Is cefexime 400 mg (once daily) with ofloxacin 200 mg (once daily) effective for typhoid fever for 14 days?

Treatment of Typhoid Fever with Cefixime and Ofloxacin Combination

The combination of cefixime 400 mg once daily with ofloxacin 200 mg once daily for 14 days is not the optimal first-line treatment for typhoid fever based on current evidence. While this combination has been approved in some regions, current guidelines recommend different treatment approaches based on antibiotic resistance patterns.

Recommended Treatment Options for Typhoid Fever

First-line Treatment Options

• Azithromycin: Preferred first-line treatment due to lower relapse rates (<3%) compared to ceftriaxone (<8%) 1
• Ceftriaxone: Recommended by WHO as first-line empiric treatment 1
• Cefixime alone: Alternative option for multidrug-resistant strains 1

Treatment Selection Based on Resistance Pattern

1. For fully sensitive strains:

   • Azithromycin (preferred)
   • Alternative options: fluoroquinolones, chloramphenicol, amoxicillin, trimethoprim-sulfamethoxazole 1

2. For multidrug-resistant strains:

   • Fluoroquinolones or cefixime
   • Azithromycin as alternative 1

3. For quinolone-resistant strains:

   • Azithromycin or ceftriaxone
   • Cefixime as alternative 1

Evidence on Cefixime-Ofloxacin Combination

While the cefixime-ofloxacin combination has been approved in some regions, the evidence supporting its use is limited:

• In vitro studies showed that this combination demonstrated synergistic activity in only 11% of Salmonella Typhi isolates, with most showing indifference 2
• The combination did not show antagonism and computational analysis predicted no drug-drug interactions or toxicity 2
• However, this combination may not be effective against fluoroquinolone-resistant isolates 2

Evidence on Individual Agents

Cefixime

• Cefixime (16mg/kg/day for 14 days) showed a clinical cure rate of 71% in a recent study 3
• Mean fever clearance time with cefixime was 7.1 days 3

Ofloxacin

• Ofloxacin has been used successfully for typhoid fever but may have reduced efficacy against nalidixic acid-resistant strains 4
• Short-course ofloxacin (2-3 days) has shown efficacy for uncomplicated multidrug-resistant typhoid fever in children 5

Azithromycin

• Azithromycin showed superior clinical cure rates (85%) compared to cefixime (71%) and ciprofloxacin (62%) 3
• Mean fever clearance time was significantly shorter with azithromycin (5.8 days) compared to cefixime (7.1 days) 3
• Azithromycin has demonstrated efficacy comparable to ceftriaxone with fewer relapses 6

Important Considerations

• Resistance patterns: Local resistance patterns should guide treatment selection
• Duration of treatment: 7-14 days depending on clinical response and severity
• Monitoring: Fever clearance time typically occurs within 4-7 days with appropriate treatment 1
• Potential for relapse: Bacterial shedding may continue for several weeks after clinical recovery 1

Conclusion

While the combination of cefixime 400 mg and ofloxacin 200 mg daily for 14 days may be used in some settings, current evidence suggests that azithromycin or ceftriaxone as monotherapy would be more effective first-line options for typhoid fever. The choice should be guided by local resistance patterns, with azithromycin being particularly effective against both multidrug-resistant and quinolone-resistant strains.