Active substance: Ciprofloxacin
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.
Antibiotic randomisation was stratified according to vaccine group. Randomisation to vaccine group and antibiotic treatment was implemented using the computerised randomisation software Sortition Nuffield Department of Primary Care, Clinical Trials Unit, University of Oxford Study B was an observational challenge-re-challenge study.
Typhi or S. Antibiotic allocation in Study B was not randomised. Following the availability of preliminary results from Study A—and under the guidance of the Data Safety Monitoring Committee—the protocol was amended such that first-line treatment was changed to ciprofloxacin 500 mg twice daily.
Written informed consent was obtained from all volunteers before enrolment. Inclusion and exclusion criteria have previously been described.
Typhi Quailes strain, diagnostic criteria for typhoid fever, and clinical assessment were identical between studies, and were carried out as previously described.
Briefly, participants were reviewed daily in an outpatient setting for two-weeks following oral challenge.
Solicited symptoms of typhoid fever and twice-daily self-measured oral temperatures were recorded by participants on an electronic diary for 21 days inclusive of the two-week challenge period. Antibiotic treatment was commenced if participants were diagnosed with typhoid fever, based on pre-specified composite criteria S.
Diagnosed participants attended between four to seven additional daily visits after commencing antibiotics to assess treatment response.
Antibiotic allocation was unblinded. In instances where treatment was changed, the antibiotic switch was performed at the discretion of the treating clinician and Chief Investigators either for adverse reactions, possibly related to antibiotic allocation e.
Challenge strain Typhoid challenge was performed using S.
Typhi Quailes strain genotype 3. Challenge strain stocks were fully sensitive to ciprofloxacin and azithromycin as assessed using disc diffusion zone of inhibition to ciprofloxacin 37 mm, azithromycin 24 mm.
The MIC of S.