Therapy of Multidrug Resistant Typhoid in 58 Children

Abstract

Treatment of children with infections caused by Salmonella typhi strains resistant to the commonly used oral antimicrobials is a special problem. As children cannot be treated with quinolones, there is no form of oral therapy. Third generation cephalosporins, which have been shown to be effective against typhoid caused by ampicillin sensitive strains of S. typhi were effective against typhoid caused by ampicillin, chloramphenicol and sulfamethoxazole/trimethoprim-resistant strains. We treated 28 children with ceftriaxone and 8 with cefotaxime. We found ceftriaxone to be more effective than cefotaxime with significantly lower relapse rate. Antibiotic therapy of 19 other children, initially treated in a similar manner, was altered for ease of therapy or due to poor response to therapy. The high cost of this parenteral therapy and the problems in its delivery point to the need for safe, effective oral therapy.

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

“…Our data provide additional evidence that a 7-day course of therapy with CRO was associated with a significantly higher and unacceptable relapse rate in Pakistani children with MDR typhoid, in comparison with concurrent controls. This relapse rate was also significantly higher than that observed previously among children from the same center with MDR typhoid who were treated with CRO for 14 days (3,7,19). The reasons for the observed high relapse rate after 7 days of therapy with CRO are uncertain.…”

“…Where the generic use of quinolones has become widespread, there are also recent disturbing reports of emerging quinolone resistance (9,25). Broad-spectrum cephalosporins have thus remained an important therapeutic alternative for the therapy of MDR typhoid in children, with excellent primary cure rates (11,12,19). We have previously described successful cures of MDR typhoid in hospitalized children receiving therapy with intravenous (i.v.)…”

Interleukin-6, gamma interferon, and tumor necrosis factor receptors in typhoid fever related to outcome of antimicrobial therapy

“…The short course of once-daily ceftriaxone for 3 days used in this trial confirms the results of Chi-kin et al (5) and Lasserre et al (13) that short courses of ceftriaxone are clinically effective against typhoid fever. Other studies of typhoid fever in Pakistan (14) and South Africa (6) also indicated that cephalosporins are useful alternatives to chloramphenicol when patients are infected with bacterial strains resistant to chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole.…”

“…In vitro resistance to chloramphenicol in Salmonella typhi occurs (6,14) but has not become prevalent in most areas where this organism is endemic (7). Chloramphenicol, on the other hand, is not an ideal treatment for typhoid fever because (i) treatment does not prevent fecal carriage of S. typhi, relapses after the end of therapy, or the complications of intestinal perforation and bleeding; (ii) residual mortality occurs during therapy; (iii) reversible bone marrow suppression develops and aplastic anemia, though rare, is a risk; and (iv) a long (14-day) course of treatment requires dosing four times a day.…”

Pharmacokinetics of ceftriaxone in patients with typhoid fever

“…In vitro resistance to chloramphenicol in Salmonella typhi occurs (5,14) but has not become prevalent in most endemic areas of the world (6). Chloramphenicol, on the other hand, is not ideal treatment for typhoid fever because (i) treatment does not prevent fecal carriage of S. typhi, relapses after the end of therapy, or the complications of intestinal perforation and bleeding; (ii) a residual mortality occurs during therapy; (iii) reversible bone marrow suppression develops and rare aplastic anemia is a risk; and (iv) a long 14-day course of treatment requires dosing four times a day.…”