Three-day treatment of typhoid fever with two different doses of ceftriaxone, compared to 14-day therapy with chloramphenicol: a randomized trial

Abstract

Fifty-nine adult Filipino patients suffering from typhoid fever documented by blood culture were randomly allocated to one of three different drug regimens. Nineteen patients received 3 g ceftriaxone iv once daily for three days. Twenty patients received 4 g ceftriaxone iv once daily for three days and 20 patients received oral chloramphenicol 3 g daily in divided doses for two days followed by 2 g daily for 12 days. Eighteen patients were cured (95%) with 3 g of ceftriaxone for three days. All patients receiving 4 g ceftriaxone per day for three days or chloramphenicol for 14 days were cured. In the ceftriaxone groups two patients developed typhoid fever 30 and 45 days respectively after completion of treatment and one further patient had evidence of reinfection. Three patients relapsed within 15 to 17 days in the chloramphenicol group. Fever subsided in most patients between six and eight days, with three patients having a prolonged and moderate fever for 11 days in the ceftriaxone groups. This study suggests that a short treatment of three days of typhoid fever with ceftriaxone (3 or 4 g once daily) is adequate and not hazardous as far as relapses are concerned.

Epidemiology, Clinical Presentation, Laboratory Diagnosis, Antimicrobial Resistance, and Antimicrobial Management of Invasive Salmonella Infections

“…The succinate ester prodrug is used for intravenous or intramuscular administration and gives lower serum levels than the oral form (436,437). Chloramphenicol has been shown to be clinically effective in a number of studies (341,(438)(439)(440)(441)(442)(443)(444)(445)(446)(447). Disadvantages of chloramphenicol are its four-times-daily administration and the need to give it for at least 2 weeks to reduce the 10 to 15% risk of relapse.…”

“…Ceftriaxone is generally safe to use, including in children, is slowly bactericidal against Salmonella serovar Typhi in vitro, and is able to penetrate and kill intracellular bacteria (463,464). Ceftriaxone has been used to treat typhoid in durations of 14 days (465-467), 7 days (342, 468-470), 5 days (440,(471)(472)(473), and 3 days (442,474,475). The proportion of patients cured has varied from 70% to more than 90%.…”

Failure of Short-Course Ceftriaxone Chemotherapy for Multidrug-Resistant Typhoid Fever in Children: a Randomized Controlled Trial in Pakistan

“…However, the cost of therapy with a 14-day course of CRO is considerable, frequently beyond the capacity of health care budgets (7). Several studies have therefore explored the potential of shorter courses of CRO for treating typhoid, ranging from 3 to 7 days, with impressive cure rates (1,11,14,17,22), but only a few such studies (1,11,22) have involved patients, especially children, with MDR typhoid.…”

Treatment of typhoid fever with ceftriaxone for 5 days or chloramphenicol for 14 days: a randomized clinical trial

“…However, newer antibiotics with good in vivo activity against Salmonella typhi are needed because of the alarming spread of R-factor-mediated chloramphenicol-resistant S. typhi throughout the world (3,4,11,23). Recently, ceftriaxone has emerged as a satisfactory alternative to chloramphenicol (1,2,5,8,10,12,13,21,22).Ceftriaxone has good broad-spectrum activity against gram-positive and gram-negative bacteria, including S. typhi (15). It has a long half-life in serum (ranging from 6.0 to 8.6 h), making it suitable for a once-daily dose regimen (16,20).…”