A 28-year-old woman from Delhi presents with a 10-day history of sustained fever, headache, and abdominal pain. Blood culture grows Salmonella typhi sensitive to fluoroquinolones, third-generation cephalosporins, and azithromycin, but resistant to chloramphenicol and trimethoprim-sulfamethoxazole. What is the drug of choice for treatment of this enteric fever?

Explanation

## Drug of Choice in Enteric Fever ### Current Treatment Guidelines **Key Point:** Ceftriaxone (third-generation cephalosporin) is the first-line drug of choice for enteric fever in India, particularly for MDR (multidrug-resistant) and ESBL-producing strains [cite:Harrison 21e Ch 157]. ### Rationale for Ceftriaxone 1. **Excellent CNS penetration** — critical for typhoid encephalopathy and meningitis complications 2. **Broad spectrum coverage** — effective against wild-type, MDR, and many ESBL strains 3. **Parenteral formulation** — reliable bioavailability in severe illness with GI involvement 4. **Reduced relapse rates** — lower recurrence compared to older agents ### Dosing in Enteric Fever - **Adult dose:** 2 g IV/IM every 6–8 hours (total 6–8 g/day) - **Duration:** 7–14 days depending on severity and clinical response - **Pediatric:** 50–80 mg/kg/day in divided doses ### When Fluoroquinolones Are Used **High-Yield:** Fluoroquinolones (ofloxacin, ciprofloxacin) are reserved for: - Uncomplicated cases with susceptible organisms - Oral step-down therapy after initial IV cephalosporin - Outpatient management of milder disease - NOT for severe typhoid, CNS involvement, or suspected resistance ### Resistance Pattern in India | Resistance Type | Prevalence | First-Line Drug | | --- | --- | --- | | Wild-type (susceptible to all) | Rare now | Fluoroquinolone or cephalosporin | | MDR (resistant to chloramphenicol, TMP-SMX, ampicillin) | Common | Cephalosporin or fluoroquinolone | | ESBL-producing | Emerging | Cephalosporin (ceftriaxone) | | Fluoroquinolone-resistant | Increasing | Cephalosporin or azithromycin | **Clinical Pearl:** In this case, the organism is susceptible to ceftriaxone, fluoroquinolones, and azithromycin but resistant to older agents—a typical MDR pattern seen in India. Ceftriaxone remains superior due to CNS penetration and broader coverage. ### Azithromycin Alternative **Key Point:** Azithromycin is increasingly used for uncomplicated enteric fever and is oral-bioavailable, but cephalosporins remain the gold standard for moderate-to-severe disease and complicated typhoid.