Oral azithromycin effective treatment option for uncomplicated typhoid fever
UK: Oral azithromycin at a dose of 500mg daily is an effective treatment for uncomplicated enteric fever (typhoid fever) in outpatient adults but treatment response may be delayed and associated with prolonged bacteremia when compared with ciprofloxacin, according to a recent study published in the journal PLOS Neglected Tropical Diseases.
The findings demonstrate that azithromycin should be considered first in countries where fluoroquinolone resistance is common.
Typhoid fever or enteric fever remains a major global health problem in low-and middle-income countries. Its treatment is complicated by the emergence of antimicrobial-resistant Salmonella Typhi.
Azithromycin is presently one of the few oral antibiotic options that can be reliably used for typhoid treatment, although concerns persist regarding variations in response to treatment and emerging resistance. Azithromycin's response to treatment may be sub-optimal in some patient groups when compared with fluoroquinolones.
Celina Jin, Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK, and colleagues performed an analysis of responses to treatment with azithromycin (500mg once daily for 14 days) or ciprofloxacin (500mg twice daily for 14 days) in healthy UK volunteers (18-60 years ) enrolled into two Salmonella controlled human infection studies.
Study A was a single-center, open-label, randomized trial. The participants were randomized in the ratio 1:1 to receive open-label oral ciprofloxacin or azithromycin, stratified by vaccine group (Vi-polysaccharide, Vi-conjugate or control Men-ACWY vaccine).
Study B was an observational challenge/re-challenge study, where participants were randomized to challenge with Salmonella Typhi or Salmonella Paratyphi A. Outcome measures included fever clearance time, blood-culture clearance time and a composite measure of prolonged treatment response (persistent fever ≥38.0°C for ≥72 hours, persistently positive S. Typhi blood cultures for ≥72 hours, or change in antibiotic treatment).
Key findings of the study include:
- In 81 participants diagnosed with S. Typhi in two studies, treatment with azithromycin was associated with prolonged bacteremia (median 90.8 hours vs. 20.1 hours and prolonged fever clearance times <37.5°C (hazard ratio 2.4).
- Results were consistent when studies were analyzed independently and in a sub-group of participants with no history of vaccination or previous challenge.
- A prolonged treatment response was observed significantly more frequently in the azithromycin group (28/52 [54.9%]) compared with the ciprofloxacin group (1/29 [3.5%]).
- In participants treated with azithromycin, observed systemic plasma concentrations of azithromycin did not exceed the minimum inhibitory concentration (MIC), whilst predicted intracellular concentrations did exceed the MIC.
- In participants treated with ciprofloxacin, the observed systemic plasma concentrations and predicted intracellular concentrations of ciprofloxacin exceeded the MIC.
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"In an era of increasing antimicrobial resistance, further studies are required to define appropriate azithromycin dosing regimens for enteric fever and to assess novel treatment strategies, including combination therapies," the authors concluded.
The bottom line of the study is --> 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.
The study, "Treatment responses to Azithromycin and Ciprofloxacin in uncomplicated Salmonella Typhi infection: A comparison of Clinical and Microbiological Data from a Controlled Human Infection Model," is published in the journal PLOS Neglected Tropical Diseases.