Is a combined regimen of cefexime (third-generation cephalosporin) 200mg and ofloxacin (fluoroquinolone) 200mg twice daily effective for treating typhoid in India?

Treatment of Typhoid Fever in India

The combination of cefixime 200mg and ofloxacin 200mg twice daily is not the most effective treatment for typhoid fever in India due to high rates of fluoroquinolone resistance; azithromycin is the preferred first-line treatment for typhoid fever in India. 1

Current Resistance Patterns and Treatment Considerations

Typhoid fever treatment in India faces significant challenges due to antimicrobial resistance:

• 96% of Salmonella Typhi isolates show resistance to nalidixic acid
• 58% are multidrug-resistant 1
• Fluoroquinolones (including ofloxacin) have decreasing effectiveness due to emerging resistance 2

Recommended Treatment Options

First-Line Treatment

• Azithromycin (20 mg/kg/day for 7 days)
  • Superior to ofloxacin for treating typhoid fever
  • Lower risk of clinical failure (OR 0.48; 95% CI 0.26-0.89)
  • Shorter hospital stays (-1.04 days; 95% CI -1.73 to -0.34 days)
  • Faster fever clearance times (<4 days)
  • Lower relapse rates (<3%) 1

Alternative Options Based on Susceptibility

1. For fully sensitive strains:

   • Azithromycin (preferred)
   • Fluoroquinolones, chloramphenicol, amoxicillin, or trimethoprim-sulfamethoxazole

2. For multidrug-resistant strains:

   • Fluoroquinolones or cefixime
   • Azithromycin as alternative

3. For quinolone-resistant strains:

   • Azithromycin or ceftriaxone
   • Cefixime as alternative 1

Evidence for Cefixime-Ofloxacin Combination

While the combination of cefixime and ofloxacin has been approved by the Drug Controller General of India, the evidence supporting its use is mixed:

• A 2019 study reported that the combination showed quick time to defervescence (~3 days) and complete clinical cure in ~7 days in Indian patients 3
• However, in vitro studies showed synergistic activity in only 11% of isolates, with the majority showing indifference 4
• The combination might be effective against moderately susceptible fluoroquinolone S. Typhi but not against fluoroquinolone-resistant isolates 4

Treatment Algorithm for Typhoid Fever in India

1. First choice: Azithromycin 20 mg/kg/day for 7 days

   • Effective against both susceptible and resistant strains
   • Safe for children and pregnant women

2. If azithromycin unavailable or contraindicated:

   • For known susceptible strains: Ceftriaxone or cefixime
   • For suspected multidrug-resistant strains: Consider cefixime-ofloxacin combination only if susceptibility is confirmed

3. For severe cases or complications:

   • Parenteral therapy with ceftriaxone

Monitoring and Response

• Clinical improvement typically occurs within 48-72 hours of starting appropriate therapy
• If no improvement after 72 hours, reassess diagnosis and consider alternative antibiotics
• Complete resolution of symptoms typically occurs within 4-7 days with appropriate treatment 1

Cautions

• Fluoroquinolones (including ofloxacin) should be avoided in children and pregnant women when possible 1
• The emergence of resistance to both cephalosporins and fluoroquinolones is concerning
• Treatment should ideally be guided by local resistance patterns and susceptibility testing when available

While cefixime-ofloxacin combination has shown some promise in specific Indian settings, the current evidence and guidelines suggest that azithromycin remains the more reliable and effective option for treating typhoid fever in India, especially given the high rates of fluoroquinolone resistance.