Melioidosis

Reviewed and revised 22 February 2025

OVERVIEW

• Melioidosis is a severe infectious disease caused by the bacterium Burkholderia pseudomallei.
• Common in Southeast Asia and Northern Australia, with increasing recognition in other tropical and subtropical regions.
• Presents with a wide range of clinical manifestations, from localized infections to severe sepsis and septic shock.
• Melioidosis has also been known as Whitmore’s disease, pseudoglanders, Nightcliff Gardener’s disease, “The Great Masquerader”, and the “Vietnam Time bomb”.

CAUSE

• Underlying Cause: Infection by Burkholderia pseudomallei, a gram-negative, aerobic, motile rod-shaped bacterium. The organism inhabits wet soils in tropical and subtropical regions, as well as stagnant waters.
• RISK FACTORS:
  • Travel to endemic areas (e.g. SE Asia, Northern Australia), especially in wet season
  • High risk activities in endemic areas (e.g. farming, outdoor sports), especially with broken skin
  • Diabetes mellitus
  • Heavy alcohol use
  • Chronic kidney disease
  • Chronic lung disease (e.g., cystic fibrosis, COPD, bronchiectasis)
  • Liver disease
  • Thalassemia
  • Cancer
  • Immunosuppression

PATHOGENESIS

• Pathophysiological Processes:
  • Entry through skin abrasions, inhalation, or ingestion.
  • Bacteria survive within macrophages, evading the immune system.
  • Dissemination to various organs, causing localized or systemic infection.
• Complications:
  • Septic shock
  • Pneumonia
  • Abscess formation in various organs
  • Chronic infection (10% of cases)

CLINICAL ASSESSMENT

• HISTORY:
  • Symptoms vary according to site infected and systemic involvement: Fever, cough, chest pain, weight loss, abscesses.
  • Specific Questions: Recent travel to endemic areas, contact with soil or water, pre-existing conditions.
• EXAMINATION:
  • Physical Findings may includ: Fever, respiratory signs, abscesses, hepatosplenomegaly.

Types of meliodosis

• Localized Infection:
  • Presents as an ulcer, nodule, or skin abscess.
  • Parotid involvement seen in children in SE asia.
  • Prostate involvement seen in indigenous adult males in Northern Australia
  • Symptoms: Fever, localized pain, and swelling.
• Pulmonary Infection:
  • Most common presentation (50%)
  • Symptoms: Cough (productive or nonproductive), high fever, chest pain, headache, anorexia, myalgias.
  • Can range from mild bronchitis to severe pneumonia.
• Septicaemia:
  • Symptoms: Fever, chills, rigors, abdominal pain, joint pain, headache, disorientation.
  • High mortality rate if not promptly treated.
• Disseminated Infection:
  • Multiple abscesses in organs such as liver, spleen, prostate, and kidneys.
  • Symptoms: Fever, weight loss, muscle or joint pain, abdominal discomfort.
• Chronic Melioidosis:
  • Mimics tuberculosis with chronic cough, weight loss, and night sweats.
  • Can persist for months to years before diagnosis.

INVESTIGATIONS

• BEDSIDE TESTS:
  • ECG: possible pericardial involvement or septic cardiomyopathy
  • Blood Gas: Assess acid-base status and oxygenation.
  • POCUS: Evaluate for collections and abscesses where relevant
• LABORATORY TESTS:
  • Blood Cultures: detect bacteraemia
  • Sputum Culture: Positive in pulmonary involvement.
  • Urine Culture: Positive in urinary tract involvement.
  • Serology: Detects antibodies against B. pseudomallei (not reliable for diagnosis)
  • PCR: Rapid identification of B. pseudomallei.
  • Swabs (e.g. rectal for prostate involvement) – should use Ashdown’s medium (contains crystal violet and gentamicin) to promote selective growth of B. pseudomallei)
• IMAGING:
  • Chest X-ray (CXR): Consolidation, nodules, or abscesses.
  • CT Scan: Detailed imaging of abscesses in lungs, liver, spleen. Consider imaging of specific sites (e.g. parotids, prostate)
  • Echo: consider if possible pericardial involvement or septic cardiomyopathy

MANAGEMENT

• RESUSCITATION:
  • Coordinated team-based approach to resuscitation in a suitably equipped setting to address the following life threats:
    • Airway compromise: if local infection (e.g. abscess), assess for difficult airway and facilitate safe endotracheal intubation
    • Respiratory failure: treat hypoxia and hypercapnea (e.g. melioidosis pneumonia) with supplemental oxygen, non-invasive ventilation, or intubation and mechanical ventilation as indicated
    • Hypotension and shock: treat septic shock (e.g. IV fluids and vasopressors, and specific therapies below) if present. Consider tamponade if pericardial collection (requires urgent drainage)
• SPECIFIC MANAGEMENT:
  • Initial Intensive Antimicrobial Therapy:
    • Ceftazidime IV 2 g every 6-8 hours for 10-14 days, or
    • Meropenem IV 1 g every 8 hours in severe cases.
  • Subsequent Eradication AntimicrobialTherapy:
    • Trimethoprim-Sulfamethoxazole (TMP-SMX) 160/800 mg orally every 12 hours for 3-6 months.
    • Doxycycline 100 mg orally every 12 hours as an alternative or adjunct.
  • Early source control if abscess or other collection present
  • Consider granulocyte colony-stimulating factor (G-CSF) if admitted to ICU (as per Royal Darwin Hospital protocol)
    • filgrastim 300 microgram IV daily for 10 days or for duration of ICU stay, starting once microbiologically confirmed
    • contraindications: acute coronary syndrome, WBC >50,000 x 10E6/L
• SUPPORTIVE CARE:
  • FASTHUGSINBED please
• SEEK & TREAT COMPLICATIONS:
  • Monitor for and treat complications such as abscess formation, septic shock, and multi-organ failure.
  • See initial management of sepsis
• DISPOSITION:
  • Consult an infectious disease specialist, especially for complex cases.
  • Admit to ICU for severe cases with septic shock or respiratory failure.
  • Step-down to general ward once stabilized.
  • Follow-up with infectious disease and primary care for ongoing management.

PROGNOSIS

• Prognostic Factors:
  • Morbidity: Chronic lung disease, diabetes, heavy alcohol use.
  • Mortality: Septic shock, multi-organ failure.
• Expected Outcomes:
  • Mortality rate: 10-40% depending on severity and promptness of treatment.
  • Chronic infection: 10% of cases.

CONTROVERSIES

• Optimal duration of eradication therapy.
• Role of adjunctive therapies such as immunomodulators.
• Challenges in early diagnosis due to non-specific symptoms.
• Role of G-CSF in the treatment of septic shock due to melioidosis:
  • G-CSF was introduced at the Royal Darwin Hospital in 1998 to treat patients with septic shock due to melioidosis. Observational data suggested a dramatic reduction in mortality from 95% to 10% after the introduction of G-CSF (Cheng et al, 2004).
  • Conducting randomized controlled trials (RCTs) to evaluate G-CSF’s efficacy posed ethical challenges (Cheng et al, 2003). The significant observed benefit made it difficult to justify withholding the treatment from control groups. However, other changes in clinical management, such as improved intensive care management, may have contributed to the observed reduction in mortality, complicating the attribution of benefits solely to G-CSF.
  • A randomized, placebo-controlled trial in Thailand assessed the efficacy of G-CSF in patients with severe sepsis caused by suspected melioidosis. The results did not show a significant benefit, raising questions about the initial observational findings (Cheng et al, 2007).
  • A systematic review and network meta-analysis found a non-significant benefit of ceftazidime plus G-CSF over other treatments for severe melioidosis (Anothaisintawee et al, 2023).

PRACTICAL TIPS

• Maintain high suspicion in patients with risk factors and travel history to endemic areas.
• Early and aggressive treatment is crucial for improving outcomes.
• Regularly monitor for complications and adjust treatment accordingly.
• Educate patients on preventive measures, especially in endemic areas.

CONCLUSION

• Melioidosis is a severe and potentially fatal disease requiring prompt diagnosis and aggressive management.
• Key points:
  • High index of suspicion in at-risk populations.
  • Early initiation of appropriate antibiotics.
  • Comprehensive supportive care and monitoring for complications.
  • Long-term follow-up to prevent relapse.

REFERENCES

• Anothaisintawee T, Harncharoenkul K, Poramathikul K, Phontham K, Boonyarangka P, Kuntawunginn W, Spring M, Boudreaux D, Livezey J, Chantratita N. Efficacy of drug treatment for severe melioidosis and eradication treatment of melioidosis: A systematic review and network meta-analysis. PLoS Negl Trop Dis. 2023 Jun 12;17(6):e0011382. doi: 10.1371/journal.pntd.0011382. PMID: 37307278; PMCID: PMC10289671.
• Cheng AC, Lowe M, Stephens DP, Currie BJ. Ethical problems of evaluating a new treatment for melioidosis. BMJ. 2003 Nov 29;327(7426):1280-2. doi: 10.1136/bmj.327.7426.1280. PMID: 14644975; PMCID: PMC286254.
• Cheng AC, Stephens DP, Anstey NM, Currie BJ. Adjunctive granulocyte colony-stimulating factor for treatment of septic shock due to melioidosis. Clin Infect Dis. 2004 Jan 1;38(1):32-7. doi: 10.1086/380456. Epub 2003 Dec 4. PMID: 14679445.
• Cheng AC, Currie BJ. Melioidosis: epidemiology, pathophysiology, and management. Clin Microbiol Rev. 2005 Apr;18(2):383-416. doi: 10.1128/CMR.18.2.383-416.2005. Erratum in: Clin Microbiol Rev. 2007 Jul;20(3):533. Dosage error in article text. PMID: 15831829; PMCID: PMC1082802.
• Cheng AC, Limmathurotsakul D, Chierakul W, Getchalarat N, Wuthiekanun V, Stephens DP, Day NP, White NJ, Chaowagul W, Currie BJ, Peacock SJ. A randomized controlled trial of granulocyte colony-stimulating factor for the treatment of severe sepsis due to melioidosis in Thailand. Clin Infect Dis. 2007 Aug 1;45(3):308-14. doi: 10.1086/519261. Epub 2007 Jun 15. PMID: 17599307.
• Currie BJ. The 2024 revised Darwin Melioidosis Treatment Guideline. The Northern Territory Disease Control Bulletin 30.4 (2023): 3-12. [pdf]
• Devi KJ, Kalaiarasi R, Sivaraman G, et al. Melioidosis of the Parotid Gland: Lessons Learned from a Fatal Case. Indian J Otolaryngol Head Neck Surg (2024). https://doi.org/10.1007/s12070-024-05191-9
• Gupta N, Malla S, Boodman C, Kumar TP, Varma M, Mukhopadhyay C. Abscesses due to Melioidosis: A case-based review. Curr Res Microb Sci. 2024 Nov 19;8:100321. doi: 10.1016/j.crmicr.2024.100321. PMID: 39664108; PMCID: PMC11629200.
• Limmathurotsakul D, Golding N, Dance DA, Messina JP, Pigott DM, Moyes CL, Rolim DB, Bertherat E, Day NP, Peacock SJ, Hay SI. Predicted global distribution of Burkholderia pseudomallei and burden of melioidosis. Nat Microbiol. 2016 Jan 11;1:15008. doi: 10.1038/nmicrobiol.2015.8. PMID: 27571754.
• CDC. Clinical Overview of Melioidosis. [Accessed 12 Feb 2024]
• Sridharan S, Princess IB, Ramakrishnan N. Melioidosis in Critical Care: A Review. Indian J Crit Care Med. 2021 May;25(Suppl 2):S161-S165. doi: 10.5005/jp-journals-10071-23837. PMID: 34345132; PMCID: PMC8327795
• Verdecia JL, Jankowski CA, Isache CL, Neilsen CD, McCarter YS, Sands ML, Ravi M. A Case Report of Melioidotic Prostatic Abscess in a Traveler. Open Forum Infect Dis. 2022 Jul 4;9(7):ofac284. doi: 10.1093/ofid/ofac284. PMID: 35891686; PMCID: PMC9308449.
• Yartsev, D. Meliodiosis. DerangedPhysiology.com. [Accessed 12 Feb 2024]
• Wiersinga WJ, Virk HS, Torres AG, Currie BJ, Peacock SJ, Dance DAB, Limmathurotsakul D. Melioidosis. Nat Rev Dis Primers. 2018 Feb 1;4:17107. doi: 10.1038/nrdp.2017.107. PMID: 29388572; PMCID: PMC6456913.

LITFL links

• Cadogan M. Melioidosis a disease of surprises (2020)
• Cadogan M. Melioidosis – Lab without walls (2020)