What is the treatment for enteric fever?

Treatment of Enteric Fever

For uncomplicated enteric fever, azithromycin 20 mg/kg/day (maximum 1g/day) orally for 7 days is the preferred first-line treatment, particularly in regions with high fluoroquinolone resistance, while ceftriaxone 50-80 mg/kg/day (maximum 2g/day) IV for 5-7 days should be used for severe cases requiring hospitalization. 1, 2

First-Line Treatment Selection

For Outpatient/Uncomplicated Cases

• Azithromycin is superior to fluoroquinolones, demonstrating lower clinical failure rates (OR 0.48,95% CI 0.26-0.89), shorter hospital stays (-1.04 days), and dramatically lower relapse rates (OR 0.09,95% CI 0.01-0.70) compared to ceftriaxone 3, 1
• Azithromycin achieves a 94% cure rate in children with typhoid fever 1
• Dosing: 20 mg/kg/day (maximum 1g/day) orally for 7 days 1, 2, 4

For Hospitalized/Severe Cases

• Ceftriaxone is the preferred parenteral agent, particularly given that over 70% of S. typhi isolates globally now demonstrate fluoroquinolone resistance 2, 4, 5
• Dosing: 50-80 mg/kg/day (maximum 2g/day) IV for 5-7 days initially 1, 2
• All organisms remained susceptible to ceftriaxone throughout 2005-2014 in major studies, while fluoroquinolone MICs rose significantly 6
• Switch to oral therapy (azithromycin or cefixime) once temperature normalizes for 24 hours and clinical improvement occurs 2, 4

Alternative Oral Options

Cefixime

• Dosing: 8 mg/kg/day as single daily dose for 7-14 days 1
• Cefixime performs less well than fluoroquinolones when organisms are susceptible, with increased clinical failure (RR 13.39,95% CI 3.24-55.39), microbiological failure (RR 4.07), and relapse rates (RR 4.45) 7
• Fever clearance is 1.74 days longer compared to fluoroquinolones 7
• Consider as step-down therapy after initial parenteral treatment rather than primary therapy 1

Treatment Based on Resistance Patterns

Fluoroquinolone-Susceptible Strains (Rare)

• Ofloxacin or ciprofloxacin may be used only if documented susceptibility exists 3
• Critical caveat: Over 70% of isolates from South Asia are fluoroquinolone-resistant; avoid empiric use for cases from this region 2, 4, 5
• Fluoroquinolone resistance is a class effect and increasing globally 1, 6

Multidrug-Resistant (MDR) Strains

• Fluoroquinolones historically recommended, but resistance now precludes this approach 3, 7
• Use ceftriaxone or azithromycin instead 3, 4

Extensively Drug-Resistant (XDR) Strains

• Emerging from Pakistan since 2016 with limited treatment options 5, 8
• Azithromycin and carbapenems may be only effective options 5, 8

Treatment Duration and Monitoring

• Standard duration: 7 days for uncomplicated cases with azithromycin or oral cephalosporins 1, 4
• Extended duration: Consider 14 days to reduce relapse risk, particularly with ceftriaxone 4
• Expected fever clearance: 4-5 days with appropriate therapy 1
• Relapse rates: <3% with azithromycin, <8% with ceftriaxone, higher with fluoroquinolones 4

Diagnostic Considerations Before Treatment

• Obtain blood cultures before starting antibiotics whenever possible, as they have highest yield in first week of symptoms 2, 4
• For patients with sepsis features, start broad-spectrum therapy immediately after blood culture collection 2, 4
• Stool and urine cultures become positive after first week but have lower sensitivity 4

Critical Pitfalls to Avoid

1. Do not use fluoroquinolones empirically for cases from South Asia or other high-resistance areas 2, 4, 5
2. Do not rely on older antibiotics (chloramphenicol, ampicillin, trimethoprim-sulfamethoxazole) as they show higher clinical failure rates than fluoroquinolones, which themselves are now largely ineffective 3
3. Do not use cefixime as first-line monotherapy when azithromycin or ceftriaxone are available, given inferior outcomes 7
4. Do not discontinue antibiotics prematurely before symptom resolution to prevent relapse 2
5. Do not ignore local resistance patterns, which vary geographically and change over time 1, 2, 7

Special Clinical Scenarios

Non-Response to Initial Therapy

• Approximately 10% of patients show clinical non-response despite in vitro susceptibility 9
• Consider switching antibiotic class or adding combination therapy 9
• Evaluate for complications (perforation, bleeding, abscess formation) if fever persists beyond 5 days 2

Complications Requiring Monitoring

• Gastrointestinal bleeding, intestinal perforation, and typhoid encephalopathy occur in 10-15% of patients 4
• More likely if illness duration exceeds 2 weeks before treatment 4
• Consider CT imaging for persistent peritoneal signs or failure of bowel function to normalize 2