What is a pregnancy-safe drug for treating typhoid?

Pregnancy-Safe Drug for Typhoid Fever

Azithromycin is the preferred first-line antibiotic for treating typhoid fever in pregnancy, given at 500 mg once daily for 7-14 days, based on its superior efficacy profile and lack of documented fetal harm. 1, 2, 3

Treatment Algorithm for Pregnant Women with Typhoid

First-Line Therapy

• Azithromycin 500 mg orally once daily for 7-14 days is the optimal choice for pregnant women with uncomplicated typhoid fever 1, 3
• Azithromycin demonstrates lower risk of clinical failure (OR 0.48) and shorter hospital stays compared to fluoroquinolones 4, 3
• Risk of relapse is significantly lower with azithromycin (OR 0.09) compared to ceftriaxone 4, 3
• A systematic review found no evidence of association between fluoroquinolone exposure during pregnancy and pregnancy loss or birth defects, but azithromycin remains preferred due to superior efficacy in resistant strains 4

Second-Line Therapy for Severe Cases

• Ceftriaxone 1-2g IV/IM daily for 5-7 days should be used for severe or complicated typhoid requiring hospitalization 1, 5
• Ceftriaxone achieves rapid clinical response with mean defervescence of 4 days and allows short treatment courses of 5-8 days 5, 6
• Blood cultures become negative faster with ceftriaxone compared to chloramphenicol (0% vs 60% positive on day 3) 6

Alternative Options When Susceptibility is Confirmed

• Ciprofloxacin 500 mg every 8 hours orally can be used if susceptibility testing confirms sensitivity, though this should be avoided for cases originating from South Asia where resistance exceeds 70-96% 1, 7
• Fluoroquinolones have not been associated with pregnancy loss or birth defects in systematic reviews 4

Critical Considerations for Pregnancy

Safety Profile

• Historical data from 160 published cases showed 67% maternal fatality and 74% pregnancy loss when typhoid was untreated during pregnancy 4
• With antimicrobial treatment, maternal fatality decreased to 29% and pregnancy loss to 62%, emphasizing the critical importance of prompt therapy 4
• Pregnant women with typhoid are at increased risk for preterm birth, hemorrhage, and potential maternal-fetal transmission 4
• A study of 30 pregnant women treated with chloramphenicol, ampicillin, or cotrimoxazole showed effective infection resolution with only 3 abortions and 2 malformed babies, though these older agents are no longer first-line 8

Drugs to Avoid in Pregnancy

• Avoid fluoroquinolones as empiric therapy for cases from South or Southeast Asia due to resistance rates approaching 96% 1, 7
• Streptomycin should not be used due to documented irreversible fetal ototoxicity 4
• Gentamicin is preferred over streptomycin among aminoglycosides if this class is required, though azithromycin or ceftriaxone are better choices 4

Diagnostic Approach Before Treatment

• Obtain blood cultures immediately before starting antibiotics whenever possible, as they have the highest diagnostic yield within the first week of symptoms 1, 2
• For patients with sepsis features, start broad-spectrum therapy immediately after collecting cultures rather than delaying treatment 1, 2
• A case report of ceftriaxone-resistant typhoid in a pregnant traveler from Pakistan highlights that pregnancy and unawareness of resistance patterns can delay appropriate therapy 9

Monitoring and Expected Response

• Expect fever clearance within 4-5 days of appropriate antibiotic therapy 1, 2
• If no clinical improvement occurs by day 5, consider antimicrobial resistance or alternative diagnosis 1
• Complete the full 7-14 day course to prevent relapse, which occurs in 10-15% of inadequately treated cases 1, 3
• Monitor for complications including intestinal perforation (10-15% risk if illness duration exceeds 2 weeks), gastrointestinal bleeding, and typhoid encephalopathy 3

Common Pitfalls to Avoid

• Never use ciprofloxacin empirically for cases originating from South Asia due to widespread fluoroquinolone resistance exceeding 70% 1, 2, 7
• Do not discontinue antibiotics prematurely even if fever resolves early; complete the full course to prevent relapse 1
• Do not delay treatment due to pregnancy concerns; the risks of untreated typhoid far outweigh potential medication risks 4
• Be aware that ceftriaxone-resistant strains are now emerging from Pakistan, and meropenem may be warranted in severe cases from this region 9

Resistance Pattern Considerations

• Over 70% of S. typhi isolates globally are now resistant to fluoroquinolones, making azithromycin or ceftriaxone better empiric choices 2, 7
• For quinolone-resistant strains (common in South Asia), azithromycin or ceftriaxone are recommended as first-line therapy 4, 3
• Always consider local resistance patterns when selecting empiric therapy, as these vary geographically and change over time 1, 2