When should typhoid be suspected?

Any patient presenting with fever with no clear focus of infection in an endemic setting, for more than 3 days, should be suspected to have typhoid fever. The guideline also requires you to rule out malaria, dengue and other causes of acute febrile illness of more than 3 days duration.

Can Widal or TyphiDOT diagnose typhoid?

No. The MMIDSP 2022 guideline states that positive serological tests such as Widal and TyphiDOT are not recommended for the diagnosis of enteric fever and are not included in the case definitions of typhoid. It adds that serological tests should never be ordered or relied upon to diagnose or rule out enteric fever. Blood culture is the diagnostic standard.

How many blood cultures should be taken?

Two sets of blood culture are optimal before starting antibiotic therapy, and also in patients already on antibiotics who are not responding. In bacteraemic patients automated cultures can turn positive as early as 4 hours, with final identification and susceptibility in the following 48 hours.

Typhoid caused by S. Typhi strains resistant to all recommended antibiotics for typhoid fever — first-line drugs, fluoroquinolones and third-generation cephalosporins — but still sensitive to carbapenems and azithromycin. This is why ceftriaxone fails in many Pakistani patients.

What is the azithromycin dose for XDR typhoid?

For a clinically stable patient, dosed by body weight: under 60 kg, a 1 g oral loading dose followed by 500 mg every 24 hours for 7–10 days; over 60 kg, 1 g every 24 hours. Paediatric dosing is 8–10 mg/kg. If the patient cannot take orally, is haemodynamically unstable, is deteriorating or develops complications, admit or refer and use a carbapenem.

Why does the fever not settle quickly?

Fever defervescence is prolonged in typhoid and may take 5–7 days to improve. The guideline explicitly warns not to rush to change antibiotics — monitor for improvement in the frequency and intensity of fever instead. Appetite and general condition often improve before the fever does.

How long should treatment last?

Most categories require 14 days. For XDR typhoid, azithromycin is given for 7–10 days, or a carbapenem for 10–14 days with de-escalation to oral azithromycin to complete a total of 14 days. For MDR typhoid the guideline warns that shorter cephalosporin courses may lead to relapse.

Which empiric antibiotic should I start?

The guideline states two different empiric regimens in two separate sections — azithromycin or a carbapenem in the Treatment section, and cefixime or ceftriaxone in the Management guidelines section. This tool reproduces both verbatim with their sections and does not choose between them, because in a setting with high XDR prevalence they are not equivalent. Decide based on local resistance patterns and your patient.

How long should patients be followed up?

Despite completion of treatment, patients should be monitored for relapse or complications for 3 months after treatment has commenced.

Typhoid Management Wizard (Pakistan, MMIDSP 2022) — XDR, MDR & ESBL

Step 1 · Should you suspect typhoid?

MMIDSP 2022 · Presentation

Any patient presenting with fever with no clear focus of infection in an endemic setting, for more than 3 days should be suspected to have typhoid fever.

Fever for more than 3 days with no clear focus of infection, in an endemic setting Malaria, dengue and other causes of acute febrile illness have been considered

Fever patternTyphoid fever begins 7–14 days after ingestion of the organism. The fever pattern is stepwise — rising over the course of each day and dropping by the following morning, with peaks and troughs rising progressively over time.

Step 2 · Diagnose by blood culture

MMIDSP 2022 · Management guidelines

Widal and TyphiDOT are not diagnostic. Positive serological tests (such as Widal and TyphiDOT) are NOT recommended for diagnosis of enteric fever and are not included in case definitions of typhoid. Serological tests should never be ordered or relied upon to diagnose or rule out enteric fever.

Two sets of blood culture are optimal before starting antibiotic therapy, and in those patients who are already on antibiotics but not responding to therapy.

In bacteraemic patients, automated blood cultures can turn positive as early as 4 hours, with final identification and susceptibility results available in the following 48 hours.

Two sets of blood culture have been sent

If cultures are negativeIn the absence of a positive blood culture, or if a blood culture shows no growth, re-evaluate the diagnosis and stop or modify antibiotics if not typhoid.

Step 3 · Is this complicated typhoid?

MMIDSP 2022 · Complicated typhoid

Suspected or culture-proven enteric fever with jaundice, drowsiness, severe abdominal pain and intestinal haemorrhage, severe sepsis or septic shock.

Jaundice Drowsiness or altered consciousness Severe abdominal pain Intestinal haemorrhage Severe sepsis or septic shock

Step 4 · Empiric therapy, pending culture

MMIDSP 2022 · two sections — see note

The guideline states two empiric regimens. The guideline states two empiric regimens in two different sections. In a setting with high XDR prevalence these are not equivalent — cefixime and ceftriaxone are ineffective against XDR strains. Both are reproduced here with their source section; choose according to local resistance patterns and your patient.

§Treatment → Empiric treatment“Based on clinical status, start oral or intravenous empiric treatment, until blood culture results are available: Oral Azithromycin or IV Carbapenem.”

§Management guidelines“After sending baseline investigations, including blood cultures, commence empirical treatment for suspected enteric fever with either oral cefixime or IV ceftriaxone depending on the severity of the disease.”

Escalation. If the initial therapy was oral, switch to IV carbapenem if there are no clinical signs of improvement after 5 days of treatment, or if any signs of complications appear.

Referral. Refer to a secondary or tertiary care centre where no clinical improvement is seen despite switching to IV antibiotics for at least 48 hours and blood cultures remain negative.

Step 5 · Definitive therapy once susceptibility is known

MMIDSP 2022 · Definitive treatment · Classification by drug resistance

Select the resistance category reported by the laboratory.

Non-resistant (drug-sensitive) typhoid fever

Strains sensitive to first-line drugs (chloramphenicol, ampicillin, trimethoprim-sulfamethoxazole) and third-generation cephalosporins, with or without resistance to second-line drugs (fluoroquinolones).

MDR typhoid fever

Strains resistant to first-line drugs (ampicillin, trimethoprim-sulfamethoxazole, chloramphenicol) and/or fluoroquinolones, but sensitive to third-generation cephalosporins.

XDR typhoid fever

Strains resistant to all recommended antibiotics for typhoid fever (first-line, second-line and third-generation cephalosporins), but sensitive to carbapenems and azithromycin.

ESBL-positive typhoid fever

Strains resistant to third-generation cephalosporins but sensitive to carbapenems and azithromycin, as well as to chloramphenicol, cotrimoxazole or fluoroquinolones. MMIDSP added this category on reports of strains resistant to third-generation cephalosporins but sensitive to chloramphenicol, cotrimoxazole or fluoroquinolones.

Step 6 · Course, monitoring and follow-up

MMIDSP 2022 · Management guidelines · Treatment

Practice points

Fever defervescence is prolonged in typhoid and may take 5–7 days to improve. Do not rush to change antibiotics — monitor for improvement in the frequency and intensity of fever.
The appetite and general condition of the patient may improve before any improvement in fever is noticed.
Monitor for complications such as abdominal distension, tenderness, vomiting, alteration of GCS, and laboratory parameters such as bicytopenia.
Typhoid is usually treated with a single antibiotic agent.
Always aim to switch from IV to oral once the patient is clinically stable and able to take orally, and de-escalate from broad- to narrow-spectrum once a susceptible strain is isolated.
Despite completion of treatment, patients should be monitored for relapse or complications for 3 months after treatment has commenced.

Supportive treatment

Antipyretics as required.
Adequate rest, hydration, and correction of fluid–electrolyte imbalance.
Adequate nutrition — a soft, easily digestible diet should be continued unless the patient has abdominal distension or ileus.
In severe illness monitor blood pressure, blood sugar, electrolytes, haemoglobin, platelet counts and liver function as indicated.

Typhoid Management Wizard