Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

INITIAL

suspected enteric fever

1st line – empirical antibiotic therapy + supportive care

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INITIAL
|
suspected enteric fever
1st line – 

empirical antibiotic therapy + supportive care

When considering treatment options, the country in which the disease was acquired, with its known antibiotic resistance patterns, should be taken into account together with disease severity.[13][65]​​ Consult local guidelines, where available.

Supportive care includes antipyretics and hydration.

Empirical antibiotic therapy should be started while waiting for definitive diagnosis and drug sensitivity testing results.

Azithromycin and third-generation cephalosporins (e.g., ceftriaxone, cefixime) have low rates of resistance globally, and are therefore generally recommended as empirical treatment for enteric fever.[13]​​[38][40]​​​[69][70][71]

Studies have demonstrated the potential of combination therapy with a third-generation cephalosporin plus azithromycin instead of ceftriaxone alone in reducing the febrile duration. Combination therapy is an important option, particularly for disease acquired in the Indian subcontinent and is the lead author's preference.[72][73]​​ Further clinical trials of this combined regimen therapy are ongoing.

Extensively drug-resistant (XDR) S typhi is resistant to chloramphenicol, ampicillin, trimethoprim/sulfamethoxazole, fluoroquinolones, and ceftriaxone.​[19]​ XDR S typhi emerged in Pakistan in 2016 and has since been documented in other countries, including the US, mostly associated with travel to Pakistan but also in patients who report no history of international travel in the 30 days before their illness and no close contact with anyone ill.[13][20][21][22][23]​​[24]​ The US Centers for Disease Control and Prevention (CDC) recommends that patients with suspected typhoid who have travelled to Pakistan or Iraq, or who did not travel internationally before their illness began, should be treated with azithromycin for uncomplicated illness and with a carbapenem antibiotic (e.g., meropenem) for severe or complicated disease.[40]

Primary options

ceftriaxone: children: 50-100 mg/kg/day intravenously given in divided doses every 12-24 hours, maximum 4000 mg/day; adults: 60 mg/kg intravenously every 24 hours, maximum 4000 mg/day

OR

cefixime: children: 15-20 mg/kg/day orally given in 2 divided doses, maximum 400 mg/day; adults: 200 mg orally twice daily

OR

azithromycin: children: 8-20 mg/kg orally once daily, maximum 1000 mg/day; adults: 500-1000 mg orally once daily

OR

ceftriaxone: children: 50-100 mg/kg/day intravenously given in divided doses every 12-24 hours, maximum 4000 mg/day; adults: 60 mg/kg intravenously every 24 hours, maximum 4000 mg/day

or

cefixime: children: 15-20 mg/kg/day orally given in 2 divided doses, maximum 400 mg/day; adults: 200 mg orally twice daily

-- AND --

azithromycin: children: 8-20 mg/kg orally once daily, maximum 1000 mg/day; adults: 500-1000 mg orally once daily

OR

meropenem: children: 20 mg/kg intravenously every 8 hours, maximum 1 g/dose; adults: 1 g intravenously every 8 hours

ACUTE

confirmed enteric fever

1st line – directed antibiotic therapy + supportive care

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ACUTE
|
confirmed enteric fever
1st line – 

directed antibiotic therapy + supportive care

The antibiotic treatment regimen may be adjusted once infection is confirmed and antimicrobial sensitivity results are available.

Ciprofloxacin is widely considered the treatment of choice in adults with infections that are susceptible to fluoroquinolones. However, if the patient is already taking azithromycin and/or a cephalosporin and is responding to treatment, there is no need to change. Clinicians should be aware that fluoroquinolones have been rarely associated with disabling and potentially irreversible musculoskeletal or nervous system adverse events.[76][77]​

If the strain is resistant to fluoroquinolones, treatment with a third-generation cephalosporin (e.g., ceftriaxone, cefixime), preferably with azithromycin, is recommended.

Patients with confirmed XDR typhoid fever may be started on or continue to be treated with azithromycin and meropenem, either as monotherapy or in combination.[13]​​[38][40]​​​[69][70]

Chloramphenicol, ampicillin, or trimethoprim/sulfamethoxazole may be appropriate alternatives for treatment of infection that is not multidrug resistant (as resistance has declined over time while other antibiotics have been widely used).

Supportive care includes antipyretics and hydration.

Fever clearance times can be slow and patients may continue to have fever for around five days after starting antibiotic treatment.[13]​​[38][40]​​​[69][70]​ If fever persists and the patient is receiving monotherapy (azithromycin or a cephalosporin) then combination antibiotic therapy may be considered at this point. If there is persistent fever as well as persistence of other symptoms after seven days then the antibiotic regimen may be failing. Verify that the pathogen is not XDR, particularly if the patient has recently returned from Pakistan or neighbouring countries, otherwise perform tests for metastatic infection.

Primary options

ciprofloxacin: children: 15-30 mg/kg/day orally given in 2 divided doses, maximum 500 mg/dose; adults: 500 mg orally twice daily

OR

ceftriaxone: children: 50-100 mg/kg/day intravenously given in divided doses every 12-24 hours, maximum 4000 mg/day; adults: 60 mg/kg intravenously every 24 hours, maximum 4000 mg/day

OR

cefixime: children: 15-20 mg/kg/day orally given in 2 divided doses, maximum 400 mg/day; adults: 200 mg orally twice daily

OR

azithromycin: children: 8-20 mg/kg orally once daily

OR

ceftriaxone: children: 50-100 mg/kg/day intravenously given in divided doses every 12-24 hours, maximum 4000 mg/day; adults: 60 mg/kg intravenously every 24 hours, maximum 4000 mg/day

or

cefixime: children: 15-20 mg/kg/day orally given in 2 divided doses, maximum 400 mg/day; adults: 200 mg orally twice daily

-- AND --

azithromycin: children: 8-20 mg/kg orally once daily, maximum 1000 mg/day; adults: 500-1000 mg orally once daily

OR

meropenem: children: 20 mg/kg intravenously every 8 hours, maximum 1 g/dose; adults: 1 g intravenously every 8 hours

OR

meropenem: children: 20 mg/kg intravenously every 8 hours, maximum 1 g/dose; adults: 1 g intravenously every 8 hours

and

azithromycin: children: 8-20 mg/kg orally once daily, maximum 1000 mg/day; adults: 500-1000 mg orally once daily

Secondary options

chloramphenicol: children and adults: 50-100 mg/kg/day intravenously given in divided doses every 6 hours, maximum 4000 mg/day

More

OR

ampicillin: children and adults: 50-100 mg/kg/day intravenously given in divided doses every 6 hours

OR

trimethoprim/sulfamethoxazole: children ≥2 months of age: 8 mg/kg/day intravenously/orally given in divided doses every 6-12 hours, maximum 320 mg/day; adults: 160 mg intravenously/orally every 12 hours

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Consider – high-dose dexamethasone

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ACUTE
|
confirmed enteric fever
|
with encephalopathic complications
Consider – 

high-dose dexamethasone

Additional treatment recommended for SOME patients in selected patient group

Patients with encephalopathic complications such as delirium, obtundation, stupor, coma, or shock may benefit from the prompt administration of dexamethasone.[82] 

Dexamethasone may rarely be contraindicated (e.g., in patients with structural brain lesions).

Primary options

dexamethasone: 3 mg/kg intravenously initially, followed by 1 mg/kg every 6 hours for 8 doses

Plus – prolonged antibiotic therapy ± surgical intervention

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ACUTE
|
confirmed enteric fever
|
with secondary metastatic foci
Plus – 

prolonged antibiotic therapy ± surgical intervention

Treatment recommended for ALL patients in selected patient group

Secondary metastatic foci may occur in many organs: for example, splenic abscesses, endocarditis, osteomyelitis, arthritis, and acute cholecystitis. In these cases a prolonged antibiotic course might be needed and sometimes additional surgical intervention (e.g., cholecystectomy).

ONGOING

relapse

1st line – re-treatment with antibiotics

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ONGOING
|
relapse
1st line – 

re-treatment with antibiotics

Relapse may occur, even with appropriate antimicrobial therapy, in S typhi and S paratyphi.[14] This reflects the difficulty of eradicating the organism. It is important to note that the relapse organism invariably has the same sensitivity pattern as the initial infecting isolate. In these cases, repeat antibiotic courses are needed.

chronic carriage

1st line – extended antibiotic therapy and consider cholecystectomy

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ONGOING
|
chronic carriage
1st line – 

extended antibiotic therapy and consider cholecystectomy

Some patients become chronic carriers, defined as continuing to excrete the organism in stool for more than a year but remaining asymptomatic (though able to transmit infection). Prolonged antimicrobial treatment is usually required.[40]​ Cholecystectomy may also be considered in some cases.[38][69][70]

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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