Bacteruria in Pregnancy

Pathophysiology

• Urologic Anatomic and Physiologic Changes during Pregnancy (4)
  1. Increase in renal size (≈1cm); thought to be result of increased renal vascular and interstitial volume
  2. Hydronephrosis from:
     1. Obstructive effect of the enlarging uterus (likely main factor)
     2. Progesterone mediated relaxation of smooth muscle of collecting system and bladder resulting in decreased collecting system and ureteral peristalsis, ureteral dilatation, increased bladder capacity
  3. Bladder changes; enlarging uterus displaces bladder, progesterone stimulates relaxation resulting in increased capacity; estrogen may cause bladder hypertrophy
  4. Improved renal function; glomerular filtration increases by 30-50%, and urinary protein excretion increases; values considered normal in non-pregnant females may represent renal insufficiency during pregnancy. Similarly, urinary protein in pregnancy is not considered abnormal until > 300 mg of protein in 24 hours is excreted
• Changes to the urinary tract in pregnancy that increase risk of UTI:
  1. Decreased bladder tone because of edema and hyperemia
  2. Increased urine volume in the upper collecting system as the physiologic dilation of pregnancy evolves, can increase the propensity to develop pyelonephritis
• Complications associated with bacteruria during pregnancy
  1. Pyelonephritis
  2. Prematurity and prenatal mortality
  3. Maternal anemia (conflicting evidence)
• Recurrent UTIs are not a contraindication to pregnancy
• Pregnancy in women with renal insufficiency
  • The degree of renal function impairment is the major determinant for pregnancy outcome
    • Fetal survivors of pregnant women with mild or moderate renal disease is only slightly diminished.
    • However, the perinatal mortality is approximately 4x higher with severe disease

Pathogens

• Similar to non-pregnant females

Asymptomatic bacteriuria

• One of the most common infections encountered during pregnancy.
  • Prevalence of bacteriuria in pregnant females varies from 4-7%
• Prevalence of asymptomatic bacteriuria in pregnancy is similar to that of the general population
• More likely to progress to pyelonephritis
  • Spontaneous resolution of asymptomatic bacteriuria in pregnant females is unlikely unless treated, unlike non-pregnant females who often clear their asymptomatic bacteriuria
    • Risk of UTI progression to pyelonephritis
      • Non-pregnant females: 1%§
      • Pregnant females: 20-40%
        • Factors contributing to increased risk of progression from asymptomatic bacteruria to acute clinical pyelonephritis in pregnancy (2):
          1. Anatomic and physiologic changes induced by the gravid state (see above)
          2. Urine from pregnant females exhibits a more suitable pH for growth of E. coli in all stages of gestation.
        • Treatment for asymptomatic bacteruria reduces the risk of pyelonephritis to 0-5%.

Diagnosis and Evaluation

• Labs: initial screening culture (significant false-negative rates with urinalysis or reagent strip testing) should be performed in all pregnant women during the first trimester
  • If the culture shows no growth, repeat cultures are generally unnecessary because patients who have no growth in their urine early in their pregnancy are unlikely to develop bacteriuria later

Management

• Pregnant females with bacteruria should be prescribed a full 3-7 day course of therapy
  • Pregnant females with acute pyelonephritis should be hospitalized and treated initially with parenteral antimicrobial agents.
• Agents considered safe (4):
  • Penicillins
    • Ampicillin 500mg qid
    • Amoxicillin 250mg tid
    • Penicillin V 500mg qid
  • Cephalosporins
    • Cephalexin 500mg qid
    • Cefaclor 500mg qid
  • Nitrofurantoin (if penicillin allergy) 100mg qid
    • Should be discontinued at 35 weeks (see above)
  • Fosfomycin (§)
• Agents that should be avoided:
  1. Fluoroquinolones: risk of damage to immature cartilage
  2. Trimethroprim: risk of megaloblastic anemia because of anti-folic acid action
  3. TMP/SMX: early, risk of teratogenicity; late, risk of kernicterus
  4. Nitrofurantoin: avoid during 3rd trimester due to risk of hemolytic anemia
  5. Chloramphenicol: risk of “gray baby” syndrome
  6. Erythromycin: risk of maternal cholestatic jaundice
  7. Tetracyclines: risk acute liver decompensation in the mother and inhibition of new bone growth in the fetus
• Follow-up cultures should be obtained to document absence of infection.
  • If the culture is positive, the cause of bacteriuria must be determined to be lack of resolution, bacterial persistence, or reinfection.
    • If the infection is unresolved, proper selection and administration of another drug probably will solve the problem.
    • If the problem is bacterial persistence or rapid reinfection, antimicrobial suppression of infection or prophylaxis throughout the remainder of the pregnancy should be considered.
• If a pregnant female has a single episode of pyelonephritis or two episodes of cystitis, daily suppression with either nitrofurantoin or cephalexin should be considered until delivery.

References

• Wein AJ, Kavoussi LR, Partin AW, Peters CA (eds): CAMPBELL-WALSH UROLOGY, ed 11. Philadelphia, Elsevier, 2015, vol 2, chap 12