Urinary Tract Infections in Pregnancy

INTRODUCTION

Background: Urinary tract infection (UTI) is defined as more than 100 organisms per milliliter of urine in a symptomatic patient (or greater than 100,000 organisms per milliliter of urine in an asymptomatic patient) with accompanying pyuria (>7 WBCs/mL). For the purpose of this discussion, it is assumed that the symptomatic patient with greater than 100 organisms per milliliter is not immunosuppressed and the culture yields an organism considered to be a uropathogen. When there is a symptomatic UTI, 2 clinical entities are recognized: lower UTI (cystitis) and upper UTI (pyelonephritis). Pregnant patients are considered compromised UTI hosts because of the physiologic changes associated with pregnancy. These are discussed in a later section. These changes increase a healthy, pregnant woman's chance of serious infectious complications from symptomatic and asymptomatic urinary infections.

Asymptomatic bacteriuria (ASB) is commonly defined as 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% develop) and pyelonephritis (25-30% develop) in pregnancy. These cases account for 70% of all cases of symptomatic UTI in pregnancy in the unscreened population.

Acute cystitis involves only the lower urinary tract; it is an inflammation of the bladder due to bacterial or nonbacterial causes (ie, radiation, viral). It occurs in approximately 1% of pregnant patients, of whom 60% have a negative initial screening. Signs/symptoms include hematuria, dysuria, suprapubic discomfort, frequency, urgency, and nocturia. These symptoms are often times difficult to distinguish from those due to pregnancy itself.

Acute cystitis is complicated by upper urinary tract disease (pyelonephritis) 15-50% of the time. Pyelonephritis is the most common urinary tract complication of pregnancy, occurring in approximately 2% of all pregnancies. Acute pyelonephritis is the presence of fever, flank pain, and tenderness in addition to significant bacteriuria. Other symptoms may include nausea, vomiting, frequency, urgency, and dysuria.

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 the 2 depends upon vaginal and urinary cultures.

Annual health costs for UTI exceed $1 billion. Although the condition-specific cost of ASB or UTI in pregnancy is not known, screening for ASB and UTI in pregnancy has been shown to be cost-effective when compared to treating UTI and pyelonephritis without screening. Using 1995 costs, the cost of screening and treating ASB per 1000 pregnancies was $1968 with dipstick screening and $19,264 with culture screening. On the other hand, the cost of treating pyelonephritis with no screening was $57,562 versus $40,257 with dipstick and $27,832 with culture.

Pathophysiology: Escherichia coli is the most common cause of UTI, accounting for 80-90% of cases. It originates from fecal flora 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, are also clinically important pathogens. Staphylococcus saprophyticus, an aggressive, community-acquired organism, can present with upper urinary tract disease, and the 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 nonbacterial UTIs.

Physiologic changes of pregnancy may predispose patients to bacteriuria. These include urinary retention from the weight of the enlarging uterus and urinary stasis due to ureteral smooth muscle relaxation (caused by increases in progesterone). Although progesterone influence causes a relative dilation of the ureters, ureteral tone progressively increases during pregnancy above the pelvic brim. However, there is controversy whether bladder pressure increases or decreases during pregnancy. In addition, glucosuria and aminoaciduria of pregnancy provide an excellent culture medium for bacteria in areas of urine stasis.

Frequency:
　

• In the US: The prevalence of asymptomatic bacteriuria in pregnant women is 2.5-11.0% (versus 3-8% in other women). Prevalence increases with age, low socioeconomic status, sexual activity, multiparity and untreated pathologies.

  The frequency of UTI in pregnancy is not higher than the nonpregnant rate of 0.3-1.3%. Changes in coital patterns (position, frequency, postcoital antibiotics) can offset recurrence in at-risk individuals. However, Leigh and colleagues report a 34% rate of symptomatic bacteriuria in women during the first 5 days after cesarean section that may be due to catheterization or prolonged rupture of membranes (PROM).

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

• Internationally: Versi and colleagues described a higher prevalence of bacteriuria in Caucasian women during pregnancy (6.3%) when compared to Bangladeshi women (2%). Pregnancies that resulted in preterm deliveries showed a strong association with bacteriuria in Caucasian women, which was not seen in Bangladeshi women. They hypothesized the difference could be due to differences hygiene practices and clothing.

Mortality/Morbidity:

• The primary complication of bacteriuria in pregnancy is pyelonephritis, although overt 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 Section.

Race:

• Retrospective analysis of 24,000 births indicates the prevalence of UTI during pregnancy is 28.7% in Caucasians and Asians, 30.1% in Blacks, and 41.1% in Hispanics.

• UTI is associated with preterm delivery in all races. The adjusted odds ratio for very-low-birth weight infants is 2.8 in Blacks and 5.6 in Caucasians adjusted for parity, body mass index (BMI), maternal age, marital status, cigarette smoking, education, and prenatal care. The overall Black or Caucasian relative risk for bacteriuria is estimated at 1.5-5.0 RR and for those with bacteriuria developing preterm birth is 1.8-2.3 RR.

Sex:

• These infections occur in pregnant women.

Age:

• Prevalence of UTI in pregnancy increases with age.

CLINICAL

History:

• Asymptomatic bacteriuria

• ASB is bacteriuria in the urine without clinical signs or symptoms of infection. It usually is found on random urine screening in pregnancy.

• Cystitis

  　

  • This presents with symptoms including dysuria, urgency, urge, incontinence, and frequency. A positive urine culture or urine dipstick usually shows leukocyte esterase, nitrite, hematuria, and may show some protein. Additional symptoms may consist of low abdominal pain or suprapubic tenderness.

    　

• Pyelonephritis

  　

  • This presents with variable symptoms.

    　

  • Symptoms often include fever higher than 38蚓, shaking chills, costovertebral angle tenderness, anorexia, nausea, and vomiting. Right-sided flank pain is more common than left or bilateral flank pain. Patients also may present with hypothermia, demonstrating temperatures as low as 34蚓.

• Powers suggests that pregnant women have complicated UTIs. The duration of symptoms may be quite short and progression more rapid due to the relative immunocompromised state of pregnancy. Symptoms of UTI such as dysuria, suprapubic tenderness, and others may be less pronounced in pregnant patients. The symptoms also may be related to the gravid uterus.

Physical:

• Physical examination must consider that the patient is pregnant. It also is important to place physical findings in the context of the duration of pregnancy. The differential diagnosis may change in each trimester, and the increasing size of the gravid uterus may mask or mimic findings.

  　

• ASB

  　

  • Often, there are no physical findings.

    　

  • Symptoms may arise intermittently, only to be overlooked due to lack of persistence or severity.

• Cystitis

  　

  • Patients may have suprapubic tenderness on palpation. Tenderness can be elicited with isolation of the bladder on pelvic examination.

• Pyelonephritis

• Patients have fever (usually >38°C), flank tenderness on palpation, and an ill appearance. Flank tenderness is right-sided in more than half of patients, bilateral in one fourth and left-sided in one fourth. Pain also may be found suprapubically with palpation.

• Based on gestational age, include fetal heart rate as part of the evaluation. Often due to maternal fever, 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
  • Klebsiella pneumoniae (5%)
  • Proteus mirabilis (5%)
  • Enterobacter species (3%)
  • Staphylococcus 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.

• Maternal physiologic factors

• These predispose patients to ascending infection.

• The smooth-muscle relaxation properties of progesterone and mechanical obstruction by an enlarging uterus cause dilation of the renal calices, pelves, and ureters, which leads to urinary stasis and potentiates infection. This affect Calyceal and ureteral dilation are more common on the right side; in 86% of cases, the dilation is localized on the right side. The degree of calyceal dilation also is more pronounced on the right than the left, 15 mm versus 5 mm. This dilation appears to begin by about 10 weeks gestation and worsens throughout pregnancy (Pictures 1 and 2). This is underlined by the percentage 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 urine amino acids during pregnancy are additional factors. Glucose excretion increases in pregnancy by 100-fold over nonpregnant values of 100 mg/day. Glycosuria occurs due to impaired resorption by the collecting tubule and Henle's loop of the 5% of the filtered glucose, which escapes proximal convoluted tubular reabsorption. The fractional excretion of alanine, glycine, histidine, serine, and threonine is increased throughout pregnancy. Cystine, leucine, lysine, phenylalanine, taurine, and tyrosine are elevated in the first half of pregnancy but return to normal by the second half. The mechanism of selective aminoaciduria is unknown, although their presence has been postulated to affect the adherence of E coli to the urothelium.

WORKUP

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 give a clean-catch specimen. Routine catheterization is not recommended due to 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.

• 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 gold standard for evaluation of UTI in pregnancy. A urine culture should be obtained on admission in cases of pyelonephritis and for patients who have recurrent infection or 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. Powers cites evidence that indicates that a true positive culture may have as low as 100 CFUs per milliliter of bacteria.

• Culture can identify specific organisms and antibiotic sensitivities.

• It has an average cost of approximately $40.

• Results often are not available at the time of treatment.

• Urinalysis

  　

  • Positive nitrites, leukocyte esterase, WBCs, RBCs, and protein are suggestive of a UTI. Bacteria found in the specimen can help with the diagnosis.

• Urinalysis has a specificity of 97-100%, but has a sensitivity that ranges from 25-67% when compared to culture in the diagnosis of ASB.

• Millar and Cox 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.

• Urine dip

• Several reports describe the use of urine dip for nitrites and leukocyte esterase in the evaluation of asymptomatic bacteriuria.

• Sensitivities range from 50-92% and specificity 86-97% when compared to 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 is not indicated in the evaluation of pregnancy-related UTI.

• Renal ultrasound--or limited intravenous pyelography if the minor risk of radiation is outweighed by the benefits of a definitive diagnosis--may be helpful in patients with recurrent UTI or symptoms that are suggestive of nephrolithiasis (Pictures 1-4). Urolithiasis and pyelonephritis share many common symptoms (ie, hematuria, flank pain, shaking chills or anorexia), urolithiasis usually is not associated with fever, unless urolithiasis and pyelonephritis coexist.

• Confusion about the diagnosis of urolithiasis, pyelonephritis, or both is an indication for imaging studies.

• Urolithiasis offers a unique problem in the pregnant female. The presence of a stone should initially be treated conservatively, since 50-67% of stones diagnosed during pregnancy will pass spontaneously. Conservative therapy includes appropriate antibiotic coverage, adequate hydration, and systemic analgesics (usually narcotics, which are Class C in pregnancy). Anti-inflammatories 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 very useful. Cystoscopic extraction (with fluoroscopic guidance) of a distal ureteral stone should be used sparingly due to 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 to 1 rad. Doses above 5 rads have been associated with an increase in benign and malignant tumors in the child after birth. No patient should receive over 10-14 rads.

• A renal ultrasound often is obtained initially but is often inconclusive. A limited IVP (a KUB and a 30-minute shot following injection of contrast) can be quite helpful in delineating the site of obstruction.

Other Tests:
　

• Other tests are rarely indicated in the diagnosis of UTI in 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, up to 20% of patients with acute glomerulonephritis have ASO titers within the normal range.

Procedures:
　

• Evaluation of fetal status

• Obtain fetal heart tones, if possible. This depends upon the gestational age of the patient.

• Evaluation of fetal status may help to narrow the differential diagnosis.

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, hypercholesterolinemia, and hypoalbuminemia; however, this can be confused with preeclampsia. Oval fat bodies and fatty casts can suggest membranous glomerulonephritis.

TREATMENT

Medical Care: Any discussion of treatment should be prefaced with a discussion of behavioral methods to ensure good hygiene and reduce bacterial contamination of the urethral meatus. This is important in order to prevent inadequate treatment and to prophylax against recurrent infection. These behavioral methods include: avoiding baths, wiping front-to-back, washing hands before toileting, 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

  　

  • These are the treatment of choice for ASB and cystitis.

    　

  • Although antibiotic courses of 1,3, and 7-days' durations have been evaluated, 10-14 days usually are recommended in order to eradicate the offending bacteria.

• Intravenous treatment

  　

  • The standard course of treatment for pyelonephritis is admission with intravenous (IV) antibiotics.

    　

  • Administer IV fluids with caution. Patients with pyelonephritis can become dehydrated because of nausea and vomiting. Patients are, however, 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 need to be evaluated and treated early in the course of admission.

Surgical Care:

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

• In the event of urethral or bladder diverticulum, bladder stones, urethral syndrome, lower urinary tract trauma, interstitial cystitis, or bladder cancer, cystoscopy may help establish 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, rarely are 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 and in the third trimester, with preterm labor. Urgent surgical intervention in the third trimester should be coincident with delivery of the fetus.

• Extracorporeal shock wave lithotripsy (ESWL) is contraindicated in pregnancy.

Consultations:

• Consult early in the admission with an obstetrician or a physician familiar with the care of pyelonephritis in pregnancy.

  　

• Consult a urologist if an obstructing urolithiasis or an infected collecting system is suspected.

  　

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

• 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 as tolerated; patient can be maintained on nothing-by-mouth (NPO) status until she is able to tolerate oral intake.

Activity:

• For outpatient treatment, activity is not altered.

• Patients admitted for pyelonephritis should have activity limits based on severity of symptoms.

• Patients who may lose consciousness with 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

There are some antibiotics that should not be used during pregnancy due to 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) and chloramphenicol and sulfonamides in the last trimester (Gray syndrome; hemolytic anemia in mothers with G-6-PD deficiency, jaundice and kernicterus, respectively). Macrodantin is a safe and effective drug, but probably should be avoided in the third trimester due to hemolytic effects on the newborn. It has been shown to be safe if used as a once daily prophylactic therapy.

Patients with acute pyelonephritis should be systemically treated with cephalosporins or gentamicin. Patients who are not symptomatic do not need long courses of antibiotics, but still should have at least a 7-10 day regimen. Appropriate oral regimens include Cephalexin 500mg qid, Ampicillin 500 mg qid, Nitrofurantoin 100 mg bid or Sulfisoxazole 1 g qid. Studies with cephalexin, co-trimazole and amoxicillin have indicated a single does is as effective as a 3-7 day course or therapy, but the cure rate is only 70%. Women in whom bacteriuria persist, or symptoms develop, should be treated with a 10-14 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 they are known. Often, therapy is initiated prior to the results of cultures. This requires clinical knowledge of the most common organisms (ie, E coli) and their practice/hospital specific sensitivities to medications. Several methods of treatment for ASB have been studied and are available: single-day regimens (ASB), short-course (3 d), and the more traditional 7-10 day regimens (uncomplicated cystitis). Pyelonephritis or complicated urinary tract infections (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 have prophylactic antibiotics throughout their pregnancy and should have urine testing frequently.

Maternal physiologic changes that influence pharmacokinetics are 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 due to the gross increase in blood volume and increased GFR.
　

Drug Category: Penicillins -- Bactericidal and are excreted in the urine. There is a 20-30% rate of resistance of E coli to ampicillin and amoxicillin; therefore, they are no longer considered an optimal choice for treatment of UTI.

Drug Category: Cephalosporins (beta-lactams) -- 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 the Micromonospora purpurea actinomycete, aminoglycosides can accumulate in the serum 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, 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 there are reports 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 -- Interfere with bacterial carbohydrate metabolism by inhibiting acetylcoenzyme A.

Drug Category: Sulfonamide derivatives -- Inhibit bacterial growth by inhibiting synthesis of dihydrofolic acid.

FOLLOW-UP

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, hypoxemia, and a chest radiograph (CXR) 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 O₂ 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 initiating antimicrobial therapy, although fevers may wax and wane. The majority (85%) of fevers resolve within the first 48 hours (90% within 72 h). Women who do not improve in 72 hours should undergo testing for other sources of infection, including a renal ultrasound to rule out obstructive nephrolithiasis. Continue IV antibiotic therapy for 24-48 hours after defervescence.

• If the patient fails conservative treatment, or if an infected obstructed system is suspected, then imaging studies are indicated. A renal ultrasound is often initially obtained, but is often inconclusive. A limited IVP (a KUB and a 30-min shot following injection of contrast) can be quite helpful in delineating the site of obstruction.

• Extracorporeal shock wave lithotripsy (ESWL) is contraindicated in pregnancy.

Further Outpatient Care:
　

• Generally, women are discharged with 1-2 weeks of oral antibiotic therapy. Since acute pyelonephritis places the pregnant patient at risk for recurrent antepartum UTI (38%) and recurrent antepartum pyelonephritis (7-8%), continue antibiotic prophylaxis for the remainder of the pregnancy. Although the efficacy of this approach has not been definitively proven to prevent preterm labor and low-birth-weight infants, the significant recurrence of ASB, UTI, and pyelonephritis makes prophylaxis prudent. Both continuous (daily) and postcoital prophylaxis regimens are effective. The agents of choice during pregnancy include nitrofurantoin (50-100 mg), and cephalexin (250 mg).

• Possible nonpharmacologic recommendations include early post-coital voiding (Type II-3 evidence), pushing fluids (Type II-3 evidence), and drinking cranberry juice (Type I evidence in elderly women). Personal hygiene should be reviewed to determine if the patient has certain practices, which may predispose her to infection.

In/Out Patient Meds:
　

• Other than the antibiotics prescribed for UTI and ancillary medications, no other medications are required. Administration route is dictated by the patient's diet. Tylenol is the preferred medication for fever. Most antiemetics can be used for antibiotic adverse effects, but doxylamine, Emetrol (Class A), and dimenhydrinate, metoclopramide (Class B) are preferred.

Transfer:
　

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

Deterrence/Prevention:
　

• Untreated ASB progresses to pyelonephritis 25-30% of the time; 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 describe the use of leukocyte esterase-nitrite dipsticks, treating the positive patients, and retesting using dipsticks. Only if the retest is positive does a urine culture need to be done. If the culture result is positive, then the patient is retreated and placed on suppressive therapy; however, if the prevalence of ASB is high, then screening and treatment based on urine culture with reculture (used as test of cure) are also cost-benefit effective.

• Since 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 postpartum.

• Suppressive antibiotic therapy should be instituted for patients who suffer acute cystitis or pyelonephritis during pregnancy. It is recommended that those patients treated for ASB during pregnancy and have recurrence or persistence of ASB upon retest should also be prescribed prophylactic antibiotics. Penicillins (including ampicillin, clavulanic acid), cephalosporins, and nitrofurantoin are safe in pregnancy. Some warn against the use of nitrofurantoin in women with G-6-PD deficiency due to the possibility of hemolytic anemia; however, data do not support this. Sulfonamides are associated with fetal kernicterus and should be avoided during the 3rd trimester. Similarly, quinolones are Class C drugs and no controlled human data are published regarding their safety in pregnancy. In fact, pregnant animal studies using quinolones in the first trimester resulted in major fetal malformations, and, therefore, quinolones should not be used in pregnancy.

• Pregnant women with sickle-cell hemoglobinopathies are also at increased risk for UTI, as are patients with renal transplantation or orthotopic diversions. Patients with these high-risk conditions may benefit from more aggressive screening (culture vs dipstick) and antibiotic prophylaxis.

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 will progress to 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. The majority of cases (73%) 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 due primarily to bacterial endotoxin damage. Ten to fifteen percent of pregnant women with pyelonephritis develop bacteremia. Respiratory insufficiency occurs in 2-8% of patients because of endotoxin alveolar damage and pulmonary edema. Respiratory embarrassment can be exacerbated by iatrogenic fluid overload and tocolytics. Renal dysfunction can occur 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 been called into question recently.

• 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 mild preeclamptics and 35.9% in severe preeclamptics. The authors hypothesize that underlying renal damage weakens the patients' systemic defense mechanisms against ascending infection.

    　

• Effects on fetus

  　

  • Maternal UTI has few direct fetal sequelae, since 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 the majority of cases of bacteriuria and UTI in pregnancy, 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 keep 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 1 hand, spread the labia, then
         　
      2. With the other, 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 her bladder contents into the toilet and
         　
      4. Catch the middle portion in the sterile collection container, all the while keeping her labia spread with her 1st hand
  • However, a recent study on pregnant adolescents suggests the cleansing process does not prevent contamination.

MISCELLANEOUS

Medical/Legal Pitfalls:
　

• Twenty-five percent of untreated ASB cases progress to pyelonephritis. No landmark cases of failure to diagnose exist; however, medicolegal liability might be encountered if complications from pyelonephritis develop.

Special Concerns:
　

• Beta streptococcus
  • Beta streptococcus is an important pathogen in pregnancy, since early and late complications of neonatal beta-streptococcal infection are well documented. Incidental documentation of beta-streptococcal bacteriuria deserves acute treatment and antibiotic prophylaxis when the patient presents in labor.
    　
  • Questions exist whether beta streptococcus is associated with preterm labor. McKenzie and colleagues prospectively found no relation of beta-streptococcal bacteriuria to pre-term labor, but describe the use of urinary antibodies to identify at-risk women. Women with E coli antibodies at initial visit and at 28 weeks, and women with beta streptococcus antibodies at 28 weeks had a significantly higher chance of preterm delivery in 2043 consecutive women.

    　

• Caesarean section
  • Cesarean section is associated with UTI (2.7 times more likely), but may be confounded by bladder catheterization or 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. One example is orthotopic continent diversion (OCD), where 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 extrophy of the bladder, in whom primary reconstruction has failed. Recurrent UTI and hydronephrosis are common due to 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. They concluded that outpatient therapy is as safe and effective in the treatment of pyelonephritis before 24 weeks' gestation. However, the prevailing attitude still dictates that aggressive inpatient hydration and parenteral antibiotics is necessary. In early pregnancy, pyelonephritis places the patient at risk for spontaneous abortion and, after 24 weeks, preterm labor.

    In their study, Millar et al treated outpatients with 2 doses of intramuscular ceftriaxone and 10 days of oral cephalexin. Equal numbers of patients failed initial outpatient therapy and traditional inpatient therapy. Benefits include the obvious cost savings and psychosocial benefits for the patient. Risks include the development of septic shock or respiratory insufficiency at home during outpatient therapy and strict guidelines for an observation period before ED discharge, patient education, and home nursing are discussed. If you consider outpatient therapy, then only selected patients in their second trimester should be considered. More study is necessary before considering a change in your practice pattern.