily prophylactic antibiotics for the duration of their pregnancy.

Annual health costs for UTI exceed $1 billion. Although the condition-specific cost of asymptomatic bacteriuria or UTI in pregnancy is unknown, screening for these conditions in pregnant women is cost-effective, compared with treating UTI and pyelonephritis without screening. Goals for future research include targeting low-income groups and women in developing countries for screening and early treatment, as well as determining whether a causal relation exists between maternal UTI and childhood neurologic consequences.

For patient education information, see the Kidneys and Urinary System Center and Pregnancy and Reproduction Center, as well as Urinary Tract Infections, Pregnancy, Bladder Control Problems, and Blood in the Urine.

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. These cases account for 70% of all cases of symptomatic UTI in unscreened pregnant women.

Acute 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% 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 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. Furthermore, women with additional risk factors (eg, immunosuppression, diabetes, sickle cell anemia, neurogenic bladder, recurrent or persistent UTIs before pregnancy) are at an increased risk for a complicated UTI.

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 and urinary stasis due to progesterone-induced ureteral smooth muscle relaxation. Blood-volume expansion is accompanied by increases in 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 and the presence of vesicoureteral reflux predispose some women to upper urinary tract infections (UTIs) and acute pyelonephritis.

Calyceal and ureteral dilatation are more common on the right side; in 86% 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 worsens throughout pregnancy. 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.

Although the influence of progesterone causes relative dilatation of the ureters, ureteral tone progressively increases above the pelvic brim during pregnancy. However, whether bladder pressure increases or decreases during pregnancy is controversial.

Glycosuria 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 resorption by the collecting tubule and loop of Henle of the 5% of the filtered glucose, which escapes proximal convoluted tubular resorption.

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.

Etiology

Infection

E coli is the most common cause of urinary tract infection (UTI), accounting for approximately 80-90% of cases. It originates from fecal flora colonizing the periurethral area, causing an ascending infection. Other pathogens include the following[2] :

  • Klebsiella pneumoniae (5%)
  • Proteus mirabilis (5%)
  • Enterobacter species (3%)
  • Staphylococcus saprophyticus (2%)
  • Group B beta-hemolytic Streptococcus (GBS; 1%)
  • Proteus species (2%)

Gram-positive organisms, particularly Enterococcus faecalis and GBS, are clinically important pathogens. 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. In a prospective study, McKenzie et al found no relation between beta-streptococcal bacteriuria and preterm labor, but they described the use of urinary antibodies to identify at-risk women.[3] In 2043 consecutive women, those with E coli antibodies at the initial visit and at 28 weeks’ gestation and women with beta-streptococcal antibodies at 28 weeks’ gestation had a significantly higher chance of preterm delivery.

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

Many women who, in the past, would have been counseled against pregnancy are now attempting pregnancy. 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.

Epidemiology

United States statistics

The frequency of urinary tract infection (UTI) in pregnant women (0.3-1.3%) is similar to that in nonpregnant women.[4] 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

  • 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

  • The 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 40% of these cases, bacteriuria may progress to symptomatic upper UTI or pyelonephritis; this rate is significantly higher than that seen in nonpregnant women.[5]

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 diabetes mellitus,[6] neurogenic bladder retention, history of vesicoureteral reflux (treated or untreated),[7] previous renal transplantation,[8] and a history of previous UTIs.

International statistics

Versi et al described a higher prevalence of bacteriuria in pregnant white women (6.3%) than in pregnant Bangladeshi women (2%).[9] 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[10] and a 2.3% rate of symptomatic UTI.[11] 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.[10] 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.[11]

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.[12]

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.

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.[13, 14] 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.[10] A prospective cohort study of pregnant patients also suggested an association between maternal UTI and childhood asthma.[15]

Preeclampsia

 A case-control study demonstrated an increased odds (1.22-fold) of preeclampsia in women with any UTI during pregnancy versus those without UTI.[16] A multicenter retrospective study found that the presence of 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.[17]

 

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, and hematuria 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 symptoms on presentation vary. They often include fever (>38°C), shaking chills, costovertebral angle tenderness, anorexia, nausea, and vomiting. Right-side flank pain is more common than left-side or bilateral flank pain. Patients may also present with hypothermia (as low as 34°C). Lower UTI symptoms are common but not universal.

Physical Examination

During the physical examination, the 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 in more than half of patients, bilaterally in one fourth, and on the left side in one fourth. 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.

Complications

The primary complication of bacteriuria during pregnancy is cystitis, though the primary morbidity is due to pyelonephritis. Other complications may include the following:

  • Perinephric cellulitis and abscess

  • Septic shock (rare)

  • Renal dysfunction (usually transient, but as many as 25% of pregnant women with pyelonephritis have a decreased glomerular filtration rate)

  • Hematologic dysfunction (common but seldom of clinical importance)

  • Hypoxic fetal events due to maternal complications of infection that lead to hypoperfusion of the placenta

  • Preeclampsia[17]

  • Premature delivery leading to increased infant morbidity and mortality

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.

 

DDx

Diagnostic Considerations

The differential diagnosis of urinary tract infection (UTI) in pregnancy includes the following:

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

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.

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

Urine Studies

Urine specimen collection

In all pregnant patients, a urine specimen should be carefully collected for urinalysis and culturing during the first prenatal visit or at 12-16 weeks’ gestation.[18] 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 on pregnant adolescents suggests that the cleansing process does not completely prevent contamination.

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.

Several methods are available for specimen evaluation; all have benefits and limitations. The clean-catch specimen reduces, but does not eliminate, the possibility of cross-contamination from the urethra and vagina. The presence of more than 1 organism in a culture usually indicates a contaminated specimen.

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. Refrigerate the specimen at 4°C if it cannot be transported immediately.

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:

  • Recurrent UTI

  • Pyelonephritis

  • Failure to respond to initial treatment regimens

  • History of recent instrumentation

  • Hospital admission

Two consecutive voided specimens with isolation of the same bacterial strain, at a colony count of 100,000 colony-forming units (CFUs) per milliliter or higher, has historically been used to define a positive culture result. A single catheterized specimen yielding a colony count of at least 100 CFU/mL is also diagnostic.[19] Counts lower than 100,000 CFU/mL, with 2 or more organisms, 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. Urine culture has an average cost of approximately $40. Results are often unavailable at the time of treatment.

Urinalysis

Positive results for nitrites, leukocyte esterase, WBCs, red blood cells (RBCs), and protein suggest UTI. Bacteria found in the specimen can help with the diagnosis.

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.

Millar and Cox indicate that 1-2 bacteria in an unspun catheterized specimen or more than 20 bacteria per high-power field (HPF) in spun urine correlate closely with bacterial colony counts higher than 100,000 CFU/mL on a urine culture.[20]

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.

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.[21]

Other tests

Urine cytology may be a useful adjunct in detecting upper tract UTIs.

An antistreptolysin-O (ASO) titer greater than 200 Todd units suggests recent group A streptococcal infection; however, as many as 20% of patients with acute glomerulonephritis have ASO titers within the reference range.

The sulfosalicylic acid (SSA) test measures urine turbidity when a small amount of aspirin is added to the urine specimen. A finding of +2 to +4 suggests bacteriuria.

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 also undergo imaging.

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 o 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.
Color-flow Doppler highlights normal flow in right 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.
25-year-old pregnant woman with right lower quadra 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.

Urolithiasis and pyelonephritis have many symptoms in common (eg, hematuria, flank pain, shaking chills, anorexia). Urolithiasis is usually not associated with fever, except in patients 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.

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 and 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.

 

Treatment

Approach Considerations

Treatment of bacteriuriaand cystitis

Because of the dangers of maternal and fetal complications, acute care (eg, in the emergency department [ED]) 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.[22] ED care may involve the following:

  • Administration of appropriate antibiotics
  • Administration of fluid if the patient is dehydrated
  • Admission if any indication of complicated UTI exists

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. Appropriate oral regimens include the following:

  • Cephalexin 500 mg 4 times daily
  • Ampicillin 500 mg 4 times daily
  • Nitrofurantoin 100 mg twice daily
  • Sulfisoxazole 1 g 4 times daily

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. Fosfomycin, a phosphonic acid derivative, is useful in the treatment of uncomplicated UTIs caused by susceptible strains of E coli and Enterococcus species. Fosfomycin is a US Food and Drug Administration (FDA) category B agent in pregnancy (ie, animal studies have not demonstrated a risk to the fetus and there are no adequate and well-controlled studies in pregnant women).

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.[23]

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 therapy. A nonnegative culture result is an indication for a 10- to 14-day course of a different antibiotic, followed by suppressive therapy (eg, nitrofurantoin 50 mg at bedtime) until 6 weeks postpartum.

Mathai et al suggest the need for disseminated guidelines for practitioners in developing countries such as India.[24] Their study documented inappropriate use of antibiotics in terms of safety, cost, susceptibility, and threat for developing resistance.

Treatment of pyelonephritis

The standard course of treatment for pyelonephritis consists of hospital admission and intravenous (IV) administration of cephalosporins or gentamicin. 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. Most antiemetics can be used for adverse effects caused by antibiotics, but doxylamine, Emetrol (Wellspring, Sarasota, FL; pregnancy class A), dimenhydrinate, and metoclopramide (pregnancy class B) are preferred.

Preterm labor and delivery are additional risks associated with pyelonephritis. These risks must be evaluated and treated early in the course of admission.

In a randomized, controlled trial of outpatient treatment of pyelonephritis in pregnancy, Millar et al concluded that outpatient therapy is as safe and effective as inpatient care in the treatment of pyelonephritis before 24 weeks’ gestation.[25] However, the prevailing view is still that aggressive inpatient hydration and parenteral antibiotics are necessary. Pyelonephritis places the patient at risk for spontaneous abortion in early pregnancy and for preterm labor after 24 weeks’ gestation.

In their study, Millar et al treated outpatients with 2 doses of intramuscular (IM) ceftriaxone and 10 days of oral cephalexin.[25] Initial outpatient therapy and traditional inpatient therapy failed to cure equal numbers of patients. Benefits include the obvious cost savings and the psychosocial benefits for the patient. Risks include septic shock and respiratory insufficiency at home during outpatient therapy.

Strict guidelines for an observation period before ED discharge, patient education, and home nursing have been discussed. In addition, approximately two thirds of the outpatient treatment group did not complete the study because the subjects developed 1 or more complications.[25] If outpatient therapy is considered, only selected patients in their second trimester should be considered. 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 and congenital defects)

  • Trimethoprim in the first trimester (facial defects and cardiac abnormalities)

  • Chloramphenicol (gray syndrome)

  • Sulfonamides in the third trimester (hemolytic anemia in mothers with glucose-6-phosphate dehydrogenase [G6PD] deficiency, jaundice, and kernicterus)

Fluoroquinolones are to be used with caution in pregnancy. Both ciprofloxacin and levofloxacin have been assigned pregnancy category C by the FDA (fetal risk is not confirmed by human studies but has been shown in some animal studies). Although not a first-line option for treatment of UTI in pregnancy, in certain clinical situations the benefits of using a fluoroquinolone may outweigh the risks to the developing fetus.

Risks to the mother from fluoroquinolones must also be considered. In May 2016 the FDA advised that the risks of fluoroquinolones generally outweigh the benefits for patients with uncomplicated infections, including UTIs, and recommended reserving fluoroquinolones for patients who do not have alternative treatment options. Disabling and potentially permanent serious adverse effects associated with fluoroquinolones have involved tendons, muscles, joints, nerves, and the central nervous system.[26]

Nitrofurantoin is safe and effective; however, poor tissue penetration has limited its use in pyelonephritis. In the past, nitrofurantoin was completely avoided in the third trimester because of hemolytic effects on the newborn. Currently, restriction of this agent is limited to the last several weeks of pregnancy. Use during this period can cause hemolytic anemia in the fetus or neonate as a consequence of their immature erythrocyte enzyme systems (glutathione instability). Nitrofurantoin is also safe and effective for once-daily prophylactic therapy during pregnancy.[27]

Macrolides are not first-line agents for UTI in pregnancy. However, they are well tolerated by mother and fetus. 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.[28, 23] 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 regimens are summarized in Table 1 below.

Table. Treatment Regimens for Pregnant Women with UTI (Open Table in a new window)

First-line therapy

  • Nitrofurantoin monohydrate/macrocrystals 100 mg orally twice daily for 5-7 days or

  • Amoxicillin 500 mg orally twice daily (alternative: 250 mg orally three times daily) for 5-7 days or

  • Amoxicillin-clavulanate 500/125 mg orally twice daily for 3-7 days (alternative: 250/125 mg orally three times daily for 5-7 days) or

  • Cephalexin 500 mg orally twice daily for 3-7 days

Second-line therapy

  • Fosfomycin 3 g orally as single dose with 3-4 oz. of water

Surgical treatment

Surgical care is rarely indicated, unless one of the pathologic causes listed in the differential diagnoses is suspected.

In patients with urethral or bladder diverticulum, bladder stones, urethral syndrome, lower urinary tract trauma, interstitial cystitis, or bladder cancer, cystoscopy may aid in establishing the diagnosis.

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,[29] 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 miscarriage; surgery in the third trimester is associated with 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.

Antibiotics

Nitrofurantoin (Furadantin, Macrobid, Macrodantin)

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 "B, I" rating in the 1999 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)

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 twice daily for 3-7 days.

Amoxicillin and clavulanate (Augmentin, Amoclan)

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 twice daily for 3-7 days.

Amoxicillin (Moxatag)

Amoxicillin interferes with synthesis of cell wall mucopeptides during active multiplication, resulting in bactericidal activity against susceptible bacteria. Administer 500 mg orally twice daily for 5-7 days.

Cefuroxime (Ceftin, Zinacef)

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)

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

 

Questions & Answers

Overview

Which factors increase the risk of urinary tract infection (UTI) during pregnancy?

Why is the risk of serious complications of urinary tract infection (UTI) increased during pregnancy?

What are the treatment options for urinary tract infection (UTI) during pregnancy?

What is the economic burden of urinary tract infection (UTI)?

Where can patient education information be found regarding urinary tract infection (UTI) during pregnancy?

How are urinary tract infections (UTIs) defined?

What risks are increased with asymptomatic bacteriuria during pregnancy?

What are the signs and symptoms of acute cystitis during pregnancy?

What are the signa and symptoms of acute pyelonephritis during pregnancy?

What is the pathogenesis of urinary tract infection (UTI) during pregnancy?

What is the role of calyceal and ureteral dilation in the pathogenesis of urinary tract infection (UTI) during pregnancy?

What is the role of bladder pressure in the pathogenesis of urinary tract infection (UTI)?

What is the role of glucose in the pathogenesis of urinary tract infection (UTI)?

What is the role of amino acids in the pathogenesis of urinary tract infection (UTI) during pregnancy?

Which pathogens cause urinary tract infection (UTI) during pregnancy?

Which pathogens are clinically significant in urinary tract infection (UTI) during pregnancy?

What is the role of urea-splitting bacteria in the etiology of urinary tract infection (UTI) during pregnancy?

Why should all pregnancy women be screened for group B beta-hemolytic Streptococcus (GBS) colonization?

What is the incidence of urinary tract infection (UTI) following cesarean delivery?

How should women with orthotopic continent urinary diversion be managed during pregnancy?

What is the frequency of urinary tract infection (UTI) during pregnancy in the US?

Why are urinary tract infections (UTIs) more common in women than in men?

How does the prevalence of urinary tract infection (UTI) differ between pregnant and nonpregnant women in the US?

What are the risk factors for bacteriuria during pregnancy?

Why is the prevalence of urinary tract infection (UTI) during pregnancy thought to be higher among white women?

What is the incidence of urinary tract infection (UTI) in pregnant Israeli women?

How does age affect the prevalence of urinary tract infection (UTI) during pregnancy?

How does the prevalence of urinary tract infection (UTI) vary among racial and ethnic groups?

What is the prognosis of urinary tract infection (UTI) during pregnancy?

How does maternal urinary tract infection (UTI) affect the fetus?

What is the morbidity of untreated upper urinary tract infection (UTI) during pregnancy?

How does preeclampsia effect the risk of urinary tract infection (UTI) during pregnancy?

Presentation

Which factors affect the presentation of urinary tract infection (UTI) during pregnancy?

What is the most significant symptom of cystitis in pregnant women?

What are the signs and symptoms of pyelonephritis during pregnancy?

How does the duration of pregnancy affect the physical findings of urinary tract infection (UTI)?

Which physical findings are characteristic of asymptomatic bacteriuria during pregnancy?

When is pelvic exam indicated to evaluate suspected urinary tract infection (UTI) during pregnancy?

Which physical findings are characteristic of pyelonephritis during pregnancy?

When is fetal heart rate assessed in the physical exam of maternal urinary tract infection (UTI)?

What are possible complications of urinary tract infection (UTI)?

What causes pulmonary injury in pregnant women with urinary tract infection (UTI)?

DDX

Which conditions should be included in the differential diagnoses of urinary tract infection (UTI) during pregnancy?

Which disorders may be considered in the differential diagnosis of urinary tract infection (UTI)?

How are vaginal infections differentiated from urinary tract infections (UTIs) in pregnant women?

Workup

Which lab studies are performed in the workup of urinary tract infection (UTI) during pregnancy?

Which imaging studies are performed in the workup of urinary tract infection (UTI) during pregnancy?

What is the role of blood tests in the diagnosis of urinary tract infection (UTI) during pregnancy?

What is the role of urine testing in the diagnosis of urinary tract infection (UTI) during pregnancy?

What is the technique for urine collection in the evaluation of urinary tract infection (UTI) during pregnancy?

When should a catheterized specimen be collected for the diagnosis of urinary tract infection (UTI) during pregnancy?

How are urine specimens evaluated in the diagnosis of urinary tract infection (UTI) during pregnancy?

What is the role of urine culture in the diagnosis of urinary tract infection (UTI)?

How are urinary tract infections (UTIs) diagnosed during pregnancy?

How are culture results used for the management of urinary tract infection (UTI) during pregnancy?

Which urinalysis results suggest urinary tract infection (UTI) during pregnancy?

What is the role of dipstick testing in the diagnosis of urinary tract infection (UTI) during pregnancy?

What is the role of urine cytology in the diagnosis of urinary tract infection (UTI) during pregnancy?

What is the role of an antistreptolysin-O (ASO) titer measurement in the diagnosis of urinary tract infection (UTI) during pregnancy?

How is a sulfosalicylic acid (SSA) test used for the diagnosis of urinary tract infection (UTI) during pregnancy?

What is the role of imaging studies in the diagnosis of urinary tract infection (UTI) during pregnancy?

What is the role of renal ultrasonography in the diagnosis of urinary tract infection (UTI) during pregnancy?

How are urolithiasis and pyelonephritis differentiated in pregnancy?

How is urolithiasis managed during pregnancy?

What is the role of ultrasonography in the management of urolithiasis during pregnancy?

What are the limits for ionizing radiation in the diagnosis of urinary tract infection (UTI) during pregnancy?

What are the findings on renal ultrasonography suggestive of urinary tract infection (UTI) during pregnancy?

What are the histologic findings characteristic of urinary tract infection (UTI) during pregnancy?

Treatment

What is the focus of acute care of urinary tract infection (UTI) in pregnant women?

What is included in the emergency department (ED) care of pregnant women with urinary tract infection (UTI)?

Which behavioral measures are used in the management of urinary tract infection (UTI) during pregnancy?

What are oral regimens used for the treatment of urinary tract infection (UTI) during pregnancy?

What is the role of fosfomycin in the treatment of urinary tract infection (UTI) during pregnancy?

What is the optimal duration of antibiotic therapy for the treatment of urinary tract infection (UTI) during pregnancy?

How is treatment success determined for urinary tract infection (UTI) during pregnancy?

What are the treatment options for pyelonephritis in pregnant patients?

How is fever managed in pregnant patients with pyelonephritis?

What are delivery risks associated with pyelonephritis during pregnancy?

What are the differences in efficacy between outpatient and inpatient care of pyelonephritis during pregnancy?

Which patients should be considered for outpatient treatment of pyelonephritis during pregnancy?

What is the basis for antibiotic selection for the treatment of urinary tract infection (UTI) during pregnancy?

What is the significance of institution-specific drug resistances in the treatment of urinary tract infection (UTI) during pregnancy?

Which physiologic changes during pregnancy influence antibiotic selection for urinary tract infection (UTI)?

Which antibiotics are contraindicated for the treatment of urinary tract infection (UTI) during pregnancy?

What is the role of fluoroquinolones in the management of urinary tract infection (UTI) during pregnancy?

What are the risks of using fluoroquinolones to treat urinary tract infection (UTI) during pregnancy?

What is the role of nitrofurantoin in the treatment of urinary tract infection (UTI) during pregnancy?

What is the role of macrolides in the treatment of urinary tract infection (UTI) during pregnancy?

When is surgical care indicated for the treatment of urinary tract infection (UTI) during pregnancy?

Which factors may aid in establishing the diagnosis of urinary tract infection (UTI) during pregnancy?

What is the role of a retrograde stent in the treatment of urinary tract infection (UTI) during pregnancy?

During which trimester is surgery performed for the treatment of urinary tract infection (UTI)?

Medications

What are the goals of drug treatment for urinary tract infection (UTI)?

Which medications in the drug class Antibiotics are used in the treatment of Urinary Tract Infections in Pregnancy?