Active substances: Ciprofloxacin
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. Typhi Quailes strain to ciprofloxacin was 0. Outcome measures The primary objective of the study was to compare the effect of ciprofloxacin with azithromycin on the time to bacteraemia clearance and fever clearance in individuals diagnosed with typhoid fever.
Time to bacteraemia clearance was defined as time from initiation of antibiotics to time of collection of first persistently negative blood culture for S. Only individuals who were bacteraemic at the time of initiation of antibiotics were included in the analysis of blood culture duration.
Individuals who cleared their fever before antibiotic initiation were excluded from the fever clearance analysis. Typhi stool culture if this occurred after starting antibiotics, and prolonged treatment response defined as persistent S.
Laboratory assays Blood and stool culture samples were collected at 12 hours after challenge and daily thereafter until 96 hours post initiation of treatment. Additional pharmacokinetic studies measurement of ciprofloxacin or azithromycin drug levels in plasma and comparison of liver enzyme derangement were carried out in Study A participants.
Plasma samples from Study A participants were collected at the time of diagnosis prior to commencing antibiotics and 12, 24, 48, 72- and 96-hours post-diagnosis for pharmacokinetic studies.
Separation was achieved using a rapid stepwise gradient. Mobile phase A consisted of 0. The column was then equilibrated to the initial conditions over 6 minutes azithromycin or 4 minutes ciprofloxacin.
The triple quadrupole mass spectrometer TSQ Quantum Access; Thermo Electron Corporation was operated in positive ionization mode, and detection and quantification performed using selective reaction monitoring.
Inter-day precision, based on CV of quality controls, was between 1. All quality controls readings at low, medium and high levels were consistent and reproducible.
Pharmacokinetic PK Monte-Carlo simulations To simulate predicted azithromycin plasma and intracellular pharmacokinetic profiles, we applied a model previously described by Sampson and colleagues and replicated using the simulator tool in Pmetrics.
For each dosing scenario, we simulated the PK profile of azithromycin in plasma and intracellularly mononuclear cells in 1,000 patients. The PK profile of ciprofloxacin in systemic plasma was simulated in 1,000 patients for each dosing scenario using the model reported by Sanchez Navarro and colleagues and was again replicated using the simulator tool of Pmetrics.
Statistical analysis Intention-to-treat analyses were used to assess outcome measures for Study A antibiotic allocated based on randomisation and Study B first antibiotic treatment used. For urinary tract or serious kidney infections: Adults—250 to 500 milligrams mg 2 times a day, taken every 12 hours for 7 to 14 days.
The dose is usually 10 to 20 milligrams mg per kilogram kg of body weight every 12 hours for 10 to 21 days. However, the dose is usually not more than 750 mg per day.
Missed Dose If you miss a dose of this medicine, take it as soon as possible.
However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses. Do not take more than one extended-release tablet each day.