In an adult patient with a positive Typhoid IgM and no drug allergies or contraindications, what is the recommended first‑line treatment regimen?

Treatment of Typhoid IgM Positive Adult Patient

Azithromycin 500 mg once daily for 7-14 days is the recommended first-line treatment for adults with typhoid fever, given widespread fluoroquinolone resistance exceeding 70% in South Asia and superior clinical outcomes compared to other agents. 1

First-Line Treatment: Azithromycin

Azithromycin demonstrates the best overall outcomes with significantly lower clinical failure rates (OR 0.48) compared to fluoroquinolones and dramatically lower relapse rates (OR 0.09) compared to ceftriaxone. 1, 2 Hospital stays are approximately 1 day shorter with azithromycin compared to fluoroquinolones. 1

Dosing Regimen

• Adults: 500 mg orally once daily for 7-14 days 1, 2
• Expect fever clearance within 4-5 days of starting therapy 2, 3

Evidence Supporting Azithromycin

Clinical trials demonstrate azithromycin achieves clinical cure or improvement in 88% of patients by day 8 and 100% by day 14, with 100% bacteriological eradication. 4 A randomized trial comparing azithromycin to ciprofloxacin showed similar efficacy against both sensitive and multidrug-resistant strains, with defervescence occurring at 3.8 days versus 3.3 days respectively. 5

Second-Line Treatment: Ceftriaxone

If azithromycin is unavailable or contraindicated, ceftriaxone is the preferred alternative, particularly for quinolone-resistant strains or when first-line agents fail. 1

Dosing Regimen

• Adults: 2-4 g IV once daily for 5-7 days 1, 3
• Fever clearance occurs within 4-5 days 1, 3
• Clinical cure rates of 79-83% in randomized trials 1

Important Caveat

Ceftriaxone has significantly higher relapse rates (OR 11.1) compared to azithromycin, making it inferior when both options are available. 1, 2 Recent data from India shows ceftriaxone as first-line treatment in hospitalized children, with mean defervescence time of 6.4 days, though 10% required additional antibiotics due to clinical non-response. 6

Critical Geographic Considerations

Never use ciprofloxacin or other fluoroquinolones empirically for cases from South/Southeast Asia, where fluoroquinolone resistance exceeds 70% and approaches 96% in some regions. 2 Infection with nalidixic acid-resistant S. typhi (NARST) is associated with longer duration of fever at presentation (median 10 vs. 4 days), higher frequency of hepatomegaly (57% vs. 15%), and all complications occurring in NARST-infected patients. 7

When to Switch Therapy

If fever persists beyond 5 days on ceftriaxone without clinical improvement, switch immediately to azithromycin. 2, 3 However, do not change antibiotics on day 2 based solely on persistent fever if the patient is clinically stable, as median fever resolution time is 4-5 days, with some patients requiring up to 7-8 days. 3

Indicators for Treatment Change

• No clinical improvement after 4-5 days of appropriate therapy 2, 3
• Clinical deterioration or new complications (intestinal perforation, septic shock) 2, 3
• Hemodynamic instability 3

Common Pitfalls to Avoid

Complete the full 7-14 day course even if fever resolves early, as premature discontinuation increases relapse risk to 10-15%. 2 The FDA label for chloramphenicol recommends continuing therapeutic levels for 8-10 days after the patient becomes afebrile to lessen relapse possibility. 8

Obtain blood cultures before initiating therapy, as culture results guide definitive therapy and identify resistance patterns. 2 For suspected enteric fever with sepsis features, treat empirically with broad-spectrum antimicrobial therapy after blood, stool, and urine culture collection, then narrow therapy when susceptibility results become available. 9

Avoid antimotility drugs (loperamide) in suspected or proven inflammatory diarrhea or diarrhea with fever, as toxic megacolon may result. 9

Monitoring During Treatment

• Expect fever clearance within 4-5 days; if no response by day 5, consider resistance or alternative diagnosis 1, 2
• Monitor for azithromycin adverse effects: nausea, vomiting, abdominal pain, diarrhea 2
• Watch for QT-prolonging drug interactions with azithromycin 2
• Monitor for complications including intestinal perforation, which occurs in 10-15% when illness duration exceeds 2 weeks 2
• Daily evaluation should include temperature, vital signs, abdominal symptoms, and hydration status 3

Supportive Care

Reduced osmolarity oral rehydration solution (ORS) is recommended as first-line therapy for mild to moderate dehydration from any cause of diarrhea. 9 Isotonic intravenous fluids (lactated Ringer's or normal saline) should be administered for severe dehydration, shock, or altered mental status. 9

Asymptomatic Carriers

Asymptomatic people with S. Typhi in stool who practice hand hygiene and live/work in low-risk settings do not need treatment, except they may be treated empirically to reduce transmission potential. 9 Those in high-risk settings (healthcare, childcare, food service) should be treated according to local public health guidance. 9