Typhoid Fever
Clinical Snapshot
Typhoid fever (and the related paratyphoid fever) — together often called enteric fever — is a systemic bacterial infection caused by Salmonella enterica serotype Typhi (typhoid) or serotypes Paratyphi A, B, or C (paratyphoid), transmitted exclusively human-to-human through food or water contaminated by the feces or urine of an acutely infected person, a convalescent, or an asymptomatic chronic carrier — humans are the only reservoir.[1] For Canadian travellers, risk is concentrated in South Asia (Bangladesh, India, Nepal, Pakistan, and neighbouring countries), where the Committee to Advise on Tropical Medicine and Travel (CATMAT) estimates risk at roughly 1 in 3,000 travellers, versus roughly 1 in 50,000-100,000 for intermediate-risk destinations and under 1 in 300,000 for low-risk destinations.[2]
Two licensed vaccines — oral live-attenuated Ty21a and injectable Vi polysaccharide — reduce but do not come close to eliminating risk (roughly 50% efficacy for both), and neither reliably protects against paratyphoid fever, so food and water safety precautions remain essential for every traveller regardless of vaccination status.[2][1] Once infection is confirmed or strongly suspected, treatment selection has a genuinely current, high-stakes twist: fluoroquinolones — the older first-line teaching — are no longer reliable empiric therapy for infection acquired in South Asia, where well over 99% of isolates now show decreased ciprofloxacin susceptibility; azithromycin or ceftriaxone are the correct current empiric choices in that setting.[1][3] A small proportion of infected individuals — roughly 1-4% — become long-term asymptomatic biliary carriers, a distinct public-health consideration with real food-handler and occupational implications, including in Canada.[1][4]
Recognize the Condition
Typical presentation
Onset is classically insidious: fatigue and a fever that increases gradually day over day, typically reaching 39-40°C by day 3-4, with a lower morning trough and a higher evening peak — the "stepwise" fever pattern often described in textbooks.[1] Headache, anorexia, and malaise are nearly universal; abdominal pain is common, with constipation more typical in adults and diarrhea more typical in children.[1] Hepatosplenomegaly is often detectable on examination, and dry cough, myalgia, and sore throat are also reported.[1] Incubation is typically 6-30 days (most commonly 8-14 days) after ingestion of contaminated food or water; untreated illness lasts approximately a month.[1]
2 classic signs worth knowing honestly, not just by name
Relative bradycardia and rose spots — genuinely useful when present, but neither can rule the diagnosis out when absent
Relative bradycardia (Faget sign / pulse-temperature dissociation)
A pulse rate lower than expected for the degree of fever (each 1°C above 38.3°C would normally raise heart rate by roughly 8-10 beats/minute). This is a classic teaching point for typhoid, but its real-world sensitivity is low — about 15-20% — while its specificity when present is genuinely high, around 94.7%.[5] In practice: its presence is a meaningfully useful clue that supports the diagnosis, but its absence — which is the more common scenario — must never be used to argue against typhoid in a febrile returned traveller.
Rose spots
A transient, blanching, maculopapular rash, most often on the trunk, seen in only a minority of patients — and considerably harder to detect on darker skin tones, which is a real and clinically relevant examination-bias point, not just a textbook footnote.[1] Their absence is common and does not exclude the diagnosis.
Paratyphoid fever — clinically similar, epidemiologically distinct, and not reliably vaccine-preventable
Salmonella Paratyphi A causes a presentation essentially indistinguishable from typhoid at the bedside, but its epidemiology is shifting in a way that matters for counselling: it now accounts for up to roughly 35% of enteric fever in India and Nepal and over 60% in China, and its relative contribution to overall enteric fever incidence in South Asia is rising.[3] Neither licensed typhoid vaccine reliably protects against Paratyphi A; limited trial data suggest Ty21a may offer some cross-protection against Paratyphi B specifically, but this is not considered reliable enough to base counselling on, and there is no equivalent suggestion of cross-protection against Paratyphi A.[2]
Risk Factors
- Travel to South Asia (Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan, Sri Lanka) without vaccination — the highest-risk destination group for Canadian travellers, at roughly 1 in 3,000 travellers.[2]
- Visiting friends and relatives (VFR travel) — disproportionately affected due to longer stays, residing in family homes rather than tourist accommodation, and typically less cautious food/water behaviour, similar to the VFR risk pattern seen in malaria.[2]
- Extended-duration travel, which prolongs cumulative exposure to potentially contaminated food and water even outside South Asia.[2]
- Travel to other endemic regions — sub-Saharan Africa, Southeast Asia, and parts of Latin America — which carries intermediate-to-low average risk but should still prompt individualized counselling in the presence of other risk factors above.[2]
- Consuming raw produce, street food, tap water, or ice made from untreated water in an endemic area.
- Assuming vaccination alone is sufficient protection and relaxing food/water precautions as a result — neither licensed vaccine is close to fully protective.[1]
- Ongoing exposure to a known or unrecognized chronic carrier — the Ottawa, Canada outbreak (2018-2022) demonstrated that this risk is not purely a travel-medicine issue: 7 locally acquired cases over nearly 4 years were traced to a single asymptomatic food-handler carrier who had likely acquired the infection before immigrating to Canada.[4]
- Unknown vaccination status combined with a false sense of protection from a remembered childhood vaccination — Ty21a and Vi polysaccharide protection both wane over years and require destination-appropriate revaccination for repeat travel (see Choose Initial Treatment).
Red Flags & Refer
Any of the following needs urgent medical evaluation, not community-pharmacy management alone:
- Fever in a traveller returned from, or a resident of, a typhoid-endemic region should prompt urgent blood culture and medical assessment — do not use the absence of relative bradycardia or rose spots to argue against the diagnosis, since both are insensitive when present at all.[5]
- Any sign of severe or complicated disease: altered mental status, shock, an acute abdomen or signs of peritonitis (possible intestinal perforation), or gastrointestinal bleeding (melena, hematochezia, hematemesis) — these need immediate hospitalization, and an acute abdomen needs an urgent surgical consult.[6]
- Fever that has not improved after 5 full days of appropriate antibiotic therapy — this genuinely can be a normal, expected course rather than treatment failure (see Monitoring & Follow-Up), but it still needs reassessment rather than simple reassurance.[1][6]
- Any malaria diagnosis in a pregnant patient — typhoid in pregnancy carries real maternal and fetal risk and needs prompt obstetric involvement alongside infectious disease input.
- Any patient identified as a possible or confirmed chronic carrier (positive stool/urine culture 12 months or more after acute infection, or an epidemiologic link to a cluster of cases without travel history) — this triggers mandatory public health reporting and, for a food handler or healthcare worker, occupational exclusion until clearance is documented.[4]
- Recurrence of fever 2-3 weeks after apparent recovery — genuine relapse occurs in up to about 10% of patients and needs retreatment.[1]
Assessment & Diagnosis
Blood culture — the diagnostic gold standard, with a genuine sensitivity limitation
Blood culture remains the reference standard for diagnosis, but a single culture is positive in only approximately 50% of true cases — a limitation that pharmacists should understand honestly rather than treat blood culture as a perfectly sensitive test.[1] Sensitivity is reduced further by prior antibiotic exposure (common in a patient who self-medicated abroad or received empiric treatment before the culture was drawn) and by low blood-volume sampling; larger blood volumes and repeat cultures both improve diagnostic yield, and cultures may need up to 7 days of incubation before a negative result can be reported with confidence.[1]
Other diagnostic tests
Bone marrow culture is substantially more sensitive — approximately 80% — and, importantly, its sensitivity is not reduced by recent antibiotic exposure, making it a genuinely useful option when blood culture is negative but clinical suspicion remains high, though its invasiveness means it is reserved for that specific scenario rather than used routinely.[1] Stool and urine cultures are less sensitive than blood culture during the first week of illness but become more useful later in the illness course and are the basis for chronic-carrier detection (see Monitoring & Follow-Up).[1] The Widal serologic test, which measures antibody titres, is unreliable — it cannot distinguish acute infection from past infection or prior vaccination — but remains widely used in low-resource endemic settings because of its low cost; a traveller who returns with only a positive Widal result from abroad should not be considered definitively diagnosed on that basis alone, and should still be worked up with culture where possible.[1]
When to test
Any fever in a traveller returned from a typhoid-endemic region — especially South Asia — warrants active testing rather than reassurance based on a benign-appearing early presentation, mirroring the same testing discipline used for a febrile returned traveller from a malaria-endemic area.
Treatment Targets
- Prevent infection in the first place through destination-appropriate pretravel vaccination plus food and water safety counselling — never one without the other, since neither vaccine is close to fully protective.
- Confirm the diagnosis promptly (ideally before starting antibiotics, since prior antibiotic exposure reduces blood-culture sensitivity) and initiate appropriate empiric therapy without unnecessary delay.
- Select empiric antibiotic therapy that reflects current regional resistance patterns rather than older fluoroquinolone-first teaching, particularly for infection acquired in or of uncertain origin from South Asia.
- Recognize and urgently manage the serious complications of untreated or delayed-treated disease — intestinal perforation and gastrointestinal hemorrhage foremost among them.
- Identify and appropriately manage the chronic carrier state, including the food-handler/occupational and public-health reporting obligations it carries.
- Counsel every traveller — vaccinated or not — that food and water safety precautions remain necessary for the full duration of travel to an endemic area.
Choose Initial Treatment
Step 1 — decide whether pretravel vaccination is indicated
CATMAT suggests typhoid vaccination (either Ty21a or Vi polysaccharide) for most Canadian travellers to South Asia (Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan, Sri Lanka) — a conditional recommendation reflecting moderate-confidence evidence, but still the correct default for this destination group.[2] For travel to other endemic regions (sub-Saharan Africa, Southeast Asia, Latin America), CATMAT does not routinely recommend vaccination, but explicitly directs an individualized discussion when other risk factors are present — visiting friends and relatives, longer trip duration, or accommodation/itinerary with limited access to safe food and water; vaccination is not routinely recommended for short resort-based travel with reliable food and water access.[2]
Step 2 — choose between the 2 licensed vaccines
Both vaccines provide comparable, moderate protection (roughly 50% efficacy against clinical disease over about 2-3 years of follow-up in trial data) — genuinely useful, but nowhere close to complete, which is the basis for the food/water counselling message that must accompany either choice.[2]
Ty21a (oral, live-attenuated) versus Vi polysaccharide (injectable)
Ty21a — oral, live-attenuated
4 enteric-coated capsules taken on alternate days (days 1, 3, 5, 7); protection is considered established about 1 week after the final capsule.[7] Approved from age 6 years. Longer duration of protection than Vi polysaccharide — CATMAT and the Canadian Immunization Guide describe revaccination for continued risk at approximately every 7 years, though this varies by jurisdiction (US guidance uses a shorter, more conservative 5-year interval) — when in doubt, or for a traveller with frequent repeat exposure, the shorter interval is the reasonable default to use.[2][8] Contraindicated in pregnancy, in immunocompromised individuals (including HIV infection), and in anyone with an acute gastrointestinal illness or acute febrile illness at the time of dosing.[7]
Vi polysaccharide — injectable
A single 0.5 mL intramuscular injection (deltoid), given at least 2 weeks before potential exposure.[9] Approved from age 2 years. Shorter duration of protection than Ty21a — revaccination for continued risk approximately every 3 years per Canadian sources (again, a shorter US-guidance interval of 2 years exists and is a reasonable default when in doubt).[2][8] Not a live vaccine, so it is the safer option for an immunocompromised traveller who still needs some protection, and it avoids the antibiotic-timing interaction problem described below entirely.[1]
Step 3 — Ty21a-specific counselling: administration and antibiotic/antimalarial timing (a genuine, high-yield counselling point)
Administration: each capsule must be swallowed whole (never chewed) with cool or lukewarm water — specifically water no warmer than body temperature, since heat can inactivate the live bacterial strain — taken at least 1 hour before a meal and at least 2 hours after the previous meal; alcohol should be avoided for roughly 1 hour before and 2 hours after each dose.[7] Capsules must be kept refrigerated (2-8°C) in their original blister packaging and never frozen.[7]
Antibiotic interaction — the single most important counselling point for this vaccine: Ty21a must not be given concurrently with any antibacterial antibiotic, because the antibiotic can kill the live attenuated vaccine strain before it can establish the intestinal immune response the vaccine depends on.[7] Complete the full Ty21a course either at least 3 days before starting an antibiotic, or delay starting Ty21a until at least 3 days after finishing one.[2]
Antimalarial timing: this is not a uniform rule across antimalarial agents. Chloroquine and mefloquine do not require the same 3-day separation as antibiotics — for mefloquine specifically, spacing doses at least 12 hours apart from a Ty21a capsule is a reasonable practical approach to avoid any theoretical interference.[2] Atovaquone-proguanil is different again: because proguanil has intrinsic antibacterial activity, it should not be started until at least 10 days after completing the Ty21a course.[1] When a traveller needs both malaria chemoprophylaxis and typhoid vaccination on a tight pretravel timeline, sequence Ty21a first and plan the antimalarial start date around it, or use Vi polysaccharide instead to avoid the interaction question altogether.
Step 4 — counsel every vaccinated traveller on the same point, without exception
Neither vaccine is close to fully protective (roughly 50% efficacy), and neither reliably protects against paratyphoid fever at all.[2][3] Food and water safety precautions — safe water sources, cooked/peeled food, avoiding ice of uncertain origin — remain necessary for the entire trip regardless of vaccination status; vaccination reduces risk, it does not replace behavioural precautions.
Step 5 — treatment of confirmed or strongly suspected infection: severity and likely region of acquisition set the antibiotic choice
Obtain blood cultures urgently, ideally before starting antibiotics.[1] Do not default to empiric fluoroquinolone therapy for infection acquired in, or of uncertain origin from, South Asia — well over 99% of Salmonella Typhi and Paratyphi A isolates from this region now show decreased ciprofloxacin susceptibility, and empiric fluoroquinolone use in this setting is a genuinely outdated and unsafe default, not merely a conservative preference.[1][3]
Uncomplicated disease, tolerating oral intake
First-line oral options
Preferred azithromycin 500 mg to 1 g PO once daily for 7 days (adult), or 1 g on day 1 then 500 mg once daily to complete 7 days — reliably effective against multidrug-resistant and extensively drug-resistant (XDR) strains, and safe in pregnancy.[6]
Alternative cefixime 200 mg PO twice daily for 10-14 days (adult) — contraindicated specifically if third-generation cephalosporin resistance is documented or strongly suspected.[6]
Special situation a fluoroquinolone (e.g., levofloxacin) remains a reasonable option only when susceptibility is confirmed by culture or strongly likely based on region of acquisition (for example, parts of Latin America with lower documented resistance) — never as a blind empiric default for South-Asia-acquired infection.[1]
Severe or complicated disease
Hospitalize and start parenteral therapy immediately: ceftriaxone 2 g IV once daily (adult), or 50-100 mg/kg (maximum 4 g) IV once daily (pediatric), then transition to oral azithromycin to complete at least 7 days total once the patient is stable and tolerating oral intake.[6] For a patient with altered consciousness or shock, dexamethasone (1 mg/kg IV loading dose, then 0.25 mg/kg IV every 6 hours for 48 hours) is an established adjunct that has been shown to reduce mortality in this specific subgroup.[6] For suspected intestinal perforation or peritonitis, add metronidazole to ceftriaxone for anaerobic coverage and obtain an urgent surgical consultation — surgical exploration with simple closure is usually curative when performed promptly.[6]
Ceftriaxone resistance, while still uncommon, is a real and emerging concern — outbreaks of ceftriaxone-resistant Salmonella Typhi have been documented in Bangladesh, India, and Pakistan, layered on top of the extensively drug-resistant (XDR) strains first identified in Pakistan in 2016 that are resistant to ampicillin, chloramphenicol, ciprofloxacin, trimethoprim-sulfamethoxazole, and ceftriaxone, while remaining susceptible to azithromycin and carbapenems.[10][1] For a patient with Pakistan travel history, or any patient not improving on ceftriaxone as expected, escalate to meropenem IV plus azithromycin PO and involve infectious disease.[6][1]
Non-Pharmacologic Treatment
- Food and water safety counselling is not optional context — it is the primary defence against both typhoid and paratyphoid, since neither is fully prevented by vaccination: safe (bottled, boiled, or properly treated) water, food that is cooked and served hot, fruit the traveller peels themselves, and avoiding ice of uncertain origin.
- Meticulous hand hygiene, particularly before eating and after using the toilet — both for the traveller's own protection and, for anyone recovering from infection, to reduce onward transmission risk to others.
- During acute illness: supportive care with adequate oral or IV hydration, and an antipyretic such as acetaminophen for symptomatic fever control.
- Exclude a person with acute typhoid or paratyphoid infection from food handling and, where relevant, direct patient care duties until public health clearance criteria are met.
- Typhoid fever is a nationally notifiable disease in Canada — report every confirmed case to the relevant provincial or territorial public health authority, which leads contact tracing and any food-handler investigation.[4]
Special Populations
Pregnancy
Ty21a is contraindicated in pregnancy.[7] Vi polysaccharide has no dedicated pregnancy safety data but may reasonably be considered when travel to a high-risk destination cannot be deferred and exposure is genuinely likely, following an explicit discussion of benefits and unknowns — deferring travel to South Asia altogether is preferable when feasible.[1] For treatment of confirmed infection in pregnancy, azithromycin and ceftriaxone are both considered safe; avoid fluoroquinolones as a matter of standard obstetric caution, using azithromycin or a cephalosporin instead.[6]
Pediatrics
Ty21a is approved from age 6 years; Vi polysaccharide is approved from age 2 years — for a younger child, Vi polysaccharide is the only licensed option.[7][9] Dose all treatment antibiotics by current body weight (see Drug Tables). Fluoroquinolone use in children has traditionally been limited by a theoretical arthropathy concern from animal data; in practice, this is weighed against the risk of a life-threatening, difficult-to-treat infection, and a fluoroquinolone may still be reasonable in a child with a confirmed-susceptible or highly resistant infection where better options are unavailable — this is a specialist-level judgment call, not a default choice.
Immunocompromise, including HIV
Ty21a is contraindicated in any immunocompromised traveller, including HIV infection, since it is a live attenuated vaccine.[7] Vi polysaccharide is not a live vaccine and is the appropriate alternative for this population, with the same caveat that it remains only moderately effective.[1]
Breastfeeding
Both licensed vaccines and the standard treatment antibiotics discussed in this chapter (azithromycin, ceftriaxone) are generally considered compatible with breastfeeding; individualize any specific concern with the treating clinician.
Food handlers and healthcare workers
This population needs explicit counselling that a confirmed infection carries occupational, not just personal, implications — exclusion from food handling or direct patient care is required until clearance testing criteria are met, and any identified chronic carrier in this occupational group needs coordinated public health and workplace follow-up, as illustrated directly by the Ottawa, Canada outbreak.[4]
Monitoring & Follow-Up
Fever can reasonably take 3-5 days to resolve even on fully appropriate antibiotic therapy — this is an expected part of the clinical course, not evidence of treatment failure, and should be explained to the patient in advance to avoid unnecessary alarm or premature antibiotic switching.[1][6] If fever has not meaningfully improved by day 5 of appropriate therapy, reassess for a resistant organism (repeat cultures with susceptibility testing), an undrained focus of infection (abscess), or an alternative diagnosis, rather than simply extending the same regimen.[1]
Relapse: genuine relapse can occur in up to about 10% of patients, typically 2-3 weeks after apparent recovery, and is not usually related to antimicrobial resistance in the original strain — counsel every patient to seek care promptly if fever recurs after a period of feeling well, and retreat with an appropriate course when this occurs.[1][6]
Chronic carrier follow-up: roughly 1-4% of treated patients become long-term asymptomatic biliary carriers (defined as continued organism shedding 12 months or more after acute infection), most often related to gallstones providing a surface for persistent bacterial biofilm in the gallbladder.[1] Arrange stool and/or urine culture follow-up per local public health guidance, particularly for any food handler or healthcare worker — this is exactly the scenario that produced the Ottawa, Canada outbreak, where a carrier who had likely acquired the infection abroad before immigrating went on to cause 7 additional locally acquired cases over nearly 4 years before being identified.[4]
Report every confirmed case — acute infection or identified chronic carrier — to the relevant provincial or territorial public health authority; typhoid is a nationally notifiable disease in Canada, and carrier identification specifically triggers occupational food-handling exclusion until clearance is documented.[4]
Common Errors to Avoid
- Treating typhoid vaccination as complete protection and relaxing food/water safety counselling — neither licensed vaccine is close to fully protective, and neither reliably covers paratyphoid fever at all.[2][3]
- Defaulting to empiric fluoroquinolone therapy for infection acquired in, or of uncertain origin from, South Asia — this is outdated teaching given well over 99% documented decreased ciprofloxacin susceptibility in that region.[1][3]
- Excluding typhoid from the differential because relative bradycardia or rose spots are absent — both signs are genuinely insensitive (relative bradycardia sensitivity is only about 15-20%) even though they are useful when present.[5]
- Treating a single negative blood culture as definitively ruling out typhoid, especially in a patient who received antibiotics before the sample was drawn — sensitivity is only about 50% for a single culture.[1]
- Co-administering Ty21a with an antibiotic, or failing to separate it appropriately from atovaquone-proguanil (at least 10 days) — this can inactivate the live vaccine strain and leave the traveller unprotected without either party realizing it.[1]
- Giving Ty21a to a pregnant or immunocompromised traveller — use Vi polysaccharide instead.[7]
- Declaring antibiotic treatment a failure before day 5, when 3-5 days of ongoing fever on appropriate therapy can be an expected part of the clinical course.[1]
- Missing chronic-carrier screening and follow-up in a food handler or healthcare worker after a confirmed infection — this is exactly the gap that allowed the Ottawa, Canada outbreak to continue undetected for nearly 4 years.[4]
- Assuming a returned traveller's paratyphoid risk was covered by their typhoid vaccination — it generally was not.[2]
- Missing an acute abdomen or GI bleeding as a typhoid complication in a patient roughly 2-3 weeks into untreated or inadequately treated illness — this is exactly the window when intestinal perforation and hemorrhage most often occur.[6]
Clinical Decision Algorithm
Drug Tables
How to use this table: Doses are adult doses and require patient-specific confirmation (renal/hepatic function, weight, allergy history). Pediatric dosing is weight-based per the current product monograph unless stated. Drug pricing is intentionally omitted. Select any drug name to open its complete Pharmasist Drug Database page.
Typhoid Vaccines
Neither vaccine is in this platform's drug database (vaccines are outside its scope) — both are rendered here as plain text. Both are roughly 50% effective and neither reliably covers paratyphoid fever.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Ty21a (oral, live-attenuated) | Primary series: 4 enteric-coated capsules, taken orally on alternate days (days 1, 3, 5, 7) Administration: Swallow whole with cool/lukewarm water (not warmer than body temperature); take ≥1 hour before a meal and ≥2 hours after the previous meal; avoid alcohol ~1 hour before and 2 hours after each dose Protection begins: Approximately 1 week after the final capsule Revaccination if risk continues: Approximately every 7 years (Canadian sources); some jurisdictions use a shorter 5-year interval | Abdominal pain, nausea, diarrhea, vomiting, low-grade fever, rash | Must not be co-administered with antibiotics (kills the live strain) — separate by at least 3 days each direction. Atovaquone-proguanil: wait at least 10 days after completing Ty21a. Mefloquine: separate doses by at least 12 hours as a practical precaution. | Refrigerate 2-8°C, do not freeze. Contraindicated in pregnancy, immunocompromise, and acute GI/febrile illness. Approved from age 6 years.[7] |
| Vi polysaccharide (injectable) | Dose: Single 0.5 mL intramuscular injection (deltoid) Timing before travel: At least 2 weeks before potential exposure Revaccination if risk continues: Approximately every 3 years (Canadian sources); some jurisdictions use a shorter 2-year interval | Injection-site pain/erythema, headache, myalgia, malaise, occasional fever/GI symptoms | None significant — not a live vaccine, no antibiotic-timing interaction | Preferred over Ty21a in immunocompromise. Approved from age 2 years.[9] |
First-Line Treatment — Macrolide and Cephalosporins
Preferred for South-Asia-acquired or resistance-unknown infection given high regional fluoroquinolone resistance.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Azithromycin | Adult: 500 mg to 1 g PO once daily for 7 days (or 1 g on day 1, then 500 mg once daily to complete 7 days) Pediatric: 10-20 mg/kg (maximum 1 g) PO once daily for 7 days | GI upset, rare QT prolongation | None significant at standard doses | First-line for uncomplicated disease of any origin, including South-Asia-acquired and XDR infection. Reliable against multidrug-resistant strains. Safe in pregnancy.[6] |
| Ceftriaxone | Adult: 2 g IV once daily Pediatric: 50-100 mg/kg (maximum 4 g) IV once daily | GI upset, biliary sludging with prolonged use, hypersensitivity | None significant at standard doses | First-line parenteral therapy for severe/complicated disease or intolerance of oral therapy. Transition to oral azithromycin once stable to complete at least 7 days total.[6] |
| Cefixime | Adult: 200 mg PO twice daily for 10-14 days Pediatric: 10 mg/kg (maximum 200 mg) PO twice daily for 10-14 days | GI upset, diarrhea | None significant at standard doses | Oral cephalosporin alternative for uncomplicated disease. Avoid if third-generation cephalosporin resistance is documented or strongly suspected.[6] |
Fluoroquinolones — Confirmed-Susceptible Infection Only
No longer appropriate as a blind empiric default, particularly for South-Asia-acquired infection, given well over 99% documented decreased ciprofloxacin susceptibility in that region.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Ciprofloxacin | GI upset, tendinopathy, QT prolongation, CNS effects | Chelation with divalent/trivalent cations (antacids, iron, calcium, dairy) reduces absorption | No standalone systemic monograph in this database (only ophthalmic/otic combination products exist). Historical first-line agent; now reserved for confirmed or strongly likely susceptible infection.[1] | |
| Levofloxacin | Adult: 500-750 mg PO/IV once daily for 7-10 days | GI upset, tendinopathy, QT prolongation, CNS effects | Chelation with divalent/trivalent cations reduces absorption | Reserve for confirmed or strongly likely fluoroquinolone-susceptible infection (e.g., some Latin American destinations) rather than empiric use for South-Asia-acquired disease.[1] |
Severe/Complicated Disease — Carbapenem and Adjuncts
For extensively drug-resistant (XDR) or ceftriaxone-resistant infection, and for the shock/altered-consciousness or perforation subgroups of severe disease.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Meropenem | Adult: Per current product monograph weight/renal-based IV dosing | GI upset, seizure risk at high doses or renal impairment, hypersensitivity | May reduce valproic acid levels | Reserve for confirmed or strongly suspected XDR/ceftriaxone-resistant infection, especially with Pakistan travel history; pair with azithromycin. Infectious disease consultation recommended.[1] |
| Dexamethasone | Adult: 1 mg/kg IV loading dose, then 0.25 mg/kg IV every 6 hours for 48 hours | Hyperglycemia, immunosuppression, GI bleeding risk | May reduce efficacy of live vaccines given concurrently | Adjunct strictly for severe disease with shock or altered consciousness — established mortality benefit in this specific subgroup, not a routine adjunct.[6] |
| Metronidazole | Adult: Per current product monograph dosing | GI upset, metallic taste, disulfiram-like reaction with alcohol | Avoid alcohol during and for 48 hours after use | Added anaerobic coverage for suspected intestinal perforation/peritonitis, given with ceftriaxone (not needed if meropenem is used). Always paired with urgent surgical consultation.[6] |
References
- Typhoid and Paratyphoid Fever — Centers for Disease Control and Prevention. CDC Yellow Book 2026: Health Information for International Travel — published 2025-04-23
- Statement on international travellers and typhoid — Committee to Advise on Tropical Medicine and Travel (CATMAT), Public Health Agency of Canada. Canada Communicable Disease Report (CCDR) 2014;40(4)
- Trends in antimicrobial resistance amongst Salmonella Paratyphi A isolates in Bangladesh: 1999–2021 — PLOS Neglected Tropical Diseases. PLoS Negl Trop Dis. 2023;17(11):e0011723
- Locally acquired typhoid fever outbreak linked to chronic carriage in Ottawa, Canada, 2018–2022 — Canada Communicable Disease Report (CCDR) / Public Health Agency of Canada. CCDR, 2024
- Systematic review of relative bradycardia in clinical practice — World Journal of Advanced Research and Reviews (WJARR). WJARR 2026
- Enteric (typhoid and paratyphoid) fevers — Médecins Sans Frontières. MSF Medical Guidelines — Clinical Guidance
- VIVOTIF (Typhoid Vaccine Live Oral Ty21a) Product Monograph — Health Canada Drug Product Database. Health Canada-approved product monograph
- Typhoid vaccines — Public Health Agency of Canada. Canadian Immunization Guide, Part 4 — Active Vaccines
- TYPHIM Vi (Typhoid Vi Polysaccharide Vaccine) Product Monograph — Health Canada Drug Product Database. Health Canada-approved product monograph
- Outbreak of Ceftriaxone-Resistant Salmonella enterica Serovar Typhi, Bangladesh, 2024 — Emerging Infectious Diseases, Centers for Disease Control and Prevention. Emerg Infect Dis. 2025;31(7)
Professional reference only. Apply clinical judgment and verify patient-specific decisions against current authoritative guidance and product information.