Urinary Tract Infections in Pregnancy Treatment & Management

Treatment of bacteriuria and cystitis

Because of the dangers of maternal and fetal complications, acute care (eg, in the emergency department [ED]) should focus on identifying and treating asymptomatic and symptomatic bacteriuria, along with ensuring that an alternate process is not the cause of the symptoms.

Treatment of asymptomatic bacteriuria in pregnant patients is important because of the increased risk of urinary tract infection (UTI) and its associated sequelae.^[16] ED care may involve the following:

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

Behavioral methods

Any discussion of treatment should be prefaced with a discussion of behavioral methods that may be used to ensure good hygiene and reduce bacterial contamination of the urethral meatus, thereby preventing inadequate treatment and recurrent infection. Behavioral methods include the following:

• Avoid baths
• Wipe front-to-back after urinating or defecating
• Wash hands before using the toilet
• Use washcloths to clean the perineum
• Use liquid soap to prevent colonization from bar soap
• Clean the urethral meatus first when bathing

Antibiotic therapy

Oral antibiotics are the treatment of choice for asymptomatic bacteriuria and cystitis. Appropriate oral regimens include the following:

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

The resistance of E coli to ampicillin and amoxicillin is 20-40%; accordingly, these agents are no longer considered optimal for treatment of UTIs caused by this organism. Fosfomycin, a phosphonic acid derivative, is useful in the treatment of uncomplicated UTIs caused by susceptible strains of E coli and Enterococcus species. Fosfomycin is a category B agent in pregnancy (ie, fetal risk is not confirmed by human studies but has been shown in some animal studies).

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%. The data are insufficient to justify abandoning the more traditional long-term regimens.

Treatment success depends on eradication of the bacteria rather than on the duration of therapy. A test-for-cure urine culture should show negative findings 1-2 weeks after therapy. A nonnegative culture result is an indication for a 10- to 14-day course of a different antibiotic, followed by suppressive therapy (eg, nitrofurantoin 50 mg at bedtime) until 6 weeks postpartum.

Mathai et al suggest the need for disseminated guidelines for practitioners in developing countries such as India.^[17] Their study documented inappropriate use of antibiotics in terms of safety, cost, susceptibility, and threat for developing resistance.

Treatment of pyelonephritis

The standard course of treatment for pyelonephritis consists of hospital admission and intravenous (IV) administration of cephalosporins or gentamicin. IV fluids must be administered with caution. Patients with pyelonephritis can become dehydrated because of nausea and vomiting and need IV hydration. However, they are at high risk for the development of pulmonary edema and acute respiratory distress syndrome (ARDS).

Fever should be managed with antipyretics (preferably, acetaminophen) and nausea and vomiting with antiemetics. Most antiemetics can be used for adverse effects caused by antibiotics, but doxylamine, Emetrol (Wellspring, Sarasota, FL; pregnancy class A), dimenhydrinate, and metoclopramide (pregnancy class B) are preferred.

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

In a randomized, controlled trial of outpatient treatment of pyelonephritis in pregnancy, Millar et al concluded that outpatient therapy is as safe and effective as inpatient care in the treatment of pyelonephritis before 24 weeks’ gestation.^[18] However, the prevailing view is still that aggressive inpatient hydration and parenteral antibiotics are necessary. Pyelonephritis places the patient at risk for spontaneous abortion in early pregnancy and for preterm labor after 24 weeks’ gestation.

In their study, Millar et al treated outpatients with 2 doses of intramuscular (IM) ceftriaxone and 10 days of oral cephalexin.^[18] Initial outpatient therapy and traditional inpatient therapy failed to cure equal numbers of patients. Benefits include the obvious cost savings and the psychosocial benefits for the patient. Risks include septic shock and respiratory insufficiency at home during outpatient therapy.

Strict guidelines for an observation period before ED discharge, patient education, and home nursing have been discussed. In addition, approximately two thirds of the outpatient treatment group did not complete the study because the subjects developed 1 or more complications.^[18] If outpatient therapy is considered, only selected patients in their second trimester should be considered. More study is necessary before a change in the physician’s practice pattern is considered.

Antibiotic selection

Antibiotic selection should be based on urine culture sensitivities, if known. Often, therapy must be initiated on an empirical basis, before culture results are available. This requires clinical knowledge of the most common organisms and their practice-specific or hospital-specific sensitivities to medications.

Institution-specific drug resistances should also be considered before a treatment antibiotic is chosen. For instance, with E coli infection alone, resistance to ampicillin can be as high as 28-39%. Resistance to trimethoprim-sulfamethoxazole has been described as 31%, and resistance to first-generation cephalosporins may be as high as 9-19%.

Maternal physiologic changes that influence pharmacokinetics include increased glomerular filtration rate (GFR) and renal plasma flow, increased volume of distribution, decreased gastric motility and emptying, and decreased albumin levels. Serum levels of antibiotics are lower in pregnancy because of the gross increase in blood volume and the increased GFR.

Some antibiotics should not be used during pregnancy, because of their effects on the fetus. These include tetracyclines (adverse effects on fetal teeth and bones and congenital defects), trimethoprim in the first trimester (facial defects and cardiac abnormalities), chloramphenicol (gray syndrome), and sulfonamides (hemolytic anemia in mothers with glucose-6-phosphate dehydrogenase [G6PD] deficiency, jaundice, and kernicterus) in the third trimester.

Fluoroquinolones are contraindicated in pregnancy. Although in utero exposure is not an indication for termination, fetal exposure to fluoroquinolones has been associated with myelomeningocele, hydrocephaly, hypospadias, maldescended testes, inguinal hernia, bilateral hip dysplasia, and atrial septal defects. That the anomalies seem not to follow a particular pattern may be reassuring; however, a causal relation cannot be excluded.

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

Macrolides are not first-line agents for UTI in pregnancy. However, they are well tolerated by mother and fetus. A meta-analysis concluded that although antibiotic treatment is effective in patients with UTIs, the data are insufficient to recommend any specific regimen for treatment of symptomatic UTIs during pregnancy.^{[19, 31]} All of the antibiotics studied were effective in terms of both increasing cure rates of UTI in pregnancy and decreasing the incidence of associated adverse outcomes. Current regimens are summarized in Table 1 below.

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

Surgical treatment

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

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

A retrograde stent or a percutaneous nephrostomy tube should be placed to relieve ureteral colic or decompress an obstructed infected collecting system. More invasive procedures, such as ureteroscopic stone extraction,^[30] are rarely indicated. Extracorporeal shock wave lithotripsy (ESWL) is contraindicated in pregnancy.

In the rare patient for whom invasive surgical therapy is indicated, the operation should be planned for the second trimester. Surgical intervention during the first trimester is associated with miscarriage; surgery in the third trimester is associated with preterm labor. Urgent surgical intervention in the third trimester should coincide with delivery of the fetus.