Continuing Education Activity

Urinary tract infections (UTIs) are frequently encountered in pregnant women. Pyelonephritis is the most common serious medical condition seen in pregnancy and may present similarly and may even result from inadequate treatment of urinary tract infections. Thus, it is crucial for providers to be able to distinguish normal versus abnormal findings of both the urinary tract and kidneys, evaluate abnormalities, and treat disease. Fortunately, urinary tract infections in pregnancy are usually easy to treat and respond well to treatment. This activity reviews the evaluation and management of urinary tract infection in pregnancy and highlights the role of interprofessional team members in collaborating to provide well-coordinated care and enhance outcomes for affected patients.

Objectives:

• Identify the etiology of urinary tract infections pregnancy.
• Explain how to diagnose urinary tract infections in pregnant patients.
• Summarize the treatment options available for urinary tract infections in pregnant patients.
• Review interprofessional team strategies for improving care and outcomes in pregnant patients with urinary tract infections.

Introduction

Urinary tract infections (UTIs) are frequently encountered in pregnant women. Pyelonephritis is the most common serious medical condition seen in pregnancy. Thus, it is crucial for providers of obstetric care to be knowledgeable about normal findings of the urinary tract, evaluation of abnormalities, and treatment of disease. Fortunately, UTIs in pregnancy are most often easily treated with excellent outcomes. Rarely, pregnancies complicated by pyelonephritis will lead to significant maternal and fetal morbidity.

Changes of the urinary tract and immunologic changes of pregnancy predispose women to urinary tract infection. Physiologic changes of the urinary tract include dilation of the ureter and renal calyces; this occurs due to progesterone-related smooth muscle relaxation and ureteral compression from the gravid uterus. Ureteral dilation may be marked. Decreased bladder capacity commonly results in urinary frequency. Vesicoureteral reflux may be seen. These changes increase the risk of urinary tract infections.

Etiology

During pregnancy, urinary tract changes predispose women to infection. Ureteral dilation is seen due to compression of the ureters from the gravid uterus.  Hormonal effects of progesterone also may cause smooth muscle relaxation leading to dilation and urinary stasis, and vesicoureteral reflux increases. The organisms which cause UTI in pregnancy are the same uropathogens seen in non-pregnant individuals. As in non-pregnant patients, these uropathogens have proteins found on the cell-surface which enhance bacterial adhesion leading to increased virulence. Urinary catheterization, frequently performed during labor, may introduce bacteria leading to UTI. In the postpartum period, changes in bladder sensitivity and bladder overdistention may predispose to UTI.

Pregnancy is a state of relative immunocompromise. This immunocompromise may be another cause for the increased frequency of UTIs seen in pregnancy.

Epidemiology

The most significant factor predisposing women to UTI in pregnancy is asymptomatic bacteriuria (ASB). ASB is defined as more than 100,000 organisms/mL on a clean catch urinalysis obtained from an asymptomatic patient. If asymptomatic bacteriuria is untreated in pregnancy, the rate of subsequent UTI is approximately 25%.[1] Due to both to the high rate and potential seriousness of pyelonephritis, it is recommended that all pregnant women be screened for ASB at the first prenatal visit. This is most often done with a clean catch urine culture. Treatment of ASB decreases the rate of clinical infection to 3% to 4%.  

The rate of asymptomatic bacteriuria in non-pregnant women is 5% to 6% which compares similarly to estimated rates in pregnancy of 2% to 7%. ASB is seen more frequently in parous women and women of low socioeconomic status. Women who are carriers for sickle cell trait also have a higher incidence of ASB.[1]

UTIs are a common cause of serious infection in pregnant women. In one study, 3.5% of antepartum admissions were due to UTI.[2] Pyelonephritis is the most common cause of septic shock in pregnant women. Risk factors for UTIs in pregnancy include low socioeconomic status, young age, and nulliparity. As with ASB some patients may be predisposed to infection and may report a history of having had ASB, cystitis or pyelonephritis in the past. Pyelonephritis is more often right-sided however may be bilateral in up to 25% of cases.

Pathophysiology

Organisms causing UTI in pregnancy are the same uropathogens which commonly cause UTI in non-pregnant patients. Escherichia coli is the most common organism isolated. An 18-year retrospective analysis found E. coli to be the causative agent in 82.5% of cases of pyelonephritis in pregnant patients.[3] Other bacteria which may be seen include Klebsiella pneumoniae, Staphylococcus, Streptococcus, Proteus, and Enterococcus species.

History and Physical

Patients with asymptomatic bacteriuria have no symptoms; thus, it is important to screen for the disease. These patients may have a history of frequent UTI or may have experienced ASB in a prior pregnancy.  

Cystitis presents with the same symptoms seen in non-pregnant individuals. Symptoms may include pain or burning with urination (dysuria), urinary frequency or urinary urgency. Suprapubic pain and tenderness may be noted.

Likewise, patients with pyelonephritis exhibit symptoms seen in non-pregnant patients with the same disease. Symptoms may include flank pain, fever, and chills. Non-specific symptoms such as malaise, anorexia, nausea, and vomiting may be reported thus the differential diagnosis on initial presentation is often broad. Differential diagnosis includes acute intraabdominal processes such as appendicitis, cholecystitis, and pancreatitis as well as pregnancy complications including preterm labor and placental abruption. Patients may report contractions or contractions may be seen with uterine monitoring. This uterine activity often is due to smooth muscle irritability caused by infection. Patients should be assessed, and if cervical dilation is not found, treatment is typically not needed for preterm labor. Patients should be monitored closely however as preterm labor may develop.

Signs and symptoms of sepsis may be present. These include tachycardia and hypotension. Such patients require prompt evaluation and interventions.

A full physical examination should be performed with special attention to vital signs and exam of the heart and lungs. An abdominal exam may reveal tenderness, and costovertebral tenderness is usually able to be elicited. A genitourinary (GU) exam should be performed to assess for cervical infection and assess cervical dilation on admission. Even when pregnancy complications are not a concern initially, it is still reasonable to evaluate if contractions or other abnormalities occur during hospitalization.

Evaluation

Evaluation will include urinalysis and clean catch urine culture. In the collection of urinary specimens in pregnancy a few considerations are noteworthy. Patients who are well hydrated may excrete dilute urine rendering some assessed parameters to be less accurate. Hematuria may be seen as a result of contamination, particularly when specimens are collected from laboring or postpartum patients. Due to reduced reabsorption of protein, small amounts of protein may normally be excreted. Contamination, as may occur with mucous discharge, may also contribute to the presence of proteinaceous material in the urine of pregnant women.

Laboratory analysis should include complete blood count (CBC), electrolytes and serum creatine. Tailored studies should be included as appropriate to exclude other causes of patient symptoms, for example, amylase and lipase if pancreatitis is being considered as a diagnosis. If there is a concern for sepsis lactic acid and blood cultures should be obtained. All cultures should be obtained as soon as possible and before starting antibiotic therapy.

When the fetus is viable, fetal heart rate and contraction monitoring should occur. Consideration should be given to obtaining cervical and GBS cultures on admission if pregnancy-related complications develop.  Infrequently, renal ultrasound may be indicated to assess for a possible renal abscess.

Treatment / Management

ASB and acute cystitis are treated with antibiotic therapy. Antibiotic choice can be tailored based on organism sensitivities when available from urine culture results. One-day antibiotic courses are not recommended in pregnancy, although 3-day courses are effective.[4] Antibiotics commonly used include amoxicillin, ampicillin, cephalosporins, nitrofurantoin, and trimethoprim-sulfamethoxazole.  Fluoroquinolones are not recommended as a first-line treatment in pregnancy due to conflicting studies regarding teratogenicity. Short courses are unlikely to be harmful to the fetus, and thus, it is reasonable to use this class of drugs with resistant or recurrent infections.

Recently evidence has developed suggesting a link between the use of sulfa derivatives and nitrofurantoin and congenital disabilities when these medications are prescribed in the first trimester. These studies have had limitations; however, it is currently recommended to avoid the use of these medications in the first trimester when alternatives are available.[5] Because the potential consequences of untreated UTI in pregnancy are significant, it is reasonable to use these medications when needed as the benefit strongly outweighs the risk of use. Additional cautions exist with respect to these 2 classes of antibiotics. Patients with G6P deficiency should not be prescribed sulfa derivatives or nitrofurantoin as these medications can precipitate hemolysis. In the late third trimester, trimethoprim-sulfamethoxazole should be avoided due to the potential risk for development of kernicterus in the infant following delivery.

If Group B Streptococcus  (GBS) is noted on urine culture, patients should receive intravenous (IV) antibiotic therapy at the time of delivery in addition to indicated treatment for ASB or UTI. This is to prevent the development of early-onset GBS sepsis which may occur in the infants of women who are colonized with GBS.

Pyelonephritis in pregnancy is a serious condition usually requiring hospitalization. Once an evaluation has been completed, treatment consists primarily of directed antibiotic therapy and IV fluids to maintain adequate urine output. Fever should be treated with a cooling blanket and acetaminophen as needed. Commonly, second or third generation cephalosporins are used for initial treatment. Ampicillin and gentamicin or other broad-spectrum antibiotics are alternatives. Patients should be monitored closely for the development of worsening sepsis.

Differential Diagnosis

Differential diagnosis includes acute intraabdominal disease such as appendicitis, pancreatitis, or cholecystitis as well as pregnancy-related complications such as preterm labor, chorioamnionitis, or placental abruption.

Complications

Patients with pyelonephritis are at risk for several significant complications.

Sepsis may worsen resulting in hypotension, tachycardia, and decreased urine output. ICU admission may be required.

Pulmonary complications are not uncommon, occurring in up to 10% of pregnant patients undergoing treatment for pyelonephritis.[4] This is due to endotoxin-mediated alveolar damage and may manifest as pulmonary edema or acute respiratory distress syndrome (ARDS).  Urine output and oxygen status should be monitored closely, and patients may require ICU admission for respiratory support.

Endotoxin release may lead to anemia, this typically resolves spontaneously following treatment. This is the most common complication seen with pyelonephritis occurring in up to 25% of patients.[3]

Endotoxin release may also cause uterine contractions and patients should be monitored for preterm labor; patients should be treated for preterm labor when indicated. Caution should be exercised in use of tocolytic therapy as the risk of pulmonary edema is increased in the setting of UTI.

A small number of patients may experience persistent infection. In these cases, consideration should be given to urinary obstruction or renal abscess. Antibiotic choice should be re-evaluated and culture results reviewed.

Deterrence and Patient Education

After 2 to 4 weeks following completion of treatment, urine culture should be obtained to assure that reinfection has not occurred.

Suppressive antibiotic therapy, usually with nitrofurantoin once daily, is commonly recommended especially in cases where patients have had prior UTI. This is typically continued thru pregnancy and the early postpartum period.

Enhancing Healthcare Team Outcomes

Interprofessional collaboration is crucial in the management of these ill patients. With the administration of antibiotics patients may show initial worsening due to the release of endotoxin, however, most patients improve within 72 hours. Long-term complications such as renal damage are rare.