AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
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INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Background

Pregnancy causes numerous changes in the body of a woman. Hormonal and mechanical changes increase the risk of 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, increase the frequency of urinary tract infections (UTIs) in pregnant women.

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 per milliliter of urine with accompanying pyuria (>7 WBCs/mL) in a symptomatic patient. Particularly in asymptomatic patients, a diagnosis of UTI should be supported by a uropathogen found in the culture.

Two clinical entities are recognized in patients with symptomatic UTI: lower UTI (ie, cystitis) and upper UTI (ie, pyelonephritis). In general, pregnant patients are considered immunocompromised UTI hosts because of the physiologic changes associated with pregnancy, increasing the risk of serious infectious complications from symptomatic and asymptomatic urinary infections in a healthy pregnant woman. These changes are discussed in Pathophysiology.

Asymptomatic bacteriuria (ASB) is commonly defined as the presence of more than 100,000 organisms per milliliter in 2 consecutive urine samples in the absence of declared symptoms. Untreated ASB 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 among unscreened pregnant women.

Acute cystitis involves only the lower urinary tract; it is characterized by inflammation of the bladder due to bacterial or nonbacterial causes (ie, radiation, viral). 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. 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 (immunosuppression, diabetes, sickle cell anemia, neurogenic bladder, recurrent or persistent UTIs prior to pregnancy) are at an increased risk of a complicated UTI.

Vaginal infections can cause or mimic UTIs, which are common in women of reproductive years, affecting 25-35% of women aged 20-40 years. The main method of discriminating between the two depends on vaginal and urinary cultures.

Annual health costs for UTI exceed $1 billion. Although the condition-specific cost of ASB or UTI in pregnancy is unknown, screening for ASB and UTI in pregnant women has been shown to be cost-effective compared with treating UTI and pyelonephritis without screening.

Pathophysiology

The physiologic changes during pregnancy predispose such women to bacteriuria. These physiological changes include urinary retention caused by the weight of the enlarging uterus and urinary stasis due to ureteral smooth muscle relaxation (caused by increases in progesterone). 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. In addition, glucosuria and aminoaciduria during pregnancy provide an excellent culture medium for bacteria in areas of urine stasis.

Escherichia coli infection is the most common cause of UTI, accounting for 80-90% of cases. It originates from fecal floras that colonize the periurethral area (ascending infection). Klebsiella, Enterobacter, and Proteus species cause most of the remaining cases. Gram-positive organisms, particularly Enterococcus faecalis and group B Streptococcus (GBS), are also clinically important pathogens. Infection with Staphylococcus saprophyticus, an aggressive community-acquired organism, can cause upper urinary tract disease, and the infection is more likely to be persistent or recurrent.

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.

Urea-splitting bacteria, including Proteus, Klebsiella, Pseudomonas, and coagulase-negative Staphylococcus, alkalinize the urine and may be associated with struvite stones.

Frequency

United States

The prevalence of ASB in pregnant women is 2.5-11% (as opposed to 3-8% in nonpregnant women). Risk factors include increases age, low socioeconomic status, sexual activity, multiparity, and untreated pathologies.

The frequency of UTI in pregnant women (0.3-1.3%) is similar to that in nonpregnant women. Changes in coital patterns (eg, position, frequency, postcoital antibiotics) can offset recurrence in at-risk individuals. However, Leigh and colleagues (1990) reported a 34% rate of symptomatic bacteriuria in women during the first 5 days following cesarean delivery that may be due to catheterization or prolonged rupture of membranes (PROM).¹

Parkland hospital reported a reduction in cases of acute pyelonephritis (from 4% to 1-2%) after implementing a screening and treatment program for ASB in pregnant women. Residual cases occur in unscreened women (ie, lack of prenatal care) or in women with recurrences. The incidence is increased in the puerperium to approximately 8%.

Women with risk factors have the additional risks of a first, recurrent, or persistent UTI. These women should undergo more frequent screenings. Risk factors include diabetes mellitus, including gestational diabetes; urologic abnormalities (eg, neurogenic bladder, duplicated collecting systems); prepregnancy and antepartum history of UTI prior to initiation of prenatal care (ie, 2-3 culture-proven UTIs/y); and sickle cell hemoglobinopathy. Regarding sickle cell hemoglobinopathy, many have long thought that pyelonephritis was more common in sickle cell trait carriers (both pregnant and nonpregnant persons); however, in 2006, Thurman et al suggested that increased urinary testing did not decrease the incidence of pyelonephritis in pregnant women who carried the sickle cell trait.²

International

Versi and colleagues (1997) described a higher prevalence of bacteriuria in pregnant white women (6.3%) than in pregnant Bangladeshi women (2%).³ Pregnancies that resulted in preterm deliveries were strongly associated with bacteriuria in white women; this was not observed Bangladeshi women. The authors hypothesized that the difference could be due to differences in hygiene practices and clothing.

Mortality/Morbidity

The primary complication of bacteriuria during pregnancy is cystitis, although overt pyelonephritis occurs in 25-30% of cases. Septic shock, respiratory failure, and death are reported. Hypoxic fetal events can occur because of maternal complications that lead to hypoperfusion of the placenta (eg, hypotension due to dehydration or septic shock, maternal anemia, maternal hypoxemia). Refer to Complications for further discussion.

The American College of Obstetricians and Gynecologists recommend urine culture screening for all pregnant women at their first prenatal visit.⁴

Race

• A retrospective analysis of 24,000 births indicates that the prevalence of UTI during pregnancy is 28.7% in whites and Asians, 30.1% in blacks, and 41.1% in Hispanics.
• UTI is associated with preterm delivery in 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 (BMI), 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.

Sex

These infections occur in pregnant women.

Age

The prevalence of UTI during pregnancy increases with age.

CLINICAL

Section 3 of 11  

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History

Patients with urinary tract infections (UTIs) may not have overt urinary tract symptoms. Symptomatology can be divided into lower urinary tract symptoms and upper urinary tract symptoms.

Lower urinary tract symptoms include dysuria, frequency, urgency, suprapubic pain, and hematuria in the absence of systemic symptoms. Frequency is difficult to characterize in pregnancy since most women urinate more frequently as a normal consequence of expanding blood volume, increased glomerular filtration rate, and increased renal blood flow.

Upper urinary tract symptoms include fever, chills, flank pain, nausea, and vomiting. Patients may also have lower UTI symptoms.

• Asymptomatic bacteriuria: ASB (2-7% of pregnancies) is characterized by bacteriuria in the urine without clinical signs or symptoms of infection. In pregnant women, it is usually found on random urine screening.
• Cystitis: This manifests as symptoms of dysuria, urgency, urge incontinence, and frequency. A positive result on urine culture or urine dipstick usually shows leukocyte esterase, nitrite, and hematuria and may show some protein. Additional symptoms may consist of lower abdominal pain or suprapubic tenderness.
• Pyelonephritis: The symptoms on presentation vary. Symptoms often include fever (>38°C), shaking chills, costovertebral angle tenderness, anorexia, nausea, and vomiting. Right-sided flank pain is more common than left or bilateral flank pain. Patients may also present with hypothermia (as low as 34°C).

Physical

During the physical examination, the findings should be considered in relation to the patient’s current duration of pregnancy. The differential diagnoses may change in each trimester, and the increasing size of the gravid uterus may mask or mimic findings.

• Asymptomatic bacteriuria
• • Often, no physical findings are present.
  • Symptoms may arise intermittently, only to be overlooked because of lack of persistence or severity.
• Cystitis: Patients may have suprapubic tenderness upon palpation. Tenderness can be elicited with isolation of the bladder on pelvic examination.
• Pyelonephritis
• • Patients have fever (usually >38°C), flank tenderness upon palpation, and an ill appearance. Flank tenderness is right-sided in more than half of patients, bilateral in one fourth of patients, and left-sided in one fourth of patients. Pain may also be found suprapubically with palpation.
  • Based on gestational age, include fetal heart rate as part of the evaluation. Often, owing to maternal fever, the fetal heart rate is elevated to more than 160 beats per minute.

Causes

• The most common uropathogen in the pregnant patient is E coli. This organism is isolated in 80-85% of cultures.
• Other pathogens include the following:
• • Klebsiella pneumoniae (5%)
  • Proteus mirabilis (5%)
  • Enterobacter species (3%)
  • S saprophyticus (2%)
  • Group B beta-hemolytic Streptococcus (1%)
• Infections result from ascending colonization of the urinary tract. The primary source of organisms is existing vaginal, perineal, and fecal flora.
• Various maternal physiologic factors predispose to ascending infection.
• • The smooth-muscle–relaxation properties of progesterone and mechanical obstruction by an enlarging uterus cause dilatation of the renal calices, pelves, and ureters, leading to urinary stasis and potentiating infection. Calyceal and ureteral dilatation are more common on the right side; in 86% of cases, the dilatation is localized on the right side. The degree of calyceal dilatation is also more pronounced on the right than the left (15 mm vs 5 mm). This dilatation appears to begin by about 10 weeks' gestation and worsens throughout pregnancy (see Images 1-2). This is underscored by the percentage 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 urine amino acids during pregnancy are additional factors that lead to UTI. Glucose excretion increases in pregnancy by 100-fold over nonpregnant values of 100 mg/d. 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 E coli to the urothelium.

DIFFERENTIALS

Section 4 of 11  

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Other Problems to be Considered

Bacteriuria
Glomerulonephritis
Group B streptococci colonization
Threatened or incomplete miscarriage
Urge incontinence

WORKUP

Section 5 of 11  

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Lab Studies

• Urine specimen collection
• • Obtain a midstream, clean-catch urine specimen from all patients with urinary tract symptoms. Collect a catheterized specimen from patients who are unable to provide a clean-catch specimen. 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 one organism in a culture usually indicates a contaminated specimen.
  • Send the specimen 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
• • This is the criterion standard for evaluation of a urinary tract infection (UTI) during pregnancy. A urine culture should be obtained upon admission from patients with pyelonephritis and from those with recurrent infection or those who are not responding to initial treatment regimens.
  • A colony count of 100,000 colony-forming units (CFUs) per milliliter has historically been used to define a positive culture result. Powers has reported a true positive result on culture may have as low as 100 CFUs per milliliter of bacteria.
  • 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, RBCs, and protein suggest UTI. Bacteria found in the specimen can help with the diagnosis.
  • Urinalysis has a specificity of 97-100%, but its sensitivity ranges from 25-67% when compared to culture in the diagnosis of asymptomatic bacteriuria (ASB).
  • Millar and Cox (1997) indicate that 1-2 bacteria in an unspun catheterized specimen or more than 20 bacteria per high-power field in spun urine correlate closely with more than 100,000 CFUs per milliliter of bacteria on a urine culture.⁵
• Urine dip
• • Several reports describe the use of urine dip for nitrites and leukocyte esterase in the evaluation of ASB.
  • Sensitivities range from 50-92%, and specificity is 86-97% when compared with culture in the diagnosis of ASB.
  • In the evaluation of symptomatic patients, this is a useful and inexpensive test.
  • The addition of protein and blood increases the sensitivity and specificity of the test in the evaluation of UTI.

Imaging Studies

Routine imaging studies are not indicated in the evaluation of pregnancy-related UTI.

• 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 UTI or symptoms that suggest nephrolithiasis (see Images 1-4). Urolithiasis and pyelonephritis share many common symptoms (ie, hematuria, flank pain, shaking chills, anorexia). Urolithiasis is usually unassociated with fever except in patients with concomitant pyelonephritis.
• Confusion about the diagnosis of urolithiasis, pyelonephritis, or both is an indication for obtaining imaging studies.
• • Urolithiasis offers a unique problem in the pregnant female. The presence of a stone 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 in pregnancy). Anti-inflammatory medications may cause oligohydramnios and/or premature closure of the patent ductus arteriosus and should be avoided, if possible.
  • If ultrasonography reveals a stone, then ultrasound-guided cystoscopic passage of a ureteral stent may relieve ureteral colic. In some cases (ie, pyonephrosis with an obstructing stone), percutaneous nephrostomy can be useful. Cystoscopic extraction (with fluoroscopic guidance) of a distal ureteral stone 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 rads 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 rad. Doses of more than 5 rads have been associated with an increase in benign and malignant tumors in the child after birth. No patient should receive more than 10-14 rads.
  • Renal ultrasonography is often performed initially, but the findings are often inconclusive. A limited IVP (ie, kidneys, ureters, and bladder [KUB] and a 30-min shot following injection of contrast) can be helpful in delineating the site of obstruction.

Other Tests

• Other tests are rarely indicated in the diagnosis of UTI during pregnancy.
• Urine cytology may be useful in detecting rare upper urinary tract lesions. 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.

Procedures

• Evaluation of fetal status
• • Obtain fetal heart tones, if possible. This depends on the gestational age of the fetus.
  • Evaluation of fetal status may help to narrow the differential diagnoses.

Histologic Findings

Histological findings can be described for urine cytology. Clumping WBCs and WBC casts are consistent with pyelonephritis. 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

Section 6 of 11  

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Medical Care

Any discussion of treatment should be prefaced with a discussion of behavioral methods to ensure good hygiene and to reduce bacterial contamination of the urethral meatus. This is important in preventing inadequate treatment and recurrent infection. These behavioral methods include avoiding baths, wiping front-to-back after urinating or defecating, washing hands before using the toilet, using washcloths to clean the perineum, using liquid soap to prevent colonization from bar soap, and cleaning the urethral meatus first when bathing.

• Ensure, through diagnosis and treatment, that a more serious process is not the cause of the symptoms.
• Oral antibiotics are the treatment of choice for asymptomatic bacteriuria (ASB) and cystitis.
• • Although antibiotic courses of 1, 3, and 7 days have been evaluated, 10-14 days of treatment is usually recommended to eradicate the offending bacteria. Data are insufficient to abandon these more traditional long-term regimens using evidence-based medicine.
  • Treatment success depends on eradication of the bacteria rather than the duration of therapy. A test-for-cure urine culture should show negative findings 1-2 weeks posttherapy. A non-negative culture result is an indication for switching antibiotics, followed by suppressive therapy until 6 weeks postpartum.
  • Mathai and Thomas et al suggest the need for disseminated guidelines for practitioners in developing countries such as India.⁶ In their study, they found that the use of antibiotics was inappropriate in terms of safety, cost, susceptibility, and threat for developing resistance.
• The standard course of treatment for pyelonephritis is admission with intravenous antibiotics. Administer IV fluids with caution. Patients with pyelonephritis can become dehydrated because of nausea and vomiting and need intravenous hydration. However, patients are at high risk for development of pulmonary edema and adult respiratory distress syndrome (ARDS).
• Manage fever with antipyretics (eg, acetaminophen). Manage nausea and vomiting with antiemetics.
• Preterm labor and delivery are additional risks associated with pyelonephritis, and they need to be evaluated and treated early in the course of admission.

Surgical Care

• Surgical care is rarely indicated, unless one of the pathologic causes listed in the differential diagnoses is suspected (see Differentials).
• In patients with urethral or bladder diverticulum, bladder stones, urethral syndrome, lower urinary tract trauma, interstitial cystitis, or bladder cancer, cystoscopy may help in establishing the diagnosis.
• A retrograde stent or a percutaneous nephrostomy tube should be used to relieve ureteral colic and/or to decompress an obstructed infected collecting system. More invasive procedures, such as ureteroscopic stone extraction, are rarely indicated.
• In the rare patient in whom invasive surgical therapy is indicated, timing should be planned for the second trimester. Surgical intervention during the first trimester is associated with miscarriage; in the third trimester, surgery is associated with preterm labor. Urgent surgical intervention in the third trimester should coincide with delivery of the fetus.
• Extracorporeal shock wave lithotripsy (ESWL) is contraindicated in pregnancy.

Consultations

• Early after admission, consult an obstetrician or a physician familiar with the care of pyelonephritis in pregnancy. Preterm labor and delivery are additional risks associated with pyelonephritis and need to be evaluated and treated early in the course of admission.
• Consult a urologist if an obstructing urolithiasis or an infected collecting system is suspected.
• Coexisting medical disorders that warrant consultation when found in conjunction with pyelonephritis include the following:
• • Preexisting diabetes
  • Gestational diabetes
  • Cardiac disease
  • Autoimmune disease
  • Renal disease

Diet

Diet is as tolerated. If the patient cannot tolerate oral intake, she can be maintained on nothing-by-mouth (NPO) status until she is able to tolerate oral intake. The only caveat is that the patient should remain NPO if surgical intervention is being considered.

Activity

• For outpatient treatment, activity is not altered.
• Patients admitted for pyelonephritis should limit activity based on the severity of symptoms.
• Patients who may lose consciousness upon ambulation place themselves and the fetus at significant risk.
• If the patient has no other reason for limitation of activity, routine activity as an inpatient is acceptable.

MEDICATION

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Some antibiotics should not be used during pregnancy because of their effects on the fetus. These include tetracyclines (adverse effects on fetal teeth and bones, congenital defects), quinolones (various congenital defects), trimethoprim in the first trimester (facial defects, cardiac abnormalities), and chloramphenicol and sulfonamides in the last trimester (Gray syndrome; hemolytic anemia in mothers with glucose-6-phosphate dehydrogenase [G-6-PD] deficiency, jaundice, and kernicterus, respectively).

Nitrofurantoin (Macrodantin) is a safe and effective drug. In the past, it was avoided in the third trimester because of hemolytic effects on the newborn; however, Macrodantin has subsequently been limited to use only in women during labor and delivery because of the possibility of hemolytic anemia in the fetus or the newborn infant due to their immature erythrocyte enzyme systems (glutathione instability). Macrodantin has also been shown to be safe used as a once-daily prophylactic therapy.

Patients with acute pyelonephritis should be systemically treated with cephalosporins or gentamicin. Asymptomatic patients do not need long courses of antibiotics but still should undergo a regimen of at least 7-10 days. Appropriate oral regimens include cephalexin 500 mg qid, ampicillin 500 mg qid, nitrofurantoin 100 mg bid, or sulfisoxazole 1 g qid. Studies with cephalexin, co-trimoxazole⁷ [DIH], 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%. Women in whom bacteriuria persists or in whom symptoms develop should be treated with a 10- to 14-day course of a different antibiotic. Then prophylactic antibiotics (ie, nitrofurantoin 50 mg qhs) should be administered for the rest of the pregnancy.

Antibiotic therapy should be based on urine culture sensitivities, if known. Often, therapy is initiated prior to culture-result availability. This requires clinical knowledge of the most common organisms (ie, E coli) and their practice-specific and/or hospital-specific sensitivities to medications. Several methods of treatment for asymptomatic bacteriuria (ASB) have been studied and are available, including single-day regimens (ASB), short-course (ie, 3 d), and the more traditional 7- to 10-day regimens (uncomplicated cystitis). Pyelonephritis or complicated urinary tract infections (UTIs) (ie, recurrent or persistent UTIs) should be treated with 10-14 days of therapy. Patients with pyelonephritis, recurrent UTIs, concurrent stone disease, or indwelling ureteral stents should receive prophylactic antibiotics throughout pregnancy and should undergo frequent urine testing.

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, to first-generation cephalosporins, as high as 9-19%.

Maternal physiologic changes that influence pharmacokinetics include increased glomerular filtration rate 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 increased glomerular filtration rate.

Fluoroquinolones are contraindicated in pregnancy. Although in utero exposure is not an indication for termination, fetal exposure to fluoroquinolones has resulted in myelomeningocele, hydrocephaly, hypospadias, maldescended testes, inguinal hernia, bilateral hip dysplasia, and atrial septal defects. The anomalies do not seem to follow a particular pattern, which may be reassuring. However, a causal relationship cannot be excluded.

Drug Category: Penicillins

These are bactericidal agents that are excreted in the urine. The resistance of E coli to ampicillin and amoxicillin is 20-40%; therefore, they are no longer considered an optimal choice for treatment of UTI.

Drug Category: Cephalosporins (beta-lactams)

These are categorized into first-, second-, and third-generation. Second- and third-generation medications have a greater spectrum of coverage. Cephalosporins are excreted in the urine. These medications are bactericidal, inhibiting cell wall synthesis.

Drug Category: Aminoglycosides

Derived from Micromonospora purpurea (an actinomycete), aminoglycosides can accumulate in the sera of patients with impaired renal function. The more severe the impairment, the more the dosage must be adjusted. Aminoglycosides have varying degrees of nephrotoxicity and ototoxicity. Aminoglycosides are effective treatments against Pseudomonas, Proteus, Klebsiella, Enterobacter, Serratia species, and E coli. Aminoglycosides are not indicated in the uncomplicated initial episodes of UTIs unless the organism is resistant to less toxic antibiotics. Aminoglycosides have a synergistic effect with penicillins. Aminoglycosides cross the placenta, and reports exist of streptomycin causing bilateral congenital deafness in children whose mothers received the medication during pregnancy; however, gentamicin is indicated in the treatment of neonatal sepsis.

Drug Category: Nitrofurans

These agents interfere with bacterial carbohydrate metabolism by inhibiting acetylcoenzyme A.

Drug Category: Sulfonamide derivatives

These agents inhibit bacterial growth by inhibiting synthesis of dihydrofolic acid. Although their bioavailabilities vary, all share similar actions in the fetal period. As such, they should be considered as a single group.

Drug Category: Macrolides

Macrolides are not first-line agents but are well-tolerated by mother and fetus.

Drug Category: Phosphonic acid derivatives

These agents are useful in the treatment of uncomplicated UTIs caused by susceptible strains of E coli and Enterococcus species.

FOLLOW-UP

Section 8 of 11  

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• Introduction
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• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
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Further Inpatient Care

• In addition to appropriate antibiotic and antipyretic therapy, include antepartum management of pyelonephritis through rehydration and tocolytic therapy, if appropriate.
• The most important complication of pyelonephritis is respiratory insufficiency due to bacterial endotoxin damage to the alveoli, causing pulmonary edema; therefore, fluid overload (>3 L over outputs in 48 h) must be avoided and tocolytics used sparingly. Frequent clinical evaluation allows identification of pulmonary injury early. Clinical signs include dyspnea, tachypnea, and hypoxemia and findings on a chest radiograph that are consistent with pulmonary edema ARDS. Prompt recognition can be addressed with oxygen, intubation, and mechanical ventilation, as necessary, to prevent adverse maternal and fetal outcomes. Central hemodynamic monitoring is helpful to guide fluid therapy and oxygen delivery, especially when mechanical ventilation is necessary.
• Renal dysfunction typically resolves with hydration; however, nephrotoxic medications should be dose-adjusted for changes in creatinine clearance. Likewise, maternal anemia usually resolves with the infection if iron stores are adequate.
• Clinical improvement is usually rapid after the initiation of antimicrobial therapy, although fevers may wax and wane. Most (85%) fevers resolve within the first 48 hours (ie, 90% within 72 h). Women who do not improve in 72 hours should undergo testing for other sources of infection, including renal ultrasonography to rule out obstructive nephrolithiasis. Continue intravenous antibiotic therapy for 24-48 hours after defervescence.
• If conservative treatment fails or if an infected obstructed system is suspected, imaging studies are indicated. Renal ultrasonography is often performed initially, but the findings are often inconclusive. A limited IVP (ie, a KUB and a 30-min shot following injection of contrast) can be helpful in delineating the site of obstruction.
• ESWL is contraindicated in pregnancy.

Further Outpatient Care

• Generally, women are discharged with 1-2 weeks of oral antibiotic therapy. Because acute pyelonephritis places the pregnant patient at risk for recurrent antepartum urinary tract infection (UTI) (38%) and recurrent antepartum pyelonephritis (7-8%), continue antibiotic prophylaxis for the remainder of the pregnancy. Although this approach has not been definitively proven to prevent preterm labor and low birth weight in infants, the significant recurrence of asymptomatic bacteriuria (ASB), UTI, and pyelonephritis supports the prudence of prophylaxis. Both continuous (daily) and postcoital prophylaxis regimens are effective. The agents of choice during pregnancy include nitrofurantoin (50-100 mg) and cephalexin (250 mg).
• For simple cystitis and bacteriuria, a test-for-cure urine culture should be performed approximately 1-2 weeks after the completion of therapy. Cases that are persistent (positive culture results) or recurrent (positive culture results after 2 wk) should be treated with a sensitive antibiotic and continued on a low-dose suppressive (prophylactic) antibiotic until 6 weeks postpartum.
• Possible nonpharmacologic recommendations include early postcoital voiding (type II-3 evidence), pushing fluids (type II-3 evidence), and drinking cranberry juice (type I evidence in elderly women). The patient’s hygiene should be reviewed to determine if certain practices predispose her to infection.

In/Out Patient Meds

• Aside from the antibiotics prescribed for UTI and ancillary medications, no medications are required. The administration route is dictated by the patient's diet.
• Tylenol is the preferred medication for fever.
• Most antiemetics can be used for adverse effects caused by antibiotics, but doxylamine, Emetrol (class A), dimenhydrinate, and metoclopramide (class B) are preferred.

Transfer

• The general obstetrician/gynecologist or family practitioner should be able to manage even a complicated case of pyelonephritis. However, a urologist should be consulted if the patient is not responding to treatment, if the patient has a protracted course, or to rule out other factors such as perinephric abscess or obstruction. In addition, cases involving a known stone or indwelling ureteral stent also should include consultation with a urologist. Only the most complicated cases (ie, ARDS, renal failure, septic shock) require consultation or transfer to the appropriate specialist.

Deterrence/Prevention

• Untreated ASB progresses to pyelonephritis in 25-30% of cases; therefore, routine screening for bacteriuria is recommended throughout pregnancy. The most cost-effective and cost-beneficial screening method depends on the local prevalence of ASB. Rouse and colleagues (1995) described the use of leukocyte esterase-nitrite dipsticks, treating the patients with positive results, and retesting using dipsticks.⁸ A urine culture is unnecessary unless the retest result is positive. If the culture result is positive, the patient is re-treated and placed on suppressive therapy; however, if the prevalence of ASB is high, screening and treatment based on urine culture with reculture (used as test of cure) are also cost-benefit effective.
• Because the prevalence increases with sexual activity, limited activity or postcoital antibiotic prophylaxis may be prudent. Investigate untreated pathologies. UTI before pregnancy or antepartum is predictive of bacteriuria at the first prenatal visit. Avoid in-dwelling catheterization during labor and after delivery.
• Suppressive antibiotic therapy should be instituted in patients who develop acute cystitis or pyelonephritis during pregnancy. Patients treated for ASB during pregnancy who have recurrent or persistent ASB upon retest should also receive prophylactic antibiotics. Penicillins (including ampicillin and clavulanic acid), cephalosporins, and nitrofurantoin are safe in pregnancy. Some warn against the use of nitrofurantoin in women with G-6-PD deficiency because of the possibility of hemolytic anemia; however, data do not support this. Sulfonamides are associated with fetal kernicterus and should be avoided during the third trimester. Similarly, quinolones are class C drugs, and no controlled human data regarding their safety in pregnancy have been published. In fact, pregnant animal studies using quinolones in the first trimester resulted in major fetal malformations; therefore, quinolones should not be used in pregnancy.
• Pregnant women with sickle cell hemoglobinopathies are at increased risk for UTI, as are patients who have undergone renal transplantation or orthotopic diversions. Patients with these high-risk conditions may benefit from more aggressive screening (culture vs dipstick) and antibiotic prophylaxis.
• A possible immunization for UTI: Uehling et al described a study in which repeated immunization with a vaginal mucosal vaccine prolongs the time to reinfection in women susceptible to UTIs.⁹ Women who received 6 doses of a vaginal vaccine remained infection-free significantly longer than patients who received 3 doses or placebo only. The study was a double-blind phase 2 trial of suppositories that contain Urovac, which contains 10 heat-killed uropathogens. Women who were given the vaccine developed significantly fewer UTIs than those in the control group. Phase 3 clinical trials are ongoing.

Complications

• Pyelonephritis
• • The most important primary complication of bacteriuria in pregnancy is pyelonephritis. Other rare, but serious, complications include septic shock, respiratory failure, and death. As many as 25-30% of women with untreated ASB in pregnancy eventually develop symptomatic cystitis or pyelonephritis. Antepartum UTI is also a risk factor for adverse perinatal outcomes, including low birth weight and preterm delivery. Adverse maternal outcomes include premature labor, maternal anemia, amnionitis, and hypertension or preeclampsia.
  • Acute pyelonephritis occurs in 1-2% of all pregnancies. The incidence varies depending on the local prevalence of ASB and whether it is treated. Women with urinary tract abnormalities, such as renal calculi, anomalies, or a history of pyelonephritis, are at increased risk. Most (73%) cases are discovered antepartum, with 8% identified intrapartum and 19% postpartum. Ninety percent of antepartum cases are diagnosed in the last 2 trimesters.
  • Complications associated with pyelonephritis are serious and are due primarily to bacterial endotoxin damage. Ten percent to 15% of pregnant women with pyelonephritis develop bacteremia. Respiratory insufficiency due to endotoxin alveolar damage and pulmonary edema occurs in 2-8% of patients. Respiratory compromise can be exacerbated by iatrogenic fluid overload and tocolytics. Renal dysfunction occurs in as many as 25% of antepartum cases but is usually self-limited. Maternal anemia (hematocrit <30%) due to endotoxin-induced hemolysis occurs in 25-66% of cases and typically resolves.
  • Pyelonephritis is associated with preterm birth and low birth weight; however, this association is compounded by low socioeconomic status. The strength of the association is unknown and has recently been questioned.
• Preeclampsia: Women who develop preeclampsia during pregnancy seem to be predisposed to UTI. A retrospective review of the perinatal database at a major tertiary center revealed a UTI rate of 16.2% in normotensive patients, but this increased to 27.3% in women with mild preeclampsia and 35.9% in women with severe preeclampsia. The authors hypothesize that underlying renal damage weakens the patients' systemic defense mechanisms against ascending infection.
• Effects on the fetus: Maternal UTI has few direct fetal sequelae because fetal septicemia 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.

Prognosis

• In most cases of bacteriuria and UTI in pregnancy, the prognosis is excellent; however, most long-term sequelae are due to complications associated with septic shock, respiratory failure, and hypotensive hypoxia (ie, extremity gangrene).

Patient Education

• Specimen collection
• • Since Kass described the criteria for ASB in the 1950s, physicians have struggled to prevent female patients from contaminating their own specimens. The most accepted development has been the introduction of the midstream-voided specimen after urethral and perineal cleansing.
  • The patient must be instructed on how to execute the following:
  • 1. With one hand, spread the labia.
    2. With the other hand, use a Castile soap-moistened towelette to wipe the urethral meatus downward towards the rectum and discard the towelette.
    3. Void the initial portion of the bladder contents into the toilet.
    4. Catch the middle portion of the bladder contents in the sterile collection container, while keeping the labia spread with the first hand.
  • Unfortunately, a recent study on pregnant adolescents suggests the cleansing process does not prevent contamination.
• For excellent patient education resources, visit eMedicine's Kidneys and Urinary System Center and Pregnancy and Reproduction Center. Also, see eMedicine's patient education articles Urinary Tract Infections, Pregnancy, Bladder Control Problems, and Blood in the Urine.

MISCELLANEOUS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical/Legal Pitfalls

• Because 25% of untreated asymptomatic bacteriuria (ASB) cases progress to pyelonephritis, failure to treat documented ASB followed by a complication from pyelonephritis might result in medicolegal liability.

Special Concerns

• Beta streptococci
• • Beta streptococci are important pathogens in pregnancy because early and late complications of neonatal beta-streptococcal infection are well-documented. Incidental documentation of beta-streptococcal bacteriuria suggests a higher colonization count than 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. McKenzie and colleagues (1994) prospectively found no relation of beta-streptococcal bacteriuria to preterm labor, but they describe the use of urinary antibodies to identify at-risk women.¹⁰ In 2043 consecutive women, those with E coli antibodies at 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.
• Caesarean delivery: Cesarean delivery is associated with urinary tract infection (UTI) (2.7 times more likely), but this association may be confounded by bladder catheterization or prolonged rupture of membranes (PROM). The incidence of symptomatic UTI is 9.3% and ASB 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. In this exceedingly rare case, a percutaneous nephrostomy tube or antegrade passage of a ureteral stent may be indicated.
• Outpatient treatment of pyelonephritis in pregnancy
• • In 1995, Millar and colleagues reported on a randomized, controlled trial of outpatient treatment of pyelonephritis in pregnancy.¹¹ They concluded that outpatient therapy is as safe and effective as inpatient care in the treatment of pyelonephritis before 24 weeks' gestation. However, the prevailing attitude still dictates that aggressive inpatient hydration and parenteral antibiotics are necessary. In early pregnancy, pyelonephritis places the patient at risk for spontaneous abortion and, after 24 weeks' gestation, preterm labor.
  • In their study, Millar et al (1995) treated outpatients with 2 doses of intramuscular ceftriaxone and 10 days of oral cephalexin.¹¹ Initial outpatient therapy and traditional inpatient therapy failed to cure equal numbers of patients. Benefits include the obvious cost savings and psychosocial benefits for the patient. Risks include septic shock or respiratory insufficiency at home during outpatient therapy. Strict guidelines for an observation period before emergency department 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 one or more complications. 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.

MULTIMEDIA

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment