How should typhoid fever be treated in a pregnant patient?

Treatment of Typhoid Fever in Pregnancy

Azithromycin 500 mg orally once daily for 7-14 days is the optimal antibiotic choice for pregnant women with uncomplicated typhoid fever. 1

First-Line Antimicrobial Therapy

Azithromycin demonstrates superior outcomes compared to other antibiotics in pregnant women with typhoid fever:

• Lower risk of clinical failure (OR 0.48) compared to fluoroquinolones 2, 1
• Shorter hospital stays (-1.04 days) than fluoroquinolone therapy 2
• Significantly lower relapse risk (OR 0.09) compared to ceftriaxone 2, 1
• Dosing: 500 mg orally once daily for 7-14 days 1

Alternative Antibiotic Options When Azithromycin Is Unavailable

If azithromycin cannot be used, select from these pregnancy-compatible alternatives:

• Ceftriaxone 1-2 g IV/IM daily for 10-14 days (particularly for severe disease or quinolone-resistant strains) 2, 3, 4
• Ampicillin 1-2 g IV every 6 hours for 14 days 3, 4, 5, 6
• Cefotaxime 1-2 g IV every 8 hours for 10-14 days 3, 4
• Trimethoprim-sulfamethoxazole (TMP-SMZ) 160/800 mg orally twice daily for 14 days (avoid in first trimester if possible due to neural tube defect concerns) 3, 4

Critical Contraindications in Pregnancy

Fluoroquinolones (ciprofloxacin, levofloxacin, ofloxacin) must be avoided during pregnancy despite their effectiveness in non-pregnant patients. 3, 4 While older plague guidelines list fluoroquinolones for pregnant women in bioterrorism scenarios 2, current typhoid-specific guidance prioritizes azithromycin or beta-lactams due to over 70% global fluoroquinolone resistance in S. typhi and fetal safety concerns. 2, 1

Diagnostic Approach Before Initiating Treatment

Obtain blood cultures immediately before starting antibiotics—they have the highest diagnostic yield within the first week of symptoms. 1

• Blood cultures are positive in >90% of cases during the first week 6
• Stool cultures have low yield (positive in only 2 of 5 patients in one series) 6
• Urine and cervical cultures are typically negative 6
• Widal titers can support diagnosis but should not delay treatment 6

Expected Clinical Response and Monitoring

Fever should clear within 4-5 days of appropriate antibiotic therapy. 1

• If no clinical improvement occurs by day 5, suspect antimicrobial resistance or alternative diagnosis 1
• Monitor for preterm labor, maternal hemorrhage, and signs of sepsis throughout treatment 2
• Complete the full 7-14 day course to prevent relapse, which occurs in 10-15% of inadequately treated cases 1

Severity of Untreated Typhoid in Pregnancy

The stakes are extraordinarily high—historical data demonstrates:

• 67% maternal mortality when typhoid is untreated during pregnancy 1
• 74% pregnancy loss without treatment 1
• With antimicrobial treatment, maternal mortality decreases to 29% and pregnancy loss to 62% 1
• Increased risk for preterm birth, hemorrhage, and maternal-fetal transmission 1, 7

Hospitalization Criteria

Consider hospitalization for:

• Severe dehydration requiring IV fluid replacement 3, 4
• Second or third trimester patients (for monitoring of preterm labor and hemorrhage) 2
• Signs of sepsis or severe systemic illness 2
• Inability to tolerate oral medications 2

Resistance Pattern Considerations

Over 70% of S. typhi isolates globally are now resistant to fluoroquinolones, making azithromycin or ceftriaxone superior empiric choices. 1

• For quinolone-resistant strains (particularly common in South Asia), azithromycin or ceftriaxone are first-line 2, 1
• Multidrug-resistant strains (resistant to chloramphenicol, ampicillin, TMP-SMZ) require azithromycin or third-generation cephalosporins 2

Common Pitfalls to Avoid

• Do not use chloramphenicol as first-line therapy in pregnancy despite its historical use 5, 6—azithromycin has better safety and efficacy data 2, 1
• Do not delay treatment waiting for culture results if clinical suspicion is high—typhoid in pregnancy is a medical emergency 1, 7
• Do not use antiperistaltic agents (loperamide) in pregnant women with suspected typhoid 4
• Do not assume negative stool/urine cultures rule out typhoid—blood cultures are far more sensitive 6

Supportive Care Measures

• Aggressive IV hydration for dehydration 3, 4
• Antiemetics (ondansetron or metoclopramide) for nausea/vomiting 4
• VTE prophylaxis with low-molecular-weight heparin during hospitalization 4
• Evaluate household contacts for asymptomatic carriage to prevent reinfection 3, 4