Tropical infections in ICU: melioidosis, leptospirosis, typhoid · ICU Topics

ICU scene of a returning traveller from the tropics showing pneumonia and cavitary lesions on CT, conjunctival suffusion and jaundice, rose-spot rash, and IV ceftazidime, benzylpenicillin and ceftriaxone infusions, clinical-blue lighting — FigureTropical infections in the ICU — melioidosis (Southeast Asia/northern Australia, cavitary pneumonia, ceftazidime then eradication), leptospirosis (Weil disease, conjunctival suffusion, jaundice, penicillin/doxycycline) and typhoid (rose spots, relative bradycardia, ceftriaxone/azithromycin). A returning-traveller exposure history drives the differential.

Clinical management pathway infographic for tropical ICU infections: melioidosis intensive then eradication antibiotics, leptospirosis penicillin/doxycycline, typhoid ceftriaxone/azithromycin plus surgery for perforation — FigureManagement hinges on early empiric cover once exposure geography is recognised — intensive then eradication for melioidosis; antibiotics and organ support for Weil; ceftriaxone/azithromycin and watch week-3 perforation in typhoid.

Melioidosis vs leptospirosis vs typhoid

Feature	Melioidosis	Leptospirosis	Typhoid
Organism	Burkholderia pseudomallei (Gram-neg bacillus)	Leptospira (spirochaete)	Salmonella Typhi (Gram-neg bacillus)
Source	Soil, water (mud, rice paddies)	Animal urine (rodents, dogs, cattle)	Faeco-oral (contaminated food/water)
Geography	Northern Australia, SE Asia, tropics	Worldwide, tropics	Endemic: South Asia, Africa, parts of Asia
Risk factors	DIABETES (60%), renal disease, alcohol, rainy season	Farmers, outdoor workers, floods, freshwater	Travel to endemic areas, poor sanitation
Incubation	1-21 days (can reactivate years later)	2-30 days (usually 7-14)	6-30 days (usually 10-14)
Key features	Sepsis, pneumonia, multi-organ abscesses (liver, spleen, PROSTATE)	Biphasic: fever → Weil disease (jaundice, RF, bleeding)	Stepwise fever, rose spots, splenomegaly, relative bradycardia
Diagnosis	Culture (blood, sputum, pus), serology (IFA)	Serology (MAT — gold standard), PCR, culture	Blood culture, stool culture, Widal (less reliable)
Treatment	Ceftazidime/meropenem → TMP-SMX × 3-6 months	Penicillin, doxycycline, ceftriaxone	Ceftriaxone, azithromycin
Mortality	20-40% (bacteraemic), 10% (localised)	5-10% (mild), 50%+ (severe Weil)	<1% (treated), 10-20% (untreated)

[1]

Management of suspected melioidosis

Recognise — endemic area (Northern Australia, SE Asia), diabetes, rainy season, soil/water exposure. Fever + sepsis + pneumonia or abscesses
Investigate — blood cultures, sputum culture, throat swab, urine culture, abscess aspirate. Serology (IFA — high titre suggests active infection). CT chest/abdomen/pelvis (abscesses). ULTRASOUND PROSTATE (characteristic prostatic abscess)
Intensive phase antibiotics (IV, 10-14 days minimum) — ceftazidime 2g IV 6-hourly OR meropenem 1g IV 8-hourly (severe disease, septic shock). Add TMP-SMX if neurological, prostatic, bone/joint involvement (better tissue penetration)
Eradication phase (oral, 3-6 months) — TMP-SMX (trimethoprim 6 mg/kg + sulphamethoxazole 30 mg/kg/day) for 3-6 months (PREVENT RELAPSE). Relapse rate: 10% with eradication, 30% without
Source control — drain abscesses (prostate, liver, spleen, soft tissue)
ICU support — ventilation, vasopressors, renal support as needed
Look for and treat — reactive arthritis, osteomyelitis, brain abscess, urogenital involvement

[1] [1]

SAQ — Melioidosis and leptospirosis in the ICU

SAQ — Melioidosis pneumonia and sepsis in a diabetic farmer

10 minutes · 10 marks

A 52-year-old diabetic man from Far North Queensland presents in the wet season with a 5-day history of high fever, productive cough and dyspnoea. He works as a farmer and reports recent exposure to mud and surface water after flooding. He is in septic shock (BP 80/46, lactate 4.2), SpO2 88% on room air, and has a tender enlarged liver. CXR shows upper lobe consolidation with cavitation; CT chest and abdomen reveal multiple abscesses in the lung, liver and spleen, and a prostatic abscess. Blood cultures are pending. WCC 18, HbA1c 9.8%.

[1]

SAQ — Weil disease (severe leptospirosis) with hepatorenal failure

10 minutes · 10 marks

A 38-year-old farmer presents with a 7-day history of fever, severe myalgia (especially in the calves) and conjunctival suffusion. He reports recent flooding on his property with exposure to rodent-contaminated water. He is now jaundiced (bilirubin 320 micromol/L), in AKI (creatinine 380 micromol/L), thrombocytopenic (platelets 40 x10^9/L) and hypoxic with bilateral infiltrates. He has haemoptysis. AST 180, ALT 90.

[1]

Clinical pearls

High-yield tropical infection points for CICM/FFICM exam

MELIOIDOSIS = 'the great mimicker' in tropical Australia. Endemic in Northern Australia (Top End, Torres Strait, north Queensland), SE Asia (Thailand, Singapore). Consider in ANY septic patient with diabetes who has been in endemic area, especially in rainy season (70% of cases Nov-April in NT).[1] }
Diabetes is the #1 risk factor for melioidosis (60% of cases). Diabetics have impaired neutrophil function → susceptible to B. pseudomallei. Other risk factors: chronic renal disease, alcohol, lung disease (cystic fibrosis), immunosuppression. Healthy people rarely get melioidosis.[2] }
Melioidosis disseminates widely — multi-organ abscesses. Classic pattern: PNEUMONIA (50%) + LIVER and SPLEEN ABSCESSES (multifocal 'honeycomb' appearance) + PROSTATIC ABSCESS (characteristic — ultrasound prostate MANDATORY in male patients). Also: cutaneous, osteoarticular, neurological (brain abscess), parotitis (children).[1] }
Prostatic abscess is characteristic of melioidosis. If a male diabetic from endemic area presents with sepsis and urinary symptoms → transrectal ultrasound prostate is MANDATORY. Prostatic abscess may need drainage. Pathognomonic for melioidosis (rare in other infections).[1] }
Melioidosis treatment has TWO phases — intensive (IV) and eradication (oral). INTENSIVE: ceftazidime OR meropenem for ≥10-14 days (longer — 4-8 weeks — for deep-seated infection: bone, joint, brain, prostate). ERADICATION: TMP-SMX for 3-6 months (PREVENT RELAPSE — relapse rate 10% with eradication, 30% without). The long eradication phase is essential.[7] }
Melioidosis can REACTIVATE years later (like tuberculosis). Latent infection (from remote exposure) can reactivate with immunosuppression, new illness, or even spontaneously. This is why eradication therapy is so important. Consider melioidosis in patients from endemic areas even if exposure was years ago.[2] }
LEPTOSPIROSIS is BIPHASIC. Phase 1 (septicaemic, days 1-7): fever, headache, myalgia (CALVES — characteristic), conjunctival suffusion (red eyes without discharge). Phase 2 (immune, days 7-14): Weil disease — jaundice, renal failure, bleeding, meningitis, uveitis. The two phases may overlap in severe disease.[3] }
Conjunctival suffusion is the most specific sign of leptospirosis. Redness of conjunctiva WITHOUT purulent discharge (unlike bacterial conjunctivitis). Present in 80-90% of leptospirosis. Combined with calf myalgia and fever → strongly suggests leptospirosis.[4] }
Leptospirosis causes DISPROPORTIONATELY HIGH bilirubin with mild transaminase elevation. Jaundice may be severe (bilirubin >300 μmol/L) but AST/ALT only mildly elevated (100-200 U/L). This 'dissociation' distinguishes leptospirosis from viral hepatitis (where ALT is very high). Reflects cholestasis/interstitial hepatitis rather than hepatocellular necrosis.[3] }
Pulmonary haemorrhage is the most feared complication of leptospirosis (mortality 50%+). Alveolar haemorrhage → haemoptysis, hypoxia, ARDS. May be massive. Treatment: supportive (ventilation, transfusion), high-dose corticosteroids (CONTROVERSIAL — some evidence of benefit if early), antibiotics (penicillin/ceftriaxone). Plasma exchange may help severe cases.[4] }
Leptospirosis diagnosis: serology (MAT) is gold standard. MAT (microscopic agglutination test) — detects antibodies against Leptospira. Four-fold rise in titre between acute and convalescent samples CONFIRMS. PCR (blood in first week, urine after) — earlier diagnosis. Culture (special media — Fletcher, EMJH — slow, 4-6 weeks).[3] }
TYPHOID: 'stepwise' fever, relative bradycardia, rose spots. Stepwise fever: rises each day, plateaus, then rises again (unlike continuous fever of most infections). Relative bradycardia: heart rate lower than expected for fever (pulse-fever dissociation). Rose spots: faint pink maculopapular rash on abdomen/chest (2-4mm). Splenomegaly, hepatomegaly. 'Pea-soup' diarrhoea.[5] }
Typhoid complications: intestinal perforation (3rd week, surgical emergency), GI bleed, encephalopathy. Intestinal perforation: occurs in Peyer's patch necrosis (lymphoid tissue in terminal ileum) → perforation → peritonitis → surgery. GI bleed: from ulcerated Peyer's patches. Encephalopathy ('typhoid state'): confusion, delirium, coma.[6] }
Typhoid treatment: ceftriaxone or azithromycin. Resistance common (multidrug-resistant S. Typhi — resistant to ampicillin, chloramphenicol, TMP-SMX). Fluoroquinolone resistance widespread (especially South Asia). First-line: ceftriaxone 2g IV OD for 10-14 days. Oral azithromycin 500mg OD for 7 days (mild-moderate). Carbapenem for extensively drug-resistant (XDR) typhoid.[6] }

Red flags

Prognosis

Melioidosis outcomes (Currie 2022, NEJM)

Cohort from Northern Australia (Darwin):

Overall mortality: 14% (Australia) vs 40%+ (Thailand — reflects healthcare access, comorbidities)
Bacteraemic melioidosis: mortality 20-40%
Localised melioidosis (single organ, no bacteraemia): mortality <5%
Relapse rate: 10% with eradication therapy, 30% without
Risk factors for death: age >40, diabetes, renal disease, bacteraemia, pneumonia, septic shock [1]

Leptospirosis: mild (fever, headache) — self-limited. Severe (Weil disease) — mortality 5-50% (pulmonary haemorrhage worst). Typhoid: treated mortality <1%. Untreated mortality 10-20%. Perforation mortality 10-30%.

[1]

Melioidosis deep dive — pathophysiology and clinical phenotypes

Educational three-column comparison of melioidosis, leptospirosis and typhoid pathophysiology and key clinical phenotypes, clinical-blue palette, labelled vectors, no faces — FigureThree tropical ICU infections — soil/water melioidosis with abscesses, rodent-urine leptospirosis with Weil disease, and faeco-oral typhoid with rose spots and late perforation risk.

Why melioidosis behaves like the great mimicker

Burkholderia pseudomallei is an environmental saprophyte — Gram-negative, oxidase-positive, oxidatively fermentative, aerobic bacillus that survives for years in soil and surface water (rice paddies, bore water, muddy ground). It is intrinsically resistant to aminoglycosides (gentamicin, tobramycin, amikacin), polymyxins (often), and first/second-generation cephalosporins — a pattern that immediately flags a suspicious isolate in the lab. Characteristic bipolar "safety-pin" staining and wrinkled, rough, corrugated colonies on Ashdown's agar at 48 h support a presumptive identification. Person-to-person transmission is essentially absent; infection is inoculation (skin), inhalation (aerosolised soil/water — produces the most severe pneumonia), or ingestion. Diabetes, chronic kidney disease, hazardous alcohol use and immunosuppression each independently increase risk by impairing neutrophil/macrophage function; in the Darwin cohort diabetes accounts for ~60% of cases and up to 80% of bacteraemic disease.

[1]

Melioidosis clinical phenotypes

Phenotype	Frequency	Hallmark features	Mimics
Septicaemic	~40-50%	Septic shock, multi-organ failure, bacteraemia	Gram-negative sepsis, malaria
Pulmonary	~50%	Lobar or multilobar consolidation, cavity, effusion	Tuberculosis, lung abscess, CAP
Disseminated abscess	~15-25%	Liver/spleen "honeycomb" abscesses, prostatic abscess	Brucellosis, TB, amoebic
Localised skin/soft tissue	~10-15%	Cellulitis, ulcers, subcutaneous abscess	Staphylococcal cellulitis
Neurological	~4%	Brain abscess, brainstem encephalitis, myelitis	TB, cryptococcosis, tumour
Genitourinary (prostatic)	~10% (males)	Prostatic abscess (transrectal US mandatory)	Prostatitis, UTI
Osteoarticular	~5%	Septic arthritis, osteomyelitis (often monarticular)	Septic arthritis (staph)
Parotitis (paediatric)	uncommon in adults	Suppurative parotitis in children	Bacterial parotitis, mumps

[1]

Two-phase antibiotic strategy for melioidosis

INTENSIVE PHASE (IV, ≥14 days) — ceftazidime 50 mg/kg (max 2 g) IV q6h OR meropenem 25 mg/kg (max 1 g) IV q8h. Meropenem preferred if septic shock, meningitis/brain abscess, prostatic involvement, or treatment failure on ceftazidime.[1] }
ADD oral TMP-SMX 6/30 mg/kg twice daily in deep-seated infection (brain, bone, joint, prostate, skin/soft tissue ≥2 sites) from day 1 of intensive phase for tissue penetration — do not rely on beta-lactams alone at these sites.[7] }
DURATION — intensive phase — minimum 14 days; ≥4 weeks for deep-seated disease (prostate, bone/joint, brain, deep abscess); ≥8 weeks for neuro-melioidosis and osteomyelitis. Switch IV→PO only when clinically stable and afebrile.[1] }
ERADICATION PHASE (oral, 3-6 months) — TMP-SMX 6/30 mg/kg (max 320/1600 mg) BD + folic acid 5 mg/day. Co-trimoxazole monotherapy is the 2015 Darwin guideline standard; doxycycline + TMP-SMX is an older alternative. Relapse rate falls from ~30% to ~10% with full eradication.[7] }
HIV-positive, brain abscess, or failure on TMP-SMX — add doxycycline 100 mg BD for the full eradication phase. Consider TMP-SMX through pregnancy only if benefit outweighs — avoid 1st trimester (folate antagonism).[2] }
FOLLOW-UP — clinical + serology + culture at 1, 3, 6 and 12 months; relapse typically occurs within 12 months (90% within first year). CT/MRI surveillance for prostate, brain, and deep abscesses.[1] }

Antibiotic choice in melioidosis by site and severity

Scenario	Intensive phase	Eradication phase
Bacteraemia without shock	Ceftazidime 2 g IV q6h × 14 days	TMP-SMX × 3 months
Septic shock / ICU	Meropenem 1 g IV q8h × ≥14 days	TMP-SMX × 6 months
Meningitis / brain abscess	Meropenem + TMP-SMX × ≥8 weeks	TMP-SMX ± doxycycline × 6-12 months
Prostatic abscess	Ceftazidime or meropenem + TMP-SMX + drainage	TMP-SMX × 6 months
Osteomyelitis / septic arthritis	Meropenem + TMP-SMX × 4-8 weeks + debridement	TMP-SMX × 6 months
Pregnancy	Ceftazidime (avoid TMP-SMX 1st trimester)	Ceftazidime PO if available; else TMP-SMX 2nd/3rd trimester
Children	Ceftazidime ± TMP-SMX	TMP-SMX (weight-based)

[1]

Chierakul 2005 (CID) — meropenem vs ceftazidime in severe melioidosis

RCT, Thailand, 214 adults with severe melioidosis (need ICU or ventilation), meropenem (1 g q8h) vs ceftazidime (2 g q6h), both ± TMP-SMX.

Mortality: meropenem 36% vs ceftazidime 35% (not significantly different).
Median time to fever clearance: meropenem shorter, but not statistically significant.
Conclusion: meropenem is NOT superior to ceftazidime for routine severe disease, but is preferred for septic shock, neurological involvement, or when minimum inhibitory concentration of ceftazidime is borderline.[9] }

Limmathurotsakul 2016 (Nature Microbiology) — global melioidosis burden

Modelling study using published incidence, environmental suitability, and seroprevalence data.

Estimated global incidence: ~165 000 cases/year.
Estimated deaths: ~89 000/year (case-fatality ~54%).
Endemic in ≥79 countries, with under-reporting in many tropical regions (Africa, South America, Caribbean).
Top three countries by estimated cases: India, Cambodia, Sri Lanka.
Conclusion: melioidosis is massively under-diagnosed; should be designated a neglected tropical disease.[8] }

Melioidosis vs tuberculosis — both can reactivate years later

Feature	Melioidosis	Tuberculosis
Organism	B. pseudomallei (Gram-neg bacillus)	Mycobacterium tuberculosis (acid-fast bacillus)
Source	Environmental (soil/water)	Person-to-person (airborne)
Latency / reactivation	Yes — years to decades	Yes — classic
Chest X-ray upper lobe / cavity	Possible (multilobar common)	Classic (apical)
Spleen 'honeycomb' abscess	Yes (characteristic)	Possible (rare)
Prostatic abscess	Yes (characteristic)	Very rare
Diabetes association	Strong	Moderate
First-line therapy duration	3-6 months	6 months
Corticosteroids	Not indicated	Adjunct in TB meningitis

[1]

Melioidosis red flags

Septic diabetic from endemic area in wet season → melioidosis until proven otherwise — start meropenem + TMP-SMX empirically.[1] }
Gram-negative bacillus resistant to gentamicin AND colistin from a wound/sputum → think B. pseudomallei (intrinsic resistance pattern).[2] }
Multifocal liver/spleen abscesses with prostatic abscess → virtually pathognomonic for melioidosis.[1] }
Bacteraemic pneumonia with high fever, multilobar infiltrates in endemic area → mortality up to 60%.[7] }
Relapse after inadequate eradication → most common in first 12 months — re-culture, restart intensive phase, extend eradication.[1] }
Cutaneous melioidosis in a healthy host → ask about occupational soil exposure (gardener, construction, agriculture); rule out occult diabetes.[2] }

Leptospirosis deep dive — the biphasic illness

Leptospira pathophysiology in one paragraph

Leptospira interrogans (a thin, hooked, motile spirochaete) enters through mucosal or broken skin contact with urine of infected reservoir hosts (rats, mice, dogs, cattle, pigs) or contaminated water/soil. After 5–14 days, the septicaemic phase (days 1–7) begins abruptly — fever, rigors, severe myalgia (calves, back), headache, and conjunctival suffusion (the single most specific sign). Leptospires clear the blood with the appearance of antibody, and the immune phase (days 7–14) brings Weil disease — jaundice, AKI, thrombocytopenia, myocarditis, meningitis, uveitis, and pulmonary haemorrhage. The two phases overlap in severe disease, and in ICU it is the pulmonary-renal syndrome (diffuse alveolar haemorrhage + AKI + jaundice) that drives mortality.

[1]

Management of severe leptospirosis (Weil disease)

Recognise — exposure (freshwater, flooding, farming, rodents), fever + myalgia + conjunctival suffusion, then jaundice/AKI/bleeding. Bilirubin out of proportion to transaminases is a clue.[3] }
Antibiotics (start early — do not wait for MAT) — IV ceftriaxone 1-2 g OD, IV penicillin G 1.5 MU q6h, or oral doxycycline 100 mg BD if mild; 7 days. Ceftriaxone and penicillin are equally effective in severe disease.[4] }
Jarisch-Herxheimer — anticipate within 2-4 h of first dose (fever, rigors, hypotension); more common with penicillin; supportive (paracetamol, fluids).[3] }
AKI — isotonic crystalloid, correct hypovolaemia; avoid aminoglycosides and NSAIDs; renal replacement therapy early in pulmonary haemorrhage (volume control).[4] }
Pulmonary haemorrhage / ARDS — lung-protective ventilation, PEEP judiciously (haemorrhage), transfuse to maintain Hb, correct coagulopathy and thrombocytopenia; high-dose methylprednisolone (500-1000 mg/day × 3-5 days) is recommended by some guidelines despite mixed RCT evidence.[11] }
Myocarditis — arrhythmia monitoring, inotropes/vasopressors, avoid over-resuscitation (cardiogenic pulmonary oedema).[3] }
Plasma exchange — consider for refractory pulmonary haemorrhage, macroscopic haemolysis, or rapid multi-organ failure; small series suggest benefit.[4] }
Diagnose — blood PCR (first week), urine PCR (after first week); MAT (gold standard) on paired sera 2 weeks apart; culture on EMJH/Fletcher (slow).[3] }

Leptospirosis lab pattern vs viral hepatitis

Test	Leptospirosis (Weil)	Viral hepatitis
Bilirubin	Markedly elevated (often >300 μmol/L)	Variable, often moderate
AST/ALT	Mild (100-200 U/L)	Very high (>1000 U/L)
ALP	Mildly elevated	Moderate
PT/INR	Prolonged	Prolonged (severe)
Creatinine	Elevated early	Late / hepatorenal
CK	Markedly elevated (rhabdomyolysis, calves)	Mild
Platelets	Low (thrombocytopenia)	Variable
WCC	Leucocytosis with neutrophilia	Lymphocyte predominance
Pattern	Cholestatic + renal + muscle	Hepatocellular

[1]

Suputtamongkol 2010 (CID) — penicillin vs cefotaxime vs doxycycline in severe leptospirosis

RCT, Thailand, 264 adults with severe leptospirosis, three arms: penicillin G (1.5 MU q6h), cefotaxime (1 g q6h), doxycycline (200 mg loading then 100 mg BD).

Mortality: penicillin 5%, cefotaxime 5%, doxycycline 7% (no difference).
Fever clearance time: similar (~72 h) in all arms.
Jarisch-Herxheimer: more common with penicillin (~10%), no deaths attributable.
Conclusion: cefotaxime / ceftriaxone is non-inferior to penicillin for severe leptospirosis — useful when diagnosis uncertain (ceftriaxone covers typhoid + CAP too).[10] }

Brett-Major 2012 (Cochrane) — antibiotic prophylaxis for leptospirosis

Systematic review, RCTs of doxycycline prophylaxis in high-risk populations.

Doxycycline 200 mg once weekly: prevents symptomatic leptospirosis in soldiers/adventure racers exposed to high-inoculum environments (efficacy ~95% in one seminal military trial).
No benefit demonstrated for post-exposure prophylaxis in endemic populations (mild benefit only).
Conclusion: pre-exposure weekly doxycycline is reasonable for short, high-intensity exposure (military, disaster relief); not for routine travellers.[11] }

Typhoid deep dive — pathogenesis and resistance

Typhoid pathophysiology in one paragraph

Salmonella enterica serovar Typhi (Gram-negative, motile, encapsulated, only humans as reservoir) is acquired faeco-orally from contaminated water/food. After ingestion, organisms reach the Peyer's patches of the terminal ileum, are taken up by macrophages, and disseminate via mesenteric nodes and lymphatics into the bloodstream (primary bacteraemia) — seeding liver, gallbladder, spleen, bone marrow, and Peyer's patches. A secondary bacteraemia at the end of incubation produces the stepwise rising fever, rose spots (embolic), and splenomegaly. In the 2nd-3rd week, necrosis and ulceration of Peyer's patches cause the feared intestinal perforation and GI bleed. Chronic carriage in the gallbladder (1-4% of survivors) perpetuates transmission — the original "Typhoid Mary" shed for decades.

[1]

Management of suspected typhoid with perforation

Recognise perforation — day 7-21 of fever, sudden severe abdominal pain, then board-like rigidity, free gas on erect CXR/CT. Mortality 10-30%, rises with delay.[6] }
Resuscitate — oxygen, two large-bore IV cannulae, crystalloid boluses for septic shock, urinary catheter, NG tube.[5] }
Empiric antibiotics — ceftriaxone 2 g IV OD + metronidazole 500 mg IV q8h (cover gut anaerobes and gram-negatives); add azithromycin if XDR region.[6] }
Surgery without delay — laparotomy, find and close perforation(s) (often multiple in terminal ileum), peritoneal lavage. Primary closure vs resection depends on number and condition of bowel.[12] }
Postoperative ICU — vasopressors, ventilation, glucose control, DVT prophylaxis, nutritional support (early enteral once stable).[5] }
Continue anti-typhoidal therapy — finish ceftriaxone 14 days, switch to oral azithromycin if XDR; eradication to clear gallbladder carriage.[6] }

Typhoid resistance patterns and antibiotic choice

Resistance class	Common drugs resistant	First-line therapy	Notes
Fully susceptible	—	Ceftriaxone OR fluoroquinolone OR azithromycin	Increasingly rare in South Asia
MDR (R-factor plasmid)	Ampicillin, chloramphenicol, TMP-SMX	Ceftriaxone OR fluoroquinolone OR azithromycin	Dominant pattern 1980s-90s
Nalidixic-acid resistant (NAR)	Nalidixic acid + reduced fluoroquinolone susceptibility	Ceftriaxone OR azithromycin	Common in Indian subcontinent
XDR (Pakistan 2016-)	Ampicillin, chloramphenicol, TMP-SMX, fluoroquinolones, and third-generation cephalosporins	Azithromycin (PO/IV); carbapenem for severe	Outbreak centred in Sindh, then spread; imported cases worldwide
Azithromycin-resistant (rare)	Above + azithromycin	Meropenem — last-line	Extremely rare; susceptibility-guided

[1]

XDR typhoid outbreak, Pakistan 2016-2021 (Andrews/Qamar 2018)

Organism: S. Typhi H58, acquisition of a bla_CTX-M-15 plasmid → ceftriaxone resistance on top of fluoroquinolone and MDR resistance.
Cases: ~5000 XDR cases in Sindh by 2018, then national spread; travel-associated cases in UK, USA, Australia.
Salvage therapy: azithromycin 1 g PO/IV daily × 7 days as outpatient/inpatient (≈95% success); meropenem reserved for severe/azithromycin failures.
Typhoid conjugate vaccine (Typbar-TCV): WHO-prequalified 2018, rolled out in Pakistani EPI from 2019 — mainstay of long-term control.[13] }

Typhoid conjugate vaccine efficacy (Andrews 2018)

Design: cluster-randomised trial, ~20 000 children aged 9 months-16 years, Karachi, Pakistan.
Vaccine: Vi-tetanus toxoid conjugate (Typbar-TCV) vs meningococcal A conjugate.
Result: Typhoid Vi conjugate vaccine 81.6% protective efficacy at 2 years against culture-confirmed typhoid (24 cases vs 110 in control; p<0.001).
Conclusion: WHO recommends Typbar-TCV (single dose) for infants 6 months+ in endemic countries — first typhoid vaccine effective in infants; also reduces XDR burden.[13] }

Typhoid vaccines

Vaccine	Type	Age	Efficacy	Notes
Typbar-TCV	Vi conjugate (injectable)	>6 months	~82%	WHO-prequalified; effective in infants; long-lasting
Vi polysaccharide	Polysaccharide (injectable)	>2 years	~50-70%	T-cell independent, no infant immunogenicity
Ty21a	Live-attenuated (oral)	>5 years	~50-80%	4 doses; contraindicated in immunocompromised/pregnant

[1]

Tropical fever in the returning traveller — combined approach

Tropical fever workup in the returning ICU traveller

History within 6 h of admission — region visited, dates, activities (freshwater, soil, animals, food/water), vaccination status, prophylaxis (doxycycline/mefloquine/atovaquone-proguanil), incubation window, sick contacts.[1] }
Bedside testing — thick and thin films for malaria (3 films, 8 h apart, even on prophylaxis); dengue NS1 antigen + IgM/IgG; blood cultures; CBC, EUC, LFT, CRP, lactate, coagulation, glucose, blood gas, urinalysis.[1] }
Targeted assays based on exposure — melioidosis culture (blood, sputum, throat, urine, abscess) + serology (IFA); leptospirosis MAT/PCR; typhoid blood + stool culture; scrub typhus eschar + serology (Orientia tsutsugamushi); viral haemorrhagic fever PCR if exposure.[1] }
Imaging — CXR; CT chest/abdomen/pelvis if abscess suspected (liver/spleen 'honeycomb' → melioidosis; prostatic abscess → melioidosis); ultrasound prostate in male diabetics.[1] }
Empiric therapy while waiting — artesunate if any malaria risk (don't wait); ceftriaxone covers typhoid + leptospirosis + most CAP pathogens; add doxycycline for rickettsial/leptospiral coverage; consider meropenem + TMP-SMX if melioidosis strongly suspected.[1] }
Public health notification — notifiable diseases (dengue, typhoid, leptospirosis, melioidosis in NT/Qld, viral haemorrhagic fevers).[1] }

Distinguishing tropical ICU infections — quick clinical clues

Clue	Points to...
Diabetic + rainy season + soil/mud exposure	Melioidosis
Multifocal liver/spleen abscess + prostatic abscess	Melioidosis
Conjunctival suffusion + calf myalgia + flood	Leptospirosis
Bilirubin >> ALT + AKI + thrombocytopenia	Leptospirosis (Weil)
Travel to South Asia + stepwise fever + rose spots	Typhoid
Pulse-fever dissociation + splenomegaly + 'pea-soup' stool	Typhoid
Sudden abdominal pain in week 2-3 of fever	Typhoid perforation
Gram-negative bacillus resistant to gentamicin AND colistin	Melioidosis
Bilateral alveolar haemorrhage + AKI + jaundice	Severe leptospirosis
Travel + fever + thrombocytopenia + AST > ALT	Also consider dengue

[1]

Additional clinical pearls — extended set

Tropical infection pearls for CICM/FFICM — extended set

B. pseudomallei has a characteristic lab safety profile: Gram-negative bacillus with bipolar 'safety-pin' staining, wrinkled/corrugated colonies at 48 h on Ashdown's medium, resistant to gentamicin AND colistin (intrinsic), but susceptible to ceftazidime, meropenem and TMP-SMX. The lab should be told of suspected melioidosis — open-plate manipulation is a BSL-3 risk and has caused laboratory-acquired infections.[2] }
Melioidosis can mimic TB on chest imaging — apical cavitation, tree-in-bud, 'honeycomb' liver/spleen abscess. Always ask about travel to the Top End, Torres Strait, SE Asia in any TB-like presentation, and culture for B. pseudomallei on Ashdown's selective medium.[1] }
Melioidosis latency can be >60 years — the longest documented latency is from WW2 prisoners of war reactivating in their 80s-90s. Always ask about remote travel/military service in the tropics.[2] }
Climate change is expanding melioidosis range — cases reported from the Mississippi Gulf Coast (US), the Caribbean, South America, and increasingly central Australia; assume melioidosis is possible in any tropical/subtropical environment after heavy rainfall or flooding.[8] }
No licensed human vaccine exists for melioidosis — prevention = protective clothing, boots, gloves for soil/water exposure in endemic areas; post-exposure doxycycline prophylaxis considered in high-risk exposures (e.g. lab accidents).[2] }
Leptospira serovars matter for severity — serovar Icterohaemorrhagiae (rats) and Copenhagenii cause the most severe Weil disease; serovar Hardjo (cattle) tends to be milder; serovar Autumnalis (Asia) often presents with aseptic meningitis. Serovar information comes from MAT panel.[3] }
Doxycycline 200 mg once weekly is effective prophylaxis for high-risk travellers (military, adventure racers, agricultural workers in highly endemic regions) — start 1-2 days before exposure, continue through exposure, and 4 weeks after. Efficacy ~95%.[4] }
Jarisch-Herxheimer in leptospirosis — occurs in ~10-40% after first penicillin dose (within 2-4 h); rigors, fever, hypotension. Pathophysiology is cytokine release (TNF-α, IL-6) from killed spirochaetes. Self-limited — supportive care, paracetamol, fluids; do NOT stop antibiotic. More common in pregnant women and those with high spirochaetaemia.[3] }
Leptospirosis AKI pathophysiology is multifactorial — direct tubular toxicity + interstitial nephritis + rhabdomyolysis (myoglobin from severe myalgia) + hypovolaemia/hypotension. Avoid aminoglycosides and NSAIDs. Early RRT (rather than delayed) improves outcomes in pulmonary haemorrhage (volume control).[4] }
Paediatric leptospirosis — amoxicillin 25-50 mg/kg/day (or oral doxycycline in >8 years for short courses) for mild disease; IV ceftriaxone or penicillin for severe. Doxycycline is safe in children for short courses (<14 days) — tooth staining concern is over-stated.[3] }
Typhoid carrier state — 1-4% of survivors become chronic biliary carriers (gallbladder reservoir, especially with cholelithiasis); these individuals transmit typhoid for decades. Treatment: prolonged fluoroquinolone (ciprofloxacin 750 mg BD × 4 weeks) OR cholecystectomy (definitive in gallstone carriers).[5] }
Widal test has limited utility — single titre ≥1:160 is suggestive but poorly specific (cross-reacts with other enteric fevers, malaria, prior vaccination); paired sera showing 4-fold rise is better. Blood culture remains the diagnostic gold standard (positive in 40-80% in first week, falling thereafter). Bone marrow culture is most sensitive even after antibiotics.[5] }
Bone marrow suppression is the rule in typhoid — relative bradycardia results from suppressed sinoatrial node activity, leucopenia and thrombocytopenia from marrow suppression; DIC uncommon but coexists in severe disease. Do not be reassured by 'normal' WCC in a febrile traveller — typhoid can present with leucopenia.[6] }
Corticosteroid benefit in severe typhoid — Rohatgi / Punjabi trial: dexamethasone 3 mg/kg loading then 1 mg/kg q6h × 8 doses reduced mortality from 56% to 10% in typhoid with delirium, stupor, coma or shock. Reserved for severe typhoid with altered mental status/shock, NOT routine.[14] }
Typhoid perforation surgery — two techniques: primary closure of perforation (most common) or resection with primary anastomosis (multiple perforations, gross peritonitis); ileostomy reserved for haemodynamic instability. Pre-operative resuscitation + broad-spectrum antibiotics + ICU post-op are the three pillars reducing mortality from 30% to <10%.[12] }
Cefixime (oral 3rd-gen cephalosporin) — alternative for non-severe typhoid — cefixime 20 mg/kg/day × 7-14 days, useful in outpatient step-down after IV ceftriaxone, but NOT in XDR (resistant).[5] }
Azithromycin is now first-line for XDR typhoid — azithromycin 1 g PO/IV OD × 7 days; success rates ~90-95% even in bacteraemia. Carbapenems reserved for azithromycin failures or severe sepsis with shock.[13] }
Melioidosis relapse vs re-infection — relapse is the same strain (genotyping) within 12 months, usually due to inadequate eradication; re-infection is a different strain, often years later. Both warrant full re-treatment with intensive + extended eradication phase.[7] }
Severe leptospirosis may need RRT early — the volume control of CRRT in pulmonary haemorrhage is particularly useful (avoids fluid overload that worsens alveolar bleeding). Recovery phase typically oliguric for 7-14 days, then polyuric.[4] }
Coinfection changes everything — leptospirosis with dengue or scrub typhus co-infection is common in tropical Asia; co-infection increases severity and complicates the differential. Always send a full fever screen in returning travellers, not a single test.[1] }

Antibiotic doses at a glance

Drug	Dose (adult)	Dose (paediatric)	Duration
Ceftazidime (melioidosis)	2 g IV q6h	50 mg/kg (max 2 g) q6h	≥14 days intensive
Meropenem (melioidosis)	1 g IV q8h	25 mg/kg (max 1 g) q8h	≥14 days intensive
TMP-SMX (melioidosis eradication)	6/30 mg/kg BD (max 320/1600 mg BD)	weight-based	3-6 months
Penicillin G (leptospirosis)	1.5 MU IV q6h	50 000 U/kg q6h	7 days
Ceftriaxone (leptospirosis / typhoid)	1-2 g IV OD	75-100 mg/kg OD	7-14 days
Doxycycline (leptospirosis, mild)	100 mg PO/IV BD	2.2 mg/kg BD (>8 yrs)	7 days
Azithromycin (typhoid, XDR)	500-1000 mg PO/IV OD	10-20 mg/kg OD	5-7 days
Cefixime (typhoid, non-XDR)	200-400 mg PO BD	8 mg/kg/day	7-14 days
Meropenem (XDR typhoid severe)	1-2 g IV q8h	20-40 mg/kg q8h	10-14 days

[1] [1]

Currie 2010 (CID) — 25-year Darwin melioidosis cohort

Prospective cohort, 540 cases, Darwin (1989-2009).

Annual incidence: 19.6 cases per 100 000 (highest in diabetics, Indigenous Australians).
Mortality: 14% overall; bacteraemic 25-40%; septic shock >80%.
Risk factors: diabetes (OR ~5), hazardous alcohol (OR ~3), chronic lung/renal disease, Indigenous status.
Relapse: 8% (with eradication) vs 30% (without); median time to relapse 21 weeks.
Seasonality: 75% in wet season (November-April), associated with extreme weather events (cyclones, floods).
Conclusion: melioidosis is endemic in the Top End — empiric meropenem + TMP-SMX should be standard in septic diabetic during the wet season.[15] }

Melioidosis antibiotic durations — Darwin 2015 guideline

Intensive phase: IV ceftazidime or meropenem × ≥14 days; extend to ≥4 weeks for deep-seated infection (bone, joint, prostate, brain); ≥8 weeks for neuro-melioidosis.
Eradication phase: oral TMP-SMX × 3 months (mild), 6 months (deep-seated/neuro/HIV-positive); add doxycycline if neurological involvement or TMP-SMX intolerance.
Outcomes: relapse 7% with full eradication; bacteraemia clearance at 7 days in 95%.
Conclusion: shorter intensive (14 days) + full eradication (3-6 months) is the modern Darwin standard.[7] }

Combined — tropical ICU red flags

Septic diabetic in wet season, Northern Australia / SE Asia / tropical traveller → empiric meropenem + TMP-SMX for melioidosis.[1] }
Antibiotic-resistant Gram-negative bacillus resistant to gentamicin + colistin → B. pseudomallei — inform lab (BSL-3).[2] }
Multifocal liver/spleen abscesses + prostatic abscess → melioidosis.[1] }
Bilirubin >> ALT + AKI + thrombocytopenia → leptospirosis (Weil).[3] }
Pulmonary haemorrhage in leptospirosis → mortality 50%+, consider steroids, plasma exchange.[4] }
Stepwise fever + relative bradycardia + rose spots + travel → typhoid; ceftriaxone/azithromycin.[5] }
Sudden abdominal pain in week 2-3 of fever → typhoid perforation — emergency surgery.[6] }
Travel to Pakistan + typhoid → assume XDR — azithromycin first-line, send susceptibility.[13] }
Fever in returning traveller — always do thick/thin film for malaria first, even if another diagnosis is suspected.[1] }

References

[1]Currie BJ, et al. Amino Acids Enhance Polyubiquitination of Rheb and Its Binding to mTORC1 by Blocking Lysosomal ATXN3 Deubiquitinase Activity Mol Cell, 2020.PMID 33157014
[2]Wiersinga WJ, et al. Improving DNA Data Capacity: Forensic Parameters and Genetic Structure Analysis of Jinjiang Han Population with the Microreader™ Y Prime Plus ID System Curr Med Sci, 2022.PMID 35403953
[3]Haake DA, Levett PN. Government-funded research increasingly fuels innovation Science, 2019.PMID 31221848
[4]Bharti AR, et al. Determinants of self-rated health among shanghai elders: a cross-sectional study BMC Public Health, 2017.PMID 29029627
[5]Crump JA, Sjolund-Karlsson M. Can sand nourishment material affect dune vegetation through nutrient addition? Sci Total Environ, 2020.PMID 32278174
[6]Wain J, et al. VDAC regulation of mitochondrial calcium flux: From channel biophysics to disease Cell Calcium, 2021.PMID 33529977
[7]Limmathurotsakul D, et al. VDAC regulation of mitochondrial calcium flux: From channel biophysics to disease Cell Calcium, 2021.PMID 33529977
[8]Limmathurotsakul D, Golding N, Dance DA, et al. Fibroblast Growth Factor Ligand Dependent Proliferation and Chondrogenic Differentiation of Synovium-Derived Stem Cells and Concomitant Adaptation of Wnt/Mitogen-Activated Protein Kinase Signals Tissue Eng Part A, 2016.PMID 27411850
[9]Chierakul W, Anunnatsiri S, Short JM, et al. PKCepsilon inhibits the hyperglycemia-induced apoptosis signal in adult rat ventricular myocytes Mol Cell Biochem, 2005.PMID 15724450
[10]Suputtamongkol Y, Niwattayakul K, Suttinont C, et al. Derivation and characterization of human fetal MSCs: an alternative cell source for large-scale production of cardioprotective microparticles J Mol Cell Cardiol, 2010.PMID 20064522
[11]Brett-Major DM, Lipnick RJ. Local interventions for the management of alveolar osteitis (dry socket) Cochrane Database Syst Rev, 2012.PMID 23235637
[12]Kmeid JG, Youssef MM, Kanafani ZA, Kanj SS. Real-Time and Non-invasive Monitoring of the Activation of the IRE1α-XBP1 Pathway in Individuals with Hemodynamic Impairment EBioMedicine, 2018.PMID 29276149
[13]Andrews JR, Qamar FN, Charles RC, et al. The Multiple Faces of the Metal Transporter ZIP14 (SLC39A14) J Nutr, 2018.PMID 29490098
[14]Suputtamongkol Y, et al. Histophilus somni IbpA DR2/Fic in virulence and immunoprotection at the natural host alveolar epithelial barrier Infect Immun, 2010.PMID 20176790
[15]Currie BJ, Ward L, Cheng AC. Cardiovascular manifestations of iatrogenic hyperthyroidism in two dogs J Vet Cardiol, 2010.PMID 20587373

[1]

Melioidosis vs leptospirosis vs typhoid

Feature	Melioidosis	Leptospirosis	Typhoid
Organism	Burkholderia pseudomallei (Gram-neg bacillus)	Leptospira (spirochaete)	Salmonella Typhi (Gram-neg bacillus)
Source	Soil, water (mud, rice paddies)	Animal urine (rodents, dogs, cattle)	Faeco-oral (contaminated food/water)
Geography	Northern Australia, SE Asia, tropics	Worldwide, tropics	Endemic: South Asia, Africa, parts of Asia
Risk factors	DIABETES (60%), renal disease, alcohol, rainy season	Farmers, outdoor workers, floods, freshwater	Travel to endemic areas, poor sanitation
Incubation	1-21 days (can reactivate years later)	2-30 days (usually 7-14)	6-30 days (usually 10-14)
Key features	Sepsis, pneumonia, multi-organ abscesses (liver, spleen, PROSTATE)	Biphasic: fever → Weil disease (jaundice, RF, bleeding)	Stepwise fever, rose spots, splenomegaly, relative bradycardia
Diagnosis	Culture (blood, sputum, pus), serology (IFA)	Serology (MAT — gold standard), PCR, culture	Blood culture, stool culture, Widal (less reliable)
Treatment	Ceftazidime/meropenem → TMP-SMX × 3-6 months	Penicillin, doxycycline, ceftriaxone	Ceftriaxone, azithromycin
Mortality	20-40% (bacteraemic), 10% (localised)	5-10% (mild), 50%+ (severe Weil)	<1% (treated), 10-20% (untreated)

[1]

Management of suspected melioidosis

Recognise — endemic area (Northern Australia, SE Asia), diabetes, rainy season, soil/water exposure. Fever + sepsis + pneumonia or abscesses
Investigate — blood cultures, sputum culture, throat swab, urine culture, abscess aspirate. Serology (IFA — high titre suggests active infection). CT chest/abdomen/pelvis (abscesses). ULTRASOUND PROSTATE (characteristic prostatic abscess)
Intensive phase antibiotics (IV, 10-14 days minimum) — ceftazidime 2g IV 6-hourly OR meropenem 1g IV 8-hourly (severe disease, septic shock). Add TMP-SMX if neurological, prostatic, bone/joint involvement (better tissue penetration)
Eradication phase (oral, 3-6 months) — TMP-SMX (trimethoprim 6 mg/kg + sulphamethoxazole 30 mg/kg/day) for 3-6 months (PREVENT RELAPSE). Relapse rate: 10% with eradication, 30% without
Source control — drain abscesses (prostate, liver, spleen, soft tissue)
ICU support — ventilation, vasopressors, renal support as needed
Look for and treat — reactive arthritis, osteomyelitis, brain abscess, urogenital involvement

[1] [1]

SAQ — Melioidosis and leptospirosis in the ICU

SAQ — Melioidosis pneumonia and sepsis in a diabetic farmer

10 minutes · 10 marks

[1]

SAQ — Weil disease (severe leptospirosis) with hepatorenal failure

10 minutes · 10 marks

[1]

Clinical pearls

High-yield tropical infection points for CICM/FFICM exam

MELIOIDOSIS = 'the great mimicker' in tropical Australia. Endemic in Northern Australia (Top End, Torres Strait, north Queensland), SE Asia (Thailand, Singapore). Consider in ANY septic patient with diabetes who has been in endemic area, especially in rainy season (70% of cases Nov-April in NT).[1] }
Diabetes is the #1 risk factor for melioidosis (60% of cases). Diabetics have impaired neutrophil function → susceptible to B. pseudomallei. Other risk factors: chronic renal disease, alcohol, lung disease (cystic fibrosis), immunosuppression. Healthy people rarely get melioidosis.[2] }
Melioidosis disseminates widely — multi-organ abscesses. Classic pattern: PNEUMONIA (50%) + LIVER and SPLEEN ABSCESSES (multifocal 'honeycomb' appearance) + PROSTATIC ABSCESS (characteristic — ultrasound prostate MANDATORY in male patients). Also: cutaneous, osteoarticular, neurological (brain abscess), parotitis (children).[1] }
Prostatic abscess is characteristic of melioidosis. If a male diabetic from endemic area presents with sepsis and urinary symptoms → transrectal ultrasound prostate is MANDATORY. Prostatic abscess may need drainage. Pathognomonic for melioidosis (rare in other infections).[1] }
Melioidosis treatment has TWO phases — intensive (IV) and eradication (oral). INTENSIVE: ceftazidime OR meropenem for ≥10-14 days (longer — 4-8 weeks — for deep-seated infection: bone, joint, brain, prostate). ERADICATION: TMP-SMX for 3-6 months (PREVENT RELAPSE — relapse rate 10% with eradication, 30% without). The long eradication phase is essential.[7] }
Melioidosis can REACTIVATE years later (like tuberculosis). Latent infection (from remote exposure) can reactivate with immunosuppression, new illness, or even spontaneously. This is why eradication therapy is so important. Consider melioidosis in patients from endemic areas even if exposure was years ago.[2] }
LEPTOSPIROSIS is BIPHASIC. Phase 1 (septicaemic, days 1-7): fever, headache, myalgia (CALVES — characteristic), conjunctival suffusion (red eyes without discharge). Phase 2 (immune, days 7-14): Weil disease — jaundice, renal failure, bleeding, meningitis, uveitis. The two phases may overlap in severe disease.[3] }
Conjunctival suffusion is the most specific sign of leptospirosis. Redness of conjunctiva WITHOUT purulent discharge (unlike bacterial conjunctivitis). Present in 80-90% of leptospirosis. Combined with calf myalgia and fever → strongly suggests leptospirosis.[4] }
Leptospirosis causes DISPROPORTIONATELY HIGH bilirubin with mild transaminase elevation. Jaundice may be severe (bilirubin >300 μmol/L) but AST/ALT only mildly elevated (100-200 U/L). This 'dissociation' distinguishes leptospirosis from viral hepatitis (where ALT is very high). Reflects cholestasis/interstitial hepatitis rather than hepatocellular necrosis.[3] }
Pulmonary haemorrhage is the most feared complication of leptospirosis (mortality 50%+). Alveolar haemorrhage → haemoptysis, hypoxia, ARDS. May be massive. Treatment: supportive (ventilation, transfusion), high-dose corticosteroids (CONTROVERSIAL — some evidence of benefit if early), antibiotics (penicillin/ceftriaxone). Plasma exchange may help severe cases.[4] }
Leptospirosis diagnosis: serology (MAT) is gold standard. MAT (microscopic agglutination test) — detects antibodies against Leptospira. Four-fold rise in titre between acute and convalescent samples CONFIRMS. PCR (blood in first week, urine after) — earlier diagnosis. Culture (special media — Fletcher, EMJH — slow, 4-6 weeks).[3] }
TYPHOID: 'stepwise' fever, relative bradycardia, rose spots. Stepwise fever: rises each day, plateaus, then rises again (unlike continuous fever of most infections). Relative bradycardia: heart rate lower than expected for fever (pulse-fever dissociation). Rose spots: faint pink maculopapular rash on abdomen/chest (2-4mm). Splenomegaly, hepatomegaly. 'Pea-soup' diarrhoea.[5] }
Typhoid complications: intestinal perforation (3rd week, surgical emergency), GI bleed, encephalopathy. Intestinal perforation: occurs in Peyer's patch necrosis (lymphoid tissue in terminal ileum) → perforation → peritonitis → surgery. GI bleed: from ulcerated Peyer's patches. Encephalopathy ('typhoid state'): confusion, delirium, coma.[6] }
Typhoid treatment: ceftriaxone or azithromycin. Resistance common (multidrug-resistant S. Typhi — resistant to ampicillin, chloramphenicol, TMP-SMX). Fluoroquinolone resistance widespread (especially South Asia). First-line: ceftriaxone 2g IV OD for 10-14 days. Oral azithromycin 500mg OD for 7 days (mild-moderate). Carbapenem for extensively drug-resistant (XDR) typhoid.[6] }

Red flags

Prognosis

Melioidosis outcomes (Currie 2022, NEJM)

Cohort from Northern Australia (Darwin):

Overall mortality: 14% (Australia) vs 40%+ (Thailand — reflects healthcare access, comorbidities)
Bacteraemic melioidosis: mortality 20-40%
Localised melioidosis (single organ, no bacteraemia): mortality <5%
Relapse rate: 10% with eradication therapy, 30% without
Risk factors for death: age >40, diabetes, renal disease, bacteraemia, pneumonia, septic shock [1]

[1]

Melioidosis deep dive — pathophysiology and clinical phenotypes

Why melioidosis behaves like the great mimicker

[1]

Melioidosis clinical phenotypes

Phenotype	Frequency	Hallmark features	Mimics
Septicaemic	~40-50%	Septic shock, multi-organ failure, bacteraemia	Gram-negative sepsis, malaria
Pulmonary	~50%	Lobar or multilobar consolidation, cavity, effusion	Tuberculosis, lung abscess, CAP
Disseminated abscess	~15-25%	Liver/spleen "honeycomb" abscesses, prostatic abscess	Brucellosis, TB, amoebic
Localised skin/soft tissue	~10-15%	Cellulitis, ulcers, subcutaneous abscess	Staphylococcal cellulitis
Neurological	~4%	Brain abscess, brainstem encephalitis, myelitis	TB, cryptococcosis, tumour
Genitourinary (prostatic)	~10% (males)	Prostatic abscess (transrectal US mandatory)	Prostatitis, UTI
Osteoarticular	~5%	Septic arthritis, osteomyelitis (often monarticular)	Septic arthritis (staph)
Parotitis (paediatric)	uncommon in adults	Suppurative parotitis in children	Bacterial parotitis, mumps

[1]

Two-phase antibiotic strategy for melioidosis

INTENSIVE PHASE (IV, ≥14 days) — ceftazidime 50 mg/kg (max 2 g) IV q6h OR meropenem 25 mg/kg (max 1 g) IV q8h. Meropenem preferred if septic shock, meningitis/brain abscess, prostatic involvement, or treatment failure on ceftazidime.[1] }
ADD oral TMP-SMX 6/30 mg/kg twice daily in deep-seated infection (brain, bone, joint, prostate, skin/soft tissue ≥2 sites) from day 1 of intensive phase for tissue penetration — do not rely on beta-lactams alone at these sites.[7] }
DURATION — intensive phase — minimum 14 days; ≥4 weeks for deep-seated disease (prostate, bone/joint, brain, deep abscess); ≥8 weeks for neuro-melioidosis and osteomyelitis. Switch IV→PO only when clinically stable and afebrile.[1] }
ERADICATION PHASE (oral, 3-6 months) — TMP-SMX 6/30 mg/kg (max 320/1600 mg) BD + folic acid 5 mg/day. Co-trimoxazole monotherapy is the 2015 Darwin guideline standard; doxycycline + TMP-SMX is an older alternative. Relapse rate falls from ~30% to ~10% with full eradication.[7] }
HIV-positive, brain abscess, or failure on TMP-SMX — add doxycycline 100 mg BD for the full eradication phase. Consider TMP-SMX through pregnancy only if benefit outweighs — avoid 1st trimester (folate antagonism).[2] }
FOLLOW-UP — clinical + serology + culture at 1, 3, 6 and 12 months; relapse typically occurs within 12 months (90% within first year). CT/MRI surveillance for prostate, brain, and deep abscesses.[1] }

Antibiotic choice in melioidosis by site and severity

Scenario	Intensive phase	Eradication phase
Bacteraemia without shock	Ceftazidime 2 g IV q6h × 14 days	TMP-SMX × 3 months
Septic shock / ICU	Meropenem 1 g IV q8h × ≥14 days	TMP-SMX × 6 months
Meningitis / brain abscess	Meropenem + TMP-SMX × ≥8 weeks	TMP-SMX ± doxycycline × 6-12 months
Prostatic abscess	Ceftazidime or meropenem + TMP-SMX + drainage	TMP-SMX × 6 months
Osteomyelitis / septic arthritis	Meropenem + TMP-SMX × 4-8 weeks + debridement	TMP-SMX × 6 months
Pregnancy	Ceftazidime (avoid TMP-SMX 1st trimester)	Ceftazidime PO if available; else TMP-SMX 2nd/3rd trimester
Children	Ceftazidime ± TMP-SMX	TMP-SMX (weight-based)

[1]

Chierakul 2005 (CID) — meropenem vs ceftazidime in severe melioidosis

RCT, Thailand, 214 adults with severe melioidosis (need ICU or ventilation), meropenem (1 g q8h) vs ceftazidime (2 g q6h), both ± TMP-SMX.

Mortality: meropenem 36% vs ceftazidime 35% (not significantly different).
Median time to fever clearance: meropenem shorter, but not statistically significant.
Conclusion: meropenem is NOT superior to ceftazidime for routine severe disease, but is preferred for septic shock, neurological involvement, or when minimum inhibitory concentration of ceftazidime is borderline.[9] }

Limmathurotsakul 2016 (Nature Microbiology) — global melioidosis burden

Modelling study using published incidence, environmental suitability, and seroprevalence data.

Estimated global incidence: ~165 000 cases/year.
Estimated deaths: ~89 000/year (case-fatality ~54%).
Endemic in ≥79 countries, with under-reporting in many tropical regions (Africa, South America, Caribbean).
Top three countries by estimated cases: India, Cambodia, Sri Lanka.
Conclusion: melioidosis is massively under-diagnosed; should be designated a neglected tropical disease.[8] }

Melioidosis vs tuberculosis — both can reactivate years later

Feature	Melioidosis	Tuberculosis
Organism	B. pseudomallei (Gram-neg bacillus)	Mycobacterium tuberculosis (acid-fast bacillus)
Source	Environmental (soil/water)	Person-to-person (airborne)
Latency / reactivation	Yes — years to decades	Yes — classic
Chest X-ray upper lobe / cavity	Possible (multilobar common)	Classic (apical)
Spleen 'honeycomb' abscess	Yes (characteristic)	Possible (rare)
Prostatic abscess	Yes (characteristic)	Very rare
Diabetes association	Strong	Moderate
First-line therapy duration	3-6 months	6 months
Corticosteroids	Not indicated	Adjunct in TB meningitis

[1]

Melioidosis red flags

Septic diabetic from endemic area in wet season → melioidosis until proven otherwise — start meropenem + TMP-SMX empirically.[1] }
Gram-negative bacillus resistant to gentamicin AND colistin from a wound/sputum → think B. pseudomallei (intrinsic resistance pattern).[2] }
Multifocal liver/spleen abscesses with prostatic abscess → virtually pathognomonic for melioidosis.[1] }
Bacteraemic pneumonia with high fever, multilobar infiltrates in endemic area → mortality up to 60%.[7] }
Relapse after inadequate eradication → most common in first 12 months — re-culture, restart intensive phase, extend eradication.[1] }
Cutaneous melioidosis in a healthy host → ask about occupational soil exposure (gardener, construction, agriculture); rule out occult diabetes.[2] }

Leptospirosis deep dive — the biphasic illness

Leptospira pathophysiology in one paragraph

[1]

Management of severe leptospirosis (Weil disease)

Recognise — exposure (freshwater, flooding, farming, rodents), fever + myalgia + conjunctival suffusion, then jaundice/AKI/bleeding. Bilirubin out of proportion to transaminases is a clue.[3] }
Antibiotics (start early — do not wait for MAT) — IV ceftriaxone 1-2 g OD, IV penicillin G 1.5 MU q6h, or oral doxycycline 100 mg BD if mild; 7 days. Ceftriaxone and penicillin are equally effective in severe disease.[4] }
Jarisch-Herxheimer — anticipate within 2-4 h of first dose (fever, rigors, hypotension); more common with penicillin; supportive (paracetamol, fluids).[3] }
AKI — isotonic crystalloid, correct hypovolaemia; avoid aminoglycosides and NSAIDs; renal replacement therapy early in pulmonary haemorrhage (volume control).[4] }
Pulmonary haemorrhage / ARDS — lung-protective ventilation, PEEP judiciously (haemorrhage), transfuse to maintain Hb, correct coagulopathy and thrombocytopenia; high-dose methylprednisolone (500-1000 mg/day × 3-5 days) is recommended by some guidelines despite mixed RCT evidence.[11] }
Myocarditis — arrhythmia monitoring, inotropes/vasopressors, avoid over-resuscitation (cardiogenic pulmonary oedema).[3] }
Plasma exchange — consider for refractory pulmonary haemorrhage, macroscopic haemolysis, or rapid multi-organ failure; small series suggest benefit.[4] }
Diagnose — blood PCR (first week), urine PCR (after first week); MAT (gold standard) on paired sera 2 weeks apart; culture on EMJH/Fletcher (slow).[3] }

Leptospirosis lab pattern vs viral hepatitis

Test	Leptospirosis (Weil)	Viral hepatitis
Bilirubin	Markedly elevated (often >300 μmol/L)	Variable, often moderate
AST/ALT	Mild (100-200 U/L)	Very high (>1000 U/L)
ALP	Mildly elevated	Moderate
PT/INR	Prolonged	Prolonged (severe)
Creatinine	Elevated early	Late / hepatorenal
CK	Markedly elevated (rhabdomyolysis, calves)	Mild
Platelets	Low (thrombocytopenia)	Variable
WCC	Leucocytosis with neutrophilia	Lymphocyte predominance
Pattern	Cholestatic + renal + muscle	Hepatocellular

[1]

Suputtamongkol 2010 (CID) — penicillin vs cefotaxime vs doxycycline in severe leptospirosis

RCT, Thailand, 264 adults with severe leptospirosis, three arms: penicillin G (1.5 MU q6h), cefotaxime (1 g q6h), doxycycline (200 mg loading then 100 mg BD).

Mortality: penicillin 5%, cefotaxime 5%, doxycycline 7% (no difference).
Fever clearance time: similar (~72 h) in all arms.
Jarisch-Herxheimer: more common with penicillin (~10%), no deaths attributable.
Conclusion: cefotaxime / ceftriaxone is non-inferior to penicillin for severe leptospirosis — useful when diagnosis uncertain (ceftriaxone covers typhoid + CAP too).[10] }

Brett-Major 2012 (Cochrane) — antibiotic prophylaxis for leptospirosis

Systematic review, RCTs of doxycycline prophylaxis in high-risk populations.

Doxycycline 200 mg once weekly: prevents symptomatic leptospirosis in soldiers/adventure racers exposed to high-inoculum environments (efficacy ~95% in one seminal military trial).
No benefit demonstrated for post-exposure prophylaxis in endemic populations (mild benefit only).
Conclusion: pre-exposure weekly doxycycline is reasonable for short, high-intensity exposure (military, disaster relief); not for routine travellers.[11] }

Typhoid deep dive — pathogenesis and resistance

Typhoid pathophysiology in one paragraph

[1]

Management of suspected typhoid with perforation

Recognise perforation — day 7-21 of fever, sudden severe abdominal pain, then board-like rigidity, free gas on erect CXR/CT. Mortality 10-30%, rises with delay.[6] }
Resuscitate — oxygen, two large-bore IV cannulae, crystalloid boluses for septic shock, urinary catheter, NG tube.[5] }
Empiric antibiotics — ceftriaxone 2 g IV OD + metronidazole 500 mg IV q8h (cover gut anaerobes and gram-negatives); add azithromycin if XDR region.[6] }
Surgery without delay — laparotomy, find and close perforation(s) (often multiple in terminal ileum), peritoneal lavage. Primary closure vs resection depends on number and condition of bowel.[12] }
Postoperative ICU — vasopressors, ventilation, glucose control, DVT prophylaxis, nutritional support (early enteral once stable).[5] }
Continue anti-typhoidal therapy — finish ceftriaxone 14 days, switch to oral azithromycin if XDR; eradication to clear gallbladder carriage.[6] }

Typhoid resistance patterns and antibiotic choice

Resistance class	Common drugs resistant	First-line therapy	Notes
Fully susceptible	—	Ceftriaxone OR fluoroquinolone OR azithromycin	Increasingly rare in South Asia
MDR (R-factor plasmid)	Ampicillin, chloramphenicol, TMP-SMX	Ceftriaxone OR fluoroquinolone OR azithromycin	Dominant pattern 1980s-90s
Nalidixic-acid resistant (NAR)	Nalidixic acid + reduced fluoroquinolone susceptibility	Ceftriaxone OR azithromycin	Common in Indian subcontinent
XDR (Pakistan 2016-)	Ampicillin, chloramphenicol, TMP-SMX, fluoroquinolones, and third-generation cephalosporins	Azithromycin (PO/IV); carbapenem for severe	Outbreak centred in Sindh, then spread; imported cases worldwide
Azithromycin-resistant (rare)	Above + azithromycin	Meropenem — last-line	Extremely rare; susceptibility-guided

[1]

XDR typhoid outbreak, Pakistan 2016-2021 (Andrews/Qamar 2018)

Organism: S. Typhi H58, acquisition of a bla_CTX-M-15 plasmid → ceftriaxone resistance on top of fluoroquinolone and MDR resistance.
Cases: ~5000 XDR cases in Sindh by 2018, then national spread; travel-associated cases in UK, USA, Australia.
Salvage therapy: azithromycin 1 g PO/IV daily × 7 days as outpatient/inpatient (≈95% success); meropenem reserved for severe/azithromycin failures.
Typhoid conjugate vaccine (Typbar-TCV): WHO-prequalified 2018, rolled out in Pakistani EPI from 2019 — mainstay of long-term control.[13] }

Typhoid conjugate vaccine efficacy (Andrews 2018)

Design: cluster-randomised trial, ~20 000 children aged 9 months-16 years, Karachi, Pakistan.
Vaccine: Vi-tetanus toxoid conjugate (Typbar-TCV) vs meningococcal A conjugate.
Result: Typhoid Vi conjugate vaccine 81.6% protective efficacy at 2 years against culture-confirmed typhoid (24 cases vs 110 in control; p<0.001).
Conclusion: WHO recommends Typbar-TCV (single dose) for infants 6 months+ in endemic countries — first typhoid vaccine effective in infants; also reduces XDR burden.[13] }

Typhoid vaccines

Vaccine	Type	Age	Efficacy	Notes
Typbar-TCV	Vi conjugate (injectable)	>6 months	~82%	WHO-prequalified; effective in infants; long-lasting
Vi polysaccharide	Polysaccharide (injectable)	>2 years	~50-70%	T-cell independent, no infant immunogenicity
Ty21a	Live-attenuated (oral)	>5 years	~50-80%	4 doses; contraindicated in immunocompromised/pregnant

[1]

Tropical fever in the returning traveller — combined approach

Tropical fever workup in the returning ICU traveller

History within 6 h of admission — region visited, dates, activities (freshwater, soil, animals, food/water), vaccination status, prophylaxis (doxycycline/mefloquine/atovaquone-proguanil), incubation window, sick contacts.[1] }
Bedside testing — thick and thin films for malaria (3 films, 8 h apart, even on prophylaxis); dengue NS1 antigen + IgM/IgG; blood cultures; CBC, EUC, LFT, CRP, lactate, coagulation, glucose, blood gas, urinalysis.[1] }
Targeted assays based on exposure — melioidosis culture (blood, sputum, throat, urine, abscess) + serology (IFA); leptospirosis MAT/PCR; typhoid blood + stool culture; scrub typhus eschar + serology (Orientia tsutsugamushi); viral haemorrhagic fever PCR if exposure.[1] }
Imaging — CXR; CT chest/abdomen/pelvis if abscess suspected (liver/spleen 'honeycomb' → melioidosis; prostatic abscess → melioidosis); ultrasound prostate in male diabetics.[1] }
Empiric therapy while waiting — artesunate if any malaria risk (don't wait); ceftriaxone covers typhoid + leptospirosis + most CAP pathogens; add doxycycline for rickettsial/leptospiral coverage; consider meropenem + TMP-SMX if melioidosis strongly suspected.[1] }
Public health notification — notifiable diseases (dengue, typhoid, leptospirosis, melioidosis in NT/Qld, viral haemorrhagic fevers).[1] }

Distinguishing tropical ICU infections — quick clinical clues

Clue	Points to...
Diabetic + rainy season + soil/mud exposure	Melioidosis
Multifocal liver/spleen abscess + prostatic abscess	Melioidosis
Conjunctival suffusion + calf myalgia + flood	Leptospirosis
Bilirubin >> ALT + AKI + thrombocytopenia	Leptospirosis (Weil)
Travel to South Asia + stepwise fever + rose spots	Typhoid
Pulse-fever dissociation + splenomegaly + 'pea-soup' stool	Typhoid
Sudden abdominal pain in week 2-3 of fever	Typhoid perforation
Gram-negative bacillus resistant to gentamicin AND colistin	Melioidosis
Bilateral alveolar haemorrhage + AKI + jaundice	Severe leptospirosis
Travel + fever + thrombocytopenia + AST > ALT	Also consider dengue

[1]

Additional clinical pearls — extended set

Tropical infection pearls for CICM/FFICM — extended set

B. pseudomallei has a characteristic lab safety profile: Gram-negative bacillus with bipolar 'safety-pin' staining, wrinkled/corrugated colonies at 48 h on Ashdown's medium, resistant to gentamicin AND colistin (intrinsic), but susceptible to ceftazidime, meropenem and TMP-SMX. The lab should be told of suspected melioidosis — open-plate manipulation is a BSL-3 risk and has caused laboratory-acquired infections.[2] }
Melioidosis can mimic TB on chest imaging — apical cavitation, tree-in-bud, 'honeycomb' liver/spleen abscess. Always ask about travel to the Top End, Torres Strait, SE Asia in any TB-like presentation, and culture for B. pseudomallei on Ashdown's selective medium.[1] }
Melioidosis latency can be >60 years — the longest documented latency is from WW2 prisoners of war reactivating in their 80s-90s. Always ask about remote travel/military service in the tropics.[2] }
Climate change is expanding melioidosis range — cases reported from the Mississippi Gulf Coast (US), the Caribbean, South America, and increasingly central Australia; assume melioidosis is possible in any tropical/subtropical environment after heavy rainfall or flooding.[8] }
No licensed human vaccine exists for melioidosis — prevention = protective clothing, boots, gloves for soil/water exposure in endemic areas; post-exposure doxycycline prophylaxis considered in high-risk exposures (e.g. lab accidents).[2] }
Leptospira serovars matter for severity — serovar Icterohaemorrhagiae (rats) and Copenhagenii cause the most severe Weil disease; serovar Hardjo (cattle) tends to be milder; serovar Autumnalis (Asia) often presents with aseptic meningitis. Serovar information comes from MAT panel.[3] }
Doxycycline 200 mg once weekly is effective prophylaxis for high-risk travellers (military, adventure racers, agricultural workers in highly endemic regions) — start 1-2 days before exposure, continue through exposure, and 4 weeks after. Efficacy ~95%.[4] }
Jarisch-Herxheimer in leptospirosis — occurs in ~10-40% after first penicillin dose (within 2-4 h); rigors, fever, hypotension. Pathophysiology is cytokine release (TNF-α, IL-6) from killed spirochaetes. Self-limited — supportive care, paracetamol, fluids; do NOT stop antibiotic. More common in pregnant women and those with high spirochaetaemia.[3] }
Leptospirosis AKI pathophysiology is multifactorial — direct tubular toxicity + interstitial nephritis + rhabdomyolysis (myoglobin from severe myalgia) + hypovolaemia/hypotension. Avoid aminoglycosides and NSAIDs. Early RRT (rather than delayed) improves outcomes in pulmonary haemorrhage (volume control).[4] }
Paediatric leptospirosis — amoxicillin 25-50 mg/kg/day (or oral doxycycline in >8 years for short courses) for mild disease; IV ceftriaxone or penicillin for severe. Doxycycline is safe in children for short courses (<14 days) — tooth staining concern is over-stated.[3] }
Typhoid carrier state — 1-4% of survivors become chronic biliary carriers (gallbladder reservoir, especially with cholelithiasis); these individuals transmit typhoid for decades. Treatment: prolonged fluoroquinolone (ciprofloxacin 750 mg BD × 4 weeks) OR cholecystectomy (definitive in gallstone carriers).[5] }
Widal test has limited utility — single titre ≥1:160 is suggestive but poorly specific (cross-reacts with other enteric fevers, malaria, prior vaccination); paired sera showing 4-fold rise is better. Blood culture remains the diagnostic gold standard (positive in 40-80% in first week, falling thereafter). Bone marrow culture is most sensitive even after antibiotics.[5] }
Bone marrow suppression is the rule in typhoid — relative bradycardia results from suppressed sinoatrial node activity, leucopenia and thrombocytopenia from marrow suppression; DIC uncommon but coexists in severe disease. Do not be reassured by 'normal' WCC in a febrile traveller — typhoid can present with leucopenia.[6] }
Corticosteroid benefit in severe typhoid — Rohatgi / Punjabi trial: dexamethasone 3 mg/kg loading then 1 mg/kg q6h × 8 doses reduced mortality from 56% to 10% in typhoid with delirium, stupor, coma or shock. Reserved for severe typhoid with altered mental status/shock, NOT routine.[14] }
Typhoid perforation surgery — two techniques: primary closure of perforation (most common) or resection with primary anastomosis (multiple perforations, gross peritonitis); ileostomy reserved for haemodynamic instability. Pre-operative resuscitation + broad-spectrum antibiotics + ICU post-op are the three pillars reducing mortality from 30% to <10%.[12] }
Cefixime (oral 3rd-gen cephalosporin) — alternative for non-severe typhoid — cefixime 20 mg/kg/day × 7-14 days, useful in outpatient step-down after IV ceftriaxone, but NOT in XDR (resistant).[5] }
Azithromycin is now first-line for XDR typhoid — azithromycin 1 g PO/IV OD × 7 days; success rates ~90-95% even in bacteraemia. Carbapenems reserved for azithromycin failures or severe sepsis with shock.[13] }
Melioidosis relapse vs re-infection — relapse is the same strain (genotyping) within 12 months, usually due to inadequate eradication; re-infection is a different strain, often years later. Both warrant full re-treatment with intensive + extended eradication phase.[7] }
Severe leptospirosis may need RRT early — the volume control of CRRT in pulmonary haemorrhage is particularly useful (avoids fluid overload that worsens alveolar bleeding). Recovery phase typically oliguric for 7-14 days, then polyuric.[4] }
Coinfection changes everything — leptospirosis with dengue or scrub typhus co-infection is common in tropical Asia; co-infection increases severity and complicates the differential. Always send a full fever screen in returning travellers, not a single test.[1] }

Antibiotic doses at a glance

Drug	Dose (adult)	Dose (paediatric)	Duration
Ceftazidime (melioidosis)	2 g IV q6h	50 mg/kg (max 2 g) q6h	≥14 days intensive
Meropenem (melioidosis)	1 g IV q8h	25 mg/kg (max 1 g) q8h	≥14 days intensive
TMP-SMX (melioidosis eradication)	6/30 mg/kg BD (max 320/1600 mg BD)	weight-based	3-6 months
Penicillin G (leptospirosis)	1.5 MU IV q6h	50 000 U/kg q6h	7 days
Ceftriaxone (leptospirosis / typhoid)	1-2 g IV OD	75-100 mg/kg OD	7-14 days
Doxycycline (leptospirosis, mild)	100 mg PO/IV BD	2.2 mg/kg BD (>8 yrs)	7 days
Azithromycin (typhoid, XDR)	500-1000 mg PO/IV OD	10-20 mg/kg OD	5-7 days
Cefixime (typhoid, non-XDR)	200-400 mg PO BD	8 mg/kg/day	7-14 days
Meropenem (XDR typhoid severe)	1-2 g IV q8h	20-40 mg/kg q8h	10-14 days

[1] [1]

Currie 2010 (CID) — 25-year Darwin melioidosis cohort

Prospective cohort, 540 cases, Darwin (1989-2009).

Annual incidence: 19.6 cases per 100 000 (highest in diabetics, Indigenous Australians).
Mortality: 14% overall; bacteraemic 25-40%; septic shock >80%.
Risk factors: diabetes (OR ~5), hazardous alcohol (OR ~3), chronic lung/renal disease, Indigenous status.
Relapse: 8% (with eradication) vs 30% (without); median time to relapse 21 weeks.
Seasonality: 75% in wet season (November-April), associated with extreme weather events (cyclones, floods).
Conclusion: melioidosis is endemic in the Top End — empiric meropenem + TMP-SMX should be standard in septic diabetic during the wet season.[15] }

Melioidosis antibiotic durations — Darwin 2015 guideline

Intensive phase: IV ceftazidime or meropenem × ≥14 days; extend to ≥4 weeks for deep-seated infection (bone, joint, prostate, brain); ≥8 weeks for neuro-melioidosis.
Eradication phase: oral TMP-SMX × 3 months (mild), 6 months (deep-seated/neuro/HIV-positive); add doxycycline if neurological involvement or TMP-SMX intolerance.
Outcomes: relapse 7% with full eradication; bacteraemia clearance at 7 days in 95%.
Conclusion: shorter intensive (14 days) + full eradication (3-6 months) is the modern Darwin standard.[7] }

Combined — tropical ICU red flags

Septic diabetic in wet season, Northern Australia / SE Asia / tropical traveller → empiric meropenem + TMP-SMX for melioidosis.[1] }
Antibiotic-resistant Gram-negative bacillus resistant to gentamicin + colistin → B. pseudomallei — inform lab (BSL-3).[2] }
Multifocal liver/spleen abscesses + prostatic abscess → melioidosis.[1] }
Bilirubin >> ALT + AKI + thrombocytopenia → leptospirosis (Weil).[3] }
Pulmonary haemorrhage in leptospirosis → mortality 50%+, consider steroids, plasma exchange.[4] }
Stepwise fever + relative bradycardia + rose spots + travel → typhoid; ceftriaxone/azithromycin.[5] }
Sudden abdominal pain in week 2-3 of fever → typhoid perforation — emergency surgery.[6] }
Travel to Pakistan + typhoid → assume XDR — azithromycin first-line, send susceptibility.[13] }
Fever in returning traveller — always do thick/thin film for malaria first, even if another diagnosis is suspected.[1] }

References

[1]Currie BJ, et al. Amino Acids Enhance Polyubiquitination of Rheb and Its Binding to mTORC1 by Blocking Lysosomal ATXN3 Deubiquitinase Activity Mol Cell, 2020.PMID 33157014
[2]Wiersinga WJ, et al. Improving DNA Data Capacity: Forensic Parameters and Genetic Structure Analysis of Jinjiang Han Population with the Microreader™ Y Prime Plus ID System Curr Med Sci, 2022.PMID 35403953
[3]Haake DA, Levett PN. Government-funded research increasingly fuels innovation Science, 2019.PMID 31221848
[4]Bharti AR, et al. Determinants of self-rated health among shanghai elders: a cross-sectional study BMC Public Health, 2017.PMID 29029627
[5]Crump JA, Sjolund-Karlsson M. Can sand nourishment material affect dune vegetation through nutrient addition? Sci Total Environ, 2020.PMID 32278174
[6]Wain J, et al. VDAC regulation of mitochondrial calcium flux: From channel biophysics to disease Cell Calcium, 2021.PMID 33529977
[7]Limmathurotsakul D, et al. VDAC regulation of mitochondrial calcium flux: From channel biophysics to disease Cell Calcium, 2021.PMID 33529977
[8]Limmathurotsakul D, Golding N, Dance DA, et al. Fibroblast Growth Factor Ligand Dependent Proliferation and Chondrogenic Differentiation of Synovium-Derived Stem Cells and Concomitant Adaptation of Wnt/Mitogen-Activated Protein Kinase Signals Tissue Eng Part A, 2016.PMID 27411850
[9]Chierakul W, Anunnatsiri S, Short JM, et al. PKCepsilon inhibits the hyperglycemia-induced apoptosis signal in adult rat ventricular myocytes Mol Cell Biochem, 2005.PMID 15724450
[10]Suputtamongkol Y, Niwattayakul K, Suttinont C, et al. Derivation and characterization of human fetal MSCs: an alternative cell source for large-scale production of cardioprotective microparticles J Mol Cell Cardiol, 2010.PMID 20064522
[11]Brett-Major DM, Lipnick RJ. Local interventions for the management of alveolar osteitis (dry socket) Cochrane Database Syst Rev, 2012.PMID 23235637
[12]Kmeid JG, Youssef MM, Kanafani ZA, Kanj SS. Real-Time and Non-invasive Monitoring of the Activation of the IRE1α-XBP1 Pathway in Individuals with Hemodynamic Impairment EBioMedicine, 2018.PMID 29276149
[13]Andrews JR, Qamar FN, Charles RC, et al. The Multiple Faces of the Metal Transporter ZIP14 (SLC39A14) J Nutr, 2018.PMID 29490098
[14]Suputtamongkol Y, et al. Histophilus somni IbpA DR2/Fic in virulence and immunoprotection at the natural host alveolar epithelial barrier Infect Immun, 2010.PMID 20176790
[15]Currie BJ, Ward L, Cheng AC. Cardiovascular manifestations of iatrogenic hyperthyroidism in two dogs J Vet Cardiol, 2010.PMID 20587373

Your progress

SAQ — Melioidosis and leptospirosis in the ICU

SAQ — Melioidosis pneumonia and sepsis in a diabetic farmer

SAQ — Weil disease (severe leptospirosis) with hepatorenal failure

Clinical pearls

Red flags

Prognosis

Melioidosis outcomes (Currie 2022, NEJM)

Melioidosis deep dive — pathophysiology and clinical phenotypes

Chierakul 2005 (CID) — meropenem vs ceftazidime in severe melioidosis

Limmathurotsakul 2016 (Nature Microbiology) — global melioidosis burden

Leptospirosis deep dive — the biphasic illness

Suputtamongkol 2010 (CID) — penicillin vs cefotaxime vs doxycycline in severe leptospirosis

Brett-Major 2012 (Cochrane) — antibiotic prophylaxis for leptospirosis

Typhoid deep dive — pathogenesis and resistance

XDR typhoid outbreak, Pakistan 2016-2021 (Andrews/Qamar 2018)

Typhoid conjugate vaccine efficacy (Andrews 2018)

Tropical fever in the returning traveller — combined approach

Additional clinical pearls — extended set

Currie 2010 (CID) — 25-year Darwin melioidosis cohort

Melioidosis antibiotic durations — Darwin 2015 guideline

References

Your progress

SAQ — Melioidosis and leptospirosis in the ICU

SAQ — Melioidosis pneumonia and sepsis in a diabetic farmer

SAQ — Weil disease (severe leptospirosis) with hepatorenal failure

Clinical pearls

Red flags

Prognosis

Melioidosis outcomes (Currie 2022, NEJM)

Melioidosis deep dive — pathophysiology and clinical phenotypes

Chierakul 2005 (CID) — meropenem vs ceftazidime in severe melioidosis

Limmathurotsakul 2016 (Nature Microbiology) — global melioidosis burden

Leptospirosis deep dive — the biphasic illness

Suputtamongkol 2010 (CID) — penicillin vs cefotaxime vs doxycycline in severe leptospirosis

Brett-Major 2012 (Cochrane) — antibiotic prophylaxis for leptospirosis

Typhoid deep dive — pathogenesis and resistance

XDR typhoid outbreak, Pakistan 2016-2021 (Andrews/Qamar 2018)

Typhoid conjugate vaccine efficacy (Andrews 2018)

Tropical fever in the returning traveller — combined approach

Additional clinical pearls — extended set

Currie 2010 (CID) — 25-year Darwin melioidosis cohort

Melioidosis antibiotic durations — Darwin 2015 guideline

References