Most children (60%) in the present study were school age (11-16 years) which was similar in the findings of other studies [20-22]. This could be due to outdoor eating habits of school going children in poor hygienic conditions from the street vendors. There was no difference in gender distribution, consistent with the results from Pakistan by Khan MN et al  but Singh DS et al  observed males predominance than females.
The overall mean time taken for defervescence with ceftriaxone monotherapy was 3.94 days (± 0.96 SD) is consistent with similar findings from the studies in Nepal  Egypt [24,25] and India . The mean defervescence time between blood culture positive and negative, it was observed that it took longer in culture positive than in the culture negative cases (4.6 versus 3.9 days) with statistically significance (p=0.04). Similar results were reported by Rathore MH et al , Tatli MM et al  and Khatri R et al . This most probably is explained by the bacteriologically confirmed Salmonella cases having high bacterial loads, requiring longer treatment for fever clearance.
The predominant symptoms after fever were headache and gastrointestinal symptoms. Constipation was observed more common (28%) in this study than diarrhea (13%) in contrast to findings in the separate studies in India [20,30,31] and Nepal [21,32] where diarrhea was a more frequent presentation than constipation. This could be because the age group in the current study was > 5 years and diarrhea is known to be more common in the younger age, < 5 years with enteric fever. The main clinical signs observed were coated tongue (81%), isolated hepatomegaly (78%) and splenomegaly (68%), similar to that reported by Malini et al  and Laishram et al . Relative bradycardia considered to be salient feature of enteric fever in adults was infrequently observed in our study, consistent with other studies [31,33].
The predominant laboratory findings were normal total leukocyte count (85%) and only 10% had leucopenia. Normal leucocyte has been observed by other studies done in Nepal by Singh DS et al  and in India [20,26,34]. Thus, leucopenia, relative bradycardia and diarrhea may not be common features of enteric fever in children. Thrombocytopenia was present in half of the children (50%) but none had severe thrombocytopenia nor thrombocytosis. Similar findings were reported by Malini et al  Laishram et al  and Al Reesi M et al . Thrombocytopenia was reported as a marker for severity and complications in enteric fever in the study done by Laishram et al . However, Malini et al  reported no statistical significance between thrombocytopenia and the occurrence of complications. In the present study, only one child with moderate thrombocytopenia developed pneumonia.
A significant proportion of children (73.6%) were Widal positive but only 5 of the 78 Widal positive isolated S. typhi in the blood culture. This high percentage of Widal positivity is in accord with the findings by Kumar et al , Chowta et al  and Malla et al . Despite the drawbacks on Widal test, it is commonly used for diagnosis as it is cost effective and easily available as compared to other serodiagnostic tests . Widal titre of TO/TH > 1:160/1:160 may be considered the laboratory supporting test for diagnosis of EF considering that the rate of culture positive is only 10% in Nepal . Likewise, the culture positivity in our study was only 8.5% which is comparable to the study reported by Shah G et al . This poor yield may be related to multiple factors like inadequate volume of blood collected, inadequate laboratory media and the delay in incubating the media after the blood withdrawal. The important factor in this study could be the significant proportion of children (90.6%) already on oral antibiotic therapy before blood culture collection.
Out of 9 culture positive cases, 6 isolated typhi strains and only 3 isolated paratyphi serovars in the present study. A 2/3rd cases (66.6%) of Salmonella growth had fluoroquinolone resistant strains with 33.3% yielding nalidixic acid resistant S.typhi (NARST) strains though it was from the small number of total isolates. In the last two decades, there has been a change in the pattern of EF with the emergence of MDRS. The multiple studies [13,40,41] in Kathmandu, Nepal reported paratyphi as more prevalent serovars and some studies [14,15,32] observed high prevalence of NARST. This could be due to the wide use of quinolones for the treatment of EF, along with the easy availability of oral quinolones from pharmacies without a prescription. The higher frequency of NARST isolates indicates the possibility of fluoroquinolone resistance occurring in near future as a consequence of the rampant use of fluoroquinolones. NARST strain is a marker for predicting low level resistance to ciprofloxacin among S. typhi and also an indicator of treatment failure to ciprofloxacin . Asian countries were reported to have increased rate of NARST strains as described by Ochial LR et al .
In this study, salmonella isolates showed 100% susceptible to third generation cephalosporins viz Cefixime, Ceftriaxone and Cefotaxime consistent with similar findings described by other authors in Nepal [13,21,45] and in India [20,26,46]. The response to ceftriaxone monotherapy was significant (100%) with no treatment failure nor mortality, with similar results observed by other authors [12,30].
A complication was seen in only one child in the present study which is comparable to the observation by Succinder M et al  where as other authors observed more complications including gastrointestinal and neurological [20,32]. Low incidence of complications in our study could be because of less than 2 weeks duration of illness (mean duration of fever on presentation 8.13 ±3.23 days), low yield of salmonella in the blood culture hence less bacterium inoculum, prompt adequate and appropriate antibiotic therapy and duration as per institutional standard protocol.
The main adverse effect of ceftriaxone observed was thrombophlebitis (38.7%) but no major adverse events that led to interruption or discontinuation of the ceftriaxone were seen. Thrombophlebitis could be due to mechanical or chemical irritation of veins. Ceftriaxone is known to cause chemical phlebitis. Urbanetto J S et al  observed significant association of ceftriaxone with incidence of post-infusion phlebitis, however ceftriaxone has proven safe without causing any significant adverse effects in either once daily or twice daily dosing regimens [48,49].
The results of this study might not be generalizable to the patients in all health facility since the study was done among hospitalized children only at single tertiary hospital. Majority children had taken oral antibiotic prior admission, possibility of low yielding of growth in the culture and hence the diagnoses in culture negative were based on validated clinical diagnostic features and Widal test. Though new noninvasive assays like polymerase chain reaction-based tests and proteomics for rapid diagnosis of EF are available but their utility for detection is still debated and more over it will be unaffordable for developing countries who are endemic, thus in practice Widal test still plays major role for diagnosis in spite of poor sensitivity and specificity.