Skip to main content

Susceptibility pattern of Salmonella enterica against commonly prescribed antibiotics, to febrile-pediatric cases, in low-income countries



In most low-income countries, febrile-pediatric-cases are often treated empirically with accessible antibiotics without periodic epidemiological surveillance, susceptibility testing, or minimal lethal dose calculations. With this backdrop, the study was undertaken to evaluate the susceptibility trend of Salmonella enterica against the commonly prescribed antibiotics.


All isolates of Salmonella enterica were identified by standard protocols of biotyping and serotyping, then tested against antibiotics by the modified Kirby disk-diffusion method. Minimum Inhibitory Concentration (MIC) of isolates was determined by the agar-dilution method and compared with disk diffusion results and on nalidixic-acid sensitive/resistant strains.


Among 1815 febrile-pediatric patients, 90(4.9%) isolates of Salmonella enterica [serovar: Salmonella Typhi 62(68.8%) and Salmonella Paratyphi A 28(31.1%)] were recovered. The incidence of infection was higher among males, age groups 5 to 9, and patients enrolling in the out-patient department (OPD). On the disk-diffusion test, most isolates were sensitive against first-line drugs i.e.cephalosporins, and macrolides. However, against quinolones, a huge percentile 93.3%, of isolates were resistant [including 58 Typhiand 26 Paratyphiserovar] while nearly 14% were resistant against fluoroquinolones.

When MICs breakpoint were adjusted as follows: 4 μg/ml for azithromycin, ≥1 μg/ml for ciprofloxacin, 2 μg/ml for ofloxacin, 8 μg/ml for nalidixic acid, and 1 μg/ml for cefixime, higher sensitivity and specificity achieved. Compared to other tested antibiotics, a low rate of azithromycin resistance was observed. Nevertheless, higher resistance against fluoroquinolones was observed on NARS strain.


Higher susceptibility of Salmonella enterica to the conventional anti-typhoidal drugs (amoxicillin, chloramphenicol, cotrimoxazole, cephotaxime) advocates for its reconsideration. Although, the lower susceptibility against fluoroquinolones among nalidixic-acid-resistant Salmonella (NARS) strain negates its empirical use among the study age group.

Peer Review reports


Enteric fever, a serious bloodstream infection caused by Salmonella enterica species, is a burgeoning global threat—disproportionately affecting more than 17 million people with recorded mortality 178,000,000, annually [1,2,3]. The infection prevails irrespective of any age categories; nevertheless, children of low and middle-income countries have the highest documented burden [4,5,6]. Also, the most MDR (multi-drug resistant)strains(H58 strain) had recovered from these countries [7, 8]. Therefore, the condition is excruciating, the people of these regions had to face the dual challenge of economic constraints and obstinate MDR strain. In Nepal, the MDR H58 Salmonella Typhi(S. Typhi) seems to have been substituted by non-MDR H58 carrying the S83F mutation in gyrA and other mutations—associated with reduced susceptibility to fluoroquinolones [9, 10]. Likewise, Salmonella Paratyphi A(S.Paratyphi) frequently carries fluoroquinolone non-susceptibility alleles in gyrA and parC; however, none of these isolates were MDR [11, 12]. Nevertheless, the possible transmissibility of MDR H58 could not be neglected since many cases of MDR H58 had been reported from the abutting countries: India, Pakistan, and Bangladesh [13, 14]. This background justifies the rationale of our study.

The infection is primarily treated by antimicrobial therapy; nonetheless, is becoming difficult due to changes in the susceptibility trend of the pathogen. Ironically, without a periodic epidemiological survey, susceptibility testing, and minimal lethal dose calculations; children in developing countries are still being treated empirically or even self-medicated with accessible antibiotics [15]. These could be the reasons, why there is significant morbidity and mortality in most developing countries [3, 16, 17]. Therefore, in these countries, where distinct diagnostic and therapeutic modalities could not be assessed due to economic constraints, evaluating antimicrobial susceptibility pattern of the isolate against commonly prescribed antibiotics is crucial for clinical management.


Study design and sample population

A cross-sectional study was conducted over one year (April 2017–March 2018) in International Children Friendship Hospital (ICFH), a tertiary care hospital for children, in Kathmandu, Nepal. Febrile-pediatric subjects (up to 14 years of age) with clinical suspicion of enteric fever were enrolled, in our study. The clinical investigation/suspicion to enteric fever was made by the respective unit pediatrician, relying upon the clinical history and most occurring clinical presentations—high-grade fever, abdominal pain, sore throat, loss of appetite, and generalized weakness. A pre-tested questionnaire was administered to each patient or from their guardian to ascertain demographic characteristics, symptoms, brief clinical history, and history of antibiotic use (if under therapy). Furthermore, commonly prescribed antibiotics (either from clinicians or in self-medicated cases) for enteric fever, in the record of local pharmacies, were evaluated. Data regarding personal information (patient’s demographic including residence locality) and existing other infectious diseases were coded and kept confidential.

Inclusion and exclusion criteria

All febrile-pediatric patients with clinical suspicion of enteric fever were enrolled; however, only Salmonella enterica recovered from blood samples were studied. The other isolates, nonetheless, obtained from the sample (other than blood) after a period, and from the same patient were considered as duplicated isolates, hence excluded.

Laboratory methods

The blood samples were collected aseptically (about 2-3 ml) and cultured in brain heart infusion broth (HiMedia, India) as per guidelines set by the American Society for Microbiology (ASM) for conventional blood culture [18]. Further, isolation and identification of the isolates were done by standard microbiological techniques—biotyping (colony morphology, staining reaction, and biochemical characteristics) and serotyping using specific antisera (Denka Seiken Co. Ltd., Tokyo, Japan) [18]. The samples were considered sterile if no bacterial growth was observed on the sub-culture after 7 days of aerobic incubation at 37 °C.

Antimicrobial susceptibility testing

The antimicrobial susceptibility of Salmonella enterica against antibiotics was tested by the disk diffusion method [modified Kirby-Bauer method] on Mueller Hinton agar (Hi-Media, India) in compliance with standard procedures recommended by the Clinical and Laboratory Standards Institute (CLSI), Wayne, PA, USA [19]. The antimicrobials tested were: amoxicillin (10 μg), azithromycin (15 μg), cefixime (5 μg), ceftriaxone (30 μg), cephotaxime (30 μg), chloramphenicol (30 μg), ciprofloxacin (5 μg), cotrimoxazole (25 μg), nalidixic-acid (30 μg), ofloxacin (5 μg). The interpretation of susceptibility results was made based on interpretative zone diameters suggested by CLSI. For the standardization of susceptibility testing, Escherichia coli ATCC (American Type Culture Collection) 25,922 and Staphylococcus aureus ATCC 25923 were used as control organisms.

Determination of minimum inhibitory concentrations (MICs)

Only, MICs of most prescribed antibiotics—recommended by clinicians, and self-medicated cases—recorded in the local pharmacies were done. MICs of ciprofloxacin, ofloxacin, nalidixic-acid, azithromycin, and cefixime were determined by agar dilution method as suggested by Andrews [20] based on CLSI guidelines [19]; and were classified sensitive or resistant accordingly. Of the total 90 isolates, MICs value of only 71 isolates were determined by the agar dilution method since 9 of the isolates were not preserved and 10 isolates could not be revived.

Comparison between disk-diffusion test and MICs

The results of disk-diffusion test and agar dilution test of the most commonly prescribed antibiotics (azithromycin, cefixime, ciprofloxacin, ofloxacin, and nalidixic-acid) were compared by WHONET 5.4 software.

Correlation between NARS and fluoroquinolones (FQs)

The obtained isolates were broadly classified into nalidixic-acid sensitive Salmonella (NARS) strains and nalidixic-acid sensitive Salmonella (NASS) strains and correlated against the resistance pattern of FQs.

Data management and analysis

The data obtained was entered in Microsoft Office Excel 2007 and analyzed by Statistical Package for Social Sciences (SPSS) version 16.0. The susceptibility data (with observed zone size) and MIC values of ciprofloxacin, ofloxacin, nalidixic-acid, azithromycin, and cefixime were analyzed by WHONET 5.4 software.


Patients’ demographics

During the study period, a total of 1815 febrile-pediatric patients, suspected to have enteric fever (including 997 male and 818 female patients) were enrolled. Of the total study population, the culture positivity rate was higher in males 55 (5.5%) compared to females 35 (4.2%). Similarly, the percentage was higher among the patient of age-group (5 to 9 years) and those from out-patient department (OPD). Before attending to hospital, 304 (218 on ciprofloxacin; 86 ofloxacin) had a self-medicated history, they visited our hospital when there was no symptomatic resolution (Table 1).

Table 1 Patients’ demographics

Bacterial isolates

Of total samples, 4.9% (n = 90) Salmonella enterica isolates were recovered, among them 62(68.8%) were S. Typhi and the remaining 28 (31.1%) were S.Paratyphi.

Antibiogram of Salmonellaenterica isolates on disk-diffusion test

On susceptibility testing, most of the recovered isolates were sensitive to first-line antibiotics (amoxycillin, chloramphenicol, and cotrimoxazole), third-generation cephalosporins (cephotaxime, ceftriaxone, and cefixime), and macrolides (azithromycin). However, to FQs, 93.3% of the isolate were quinolone-resistant and nearly 15% were resistant to ciprofloxacin and ofloxacin (Table 2).

Table 2 Antimicrobial susceptibility pattern of Salmonella enterica on disk diffusion test

Antibiogram of Salmonella enterica based upon MICs

Susceptibility results of 71 isolates were tested for MIC of antibiotics: ciprofloxacin, ofloxacin, nalidixic-acid, cefixime, and azithromycin are shown in Table 3. The sensitive/resistant isolates were classified according to the CLSI guideline based upon the MICs of antibiotics.

Table 3 Antimicrobial susceptibility pattern of Salmonella enterica based upon MICs

Ciprofloxacin MICs versus disk diffusion test

41 isolates with MICs ≥0.5 μg/ml had ZOI (zone of inhibition) ≤ 28 mm; 7 isolates with MICs ≥1 μg/ml and 1 isolate with MIC of ≥2 μg/ml had ZOI 22 mm; among 22 isolates with MICs ≤8 μg/ml,10 isolates had ZOI ≤17 mm while the remaining had ZOI ≤15 mm.

Ofloxacin MICs versus disk diffusion test

36 isolates with MICs ≤1 μg/ml had ZOI ≥ 17 mm except one which had ZOI 12 mm;13 isolates with MICs of ≤4 μg/ml had ZOI 17 mm; of 22 isolates with MICs ≥8 μg/ml, 19 isolates had ZOI ≤14 mm while the remaining are with 17 mm ZOI.

Nalidixic acid MICs versus disk diffusion test

58 isolates with MICs ≥32 μg/ml had ZOI ≤11 mm; among 13 isolates with MICs 16 μg/ml, 9 had ZOI ≥19 mm while the remaining had ZOI 13 mm.

Cefixime MICs versus disk diffusion test

44 isolates with MICs ≤0.5 μg/ml had ZOI ≥ 19 mm; 24 isolates with MICs ≥1 μg/ml and ≤ 8 μg/ml had ZOI 19 mm; of the remaining 3 isolates with MICs ≥32 μg/ml,1 isolate had ZOI 17 mm while the other 2 isolates had ZOI 19 mm.

Azithromycin MICs versus disk diffusion test

67 isolates with MICs ≤8 μg/ml had ZOI 19 mm; 3 isolates with MICs 16 μg/ml had ZOI 18 mm while the remaining single isolate with MICs 64 μg/ml had ZOI 17 mm.

The comparison of MIC and disk diffusion of these antibiotics is shown in Fig. 1.

Fig. 1

Scatter plot relating (I) ciprofloxacin (II) cefixime (III) ofloxacin (IV) nalidixic acid (V) azithromycin MICs to zone of inhibition diameter from respective antibiotic disk

Relying upon these results, MIC breakpoint was adjusted 4 μg/ml for azithromycin, ≥1 μg/ml for ciprofloxacin, 2 μg/ml for ofloxacin, 8 μg/ml for nalidixic-acid, and 1 μg/ml for cefixime; the zone of inhibition 19 mm, ≤ 28 mm, 17 mm, 19 mm, 19 mm for respective antibiotics was attained.

Indicators of NARS with FQs

The MICs of FQs (ciprofloxacin and ofloxacin) among NARS and NASS isolates are shown in Fig. 2. The scatter-plot correlating the MICs of ciprofloxacin, ofloxacin, and nalidixic-acid against Salmonella isolates are shown in the (supplemental fig. 1 and fig. 2). The plot reveals a simultaneous presence of reduced FQs susceptibility in NARS.

Fig. 2

MICs of FQs (ciprofloxacin and ofloxacin) among NARS and NASS isolate


The enteric fever or typhoid is one of the leading diagnosis of febrile illness in Nepal—a series of outbreaks with varying antimicrobial resistance trends have been reported [21,22,23]. Limited epidemiologic data with age categories up to 14 years are available; nevertheless, a pocket endemic region [24]. In these perspectives, estimation of the disease burden and its etiologies along with antimicrobial susceptibilities trend are obligatory factors requiring to effective prevention and control interventions.

The infection links strongly with low socio-economic status and unsanitary living conditions. Most of the urban areas of South Asia with growing population density and those lacking accessible safe water and food had sought as the high reservoirs [2, 3, 8, 25]. The highest incidence of salmonellosis up to 15.6% was recorded, in Nepal, including all age categories [26]. In pediatric population, we reported 4.9% culture-confirmed cases of  Salmonella spp. which is more than twice the reported 2.0% by Prajapati et al. in 2008 [27]. The increasing rate could be due to surging population densities and lacking hygienic food/water supply in Kathmandu. Besides, a discrepancy in sample volume collected (particularly in infants and small kids where the required volume could not be drawn) as requires for culture could be one probable reason for the low rates of culture-positive enteric fever. Additionally, self-medication prior to hospital arrival (often practiced in rural areas of Nepal) could be another factor contributing to the low culture-positivity rate. These antibiotics might have lowered the bacterial load (requiring to grow) but not had eradicated it. In our study, we noted many self-medicated cases with FQs.

While relating the age categories, the higher incidence of enteric fever was observed in age-group 5to 9 years (primary school-going children) in our study. The probable reason could be outside tiffin habits in local dhaba or hotels, where handwashing facilities are not available—even foods are also rarely fresh.

Turning to the epidemiological scenario, Salmonella Typhi (S.Typhi) is the causative agent of nearly 30% of community-acquired febrile illness in Asia and 10% in Africa; but in Nepal, India, and China the predominance etiology contributing enteric fever is Salmonella Paratyphi (S.Paratyphi) [3, 7]. In our study, out of 90 culture-confirmed cases of salmonellosis, 62(68.8%) were caused by S. Typhi and the remaining 28 (31.1%) were S. Paratyphi A. The predominance of serovar Typhi was found as per the observations made by Zellweger et al.68.5% and 30.5% and Petersial et al. 55.7% and 44.3% respectively for serovars S. Typhi and S. Paratyphi [24, 25]. Shirakawa et al., nevertheless, reported S. Paratyphi as a more prevalent serovar [28]; his finding is corresponding to Pramod et al. (35.9% S. Typhi and 64.1% S. Paratyphi) [29]. 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 water-borne transmission as requires smaller inocula than paratyphoid which requires larger inocula via a food-borne transmission [23]. Furthermore, the self-medicated cases with FQ, in our study might result in a lower rate of S. Paratyphi A cases.

FQs and nalidixic-acid are the most prescribed antibiotics against salmonellosis in low-income-countries due to their cost-effectivity, easy accessibility (even sold from the medical pharmacies without a prescription), and availability in oral forms [7, 24, 25, 30]. With the emergence of NARS strains, globally; however, their efficacy against enteric fever is now questionable [31, 32]. It has been assumed that due to mutation in the genes coding for DNA gyrase (gyrA and gyrB) and topoisomerase IV (parC and parE), a high level of nalidixic-acid resistance occurs [33]. Similarly, lower susceptibility to fluoroquinolones possibly occurs due to the enhanced active efflux and early overproduction of the AcrA pump in isolates with the gyrA mutation [33]. Turning to our study, 304 cases (218 on ciprofloxacin; 86 on ofloxacin) had self-medicated history (treated with-out knowing etiologies and drug resistance pattern); despite, this resistance trend. We observed very high rates of FQs and nalidixic-acid resistance, but relatively low rates of resistance to first-line drugs. The findings are in line with recent epidemiological studies conducted in the Nepalese population [22, 24, 25, 27]. Possibly, due to the discontinuation of the commonly used antibiotics, of these days, in the therapeutic regimen for a longer time, and possibly the high molecular weight self-transmissible plasmid inducing resistance could have lost or de novo susceptibility [22, 34].

In our study, among tested antibiotics, a low rate of azithromycin resistance was observed on MIC which is similar to Khanal et al. reported [34]. In the Nepalese population, treatment failure on azithromycin treatment is yet not reported; nevertheless, an increase in MIC was reported in the patients from other countries. Relying upon this background, we can advocate for its choice as empiric therapy against salmonellosis.

Additionally, the third-generation cephalosporins (ceftriaxone, cefotaxime, and cefixime) had shown excellent effectiveness against Salmonella serovars with sensitivity up to 100% [35, 36]. In our study, 98.8% of the isolates were sensitive against third-generation cephalosporins supporting their use as well.

Moreover, MDR Salmonella isolates with fluctuating resistance trends have been increasingly reported from Asian countries [21, 28, 37, 38]. In our study subjects, fortuitously, no MDR salmonella isolate was recovered though this has been reported earlier from Nepal [25].


Among self-medicated cases, FQ-sensitive isolates might have failed to grow contributing to the lower incidence; therefore, the exact incidence of the disease could be even greater than observed. Probably, this could be the major drawback of our study. Although, a hospital-based study, we could not evaluate the risk factors and treatment outcomes in our settings. Further, the clinical evaluations of a large study population in the multicentral health institutions, if could have possible, it would be more elucidative. Besides, lacking the molecular laboratory set-up (presumed as a necessity for high-quality data in clinical studies) in our settings was another drawback, since blood culture has limited sensitivity.


Regardless of surging drug-resistant Salmonella enterica cases elsewhere, the level of resistance was not as high as predicted in our study population. MDR trends may vary, therefore drug susceptibility testing side-by-side to empirical therapy is mandatory—particularly in developing countries where there is a practice of self-medication. Referring to our findings, higher susceptibility of Salmonella enterica to the conventional anti-typhoidal drugs was attributed compared to macrolides and fluoroquinolons. Therefore, reconsideration of these antibiotics as implicated therapies could be useful in clinical management. However, the decreased susceptibility against fluoroquinolones, alone and, in nalidixic-acid-resistance strain negates its empirical use.

Availability of data and materials

Data generated or analyzed during this study are included in this manuscript and the remaining are available from the corresponding author on reasonable request.



antimicrobial resistance


American Society for Microbiology


American Type Culture Collection


Clinical and Laboratory Standard Institute


multiple-drug resistant


nalidixic-acid resistance Salmonella


nalidixic-acid sensitive Salmonella

S. Typhi:

Salmonella Typhi

S. Paratyphi:

Salmonella Paratyphi; ZOI: zone of inhibition


  1. 1.

    Rahman MA, Lorkowski S, et al. Disease and injury incidence and prevalence collaborators G. global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Gl. Lancet. 2018;392:1789–858.

    Article  Google Scholar 

  2. 2.

    Roth GA, Abate D, Abate KH, et al. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980–2017: a systematic analysis for the global burden of disease study 2017. Lancet. 2018;392:1736–88.

    Article  Google Scholar 

  3. 3.

    Britto CD, Dyson ZA, Duchene S, Carter MJ, Gurung M, Kelly DF, et al. Laboratory and molecular surveillance of paediatric typhoidal Salmonella in Nepal: antimicrobial resistance and implications for vaccine policy. Plos Negl Trop Dis. 2018;12(4):1–19.

    Article  Google Scholar 

  4. 4.

    Britto C, Pollard AJ, Voysey M, Blohmke CJ. An appraisal of the clinical features of pediatric enteric fever: systematic review and meta-analysis of the age-stratified disease occurrence. Clin Infect Dis. 2017;64(11):1604–11.

    Article  Google Scholar 

  5. 5.

    Dahiya S, Malik R, Sharma P, et al. Current antibiotic use in the treatment of enteric fever in children. Indian J Med Res. 2019;149(2):263–9.

    CAS  Article  Google Scholar 

  6. 6.

    Britto CD, John J, Verghese VP, et al. A systematic review of antimicrobial resistance of typhoidal Salmonella in India. Indian J Med Res. 2019;149:151–63.

    CAS  Article  Google Scholar 

  7. 7.

    Browne AJ, Kashef Hamadani BH, Kumaran EAP, Rao P, Longbottom J, Harriss E, et al. Drug-resistant enteric fever worldwide, 1990 to 2018: a systematic review and meta-analysis. BMC Med. 2020;18(1):1–22.

    Article  Google Scholar 

  8. 8.

    John J, Bavdekar A, Rongsen-Chandola T, et al. Estimating the incidence of enteric fever in children in India: a multi-site, active fever surveillance of pediatric cohorts. BMC Public Health. 2018;18:594.

    Article  PubMed  PubMed Central  Google Scholar 

  9. 9.

    Holt KE, Baker S, Dongol S, Basnyat B, Adhikari N, Thorson S, et al. High-throughput bacterial SNP typing identifies distinct clusters of Salmonella Typhi causing typhoid in Nepalese children. BMC Infect Dis. 2010;10:1–9.

    Article  Google Scholar 

  10. 10.

    Baker S, Holt KE, Clements AC, et al. Combined high-resolution genotyping and geospatial analysis reveals modes of endemic urban typhoid fever transmission. Open Biol. 2011;1(2):110008.

  11. 11.

    Pokharel BM, Koirala J, Dahal RK, Mishra SK, Khadga PK, Tuladhar NR. Multidrug-resistant and extended-spectrum beta-lactamase (ESBL)-producing Salmonella enterica (serotypes Typhi and Paratyphi a) from blood isolates in Nepal: surveillance of resistance and a search for newer alternatives. Int J Infect Dis. 2006;10(6):434–8.

    CAS  Article  Google Scholar 

  12. 12.

    Chau TT, Campbell JI, Galindo CM, Hoang NVM, To SD, Nga TTT, et al. Antimicrobial drug resistance of Salmonella enterica serovar Typhi in Asia and molecular mechanism of reduced susceptibility to the fluoroquinolones. Antimicrob Agents Chemother. 2007;51(12):4315–23.

    Article  Google Scholar 

  13. 13.

    Wong VK, Baker S, Pickard DJ, Parkhill J, Page AJ, Feasey NA, et al. Phylogeographical analysis of the dominant multidrug-resistant H58 clade of Salmonella Typhi identifies inter-and intracontinental transmission events. Nat Genet. 2015;47(6):632–9.

    CAS  Article  Google Scholar 

  14. 14.

    Holt KE, Phan MD, Baker S, et al. Emergence of a globally dominant inchi1 plasmid type associated with multiple drug resistant typhoid. PLoS Negl Trop Dis. 2011;5(7):e1245.

  15. 15.

    Msemo OA, Mbwana J, Mahende C, Malabeja A, Gesase S, Crump JA, et al. Epidemiology and antimicrobial susceptibility of salmonella enterica bloodstream isolates among febrile children in a rural district in northeastern Tanzania: a cross-sectional study. Clin Infect Dis. 2019;68(Suppl 2):S177–82.

    CAS  Article  Google Scholar 

  16. 16.

    Kelly DF, Thorson S, Maskey M, Mahat S, Shrestha U, Hamaluba M, et al. The burden of vaccine-preventable invasive bacterial infections and pneumonia in children admitted to hospital in urban Nepal. Int J Infect Dis. 2011;15(1):e17–23.

    Article  PubMed  Google Scholar 

  17. 17.

    Pradhan R, Shrestha U, Gautam SC, Thorson S, Shrestha K, Yadav BK, et al. Bloodstream infection among children presenting to a general hospital outpatient Clinic in Urban Nepal. Plos One. 2012;7(10):1–7.

    Article  Google Scholar 

  18. 18.

    Isenberg HD. Clinical microbiology procedures handbook. 2nd ed. Washington Dc: ASM Press; 2004.

    Google Scholar 

  19. 19.

    CLSI. Performance standards for antimicrobial susceptibility testing. CLSI supplement M100S. In: Clinical and Laboratory standards Institute. 26th ed. Wayne: Clinical and Laboratory standards Institute; 2016.

    Google Scholar 

  20. 20.

    Andrews JM. Determination of minimum inhibitory concentrations. J Antimicrob Chemother. 2001;48(1):5–16.

    CAS  Article  Google Scholar 

  21. 21.

    Karki S, Shakya P. Leder, Karin et al. trends of etiology and drug resistance in enteric fever in the last two decades in Nepal: a systematic review and meta-analysis. Clin Infect Dis. 2013;57(10):167–76.

    Article  Google Scholar 

  22. 22.

    Shrestha KL, Pant ND, Lekhak B, et al. Re-emergence of the susceptibility of the Salmonella spp. isolated from blood samples to conventional first line antibiotics. Antimicrob Resist Infect Control. 2016;5(1):1–5.

    Article  Google Scholar 

  23. 23.

    Acharya D, Bhatta DR, Malla S, Kandel BP, et al. Salmonella enterica serovar Paratyphi a: an emerging cause of febrile illness in Nepal. Nepal Med Coll J. 2011;13(2):69–73.

    CAS  PubMed  Google Scholar 

  24. 24.

    Petersiel N, Shresta S, Tamrakar R, Koju R, Madhup S, Shresta A, et al. The epidemiology of typhoid fever in the Dhulikhel area , Nepal : A prospective cohort study. Plos One 2018;1–8. doi:

  25. 25.

    Zellweger RM, Basnyat B, Shrestha P, Prajapati KG, Dongol S, Sharma PK, et al. A 23-year retrospective investigation of Salmonella Typhi and Salmonella Paratyphi isolated in a tertiary Kathmandu hospital. Plos Negl Trop Dis. 2017;11(11):1–16.

    Article  Google Scholar 

  26. 26.

    Easow JM, Joseph NM, Dhungel BA, Chapagain B. Shivananda, P G et al. blood stream infections among febrile patients attending a teaching Hospital in Western Region of Nepal. AMJ. 2010;3(10):633–7.

    Article  Google Scholar 

  27. 27.

    Prajapati B, Rai GK, Rai SK, Upreti HC, Thapa M, Singh G, et al. Prevalence of Salmonella typhi and paratyphi infection in children: a hospital based study. Nepal Med Coll J. 2008;10(4):238–41.

    CAS  PubMed  Google Scholar 

  28. 28.

    Shirakawa T, Acharya B, Kinoshita S, Kawabata M, et al. Decreased susceptibility to fluoroquinolones and gyrA gene mutation in the Salmonella enterica serovar Typhi and Paratyphi a isolated in Katmandu, Nepal in 2003. Diagn Microbiol Infect Dis. 2006;54(4):299–303.

    CAS  Article  Google Scholar 

  29. 29.

    Pokherel P, Lekhak B, Amatya R, Pokherel P, et al. Enteric fever caused by Salmonella enterica serovar paratyphi a: an emerging health concern in Nepal. African J Microbiol Res. 2016;10(42):1784–91.

    Article  Google Scholar 

  30. 30.

    Humphries RM, Fang FC, Aarestrup FM, Hindler JA. In vitro susceptibility testing of fluoroquinolone activity against salmonella: recent changes to CLSI standards. Clin Infect Dis. 2012;55(8):1107–13.

    Article  Google Scholar 

  31. 31.

    Menezes GA, Harish BN, Khan MA, WG, Hays JP, et al. Antimicrobial resistance trends in blood culture positive Salmonella Typhi isolates from Pondicherry, India, 2005–2009. Clin Microbiol Infect. 2012;18(3):239–45.

    CAS  Article  PubMed  Google Scholar 

  32. 32.

    Acharya D, Malla S, Dumre SP, et al. Multidrug resistant Salmonella enterica serovar typhi. J Nepal Med Assoc. 2009;48(174):196–7.

    CAS  Article  Google Scholar 

  33. 33.

    Giraud E, Cloeckaert A, Chaslus-Dancla E, et al. Evidence for active efflux as the primary mechanism of resistance to ciproffoxacin in Salmonella enterica serovar typhimurium. Antimicrob Agents Chemother. 2000;44(5):1223–8.

    CAS  Article  Google Scholar 

  34. 34.

    Khanal PR, Satyal D, Bhetwal A, et al. Renaissance of conventional first-line antibiotics in Salmonella enterica clinical isolates: assessment of MICs for therapeutic antimicrobials in enteric fever cases from Nepal. Biomed Res Int. 2017;2017:2868143.

  35. 35.

    Crump JA, Sjölund-Karlsson M, Gordon MA, Parry CM, et al. Epidemiology, clinical presentation, laboratory diagnosis, antimicrobial resistance, and antimicrobial management of invasive Salmonella infections. Clin Microbiol Rev. 2015;28(4):901–37.

    CAS  Article  Google Scholar 

  36. 36.

    Kariuki S, Gordon MA, Feasey N, et al. Antimicrobial resistance and management of invasive Salmonella disease. Vaccine. 2015;33(3):C21–9.

    CAS  Article  Google Scholar 

  37. 37.

    Harish BN, Menezes GA, et al. Antimicrobial resistance in typhoidal salmonellae. Indian J Med Microbiol. 2011;29(3):223–9.

    CAS  Article  Google Scholar 

  38. 38.

    Threlfall EJ, Ward LR, Rowe B, et al. Widespread occurrence of multiple drug-resistant Salmonella typhi in India. Eur J Clin Microbiol Infect Dis. 1992;11(11):990–3.

    CAS  Article  Google Scholar 

Download references


We are profoundly obliged to all the patients participating in this study. Our special thanks go to all the laboratory staff, management, and officials of International Friendship Children’s Hospital Kathmandu for providing the opportunity to carry out this research work.


Not applicable (Nil).

Author information




PK and JT made the diagnosis, designed the manuscript, reviewed the literature, and prepared the article for submission. ST helped with the literature review, gave the concept of the research paper, and critically reviewed the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Priyatam Khadka.

Ethics declarations

Ethics approval and consent to participate

This research was approved by the Institutional Review Committee of International Friendship Children’s Hospital, Kathmandu, Nepal. A written informed consent was taken from their parents before participating in the study. Data regarding personal information and existing other infectious disease were coded and kept confidential.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Additional file 1: Supplemental Figure 1.

Scatter plot relating ciprofloxacin MICs to nalidixic acid MICs and disk. Supplemental Figure 2. Scatter plot relating ofloxacin MICs to nalidixic acid MICs and disk.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Khadka, P., Thapaliya, J. & Thapa, S. Susceptibility pattern of Salmonella enterica against commonly prescribed antibiotics, to febrile-pediatric cases, in low-income countries. BMC Pediatr 21, 38 (2021).

Download citation


  • Enteric fever
  • Low-income countries
  • Nepal
  • Pediatric
  • Salmonella enterica