Enteric fever, caused by Salmonella enterica serovars Typhi and Paratyphi, continues to be a major public health problem in many low- and middle-income countries, particularly in South Asia and sub-Saharan Africa, despite improvements in sanitation and vaccination strategies [1]. The global burden remains high, with more than 14 million new cases and over 135,000 deaths annually, disproportionately affecting children and young adults in endemic regions [2]. Historically, first-line antibiotics such as chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole were used for treatment; however, widespread resistance led to their reduced effectiveness and the introduction of fluoroquinolones and later third-generation cephalosporins, such as ceftriaxone, as the drugs of choice [3]. Ceftriaxone has long been considered highly effective due to its excellent safety profile, parenteral administration, and broad coverage, and it has therefore become the backbone of empirical therapy for hospitalized cases of enteric fever [4]. In recent years, however, the emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains has posed serious challenges to clinicians and policymakers, threatening to reverse decades of progress in controlling this disease [5].The emergence of ceftriaxone resistance in S. Typhi and S. Paratyphi is particularly alarming, as it reduces the therapeutic options for severely ill patients and often necessitates the use of expensive or less accessible antimicrobials, such as carbapenems or azithromycin [6]. Molecular studies have shown that ceftriaxone resistance is frequently mediated by plasmid-encoded extended-spectrum β-lactamases (ESBLs), particularly bla_CTX-M-15, which are easily transferable across bacterial strains, raising the risk of wider dissemination [7]. Outbreaks of ceftriaxone-resistant S. Typhi have been documented in several regions, including Pakistan, Bangladesh, and India, where the H58 lineage has played a pivotal role in the spread of resistant strains [8]. Clinical observations suggest that patients infected with ceftriaxone-resistant strains often present with prolonged fever, abdominal pain, hepatosplenomegaly, and gastrointestinal disturbances similar to ceftriaxone-sensitive cases; however, treatment failure, delayed defervescence, and complications such as intestinal perforation and septicemia are more common due to the reduced efficacy of empirical therapy [9]. This not only increases the risk of morbidity and mortality but also places an additional financial burden on families and healthcare systems, especially in resource-limited settings [10].The growing prevalence of ceftriaxone-resistant enteric fever underscores the urgent need for updated surveillance systems, antimicrobial stewardship, and judicious antibiotic use to prevent further spread of resistance. The incidence varies geographically, with higher rates reported in regions with unregulated antibiotic use and limited access to diagnostic microbiology facilities. In addition to genetic determinants, risk factors for resistance include prior antibiotic exposure, incomplete treatment courses, and community-level misuse of broad-spectrum antimicrobials. Addressing these challenges requires a multifaceted approach, including strengthening laboratory diagnostic capacity, enhancing molecular epidemiology studies to trace resistant clones, and developing region-specific treatment guidelines that incorporate resistance trends. Furthermore, newer preventive strategies, such as the rollout of typhoid conjugate vaccines (TCVs), play a critical role in reducing disease burden and indirectly limiting antimicrobial resistance by decreasing infection rates. Despite these interventions, therapeutic management of ceftriaxone-resistant enteric fever remains complex, and clinical data describing its incidence and characteristics are limited, particularly in many endemic countries. Therefore, studies aimed at evaluating the incidence, clinical features, and outcomes of ceftriaxone-resistant enteric fever are crucial to guide clinicians in early recognition, appropriate therapy, and improved patient outcomes, while also informing public health strategies for resistance containment.

Study Design: The present study was a prospective observational hospital-based time bound study. Place of Study: The present study was conducted in the Department of Pediatrics of the GMERS medical college, Gotri, Vadodara, Gujarat. Study Duration: The study was carried out over the course of 18 months, from January 2023 to July 2024. Sample Size: 50 cases. Study Variables: Age group (years) and Gender, Presenting complaints, Comorbidities, Findings , Causative organism and O titre, Duration and Findings, vital parameters across different age groups, ceftriaxone resistant enteric fever. Inclusion Criteria: The inclusion criteria for the present study were: 1. Children aged <15 years 2. Parents providing written informed consent to take part in the study 3. Febrile children diagnosed clinically with enteric fever and confirmed by blood culture Exclusion Criteria: The exclusion criteria for the present study were: 1. Those patients who have concomitant infections along with typhoid like malaria, dengue etc. 2. Patients who did not complete treatment from the hospital Statistical Analysis: Data were analyzed using descriptive and inferential statistics. Categorical variables were expressed as percentages, and continuous variables as mean ± standard deviation. Comparisons between ceftriaxone-resistant and sensitive groups were performed using Chi-square or Fisher’s exact test for categorical data and Student’s t-test for continuous data. A p-value <0.05 was considered statistically significant.

Table 1: Distribution of Age group (years) and Gender Frequency Percentage Age group (years) <5 9 18 05-10 24 48 >10 17 34 Total 50 100 Gender Female 19 38 Male 31 62 Total 50 100 Table 2: Distribution of Presenting complaints, Comorbidities, Findings, Causative organism and O titre Frequency Percentage Presenting complaints Anorexia 5 10 Nausea vomiting 21 42 Diarrhea 4 8 Abdominal pain 16 32 Headache 7 16 Rash 0 0 Comorbidities History of appendicitis 1 2 Chest pain 1 2 Epilepsy 2 4 Anemia 1 2 UTI 1 2 Severe acute malnutrition 1 2 Findings Hepatosplenomegaly 1 2 Hepatomegaly 1 2 Splenomegaly 2 4 None 46 92 Total 50 100 Findings Hepatosplenomegaly 1 2 Mesenteric lymph nodes 4 8 Multiple enlarged lymph nodes 4 8 Splenomegaly 2 4 None 39 78 Total 50 100 O titre <1/80 2 4 1/160 8 16 1/320 21 42 1/360 1 2 Negative 18 36 Total 50 100 Causative organism S. typhi 47 94 S. paratyphi 3 6 Total 50 100 Resistance Fluroquinolones 49 98 Ampicillin 12 24 Ceftriaxone 14 28 Cefixime 12 24 Azithromycin 1 2 Meropenem 0 0 Piperacillin + tazobactam 0 0 Table 3: Distribution of Mean of Duration and Findings Duration Mean SD 6.92 4.11 8.32 3.85 Findings Hb (%) 10.7 1.75 PCV 32.55 4.81 TLC (X10^3/cc) 1.1 1.73 Platelet (lakh/cc) 2.31 0.75 CRP 66.85 46.61 Table 4: Distribution of vital parameters across different age groups Findings Age groups Mean SD Heart rate <5 92.7 7.8 05-10 84.5 6.3 >10 77.9 13.6 Respiratory rate <5 27.3 4.7 05-10 23.1 3.4 >10 20.9 2.9 SpO2 <5 98.8 0.4 05-10 98.9 0.2 >10 99 1 Table 5: Factors associated with ceftriaxone resistant enteric fever Ceftriaxone resistant Ceftriaxone sensitive p-value Mean SD Mean SD Factors Mean age 9.2 4.1 7.9 3.5 0.252 Male sex 7 50 24 66.7 0.276 Duration of fever 8.1 5.1 6.5 3.6 0.221 Presenting complaints Anorexia 2 14.3 3 8.3 0.529 Nausea and vomiting 2 14.3 19 52.8 0.013 Diarrhea 2 14.3 2 5.6 0.529 Abdominal pain 6 42.9 10 27.8 0.305 Comorbidities 6 42.9 11 30.6 0.565 Laboratory findings HR 81.53 10.5 84.8 10.9 0.307 RR 23.4 4.6 22.9 3.9 0.721 SpO2 98.9 0.3 98.9 0.2 0.226 Hb 10.6 1.9 10.8 1.7 0.72 PCV 32.5 5.6 32.6 3.3 0.98 TLC 7.9 2.7 11.2 21.3 0.54 Platelet 2.4 0.7 2.3 0.8 0.54 CRP 81.4 55.9 59.4 39.9 0.002 USG findings Hepatosplenomegaly 0 0 1 2.8 0.32 Mesenteric lymph none 1 7.1 3 8.3 0.488 Multiple enlarged lymph node 3 21.4 1 2.8 0.002 Splenomegaly 0 0 2 5.6 0.665 Widal test <1/80 0 0 2 5.6 0.827 1/160 2 14.3 6 16.7 1/320 7 50 14 38.9 1/360 0 0 1 2.8 Negative 5 35.7 13 36.1 Organism S. typhi 14 100 33 91.7 0.265 S. paratyphi 0 0 3 8.3 Mean hospital stay 10.1 4.6 7.4 3.1 0.02 In our study of 50 patients, the distribution of age and gender was analyzed. Regarding age, 9 patients (18%) were younger than 5 years, 24 patients (48%) were between 5 and 10 years, and 17 patients (34%) were older than 10 years. In terms of gender distribution, 19 patients (38%) were female, while 31 patients (62%) were male. In our study of 50 patients, the most common presenting complaint was nausea and vomiting, observed in 21 patients (42%), followed by abdominal pain in 16 patients (32%), headache in 7 patients (16%), anorexia in 5 patients (10%), and diarrhea in 4 patients (8%). None of the patients presented with a rash.Comorbidities were infrequent, with 2 patients (4%) having epilepsy, and 1 patient (2%) each having a history of appendicitis, chest pain, anemia, urinary tract infection, or severe acute malnutrition.On clinical examination, 46 patients (92%) had no abnormal findings. Hepatosplenomegaly was noted in 1 patient (2%), hepatomegaly in 1 patient (2%), and splenomegaly in 2 patients (4%). Further evaluation revealed mesenteric lymph node enlargement in 4 patients (8%), multiple enlarged lymph nodes in 4 patients (8%), hepatosplenomegaly in 1 patient (2%), and splenomegaly in 2 patients (4%), while 39 patients (78%) had no detectable abnormalities.Widal O titre analysis showed <1/80 in 2 patients (4%), 1/160 in 8 patients (16%), 1/320 in 21 patients (42%), 1/360 in 1 patient (2%), and negative results in 18 patients (36%).Blood culture identified Salmonella typhi in 47 patients (94%) and Salmonella paratyphi in 3 patients (6%).Antimicrobial resistance patterns revealed high resistance to fluoroquinolones in 49 patients (98%), ceftriaxone in 14 patients (28%), ampicillin in 12 patients (24%), cefixime in 12 patients (24%), and azithromycin in 1 patient (2%). No resistance was observed to meropenem or piperacillin-tazobactam. In our study, the duration of illness among patients had a mean of 6.92 ± 4.11 days in one group and 8.32 ± 3.85 days in the other group. Hematological and inflammatory parameters showed a mean hemoglobin (Hb) level of 10.7 ± 1.75%, a packed cell volume (PCV) of 32.55 ± 4.81%, a total leukocyte count (TLC) of 1.1 ± 1.73 ×10³/cc, and a mean platelet count of 2.31 ± 0.75 lakh/cc. The mean C-reactive protein (CRP) level was 66.85 ± 46.61 mg/L, indicating a significant inflammatory response in the study population. In our study, vital signs were analyzed according to age groups. The mean heart rate was highest in patients under 5 years, at 92.7 ± 7.8 beats per minute, followed by 84.5 ± 6.3 bpm in the 5–10 years group, and 77.9 ± 13.6 bpm in patients older than 10 years.The mean respiratory rate also decreased with age: 27.3 ± 4.7 breaths per minute in children under 5 years, 23.1 ± 3.4 in the 5–10 years group, and 20.9 ± 2.9 in those over 10 years. Oxygen saturation (SpO₂) remained within the normal range across all age groups, with a mean of 98.8 ± 0.4% in children under 5 years, 98.9 ± 0.2% in the 5–10 years group, and 99 ± 1% in patients older than 10 years. In our study, the characteristics of patients with ceftriaxone-resistant (n = 14) and ceftriaxone-sensitive (n = 36) infections were compared. The mean age was slightly higher in the resistant group (9.2 ± 4.1 years) compared to the sensitive group (7.9 ± 3.5 years), but this difference was not statistically significant (p = 0.252). Male patients constituted 50% of the resistant group and 66.7% of the sensitive group (p = 0.276). The mean duration of fever was 8.1 ± 5.1 days in the resistant group and 6.5 ± 3.6 days in the sensitive group (p = 0.221). Among presenting complaints, nausea and vomiting were significantly less common in the resistant group (2 patients, 14.3%) compared to the sensitive group (19 patients, 52.8%) (p = 0.013). Other symptoms, including anorexia, diarrhea, and abdominal pain, did not differ significantly between the groups. Comorbidities were present in 6 patients (42.9%) in the resistant group and 11 patients (30.6%) in the sensitive group (p = 0.565). Laboratory findings showed no significant differences in heart rate, respiratory rate, oxygen saturation, hemoglobin, PCV, TLC, or platelet counts between the groups. However, mean C-reactive protein (CRP) levels were significantly higher in the resistant group (81.4 ± 55.9 mg/L) compared to the sensitive group (59.4 ± 39.9 mg/L) (p = 0.002).Ultrasonography findings revealed multiple enlarged lymph nodes in 3 patients (21.4%) in the resistant group versus 1 patient (2.8%) in the sensitive group, which was statistically significant (p = 0.002). Other USG findings, including hepatosplenomegaly, mesenteric lymph node enlargement, and splenomegaly, were not significantly different.Widal test titres were comparable between the groups, with the majority of resistant patients showing a titre of 1/320 (50%). Salmonella typhi was isolated in all ceftriaxone-resistant cases (100%), while S. paratyphi was found only in the sensitive group (8.3%) (p = 0.265). Mean hospital stay was significantly longer in the resistant group (10.1 ± 4.6 days) compared to the sensitive group (7.4 ± 3.1 days) (p = 0.02), indicating that ceftriaxone resistance was associated with prolonged hospitalization.

In our study of 50 pediatric patients with enteric fever, most were aged 5–10 years (48%) and predominantly male (62%), with nausea and vomiting (42%) being the most common presenting symptom, followed by abdominal pain (32%), headache (16%), anorexia (10%), and diarrhea (8%), while comorbidities were infrequent. Clinical examination and ultrasonography were largely unremarkable, although mesenteric and multiple lymph node enlargement was noted in a minority of patients. Widal O titres were mainly 1/320 (42%), and blood cultures confirmed Salmonella Typhi in 94% and Salmonella Paratyphi in 6% of cases. Antimicrobial resistance was high, with 98% resistant to fluoroquinolones, 28% to ceftriaxone, and 24% to ampicillin and cefixime, whereas meropenem and piperacillin-tazobactam remained fully effective. The mean CRP level (66.85 ± 46.61 mg/L) indicated significant systemic inflammation. On comparing ceftriaxone-resistant (n = 14) and ceftriaxone-sensitive (n = 36) cases, the resistant group had significantly higher CRP levels (81.4 ± 55.9 mg/L vs 59.4 ± 39.9 mg/L, p = 0.002), longer hospital stays (10.1 ± 4.6 days vs 7.4 ± 3.1 days, p = 0.02), and more frequent multiple enlarged lymph nodes on USG (21.4% vs 2.8%, p = 0.002), although age, gender, duration of fever, and other laboratory parameters were comparable. Interestingly, nausea and vomiting were less common in the resistant group (14.3% vs 52.8%, p = 0.013). These findings are consistent with the observations of Dahiya et al., who reported ceftriaxone-resistant Salmonella Typhi in pediatric populations with prolonged hospitalization and elevated inflammatory markers, highlighting the increasing clinical challenge of antimicrobial resistance in endemic regions [11–

In our study, pediatric patients with enteric fever were predominantly male and most commonly presented with gastrointestinal symptoms, particularly nausea and vomiting, followed by abdominal pain, headache, anorexia, and diarrhea. Comorbidities were infrequent, and the majority of patients had unremarkable clinical examinations, with only a small proportion showing hepatosplenomegaly, isolated organomegaly, or lymph node enlargement. Laboratory findings indicated systemic inflammation, and blood cultures confirmed Salmonella Typhi as the predominant pathogen, with a minority of cases caused by Salmonella Paratyphi. Antimicrobial resistance was notable, especially to fluoroquinolones, ceftriaxone, ampicillin, and cefixime, whereas meropenem and piperacillin-tazobactam remained fully effective. Comparison between ceftriaxone-resistant and ceftriaxone-sensitive cases revealed that resistance was associated with a higher inflammatory response, more frequent lymph node enlargement on imaging, and longer hospital stays, although other clinical parameters, including vital signs, comorbidities, and presenting symptoms, were largely comparable. Overall, these findings highlight the significant impact of ceftriaxone resistance on the clinical course and outcomes of pediatric enteric fever, emphasizing the need for careful antimicrobial stewardship and ongoing surveillance to guide effective treatment strategies.

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