Active Ingredients: Azithromycin
Inside parasite vacuoles, with tablets or suspension, including appropriate azithromycin dosing regimens and combination therapies. Further studies are required to assess novel treatment strategies, pulmonary and splenic tissue?
Laboratory-generated P. 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.
Azithromycin is an azalide antimicrobial widely used for the empirical treatment of uncomplicated enteric fever, benefitting from once daily oral dosing and good tissue penetration.
It has excellent in vitro activity, being concentrated within phagocytic cells and achieving intracellular concentrations of up to 200 times greater than serum.
Several randomised controlled trials have demonstrated the efficacy of azithromycin in adults and children when compared with fluoroquinolones, cephalosporins and chloramphenicol—including in the treatment of fluoroquinolone intermediate or resistant strains.
Resistance to azithromycin amongst circulating S.
Typhi strains is uncommon but appears to be an emerging problem. Typhi strains and one S.
Paratyphi strain. Azithromycin can be associated with fever-clearance times averaging 4—5 days ; prolonged bacteraemia of up to 72—96 hours post treatment and treatment failures.
Sub-optimal treatment responses are associated with increased morbidity, as well as having potentially harmful effects through prolonged treatment courses, interrupted treatment regimens prompted by escalation or switching antibiotics and increased healthcare burden.
Controlled human infection CHI models have previously been applied to study antibiotic therapy following S. Typhi challenge. Such studies offer the advantage of accurately recording clinical treatment responses in a closely monitored experimental setting with daily collection of culture samples to accurately determine the dynamics of bacteraemia.
In light of the increasingly limited treatment options for enteric fever, we sought to compare treatment responses to azithromycin and ciprofloxacin in healthy volunteers challenged with a fully antibiotic susceptible strain of S.
Typhi as part of a programme of controlled human infection studies. Both studies are registered with ClinicalTrials. Study design We performed a secondary analysis of two S.
Typhi controlled human infection studies Studies A and B comparing treatment responses to oral azithromycin and ciprofloxacin in participants diagnosed with uncomplicated typhoid fever. Typhi oral challenge 104 CFUs of S. Pre-treatment with sodium bicarbonate allowed increased passage of S.
At the time of enrolment, participants were also randomised to receive 14 days of open-label treatment with either azithromycin 500 mg daily or ciprofloxacin 500 mg twice daily.