Tropical infections in ICU: melioidosis, leptospirosis, typhoid

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Meet the patient

A 52-year-old diabetic farmer from Far North Queensland arrives in the wet season with five days of high fever, productive cough and dyspnoea after exposure to mud and floodwater. He is in septic shock, the chest X-ray shows upper-lobe consolidation with cavitation, and the CT reveals abscesses in the lung, liver, spleen and prostate. Blood cultures are pending.^[3]

This is melioidosis, the great mimicker of tropical Australia — and the prostate abscess is the giveaway: prostatic abscesses occurred in 20 percent of males in the Darwin prospective study, and pneumonia is the commonest presentation, ranging from acute fulminant sepsis to chronic infection that mimics tuberculosis.^[3][7] The two questions that decide the next hour are whether you have started ceftazidime or a carbapenem, and whether you have remembered that the intensive phase is only the start of a treatment whose oral eradication phase runs for at least 12 weeks.^[2]

Three tropical infections at a glance — know the exposure

The exposure history does most of the diagnostic work. Soil and water in a diabetic points to melioidosis; rodent-urine or floodwater exposure points to leptospirosis — leptospirosis is endemic in tropical regions and causes large epidemics after heavy rainfall and flooding; travel and faeco-oral transmission point to typhoid, which affects persons residing in, or travelling from, areas lacking safe water and sanitation.^[9][23]

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Melioidosis — the great mimicker

Burkholderia pseudomallei is a gram-negative environmental saprophyte found in wet soils in Southeast Asia and northern Australia. It is intrinsically resistant to a wide range of antimicrobials, and treating with ineffective agents produces case fatality rates exceeding 70 percent. Diagnosis is genuinely hard: melioidosis has diverse clinical manifestations and conventional bacterial identification methods are inadequate — diagnosis relies on culture of the organism.^[1][6][8]

Diabetes is a documented risk factor for primary pneumonia (Meumann: diabetes, COPD, smoking, and rheumatic heart disease or heart failure independently associated with pneumonia versus other presentations). White: B. pseudomallei mostly infects adults with an underlying predisposing condition, mainly diabetes. Seasonality is striking: 436 of 540 Darwin cases (81 percent) presented during the monsoonal wet season.^[3][7][1]

Melioidosis disseminates widely and mimics tuberculosis. Pneumonia was the principal presentation in 51 percent of Darwin cases, and the clinical range runs from acute fulminant sepsis to chronic infection mimicking tuberculosis — multilobar disease carried double the mortality of single-lobe disease (32 versus 14 percent). Abscesses form especially in the lungs, liver, spleen, skeletal muscle and prostate; prostatic abscesses occurred in 20 percent of males, so image the prostate in any male from an endemic area with sepsis, and remember that large deep abscesses such as prostatic abscesses require drainage for cure.^[1][3][7]

The classic trap — relapse after inadequate eradication. Treatment has two phases. Darwin 2020 (n=234 first-episode cases): 16 (6.8%) died during intensive phase; 6 (2.8%) had recrudescence during therapy; 10 (4.7%) had recurrent melioidosis after completing therapy. White 2003 recorded 10 percent relapse even with 20 weeks of maintenance antibiotics. Oral TMP-SMX is recommended for 12 weeks in Australia and 20 weeks in Thailand; a 658-patient RCT of 12 versus 20 weeks did not meet noninferiority for culture-confirmed recurrence (5 [2%] vs 2 [1%]) but all-cause mortality was lower with 12 weeks (1 [0.3%] vs 11 [3%]), so the authors recommend the 12-week regimen.^[2][34][1]

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The randomized evidence behind the intensive phase is Thai and sobering. In the open randomized comparison of high-dose imipenem and ceftazidime, 296 adults with suspected severe melioidosis were enrolled and 214 had culture-confirmed disease — mortality was 36.9 percent overall with no difference in survival between arms, but treatment failure after 48 hours was more common on ceftazidime, so a carbapenem is a safe and effective alternative. Adding TMP-SMX to ceftazidime during the intensive phase did not reduce acute mortality (25.1 versus 26.6 percent across two combined trials of 449 patients) — oral TMP-SMX earns its place in the eradication phase, not in acute sepsis survival. Cheng: despite ceftazidime- and carbapenem-based intravenous treatments, melioidosis still carries significant mortality from severe sepsis. Simpson: imipenem is a safe and effective alternative to ceftazidime.^[4][5][8]

Leptospirosis — the biphasic illness and Weil disease

Leptospira infection results from direct or indirect exposure to infected reservoir hosts — many wild and domestic animals — that carry the pathogen in their renal tubules and shed leptospires in their urine; the brown rat (Rattus norvegicus) is the most important source of human infections. The illness is biphasic, characterised by a leptospiraemic phase and an immunological phase: the leptospiraemic phase brings a nonspecific acute febrile illness with fever, myalgia and headache that may be confused with influenza and dengue, and conjunctival suffusion with hepatic and renal dysfunction should warrant a serology test for leptospirosis.^[9][18][19]

Weil disease is the triad of jaundice, renal failure and bleeding, and the severe pulmonary haemorrhage syndrome — due to extensive alveolar haemorrhage — has a fatality rate of over 50 percent. The liver pattern is the clue: total and direct bilirubin are elevated while transaminases and alkaline phosphatase are only mildly elevated, a predominantly direct, cholestatic picture — because bilirubin rises through hepatocellular damage and disruption of the intercellular junctions between hepatocytes, resulting in leaking of bilirubin out of the bile canaliculi. This dissociation between bilirubin and transaminases is the biochemical signature of severe leptospirosis. When oliguric renal failure occurs, prompt initiation of dialysis can be life-saving.^[9][17]

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Start antibiotics early — do not wait for serology. The head-to-head evidence: IV ceftriaxone 1 g daily for 7 days and IV penicillin G 1.5 million units every 6 hours for 7 days were equally effective for severe leptospirosis (median fever clearance 3 days in both arms, 5 deaths in each group of a 173-patient randomized trial) — and ceftriaxone has the practical advantages of once-daily administration and an extended spectrum against other bacteria. Doxycycline (7-day course) and azithromycin (3-day course) are satisfactory alternatives — azithromycin was non-inferior to doxycycline and better tolerated — and in the three-arm Thai trial cefotaxime matched penicillin G and doxycycline with no difference in mortality, defervescence or laboratory resolution. The honest caveat for the viva: Win 2024 found the evidence very uncertain about penicillin versus placebo on all-cause mortality (RR 1.57; 3 trials, 367 participants; very low-certainty).^{[10][11][12][13]}

The classic trap — Jarisch-Herxheimer within hours of the first antibiotic dose. A harmful Jarisch-Herxheimer reaction can occur within hours of treatment with beta-lactams, with chills, fever and hypotension: in a prospective New Caledonia series (n=81) JHR occurred in 48 percent (possibly 61 percent) of leptospirosis patients, alongside rising TNF, IL-6 and IL-10. It is an acute, self-limiting condition that typically resolves without the need for targeted treatment — supportive care only.^[20][21]

For the feared pulmonary haemorrhage — ventilate lung-protectively, transfuse, correct coagulopathy, and start dialysis promptly when renal failure is oliguric. Corticosteroids plus plasma exchange produced prompt improvement in a reported patient unresponsive to antibiotics and haemodialysis and may be a choice in selected patients unresponsive to conventional therapy — but a randomized trial of pulse dexamethasone in 68 patients with pulmonary involvement showed no mortality benefit and a significant increase in nosocomial infection, so adjunctive immunotherapy is not routine.^[9][15][16]

Typhoid — gradual fever, relative bradycardia, and the late perforation

Salmonella Typhi is spread by the faeco-oral route through contaminated water and food. It takes 7 to 21 days from ingestion to symptoms; the bacteria invade the submucosal layer and proliferate in the Peyer's patches, and fever with relative bradycardia and abdominal pain is the typical manifestation. Hepatosplenomegaly, intestinal bleeding and perforation are the features at various stages of the disease. Fever onset is gradual over 3 to 7 days with malaise, headache and myalgia, life-threatening complications arise in the second week of untreated illness, and blood or bone marrow culture remains the reference standard despite the low sensitivity of blood culture.^[23][24]

Three features earn viva marks. The fever is gradual, not abrupt. Relative bradycardia is a genuine diagnostic predictor: among febrile returned travellers it was present in 88 percent of culture-proven enteric fever cases versus 51 percent of controls, and it independently predicted the diagnosis (adjusted odds ratio 11.7) — though it is not specific, and in children it may be absent. Rose spots may be seen, usually with abdominal pain in the second week. Absolute eosinopenia is the companion classic sign (63 versus 38 percent).^[24][25]

The classic trap — intestinal perforation. Necrosis of the Peyer's patches produces perforation, peritonitis and secondary sepsis — the typhoid complications that require intensive care. In the SEAP surveillance series there were 16/242 (7%) deaths from Pakistan among ileal-perforation cases (249 total across Bangladesh, Nepal and Pakistan). Do not quote a pooled SEAP-wide 7 percent. This is a surgical emergency: resuscitate, give antibiotics covering the prevailing resistance pattern — XDR isolates require azithromycin and/or meropenem — and operate without delay.^[24][31][29]

Resistance decides the drug. Azithromycin, ciprofloxacin (except for infections originating in South Asia, because of drug resistance) and ceftriaxone are the recommended options, with choice guided by local resistance patterns — ceftriaxone- and azithromycin-based therapies are commonly used even in the era of extremely drug-resistant typhoid in Pakistan, where ciprofloxacin-resistant and ceftriaxone-resistant typhoid is common. Multidrug-resistant typhoid (resistant to chloramphenicol, amoxicillin and TMP-SMX) is in decline in Asia against a backdrop of high fluoroquinolone resistance, but rising in Africa. High-level ciprofloxacin resistance reaches 20 percent prevalence in South Asia; XDR typhoid has become dominant in Pakistan (70 percent of isolates in 2020) but has not established elsewhere. In Pakistani laboratory data, 57 percent of S. Typhi isolates were XDR, with resistance to ceftriaxone in 63.3 percent and ciprofloxacin in 66.4 percent — while isolates remained susceptible to azithromycin and 99.8 percent susceptible to meropenem. XDR enteric fever requires azithromycin and/or meropenem.^{[23][33][26][27][28][29]}

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For severe typhoid with delirium, obtundation, stupor, coma or shock, high-dose dexamethasone (initial dose 3 mg per kilogram) reduced case fatality from 55.6 percent (10 of 18 on placebo) to 10 percent (2 of 20) in a randomized double-blind trial of 38 patients with culture-positive severe typhoid — delirium, obtundation and stupor were grave prognostic signs. Dexamethasone is unnecessary for most patients but is recommended for all suspected typhoid patients who are delirious, obtunded, stuporous, comatose or in shock. Chronic biliary carriage is the other long-tail problem: there is a paucity of evidence to guide the antimicrobial management of chronic faecal carriers.^[30][29]

The returning-traveller workup — exposure first, malaria always

In any returning traveller with fever, rule malaria in or out first. Clinicians in non-endemic areas should consider a diagnosis of malaria in returning travellers presenting with fever, use rapid diagnostic tests in addition to microscopy, and start guideline-directed therapy without delay — delays in treatment lead to poor clinical outcomes. Meanwhile, persistent fever after the onset of jaundice — especially with rash and thrombocytopenia — should raise suspicion of a tropical infection rather than acute viral hepatitis.^[32][22]

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The trials and cohorts that set the standard

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The mantra, and the memory device

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The mantra: exposure first, malaria always, then name the infection — soil gives ceftazidime, flood gives penicillin, the late week gives the surgeon.^[32]

Ward-round test — three stems, thirty seconds each

Stem 1 — the diabetic farmer in the wet season (answer)ShowHide

A 52-year-old diabetic farmer from Far North Queensland is in septic shock in the wet season after mud and floodwater exposure. CT shows cavitating upper-lobe pneumonia with liver, spleen and prostatic abscesses. Diagnosis and antibiotic strategy? Model: This is melioidosis — the great mimicker. The epidemiological and clinical fit is classic: Far North Queensland, wet season (81 percent of Darwin cases), diabetes (Meumann pneumonia risk factor; White: mainly diabetes as a predisposing condition), occupational soil and water exposure, pneumonia — the commonest presentation, from acute fulminant sepsis to chronic infection mimicking tuberculosis — and multi-organ abscesses including the prostate (20 percent of males; image the prostate and drain it). Treat with IV ceftazidime 120 mg/kg/day or imipenem 50 mg/kg/day (Simpson, minimum 10 days). Darwin 2020 often prolonged IV therapy beyond a 2-week minimum: at least 3 weeks for bacteraemia plus single-lobe pneumonia or multilobar pneumonia without bacteraemia, and at least 4 weeks for bacteraemia plus multilobar pneumonia. Then at least 12 weeks of oral TMP-SMX eradication (Anunnatsiri recommend 12 weeks over 20). Darwin 2020: 4.7 percent recurrent after completing therapy; White 2003: 10 percent relapse historically even with 20 weeks of maintenance antibiotics.^{[2][3][4][7][34][1]}

Stem 2 — floodwater, calf myalgia and a bilirubin of 320 (answer)ShowHide

A farmer presents seven days after flooding with fever, severe calf myalgia, conjunctival suffusion, jaundice (bilirubin 320), AKI, thrombocytopenia and haemoptysis. ALT is only 90. Diagnosis, the lab pattern, and the antibiotic? Model: This is severe leptospirosis — Weil disease with pulmonary haemorrhage. The exposure (rodent-contaminated floodwater — epidemics follow heavy rainfall and flooding), myalgia and conjunctival suffusion fit, and the dissociated jaundice — bilirubin far above the transaminases — reflects the predominantly direct cholestatic pattern with disruption of the intercellular junctions between hepatocytes, unlike acute viral hepatitis where the enzymes dominate. The severe pulmonary haemorrhage syndrome carries a fatality rate above 50 percent. Start ceftriaxone 1 g daily or penicillin G 1.5 million units every 6 hours for 7 days without waiting for serology, anticipate Jarisch-Herxheimer within hours (48 percent in the prospective series; self-limiting, supportive care only), ventilate lung-protectively for the pulmonary haemorrhage, start dialysis promptly if oliguric, and reserve corticosteroids plus plasma exchange for selected patients unresponsive to conventional therapy — the randomized trial of pulse dexamethasone showed no benefit.^{[9][10][17][20][16]}

Stem 3 — late fever and sudden abdominal pain (answer)ShowHide

A traveller returning from South Asia is on day 18 of a gradual fever with rose spots and relative bradycardia, now ceftriaxone-treated. He develops sudden severe abdominal pain with board-like rigidity and free gas on the erect film. What happened and what is the management? Model: This is typhoid intestinal perforation — necrosis of the Peyer's patches in the terminal ileum late in untreated illness, a surgical emergency: intestinal perforation, peritonitis and secondary sepsis are the typhoid complications that need ICU care, and SEAP reported 16/242 (7%) deaths from Pakistan. Resuscitate with oxygen, large-bore IV access and crystalloid, give antibiotics chosen for the resistance pattern — XDR isolates require azithromycin and/or meropenem, and 99.8 percent of Pakistani isolates remained meropenem-susceptible — and operate without delay. Consider high-dose dexamethasone (initial 3 mg/kg) only if he is delirious, obtunded, stuporous, comatose or shocked.^{[24][28][29][30][31]}

References34ShowHide

1. [1]White NJ Melioidosis. Lancet, 2003.PMID 12767750
2. [2]Sullivan RP, Marshall CS, Anstey NM, et al. 2020 Review and revision of the 2015 Darwin melioidosis treatment guideline; paradigm drift not shift. PLoS Negl Trop Dis, 2020.PMID 32986699
3. [3]Currie BJ, Ward L, Cheng AC The epidemiology and clinical spectrum of melioidosis: 540 cases from the 20 year Darwin prospective study. PLoS Negl Trop Dis, 2010.PMID 21152057
4. [4]Simpson AJ, Suputtamongkol Y, Smith MD, et al. Comparison of imipenem and ceftazidime as therapy for severe melioidosis. Clin Infect Dis, 1999.PMID 10476746
5. [5]Chierakul W, Anunnatsiri S, Short JM, et al. Two randomized controlled trials of ceftazidime alone versus ceftazidime in combination with trimethoprim-sulfamethoxazole for the treatment of severe melioidosis. Clin Infect Dis, 2005.PMID 16163628
6. [6]Limmathurotsakul D, Golding N, Dance DAB, et al. Predicted global distribution of Burkholderia pseudomallei and burden of melioidosis. Nat Microbiol, 2016.PMID 27571754
7. [7]Meumann EM, Cheng AC, Ward L, Currie BJ Clinical features and epidemiology of melioidosis pneumonia: results from a 21-year study and review of the literature. Clin Infect Dis, 2012.PMID 22057702
8. [8]Cheng AC, Currie BJ Melioidosis: epidemiology, pathophysiology, and management. Clin Microbiol Rev, 2005.PMID 15831829
9. [9]Haake DA, Levett PN Leptospirosis in humans. Curr Top Microbiol Immunol, 2015.PMID 25388133
10. [10]Panaphut T, Domrongkitchaiporn S, Vibhagool A, et al. Ceftriaxone compared with sodium penicillin g for treatment of severe leptospirosis. Clin Infect Dis, 2003.PMID 12802748
11. [11]Suputtamongkol Y, Niwattayakul K, Suttinont C, et al. An open, randomized, controlled trial of penicillin, doxycycline, and cefotaxime for patients with severe leptospirosis. Clin Infect Dis, 2004.PMID 15546074
12. [12]Phimda K, Hoontrakul S, Suttinont C, et al. Doxycycline versus azithromycin for treatment of leptospirosis and scrub typhus. Antimicrob Agents Chemother, 2007.PMID 17638700
13. [13]Win TZ, Han SM, Edwards T, et al. Antibiotics for treatment of leptospirosis. Cochrane Database Syst Rev, 2024.PMID 38483092
14. [14]Win TZ, Perinpanathan T, Mukadi P, et al. Antibiotic prophylaxis for leptospirosis. Cochrane Database Syst Rev, 2024.PMID 38483067
15. [15]Dursun B, Bostan F, Artac M, et al. Severe pulmonary haemorrhage accompanying hepatorenal failure in fulminant leptospirosis. Int J Clin Pract, 2007.PMID 17229190
16. [16]Niwattayakul K, Kaewtasi S, Chueasuwanchai S, et al. An open randomized controlled trial of desmopressin and pulse dexamethasone as adjunct therapy in patients with pulmonary involvement associated with severe leptospirosis. Clin Microbiol Infect, 2010.PMID 19732091
17. [17]Cuaño CRG, Cuaño PMGM, Ong JP, et al. Determination of Liver Function Tests and Liver Ultrasonographic Findings in Patients with Leptospirosis in a Tertiary Hospital. Acta Med Philipp, 2024.PMID 38966607
18. [18]Priyankara WDD, Manoj EM Posterior Reversible Encephalopathy in a Patient with Severe Leptospirosis Complicated with Pulmonary Haemorrhage, Myocarditis, and Acute Kidney Injury. Case Rep Crit Care, 2019.PMID 31929913
19. [19]Gupta N, Wilson W, Ravindra P, et al. Clinical profile, management and outcome of patients with leptospirosis during the times of COVID-19 pandemic: A prospective study from a tertiary care centre in South India. Infez Med, 2021.PMID 35146344
20. [20]Cagliero J, Loarec A, Lebon J, et al. Anti-inflammatory cytokine profile and Jarisch-Herxheimer reaction in Leptospirosis patients: A prospective case-series study in New Caledonia. PLoS Negl Trop Dis, 2025.PMID 40986630
21. [21]Wood JM, Sbar E Jarisch-Herxheimer Reaction. StatPearls, 2026.PMID 32491752
22. [22]Samanta A, Poddar U, Sen Sarma M, et al. Persistent fever in acute hepatitis: think beyond acute viral hepatitis. Infect Dis (Lond), 2024.PMID 38465663
23. [23]Kuehn R, Rahden P, Hussain HS, et al. Enteric (typhoid and paratyphoid) fever. Lancet, 2025.PMID 40914181
24. [24]Ray B, Raha A Typhoid and Enteric Fevers in Intensive Care Unit. Indian J Crit Care Med, 2021.PMID 34345129
25. [25]Matono T, Kutsuna S, Kato Y, et al. Role of classic signs as diagnostic predictors for enteric fever among returned travellers: Relative bradycardia and eosinopenia. PLoS One, 2017.PMID 28644847
26. [26]Britto CD, Wong VK, Dougan G, Pollard AJ A systematic review of antimicrobial resistance in Salmonella enterica serovar Typhi, the etiological agent of typhoid. PLoS Negl Trop Dis, 2018.PMID 30307935
27. [27]Carey ME, Dyson ZA, Ingle DJ, et al. Global diversity and antimicrobial resistance of typhoid fever pathogens: Insights from a meta-analysis of 13,000 Salmonella Typhi genomes. Elife, 2023.PMID 37697804
28. [28]Qamar FN, Yousafzai MT, Qazi I, et al. Trends of Enteric Fever and Emergence of Extensively Drug-Resistant Typhoid in Pakistan: Population-Based Laboratory Data From 2017-2019. Open Forum Infect Dis, 2025.PMID 40212028
29. [29]Parry CM, Qamar FN, Rijal S, et al. What Should We Be Recommending for the Treatment of Enteric Fever? Open Forum Infect Dis, 2023.PMID 37274536
30. [30]Hoffman SL, Punjabi NH, Kumala S, et al. Reduction of mortality in chloramphenicol-treated severe typhoid fever by high-dose dexamethasone. N Engl J Med, 1984.PMID 6361558
31. [31]Qazi SH, Yousafzai MT, Saddal NS, et al. Burden of Ileal Perforations Among Surgical Patients Admitted in Tertiary Care Hospitals of Three Asian countries: Surveillance of Enteric Fever in Asia Project (SEAP), September 2016-September 2019. Clin Infect Dis, 2020.PMID 33258928
32. [32]Weiland AS Recent Advances in Imported Malaria Pathogenesis, Diagnosis, and Management. Curr Emerg Hosp Med Rep, 2023.PMID 37213266
33. [33]Manesh A, Meltzer E, Jin C, et al. Typhoid and paratyphoid fever: a clinical seminar. J Travel Med, 2021.PMID 33550411
34. [34]Anunnatsiri S, Chaowagul W, Teparrukkul P, et al. A Comparison Between 12 Versus 20 Weeks of Trimethoprim-sulfamethoxazole as Oral Eradication Treatment for Melioidosis: An Open-label, Pragmatic, Multicenter, Non-inferiority, Randomized Controlled Trial Clin Infect Dis, 2021.PMID 32725199