UTI in pregnancy: 6 questions to guide therapy

Lower urinary tract symptoms:

• dysuria
  
• frequency
  
• urgency
  
• suprapubic pain
  
• hematuria in the absence of fever and systemic symptoms
  

Frequency, of course, is difficult to ascertain in pregnancy, since most women experience this complication secondary to increased urinary output due to higher fluid intake, increased plasma volume expansion, and increases in renal blood flow and glomerular filtration rate.

Upper urinary tract symptoms:

• fever
  
• chills
  
• flank pain
  
• nausea and vomiting
  
• The patient may or may not have the symptoms of lower urinary tract infection, as well.
  

Positive culture and no symptoms

This profile is typical of asymptomatic bacteriuria, a lower urinary tract infection that occurs in 2% to 7% of pregnancies.¹

Positive culture with symptoms

This profile probably reflects either:

• Acute cystitis, a lower urinary tract infection affecting 1% to 2% of pregnancies,⁸ or
  
• Acute pyelonephritis, an upper urinary tract infection affecting 2% of pregnancies.⁹
  

What are the consequences of UTI in pregnancy?

Maternal complications

Asymptomatic bacteriuria does not plague the patient with bothersome effects, but if left untreated, asymptomatic bacteriuria will progress to symptomatic UTI: 25% will develop acute pyelonephritis, compared to 3% to 4% of treated patients¹⁰; 20% of women with severe pyelonephritis develop serious complications,¹¹ including:

• sepsis and septic shock,
  
• hemolysis and thrombocytopenia,¹²
  
• acute respiratory distress syndrome,¹³
  
• renal insufficiency.¹⁴
  

Adverse fetal outcomes

Untreated asymptomatic bacteriuria is associated with preterm delivery and low birthweight.^15-17

Acute pyelonephritis is linked to preterm birth.^18,19 Kaul et al,²⁰ in an experimental model of pyelonephritis in mice, confirmed that E. coli plays an important role in the pathogenesis of preterm delivery and low birthweight.

What is the best treatment regimen?

Data are insufficient to recommend any specific regimen.^21,22 The following strategies are based on evaluation of review articles.^3,23

Asymptomatic bacteriuria and acute cystitis

Nitrofurantoin monohydrate macrocrystals is my first-line treatment. Nitrofurantoin has high concentrations in the urinary tract but induces minimal resistance in gram-negative organisms.

If nitrofurantoin is not effective, I change antibiotics based on urine culture antibiotic sensitivity profiles (FIGURE 2).

Keep in mind the current resistance of E. coli to antibiotics: ampicillin, 28% to 39%; trimethoprim-sulfamethoxazole, 31%; and first-generation cephalosporins, 9% to 19%.²⁴

Single-dose treatment for pregnant women with asymptomatic bacteriuria has been evaluated, given its lower cost and better compliance. However, evidence is insufficient to determine whether single-dose or longer-duration regimens are more effective.²⁵

I recommend longer-duration dosages for now, until a large randomized controlled trial can derive conclusive data.

Remember that treatment success is not contingent upon duration of therapy—just be sure that the test-of-cure urine culture is negative 1 to 2 weeks after treatment is completed.

Acute pyelonephritis

Management should include the following:

• hospitalization
  
• urine and blood cultures
  
• laboratory studies of complete blood cell count, electrolytes, creatinine, and liver function
  
• monitoring of vital signs and urine output
  
• intravenous (IV) crystalloid fluid to maintain urine output
  
• IV antibiotics (FIGURE 3).
  

If symptoms persist after 48 hours despite adequate IV antibiotic therapy, consider other causes such as resistant organisms, nephrolithiasis, perinephric abscesses, renal obstruction, or other infections.

Consider imaging by renal ultrasound to assess the presence of nephrolithiasis, perinephric abscess, or obstruction.

I recommend inpatient treatment for pregnant women with acute pyelonephritis at this time, until further studies are available.

To evaluate outpatient treatment, Millar and colleagues randomized 120 women under 24 weeks’ gestation either to inpatient IV cefazolin until 48 hours afebrile or to outpatient ceftriaxone intramuscularly. (Both treatment arms completed a course of oral cephalexin.) There were no differences in therapeutic response or birth outcomes, but 6 patients in the outpatient arm required hospitalization for IV therapy and 1 woman developed sepsis.²⁶

The same researchers studied 92 patients of more than 24 weeks’ gestation who received 2 doses of ceftriaxone intramuscularly, then were randomized to either continued inpatient therapy until 48 hours afebrile or discharge with reevaluation as an outpatient in 48 to 72 hours. Again, there were no differences in therapeutic response or birth outcomes; however, almost two-thirds of patients were excluded from the study as they did not meet criteria for outpatient management, due to sepsis, preterm labor, or concurrent medical conditions.²⁷

Adequate antibiotic coverage is crucial

To ensure adequate antibiotic coverage when treating UTI, it is important to understand which organisms cause these infections in pregnancy.

E. coli causes 75% to 90% of UTIs in nonpregnant women.²⁸Staphylococcus saprophyticus causes 10% to 15% of UTIs in nonpregnant women, but less in pregnant women.

Group B Streptococcus (GBS)—another gram-positive organism—has important implications for pregnant women: Intrapartum prophylaxis is important, to prevent neonatal GBS disease.²⁹

Klebsiella, Enterobacter, Proteus, and Enterococcus species²⁸ infrequently cause UTI in pregnancy.

What about prophylaxis and follow-up cultures?