Approach Considerations
Treatment of bacteriuria and cystitis
Because of the dangers of maternal and fetal complications, acute care should focus on identifying and treating asymptomatic and symptomatic bacteriuria, along with ensuring that an alternative process is not the cause of the symptoms. Treatment of asymptomatic bacteriuria has been shown to reduce the incidence of low birth weight and preterm birth. [24, 28]
Behavioral practices
Any discussion of treatment should be prefaced with a discussion of behaviors that may be used to ensure good hygiene and reduce bacterial contamination of the urethral meatus, thereby preventing inadequate treatment and recurrent infection. Behavioral methods include the following:
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Avoid baths
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Wipe front-to-back after urinating or defecating
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Wash hands before using the toilet
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Use washcloths to clean the perineum
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Use liquid soap to prevent colonization from bar soap
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Clean the urethral meatus first when bathing
Antibiotic therapy
Oral antibiotics are the treatment of choice for asymptomatic bacteriuria and cystitis. Treatment is most commonly initiated empirically before culture and susceptibility results return. A meta-analysis concluded that although antibiotic treatment is effective in patients with UTIs, the data are insufficient to recommend any specific regimen for treatment of symptomatic UTIs during pregnancy. [29, 30] All of the antibiotics studied were effective in terms of both increasing cure rates of UTI in pregnancy and decreasing the incidence of associated adverse outcomes. Current oral regimens are summarized in Table 1 below.
Table. (Open Table in a new window)
Table 1. Treatment Regimens for Pregnant Women with Asymptomatic Bacteruria or UTI |
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Antibiotics most commonly given as empiric therapy are cephalexin, amoxicillin-clavulanate, or fosfomycin, due to their broader spectrum of coverage than the other antibiotic options. The resistance of Escherichia coli to ampicillin and amoxicillin is 20-40%; accordingly, these agents are no longer considered optimal for treatment of UTIs caused by this organism.
Although 1-, 3-, and 7-day antibiotic courses have been evaluated, 10-14 days of treatment is usually recommended to eradicate the offending bacteria. For example, studies with cephalexin, trimethoprim-sulfamethoxazole, and amoxicillin have indicated that a single dose is as effective as a 3- to 7-day course of therapy, but the cure rate is only 70%. A systematic review that compared single-dose antibiotic treatment with 4- to 7-day treatments concluded that single-dose regimens may be less effective than a short-course regimen, but until more data become available from large trials, pregnant women with asymptomatic bacteriuria should be treated with the standard regimen. [30]
Treatment success depends on eradication of the bacteria rather than on the duration of therapy. A test-for-cure urine culture should show negative findings 1-2 weeks after completion of therapy. A nonnegative culture result is an indication for a 10- to 14-day course of a different antibiotic.
Recurrent cystitis
Pregnant women who have three or more episodes of cystitis or bacteruria should be started on daily antibiotic prophylaxis for the remainder of pregnancy. Daily antibiotics should also be considered in pregnant women after one episode of pyelonephritis. Regimens for daily prophylaxis includes nitrofurantion 100 mg nightly, or cephalexin 250-500 mg nightly. A Cochrane review in 2015 noted that the rates of recurrent UTI were no different with a daily dose of nitrofurantoin and close surveillance versus close surveillance alone. More research needs to be done to evaluate this, especially due to the increasing prevalence of antibiotic resistance.
In patients who are immunosuppressed or have medical conditions that would increase the risk of complications from cystitis, it is reasonable to consider antibiotic prophylaxis after one episode of cystitis.
Treatment of pyelonephritis
The standard course of treatment for pyelonephritis consists of hospital admission and intravenous (IV) administration of antibiotics until the patient has been afebrile for 48 hours. The recommended IV antibiotic would be a broad spectrum beta-lactam, such as ceftriaxone. Once culture results with susceptibilities become available and the patient is clinically improved, treatment can be transitioned to an oral antibiotic regimen. For women with a history of extended-spectrum beta-lactamase (ESBL) Enterobacter, a carbapenem is recommended. Patients should be discharged with 10-14 days of antibiotic treatment, and then will need daily prophylactic antibiotics for the remainder of pregnancy.
IV fluids must be administered with caution. Patients with pyelonephritis can become dehydrated because of nausea and vomiting and need IV hydration, but they are at high risk for the development of pulmonary edema and acute respiratory distress syndrome (ARDS).
Fever should be managed with antipyretics (preferably, acetaminophen) and nausea and vomiting with antiemetics. If fever persists beyond 24 hours, urine and blood cultures should be repeated and a renal ultrasound should be performed.
Preterm labor and delivery are additional risks associated with pyelonephritis. These risks must be evaluated and treated early in the course of admission with tocolysis as necessary per the preterm labor guidelines. If the patient is septic, tocolysis is not recommended.
Inpatient versus outpatient treatment
The prevailing view is that pregnant patients with pyelonephritis require aggressive inpatient hydration and parenteral antibiotics. Pyelonephritis places the patient at risk for spontaneous abortion in early pregnancy and for preterm labor after 24 weeks’ gestation.
However, a randomized, controlled trial of outpatient treatment of pyelonephritis in pregnancy by Millar et al concluded that outpatient therapy is as safe and effective as inpatient care in the treatment of pyelonephritis before 24 weeks’ gestation. [31] Benefits of outpatient care include cost savings and the psychosocial benefits for the patient. Risks include septic shock and respiratory insufficiency. Consideration of outpatient therapy should be limited to selected patients in their second trimester. More study is necessary before a change in the physician’s practice pattern is considered.
Antibiotic selection
Antibiotic selection should be based on urine culture sensitivities, if known. Often, therapy must be initiated on an empirical basis, before culture results are available. This requires clinical knowledge of the most common organisms and their practice-specific or hospital-specific sensitivities to medications.
Institution-specific drug resistances should also be considered before a treatment antibiotic is chosen. For instance, with E coli infection alone, resistance to ampicillin can be as high as 28-39%. Resistance to trimethoprim-sulfamethoxazole has been described as 31%, and resistance to first-generation cephalosporins may be as high as 9-19%.
Maternal physiologic changes that influence pharmacokinetics include increased glomerular filtration rate (GFR) and renal plasma flow, increased volume of distribution, decreased gastric motility and emptying, and decreased albumin levels. Serum levels of antibiotics are lower in pregnancy because of the gross increase in blood volume and the increased GFR.
Some antibiotics should not be used during pregnancy, because of their effects on the fetus. These include the following:
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Tetracyclines (adverse effects on fetal teeth and bones)
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Fluoroquinolones; avoid during pregnancy and lactation (toxic to developing cartilage)
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Trimethoprim-sulfamethoxazole; avoid during first and third trimester
Aminoglycosides have been associated with ototoxicity following prolonged fetal exposure and should be avoided if possible. However, amoxicillin plus gentamicin may be considered for treatment of pyelonephritis in patients with intolerance to recommended agents. [28]
Fosfomycin does not achieve therapeutic levels in the kidneys and therefore should not be used in cases of pyelonephritis.
Nitrofurantoin is safe and effective; however, poor tissue penetration has limited its use in pyelonephritis. Use near delivery can cause hemolytic anemia in the fetus or neonate as a consequence of their immature erythrocyte enzyme systems (glutathione instability). Nitrofurantoin has also been associated with cardiac birth defects when taken in the first trimester. [32] Given this risk profile, use of nitrofurantoin is best limited to the second trimester. However, nitrofurantoin is also safe and effective for once-daily prophylactic therapy during pregnancy. [33]
Macrolides are not first-line agents for UTI in pregnancy. However, they are well tolerated by mother and fetus.
Trimethoprim-sulfamethoxazole is a safe medication to treat UTIs during the second trimester. Trimethoprim is a folic acid antagonist and has been associated with an increased risk of birth defects when taken in the first trimester during organogenesis. [32] Sulfonamides are avoided at term because they displace the bilirubin from its binding site in the newborn, which theoretically increases the risk of kernicterus.
Surgical treatment
Surgical care is rarely indicated. Cystoscopy may aid in establishing the diagnosis of urethral or bladder diverticulum, bladder stones, urethral syndrome, lower urinary tract trauma, interstitial cystitis, or bladder cancer.
A retrograde stent or a percutaneous nephrostomy tube should be placed to relieve ureteral colic or decompress an obstructed infected collecting system. More invasive procedures, such as ureteroscopic stone extraction, [34] are rarely indicated. Extracorporeal shock wave lithotripsy (ESWL) is contraindicated in pregnancy.
In the rare patient for whom invasive surgical therapy is indicated, the operation should be planned for the second trimester. Surgical intervention during the first trimester is associated with increased risk of miscarriage; surgery in the third trimester is associated with increased risk of preterm labor. Urgent surgical intervention in the third trimester should coincide with delivery of the fetus.
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Twenty-nine-year-old pregnant woman with history of reflux uropathy and ureteral reimplantation at age 21 months presents with right-side flank pain and proteinuria. Renal cortical thinning suggests chronic hydronephrosis.
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Color-flow Doppler highlights normal flow in right kidney of 29-year-old pregnant woman with history of reflux uropathy and ureteral reimplantation at age 21 months who presents with right-side flank pain and proteinuria.
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25-year-old pregnant woman with right lower quadrant pain and hematuria has proximal ureteral obstruction consistent with urolithiasis. After 25 minutes, intravenous pyelography reveals dense right nephrogram and no filling of right collecting system. Left side shows unremarkable nonhydronephrotic collecting system. This is consistent with right ureteral lithiasis.
Tables
Table 1. Treatment Regimens for Pregnant Women with Asymptomatic Bacteruria or UTI |
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