Brief Title
Typhoid Fever: Combined vs. Single Antibiotic Therapy
Official Title
Typhoid Fever: Combined vs. Single Antibiotic Therapy. A Prospective Randomized Controlled Study in Nepal.
Brief Summary
The current study goal is to examine the effect of Cephalosporins, Azithromycin and the combination of both on typhoid fever therapy in endemic population. The investigator's hypothesize that the combination of azithromycin and ceftriaxone may prove superior to each drug, ceftriaxone or azithromycin, alone.
Detailed Description
Typhoid Fever is a highly prevalent infection in the Indian subcontinent. Due to multidrug resistant strains in these areas, third generation cephalosporins, such as ceftriaxone, are the treatment of choice. However, the latter regimen exhibits a slow response with mean time of 5 to 7 days or even longer to defervescence, which could be attributed to poor penetration capability of the drug into cells, and thus difficulty to eradicate the bacteria from the intracellular niche. Attempts have been made to overcome this setback by introducing alternative antibiotic regimens, such as azithromycin. However studies comparing between azithromycin and a third-generation cephalosporin for the treatment of typhoid fever in adult population in the Indian subcontinent are lacking. Over the last few years our approach towards non-immunized travelers, who acquired typhoid fever in the Indian subcontinent, was to administer a combination therapy of intravenous ceftriaxone with oral azithromycin. The rationale of this dual regimen was its pharmacokinetic profile, which suggests a complimentary action of the two agents - ceftriaxone on the extracellular compartment and azithromycin on the intracellular compartment. Moreover, in our clinical experience, preliminary published data has proven combination therapy significantly superior to ceftriaxone alone albeit in a small group of travelers. In the current study the investigators intend to compare the efficacy of ceftriaxone vs. azithromycin and vs. combined therapy of both agents for the treatment of uncomplicated typhoid fever in terms of time to defervescence. 4 different treatment strategies will be examined (as mentioned in the arm section). All participants will be checked for vital signs, will undergo physical examination, ECG, laboratory testing, blood, urine and stool culture and tests for susceptibility to antibiotics.
Study Phase
Phase 4
Study Type
Interventional
Primary Outcome
Fever clearance time
Secondary Outcome
Treatment failure
Condition
Typhoid Fever
Intervention
ceftriaxone
Study Arms / Comparison Groups
Ceftriaxone I.V
Description: The participants in this arm will receive the following drug and dosage: adult: Ceftriaxone intravenous 2 gr once a day. Pediatric: intravenous 75 mg/kg ceftriaxone once a day (maximum dose 2.5 g/day). Patients will receive antibiotic treatment until defervescence and for 3 days afterwards. Patients will be hospitalized during the entire treatment course (including the afebrile period).
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
120
Start Date
August 2013
Completion Date
August 2015
Primary Completion Date
December 2014
Eligibility Criteria
Inclusion Criteria: - Blood culture-proven typhoid fever (S. typhi or S. paratyphi) - Signed informed consent to participate in the study. Exclusion Criteria: - Allergy to ceftriaxone or macrolides - Major typhoid fever-associated complications - Inability to swallow oral medication - Underlying illness - Pregnancy - Lactation - Treatment within the past 4 days with an antibiotic that may be effective against typhoid fever
Gender
All
Ages
2 Years - 80 Years
Accepts Healthy Volunteers
No
Contacts
Eli Schwartz, MD, DTMH, +97235308456, [email protected]
Location Countries
Nepal
Location Countries
Nepal
Administrative Informations
NCT ID
NCT02224040
Organization ID
64/12
Responsible Party
Principal Investigator
Study Sponsor
Sheba Medical Center
Study Sponsor
Eli Schwartz, MD, DTMH, Principal Investigator, Sheba Medical Center
Verification Date
August 2014