7, 13 and 14 The presence of MDR strains with intermediate susceptibility to ciprofloxacin limits the choice of enteric fever treatment, with ceftriaxone, azithromycin and gatifloxacin as potential options.15, 16 and 17 Ceftriaxone
was used as the initial empiric therapy for children admitted to hospital as it is suitable for enteric fever and other common invasive bacterial infections. In many cases after the diagnosis was confirmed and the child’s condition improved, this was changed to an oral drug. Although antimicrobial resistance to ceftriaxone is rare in invasive Salmonellae, the response to treatment is often slow. 6 The median fever clearance time in this study was 7.7 days with ceftriaxone monotherapy given for 10 days. In some patients a step-down to oral ciprofloxacin was employed with median fever clearance times of 6.6 days. When it was understood that most strains Selleckchem R428 Olaparib had intermediate susceptibility to ciprofloxacin, oral ciprofloxacin was substituted with oral azithromycin, and when given for 13 days the median fever clearance time was 4.4 days. Our data, whilst uncontrolled, suggests that in children with fever requiring hospital admission, subsequently confirmed as enteric fever, ceftriaxone followed by a step-down to oral azithromycin is a suitable regimen although the optimum time to step-down requires further investigation. Gatifloxacin has been shown to
be an acceptable alternative in other areas of high DCS prevalence 17 as it is less inhibited by the common mutations of the gyrA
gene than the older fluoroquinolones, but it is not easily available locally. Significantly, none of the isolates were fully resistant to ciprofloxacin or ceftriaxone which is an emerging problem in some areas.18 and 19 This is despite high rates of extended-spectrum β-lactamase carriage in other Enterobacteriacae circulating in children in this area.2 MDR serovar Typhi strains were present in Cambodia in the mid-1990s (C.M. Parry, personal observation) and appear not to have declined as has been described in other parts of Asia.5 Molecular genotyping of the strains in this study further 3-mercaptopyruvate sulfurtransferase demonstrates the dominance of the H58 haplotype with a gyrA mutation leading to a S83F amino acid substitution. This strain is also dominant in the Mekong delta in Vietnam and other areas of Asia and is frequently associated with an IncHI1 plasmid carrying the genes for the MDR phenotype, 13, 20 and 21 yet the factors that have led to the success of this particular strain are not yet known. The MICs against ciprofloxacin were in the range expected for isolates with intermediate susceptibility to ciprofloxacin and the values for azithromycin and gatifloxacin were comparable to other studies. 16 and 17 The reported severity of enteric fever in young children is variable across different studies.