Clinical Trial: Typhoid Fever: Combined vs. Single Antibiotic Therapy

Study Status: Completed
Recruit Status: Unknown status
Study Type: Interventional

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 Summary:

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
Sponsor: Sheba Medical Center

Current Primary Outcome: Fever clearance time [ Time Frame: One month ]

Time to fever clearance will be measured and will be defined as an oral temperature that is below 37.50 C


Original Primary Outcome: Same as current

Current Secondary Outcome: Treatment failure [ Time Frame: One month ]

Secondary endpoints will be treatment failure (defined as the need to switch antibiotic treatment according to physician's decision such as high grade fever after 5 days of treatment, appearance of typhoid complications under the treatment), clearance of bacteremia, development of typhoid-related complications, late relapse, fecal carriage and adverse drug reactions.


Original Secondary Outcome: Treatment failure [ Time Frame: One month ]

Secondary endpoints will be treatment failure (defined as the need to switch antibiotic treatment according to physician's decision), clearance of bacteremia, development of typhoid-related complications, late relapse, fecal carriage and adverse drug reactions.


Information By: Sheba Medical Center

Dates:
Date Received: August 21, 2014
Date Started: August 2013
Date Completion: August 2015
Last Updated: August 26, 2014
Last Verified: August 2014