1. Reassess severity immediately
   • Vital signs, hydration, mental status, abdominal examination, urine output.
   • Admit or escalate urgently if shock, confusion, persistent vomiting, GI bleeding, severe abdominal pain/distension, peritonitis, jaundice, oliguria, or inability to take oral fluids.
2. Do not label treatment failure from fever alone too early
   • In enteric fever, fever can persist for several days even with an active antibiotic. Six doses may represent only 2-3 days, depending on the schedule.
   • Look for overall trajectory: toxicity, hemodynamics, appetite, hydration, inflammatory markers, and new focal findings.
3. Confirm the diagnosis and obtain microbiology
   • Take at least blood cultures before changing antibiotics, if feasible, and request identification plus full antimicrobial susceptibility testing.
   • Widal serology should not be used to guide treatment because of poor specificity.
   • Consider repeat cultures if bacteremia persists or the patient deteriorates.
4. Look for an alternative diagnosis or co-infection
   • Depending on geography/exposures: malaria, dengue, viral illness, rickettsial infection, leptospirosis, acute hepatitis, urinary infection, pneumonia, intra-abdominal sepsis, etc.
   • Check CBC with differential/platelets, renal and liver function, electrolytes, glucose, CRP or similar trend marker, urinalysis, and targeted tests/imaging based on examination.
5. Evaluate for complications
   • Especially from the second week: intestinal hemorrhage or ileal perforation, encephalopathy, hepatitis, cholecystitis, myocarditis, and shock.
   • Severe localized abdominal pain, guarding, distension, melena/hematochezia, or falling hemoglobin requires urgent surgical assessment and abdominal imaging.
6. Change therapy only on clinical and microbiologic grounds
   • If the patient is clinically worsening, cultures show ceftriaxone resistance, or there is convincing failure after an adequate course, involve infectious diseases/microbiology and select an alternative guided by local resistance patterns and susceptibility results.
   • Resistant and extensively drug-resistant Salmonella Typhi occur in some regions. CDC notes that susceptibility testing should guide decisions because resistance can limit options. CDC clinical guidance
7. Supportive care and follow-up
   • Fluids, nutrition, antipyretics, electrolyte correction, and careful monitoring.
   • Document response daily and arrange follow-up for relapse or chronic carriage where indicated, particularly for food handlers or healthcare workers.

Next steps

1. Confirm clinical response
   • Fever trend, pulse/BP, hydration, ability to eat/drink, mental status, abdominal examination, urine output.
   • Fever can persist for 3-5 days after starting effective antibiotics, often declining gradually each day. CDC Yellow Book guidance
2. Continue ceftriaxone for the planned full course
   • Complete the regimen chosen for the patient based on severity, age, site of care, local protocol, and culture susceptibility.
   • In standard references, ceftriaxone courses for enteric fever are commonly 7-14 days. Do not stop at six doses unless the diagnosis has changed or a specialist directs otherwise. Goldman-Cecil Medicine, p. 3151.
3. Review blood culture and antimicrobial susceptibility
   • Ensure blood culture was sent, ideally before antibiotics, and review the final organism and sensitivity result.
   • Continue ceftriaxone only if the isolate is susceptible and the patient is responding. Susceptibility testing should guide definitive therapy because ceftriaxone-resistant/XDR Salmonella Typhi occurs in some regions. CDC clinical guidance
4. Give supportive treatment
   • Oral or IV fluids as indicated, nutrition, paracetamol/acetaminophen for fever, and correction of electrolyte abnormalities.
   • Avoid unnecessary additional antibiotics.
5. Monitor for complications
   • Urgent reassessment/admission if there is worsening abdominal pain or guarding, GI bleeding/melena, persistent vomiting, confusion, hypotension, jaundice, oliguria, or worsening fever/toxicity.
6. Plan follow-up after completion
   • Review clinically in about 1-2 weeks, or earlier if fever returns.
   • Relapse may occur about 1-3 weeks after recovery, especially after incomplete treatment. CDC follow-up information
   • Follow local public-health rules for stool clearance testing, particularly for food handlers, childcare workers, or healthcare workers.