Management of Urinary Tract Infection (UTI) in Pregnancy

Introduction

1. Asymptomatic bacteriuria (ASB)
2. Acute cystitis
3. Acute pyelonephritis

Why Pregnancy Predisposes to UTI (Pathophysiology)

• Progesterone effect: Reduces ureteral smooth muscle tone and peristalsis, causing urinary stasis
• Mechanical obstruction: The enlarging uterus compresses the ureters (more on the right), causing physiologic hydronephrosis
• Bladder changes: Decreased tone, increased capacity, and incomplete emptying promote vesicoureteral reflux
• Altered urine chemistry: Increased urinary pH (from bicarbonate excretion), glycosuria, and increased estrogen excretion all favor bacterial growth and E. coli proliferation
• The cumulative result is static columns of urine in the ureters, facilitating the ascent of bacteria to the upper urinary tract

Causative Organisms

• E. coli - >70-85% of all infections; virulent strains possess fimbriae (P-fimbriae/pili) that enable attachment to urothelial cells
• Klebsiella spp.
• Proteus spp. (especially in diabetics or obstruction)
• Enterococci
• Staphylococcus saprophyticus
• Pseudomonas spp.
• (Source: Comprehensive Clinical Nephrology, 7th Ed., Box 44.1)

1. Asymptomatic Bacteriuria (ASB)

Definition

Epidemiology

• Prevalence: 2%-11% of pregnant women
• Higher in lower socioeconomic groups and increases with age, parity, and coexistent genital infection
• More common with urinary tract anomalies, reflux nephropathy, neurogenic bladder, and diabetes
• Most cases of ASB are detected at the first prenatal visit (bacteriuria typically antedates pregnancy)

Why Treat ASB?

• Without treatment: ~40% of bacteriuric women developed pyelonephritis
• With treatment: pyelonephritis risk reduced to 1%-4%
• Untreated ASB was also associated with 2-3x higher rates of prematurity and neonatal death

Treatment of ASB

• TMP-SMX: Avoid in the first trimester (associated with NTDs, cardiac defects, choanal atresia, diaphragmatic hernia) and near term (bilirubin displacement risk causing neonatal hyperbilirubinemia)
• Ampicillin/Amoxicillin: E. coli resistance to ampicillin in the US is >30%, limiting utility
• Fluoroquinolones: Traditionally avoided due to concerns about fetal cartilage toxicity; however, accumulating human data suggest probable safety, so they may be used for highly resistant organisms (ciprofloxacin 250 mg BID or levofloxacin 250 mg daily for 7-10 days)
• Nitrofurantoin: Avoid at term (>38 weeks) due to risk of neonatal hemolytic anemia

Suppressive Therapy for Persistent/Recurrent ASB

• Nitrofurantoin macrocrystals 100 mg at bedtime (preferred, nightly for duration of pregnancy)
• TMP-SMX DS 160/800 mg at bedtime (avoid first trimester and near term)

2. Acute Cystitis

Definition and Diagnosis

Epidemiology

• Occurs in 1%-2% of pregnancies
• Risk is not associated with ASB (in contrast to pyelonephritis); thus, screening/treating ASB does not prevent acute cystitis

Treatment

Prevention of Recurrent Cystitis

3. Acute Pyelonephritis

Definition and Epidemiology

• Incidence: 1%-2.5% of pregnancies; up to 14 per 1000 deliveries in prospective studies
• Most common between 20-28 weeks' gestation
• Right kidney is affected more often (greater physiologic ureteral dilation on right)
• Recurrence in same pregnancy: 10%-18% without suppressive therapy, <10% with it
• Bacteremia: common and usually transient, but sepsis can develop
• Without universal ASB screening: ~40% of bacteriuric women develop pyelonephritis; with screening: incidence reduced by >80%

Risk Factors

• Untreated ASB (most important)
• Previous episodes of pyelonephritis
• Young maternal age, nulliparity
• Urologic abnormalities (obstruction, vesicoureteral reflux, calculi)
• Diabetes mellitus

Clinical Features

• High fever (often with rigors), nausea, vomiting
• Flank/loin pain, costovertebral angle tenderness
• Lower urinary tract symptoms may or may not precede it
• Can present as acute abdominal pain
• May trigger preterm labor (via proinflammatory cytokines in response to bacterial endotoxins)

Complications of Pyelonephritis in Pregnancy

1. Sepsis and septic shock
2. ARDS (adult respiratory distress syndrome)
3. Acute kidney injury (AKI)
4. Disseminated intravascular coagulation (DIC)
5. Preterm birth
6. Anemia (bacterial hemolysins destroy red cells)
7. Pyonephrosis and perinephric abscess (rare)

Management of Acute Pyelonephritis in Pregnancy

Initial Assessment

• Urine culture and sensitivity (blood cultures if sepsis suspected)
• FBC, renal function, electrolytes
• Renal ultrasound (to exclude obstruction or calculi; note: physiologic hydronephrosis is normal in pregnancy and should not be misinterpreted)
• Continuous fetal monitoring

General Supportive Measures

• IV fluid resuscitation (aggressive hydration - risk of pulmonary edema means careful monitoring is needed)
• Antipyretics (paracetamol/acetaminophen) - important because hyperthermia increases fetal metabolic demands and is teratogenic in early pregnancy
• Antiemetics as needed

Antibiotic Therapy (as per BOX 48.1, Creasy & Resnik's MFM)

• Ceftriaxone 1-2 g IV once daily (drug of choice) - excellent broad-spectrum coverage against major uropathogens except Enterococcus
• Ampicillin + Gentamicin (ampicillin 1-2 g IV 6-hourly + gentamicin 1.5 mg/kg 8-hourly or 5 mg/kg once daily) - some centers prefer this combination

• Both maternal and fetal nephrotoxicity and ototoxicity are possible, especially with prolonged use
• Aminoglycosides are best avoided unless:
  • The organism is resistant to other agents
  • Patient is allergic to alternatives
  • Exception: severe septic shock with highly resistant gram-negatives (Pseudomonas, Enterobacter, Citrobacter), where aminoglycosides are warranted
  • If used: monitor serum drug levels. Dose: gentamicin 3-5 mg/kg/24h in 3 divided doses OR 5 mg/kg once daily

• E. coli resistance to ampicillin in US: >30% - not recommended as monotherapy
• E. coli resistance to TMP-SMX: 5%-15% depending on geographic area
• Increasing antimicrobial resistance is complicating management

• Oral cephalosporin (e.g., cephalexin)
• TMP-SMX (if not first trimester and not near term)
• Amoxicillin-clavulanic acid
• Guided by culture and sensitivity results

• Urinary obstruction
• Perinephric abscess
• Renal calculi
• Resistant organism
• Renal ultrasound is the investigation of choice (avoid radiation)

Suppressive Therapy After Pyelonephritis (Critical)

• 30%-40% of women develop recurrent bacteriuria
• If untreated: ~25% develop recurrent pyelonephritis; 60% had recurrent pyelonephritis in some series
• With suppressive therapy: recurrence rate drops to 2.7%-10%

• Nitrofurantoin 100 mg at bedtime (preferred)
• Alternatively: TMP-SMX DS 160/800 mg at bedtime (avoid in first trimester and near term)

Summary Table: UTI in Pregnancy at a Glance

Key Points for the Exam

1. Screen all pregnant women for ASB at first antenatal visit with urine culture (not dipstick alone). The USPSTF and ACOG recommend this.
2. Treat all ASB in pregnancy - evidence (Kass, Cochrane review) supports this reduces pyelonephritis, preterm birth, and low birth weight.
3. All pregnant women with pyelonephritis require hospitalization and IV antibiotics.
4. Ceftriaxone IV is the first-line agent for acute pyelonephritis.
5. Avoid: fluoroquinolones (relatively), TMP-SMX in first trimester and near term, nitrofurantoin at term.
6. Suppressive therapy is mandatory after pyelonephritis for the remainder of pregnancy.
7. Physiologic hydronephrosis on ultrasound (especially right-sided) is a normal pregnancy finding and should not be misinterpreted as obstruction.
8. The most important complication linking ASB → pyelonephritis → preterm birth is the key pathophysiological chain to know.
9. E. coli accounts for >70-85% of all UTIs in pregnancy.
10. Recurrence of pyelonephritis: 60% without suppression vs. <10% with suppressive therapy.