Oral azithromycin: effective alternative to ciprofloxacin for enteric fever

Takeaway

• Oral azithromycin effectively treats uncomplicated enteric fever in outpatient adults but treatment response may be delayed. 

Why this matters

• An azithromycin loading dose can be administered to optimize intracellular concentrations to greater than the minimum inhibitory concentration (MIC) during the first 24 hours in outpatients with enteric fever.
• Azithromycin should be considered first in countries where fluoroquinolone resistance is common. 

Key results

• 81 participants; 52 received azithromycin and 29 received ciprofloxacin.
• Salmonella typhi bacteremia was significantly prolonged with azithromycin vs ciprofloxacin:
  • Median, 90.8 hours azithromycin vs 20.1 hours ciprofloxacin (P<.001).
  • Multivariate adjusted (a)HR: 18.9 (P<.001).
• Fever clearance was significantly prolonged in azithromycin-treated patients:
  • Median, 65 vs 45 hours ciprofloxacin (P=.02);
  • Multivariable aHR: 2.4 (P=.02).
• 53.8% (28) azithromycin vs 3.4% (1) ciprofloxacin had prolonged treatment responses.
• Pharmacokinetic simulation showed 1000 mg loading dose followed by 500 mg/day azithromycin resulted in more patients achieving intracellular concentrations greater than MIC.

Study design

• Secondary analysis comparing treatment responses to oral azithromycin (500 mg/daily q14d) to ciprofloxacin (500 mg bid q14d) among patients with uncomplicated typhoid fever enrolled in 2 controlled Salmonella infection studies.
• Funding: Bill & Melinda Gates Foundation.

Limitations

• Nonrepresentative S typhi strains.
• No randomized antibiotic allocation (second study).