Active Ingredients: Azithromycin
The treatment of typhoid fever is complicated by the emergence of widespread antibiotic resistance.
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. We used a Salmonella human challenge model to better understand response to treatment with azithromycin, as compared with ciprofloxacin.
We studied the pharmacokinetic properties of azithromycin and ciprofloxacin within the model to better characterise appropriate dosing strategies.
We conclude that oral azithromycin is an effective treatment option for uncomplicated enteric fever in the outpatient setting and should be used in high-burden countries where fluoroquinolone-resistance is common.
This study illustrates the application of human challenge models to study antibiotic treatments for typhoid fever.
Further studies are required to assess novel treatment strategies, including appropriate azithromycin dosing regimens and combination therapies. Data Availability: All relevant data are within the manuscript and its Supporting Information files.
Funding: Clinical study 1 A.
The study funders had no role in study design, data collection or analysis. Introduction Typhoid fever remains a major global-health concern and is estimated to be responsible for an estimated 10.
The recent emergence and global dissemination of multi-drug resistant and fluoroquinolone resistant strains of S.
Typhi and Paratyphi has limited effective treatment options for enteric fever.
Treatment options for enteric fever—particularly in the outpatient setting—are now severely limited. Third generation cephalosporins are commonly used in the empirical treatment of enteric fever and are a valuable treatment option in the setting of MDR and fluoroquinolone resistant isolates.
Several recent reports have described the emergence of extended spectrum beta-lactamase producing S.
Typhi —including a strain of extensively drug resistant XDR S. Typhi genotype 4.