A 23-year retrospective investigation of Salmonella Typhi and Salmonella Paratyphi isolated in a tertiary Kathmandu hospital

Abstract

BackgroundSalmonella serovars Typhi (S. Typhi) and Paratyphi A (S. Paratyphi A), the causative agents of enteric fever, have been routinely isolated organisms from the blood of febrile patients in the Kathmandu Valley since the early 1990s. Susceptibility against commonly used antimicrobials for treating enteric fever has gradually changed throughout South Asia since this time, posing serious treatment challenges. Here, we aimed to longitudinally describe trends in the isolation of Salmonella enterica and assess changes in their antimicrobial susceptibility in Kathmandu over a 23-year period.MethodsWe conducted a retrospective analysis of standardised microbiological data from April 1992 to December 2014 at a single healthcare facility in Kathmandu, examining time trends of Salmonella-associated bacteraemia and the corresponding antimicrobial susceptibility profiles of the isolated organisms.ResultsOver 23 years there were 30,353 positive blood cultures. Salmonella enterica accounted for 65.4% (19,857/30,353) of all the bacteria positive blood cultures. S. Typhi and S. Paratyphi A were the dominant serovars, constituting 68.5% (13,592/19,857) and 30.5% (6,057/19,857) of all isolated Salmonellae. We observed (i) a peak in the number of Salmonella-positive cultures in 2002, a year of heavy rainfall and flooding in the Kathmandu Valley, followed by a decline toward pre-flood baseline by 2014, (ii) an increase in the proportion of S. Paratyphi in all Salmonella-positive cultures between 1992 and 2014, (iii) a decrease in the prevalence of MDR for both S. Typhi and S. Paratyphi, and (iv) a recent increase in fluoroquinolone non-susceptibility in both S. Typhi and S. Paratyphi isolates.ConclusionsOur work describes significant changes in the epidemiology of Salmonella enterica in the Kathmandu Valley during the last quarter of a century. We highlight the need to examine current treatment protocols for enteric fever and suggest a change from fluoroquinolone monotherapy to combination therapies of macrolides or cephalosporins along with older first-line antimicrobials that have regained their efficacy.

Antimicrobial susceptibility pattern of Salmonella enterica, blood-stream isolates, among febrile children: a prospective study from Nepal

“…However, we observed a very high level of FQs and nalidixic-acid resistance, but relatively low rates to conventional drugs. The findings are in line with recent epidemiological studies conducted in the Nepalese population(11)(13)(14) (16).The low rate of resistance to conventional drugs was observed, probably due to discontinuation in the therapeutic regimen for a longer time, high molecular weight self-transmissible plasmid inducing resistance could have lost or de novo susceptible strain might have emerged in these days (11) (22). Due to mutation in the genes coding for DNA gyrase (gyrA and gyrB) and topoisomerase IV (parC and parE), the high level of nalidixic-acid resistance occurs, in general (23).…”

“…(18). There is no such well-established reason behind this variation of serovars; however, it can be assumed, the higher incidence of Typhi could be achieved via waterborne transmission as requires smaller inocula than paratyphoid which requires larger inocula via food-borne transmission (12) FQs and nalidixic-acid, owing to easily accessible (even sold from the medical pharmacies without prescription), less expensive, and availability in oral forms, are established as the mainstay of therapy against salmonellosis-particularly in developing countries like Nepal(13)(19) (16). Although, with the emergence of NARS strains around the globe, their efficacy against enteric fever is now questionable(20) (21).…”

The epidemiology of typhoid fever in the Dhulikhel area, Nepal: A prospective cohort study

“…In previous studies from Nepal, Salmonella Typhi was two to four times more common than Salmonella Paratyphi A[ 7 ] [ 15 ] [ 1 ], although the relative burden of the latter has increased gradually over the past two decades[ 8 ][ 1 ]. Our data shows that Salmonella Paratyphi infection is common in the Dhulikhel area, accounting for nearly half of all cases.…”

“…In some reports no cases were detected at all, and in the largest cohort published to date, this bacterium accounted for about 0.1% of 19,857 cases of Salmonella bacteremia in Patan Hospital in Kathmandu. [ 7 ][ 8 ][ 1 ]. The relative proportion of Salmonella Paratyphi B in our cohort is roughly 70-fold higher than those reported from Kathmandu (9/116, 7.8%), and accounts for 17.6% of all Paratyphi isolates.…”

“…In recent years, increased urbanization, a growing population density within the major cities, and the widespread lack of access to clean water and food have led to a very high prevalence of TF throughout the country [ 3 ]. In fact, Salmonella is by far the most common single pathogen isolated in blood cultures in Nepal [ 4 ][ 5 ][ 6 ][ 7 ][ 8 ]. Prior reports from Kathmandu link low socioeconomic status and unsanitary living conditions to higher prevalence of TF[ 9 ].…”