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Level 2 of 6Must-remember

Enteric (typhoid) fever: diagnosis, resistance and the third week

Assess, manage and stay safe — enough on its own

The card — assess, manage, caution

Assessment— look, ask, measure

  • Recognise the cardinal pattern: fever without localising signs in a patient ill for more than three days — nothing in enteric fever is pathognomonic, and the diagnosis is made by recognising a pattern and culturing the organism.
  • Count the day of illness, because the day of illness governs management: the temperature rises in "stepladder" fashion over 4–5 days and is higher in the evening, and the complications that kill cluster at the end of the second week and during the third.
  • Take the exposure history: the incubation period is typically 10–14 days, range roughly 5–21 days — an undifferentiated fever beginning more than 14 days after leaving an endemic area is compatible with typhoid, whereas dengue and chikungunya are effectively excluded by that interval.
  • Ask where the infection was acquired, because that determines the drug: South Asia (India, Pakistan, Bangladesh), sub-Saharan Africa, South-East Asia and parts of Latin America carry decreased ciprofloxacin susceptibility, and infection acquired in Pakistan or Iraq raises the question of an extensively drug-resistant (XDR) strain.
  • First-week features to seek: insidious onset, severe frontal headache, malaise, myalgia, anorexia, drowsiness, dry cough, abdominal tenderness, a coated tongue, and constipation in adults from swelling of lymphoid tissue around the ileocaecal junction — but diarrhoea and vomiting may be prominent early in children, so the absence of constipation must never exclude the diagnosis.
  • Count the pulse against the recorded temperature so relative bradycardia — present in fewer than 50% — is not missed.
  • Examine the upper abdomen and back in good light for rose spots: sparse, slightly raised, rose-red macules 2–4 mm across that blanch on pressure, present in about 30% and easily missed on dark skin; look also for splenomegaly from day 7–10 and hepatomegaly.
  • Record the abdominal findings in words — soft or rigid; tenderness; guarding; rebound; bowel sounds; organ size below the costal margin — because the management of weeks two and three turns on whether today's abdomen differs from yesterday's.
  • Second week: sustained high plateau fever, increasing toxaemia, abdominal distension and tenderness, marked weight loss, and delirium and apathy — the "typhoid state".
  • Danger signs demanding immediate reassessment: any abdominal sign suggesting perforation (sudden severe pain, a rigid abdomen, guarding, rebound tenderness, loss of bowel sounds); melaena, frank rectal bleeding or an unexplained fall in haemoglobin, particularly in weeks two and three; delirium, obtundation, stupor, coma, convulsion, focal deficit or neck stiffness.
  • More danger signs: systolic blood pressure below 90 mmHg, tachycardia disproportionate to the fever, prolonged capillary refill, mottling, oliguria or a rising lactate; new tachyarrhythmia, gallop rhythm, or hypotension worsening with fluid (suggesting myocarditis); and jaundice, signifying severe hepatic involvement and carrying a high mortality.
  • A falling temperature can itself be a danger sign: a drop to normal or subnormal levels in the second or third week, particularly with a rising pulse, pallor or a deteriorating abdomen, may accompany intestinal haemorrhage or perforation and is falsely reassuring — trust the pulse and the abdomen over the temperature chart.
  • Grade severity operationally: uncomplicated (alert, tolerating oral intake, no abdominal guarding or distension, haemodynamically stable, no organ dysfunction); moderate (persistent vomiting or dehydration, day 10 or later of illness, comorbidity, pregnancy or extremes of age, abnormal renal function, anaemia without overt bleeding); severe or complicated (altered consciousness, shock, gastrointestinal haemorrhage, suspected or confirmed perforation, myocarditis, jaundice with hepatic dysfunction, pneumonia, meningitis or DIC).
  • Apply the generic scores: qSOFA (respiratory rate ≥ 22/min, systolic ≤ 100 mmHg, altered mentation) identifies at ≥ 2 points infected patients at substantially increased risk of death; NEWS2 aggregate of 5–6 (or 3 in any single parameter) indicates an urgent response and ≥ 7 an emergency response; in children seek the WHO general danger signs — inability to drink or breastfeed, vomiting everything, convulsions, lethargy or unconsciousness.
  • Expect leucopenia or a normal white cell count — a useful contrast with almost every other Gram-negative bacteraemia — with relative lymphocytosis, eosinopenia, normocytic anaemia and mild thrombocytopenia; a *rising* count in established typhoid suggests perforation, peritonitis or secondary infection and should send you back to the abdomen.
  • Exclude the mimics that kill faster: send a malaria blood film (thick and thin) and rapid diagnostic test in every prolonged fever with relevant exposure, repeated if negative, and a dengue NS1 antigen or IgM — a rising haematocrit with a falling platelet count points to dengue rather than typhoid.

Management— do this, in order

  • Obtain blood cultures before the first antibiotic dose — the only investigation that produces an organism and a susceptibility profile, and its yield is destroyed by a single dose; take 10–15 mL per bottle in an adult and 1–3 mL in a small child, from separate sites.Not available at your setup — Blood culture.
  • Treat empirically, promptly, and according to local resistance patterns, not according to what worked a decade ago — prompt appropriate therapy reduces mortality from 10–30% to under 1%.
  • Uncomplicated disease suitable for oral therapy (including decreased-ciprofloxacin-susceptibility, fluoroquinolone-resistant and ESBL strains): azithromycin 500 mg (some use 1 g) orally once daily for 7 days; child 20 mg/kg orally once daily, maximum 1 g/day, for 7 days.
  • Admitted, vomiting or moderately unwell: ceftriaxone 2 g intravenously once daily (or 1 g 12-hourly) for 10–14 days; child 75 mg/kg intravenously once daily, maximum 2 g/day.Doctor / Nurse
  • Alternative parenteral cephalosporin: cefotaxime 1–2 g intravenously 8-hourly for 10–14 days; child 50 mg/kg/dose intravenously 8-hourly, maximum 2 g/dose.Doctor / Nurse
  • Severe or complicated disease (delirium, shock, bleeding, perforation): ceftriaxone 2 g intravenously once daily with organ support for at least 14 days, adding azithromycin or escalating if response is poor; child 75 mg/kg intravenously once daily.Doctor / Nurse
  • Suspected or confirmed XDR strain (Pakistan or Iraq, XDR contact, or no defervescence by day 5–7 of ceftriaxone): azithromycin 500 mg orally once daily or meropenem 1–2 g intravenously 8-hourly for 10–14 days; child azithromycin 20 mg/kg once daily (maximum 1 g) or meropenem 20 mg/kg/dose 8-hourly (maximum 1 g/dose).Doctor / Nurse
  • Only for a confirmed fully susceptible isolate: ciprofloxacin 500 mg orally twice daily (or 400 mg intravenously 12-hourly) for 7–14 days; child 15 mg/kg/dose orally twice daily, maximum 500 mg/dose.Doctor / Nurse
  • Add metronidazole 500 mg intravenously 8-hourly (child 7.5 mg/kg/dose 8-hourly) to the cephalosporin if there is perforation or peritonitis, until the source is controlled.Doctor / Nurse
  • Exclude malaria in parallel, always, and treat it if present — falciparum malaria is the mimic that kills fastest and co-infection occurs.
  • Rehydrate: most patients arrive several litres depleted after days of anorexia, sweating and vomiting — oral rehydration where tolerated, intravenous crystalloid otherwise; in shock give 500 mL over 15 minutes in an adult (10 mL/kg over 15–30 minutes in a child), reassessing after each bolus, to 20–30 mL/kg before considering vasopressor support — more cautiously if myocarditis is suspected.Doctor / Nurse
  • Correct the biochemistry: hyponatraemia and hypokalaemia, and treat hypoglycaemia in children with 10% dextrose 2 mL/kg intravenously.Doctor / NurseNot available at your setup — Serum electrolytes.
  • Antipyresis and analgesia: paracetamol 1 g orally or intravenously 6-hourly (maximum 4 g daily) in adults; 15 mg/kg 6-hourly (maximum 60 mg/kg/day) in children.
  • High-dose dexamethasone for the specific severe subgroup with delirium, obtundation, stupor, coma or shock: 3 mg/kg intravenously over 30 minutes, then 1 mg/kg intravenously 6-hourly for eight doses, given alongside — and never delaying — appropriate antibiotic therapy.Doctor / Nurse
  • Suspected perforation is a surgical emergency: resuscitate, keep nil by mouth, pass a nasogastric tube for decompression, broaden cover for anaerobes and enteric flora by adding metronidazole, give analgesia, and arrange surgery — antibiotics alone do not treat a perforated bowel and delay to laparotomy is the principal determinant of death.Doctor / Nurse
  • Intestinal haemorrhage: resuscitate with crystalloid and blood, transfusing to a haemoglobin threshold of approximately 70 g/L (80 g/L with ischaemic heart disease), correct coagulopathy, and stop all NSAIDs and anticoagulants; most bleeding stops with antibiotics, transfusion and time.Doctor / NurseNot available at your setup — Blood & blood products.
  • Infection control: enteric (contact) precautions, hand washing with soap and water — alcohol gel alone is inadequate against enteric organisms — a dedicated toilet, household advice on hand hygiene, safe water and food preparation, and notification, since enteric fever is notifiable in most jurisdictions.
  • Complete the full course and arrange follow-up, because relapse and carriage are both common — a full 7–14 day course, review for relapse, stool clearance in food handlers, and typhoid conjugate vaccination for contacts and children in endemic areas.

Caution— what harms

  • Never start the antibiotic before the blood culture — yield is approximately 80% in the first week in the antibiotic-naive, falls each subsequent week and sharply after any antibiotic dose.Not available at your setup — Blood culture.
  • Never manage on the Widal test: it is not specific, cross-reacts with other enterobacteriaceae and with malaria, is confounded by prior infection and vaccination, and needs paired sera 10–14 days apart to have even limited meaning — in endemic populations background titres are high, so a single positive result is close to meaningless and a negative does not exclude the diagnosis.
  • Never rely on rapid antigen or antibody card tests (Typhidot, Tubex and similar): sensitivities of approximately 70–80% and specificities of 80–90% are not accurate enough to replace blood culture, and a negative result cannot exclude the disease.
  • Never give NSAIDs or aspirin — the ileum is ulcerated, they promote bleeding and mask the pain of perforation, and aspirin risks Reye syndrome in children.
  • Never give antimotility agents, enemas, purgatives or laxatives: loperamide worsens toxicity and masks deterioration, and enemas and purgatives risk precipitating haemorrhage or perforation in friable bowel — offer a soft, low-residue, energy-dense diet as tolerated.
  • Do not use a fluoroquinolone empirically where decreased ciprofloxacin susceptibility is prevalent — including most of South Asia — because isolates with a ciprofloxacin MIC above 0.125 µg/mL may appear "susceptible" on older breakpoints yet fail clinically.
  • Do not change the antibiotic on day two — that wastes the drug that was working; temperature may remain elevated for up to five days after correct therapy begins, so anticipate defervescence over days, not hours.
  • Do not ignore persistence at day 5–7: consider in order a resistant organism, an undrained focus (abscess, bone, joint, gallbladder), a missed perforation or collection, drug fever, or a wrong diagnosis.
  • Do not be reassured by a falling temperature in week two or three — with a rising pulse, pallor or a worsening abdomen it suggests haemorrhage or perforation, not recovery.
  • Do not accept a negative erect chest radiograph as excluding perforation: free subdiaphragmatic gas is the fastest sign (use a left lateral decubitus film if the patient cannot sit upright) but a negative film does not exclude perforation, CT with contrast is more sensitive, and ultrasound cannot exclude perforation.
  • Do not give corticosteroids in uncomplicated enteric fever, where they may increase relapse — they are reserved for severe disease manifesting as delirium, obtundation, stupor, coma or shock.
  • Do not fluid-load blindly if myocarditis is suspected — tachycardia out of proportion, a gallop rhythm, or hypotension worsening with fluid should prompt electrocardiography (prolonged PR interval, low voltages, ST–T changes or arrhythmia), troponin and echocardiography, and more cautious fluid balance.
  • Do not perform a lumbar puncture for delirium alone — typhoid meningitis is rare, and cerebrospinal fluid examination is only indicated if meningism or focal signs are present; but exclude hypoglycaemia, hyponatraemia and cerebral malaria first.
  • Do not discharge without follow-up: relapse occurs in up to 10% of untreated survivors, typically two to three weeks after defervescence and usually milder; convalescent excretion occurs in up to 10%; and about 5% become chronic carriers beyond one year, with an established association between carriage and carcinoma of the gallbladder.

Refer / escalate

Refer immediately for surgery if perforation is suspected (sudden severe abdominal pain, rigidity, guarding, rebound, silent bowel sounds, a rising pulse, falling blood pressure or a rising white cell count in the second or third week), and escalate urgently for any severe or complicated disease — altered consciousness, shock, gastrointestinal haemorrhage, myocarditis, jaundice with hepatic dysfunction, pneumonia, meningitis or DIC — because delay to laparotomy is the principal determinant of death and mortality rises steeply with each hour of delay.

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