Case of melioidosis misdiagnosed as pulmonary tuberculosis

Abstract

Melioidosis is an endemic infection caused by Burkholderia pseudomallei predominantly reported in the coastal parts of India. A 19-year-old male student with no comorbidities presented with features suggestive of pneumonia. He was initiated on antitubercular treatment empirically elsewhere. However, due to lack of response to therapy diagnosis was revisited. Microbiological investigations were unyielding initially. Despite antitubercular treatment, he presented with complications of pneumonia and was diagnosed to have melioidosis. He was initiated on appropriate antibiotics for the intensive and eradication phase. Obtaining microbiological confirmation is of utmost importance to prevent misdiagnosis and undue morbidity and mortality due to these uncommon infections.

Background

Melioidosis is an emerging infection of prime importance in tropical countries, particularly in South East Asia. The infection has a variable spectrum of severity ranging from asymptomatic seroconversion to pneumonia and fatal septicaemia. It is often misdiagnosed in tuberculosis endemic countries like India due to the semblance of its clinical presentation to the latter, including the well-recognised latency and reactivation. Apart from this, the diagnosis may also be delayed or missed due to unawareness among clinicians, particularly in non-endemic regions. Early diagnosis and initiation of appropriate antibiotics are crucial in the management of critically ill patients to reduce mortality. We report a case of melioidosis in an immunocompetent patient from a tuberculosis endemic region.

Case presentation

A 19-year-old male student with no known comorbid illnesses had presented to a primary care centre with a 1-month history of intermittent, high-grade fever, cough with scanty mucoid expectoration and progressive dyspnoea. There was no history of chest pain, haemoptysis, constitutional symptoms or recent travel. He was a non-smoker and never consumed alcohol.

He had been started on antitubercular treatment (ATT) based on the above clinical picture and suggestive radiological findings. As there was no symptomatic or radiological improvement after 5 months of ATT, he was referred to our centre for further evaluation.

On examination, heart rate was 120 beats/min, respiratory rate was 30 breaths/min with a blood pressure of 128/70 mm Hg, and oxygen saturation of 97% on room air. Bilateral crepitations were heard with decreased intensity of breath sounds in the left haemithorax.

Investigations

Blood investigations revealed neutrophilic leucocytosis (19.64 x 10⁹/L with 92% neutrophils). HIV serology was negative. Chest radiograph showed bilateral inhomogeneous opacities with cavities in the left upper and mid-zone with left-sided pleural effusion (figure 1A). Thoracic ultrasound showed left-sided moderate pleural effusion with internal septations. On diagnostic pleurocentesis, pus was aspirated. The patient was initiated on broad-spectrum antibiotics (piperacillin/tazobactam) and an intercostal drain was inserted which resulted in partial re-expansion of the lung with persistent air leak. Microbiological examination of the sputum and pleural fluid was negative for AFB (Acid Fast Bacilli) and CBNAAT (Cartridge Based Nucleic Acid Amplification Test) by GeneXpert MTB/RIF assay (Cepheid, USA). CT of the chest showed bilateral upper lobe cavities with left lower lobe necrotising consolidation with loculated pneumothorax (figure 1C, D). The patient underwent a flexible bronchoscopy and bronchoalveolar lavage fluid was sent for infection (aerobic culture and sensitivity, AFB stain, CBNAAT and fungal cultures) and malignancy workup which was unremarkable. He was discharged with an intercostal drain tube in situ and advised to be on regular follow-up.

Figure 1.

Radiology: (A) chest radiograph showing consolidation in right and left midzone with cavitation in the left mid and lower zone, intercostal drain in situ on the left side; (B) chest radiograph after 3 months showing near-complete radiological resolution. (C, D) Chest CT showing bilateral upper lobe cavities with left lower lobe cavitating consolidation with loculated pneumothorax.

One week later, the patient presented to the emergency department with worsening dyspnoea and fever. On examination, pulse rate was 130 beats/min, blood pressure was 80 mm Hg systolic with a saturation of 70% on room air. He was intubated, initiated on mechanical ventilation, broad-spectrum antibiotics (meropenem) and vasopressors. Chest radiograph showed persistent consolidation and left pneumothorax.

As the patient was worsening on ATT, the diagnosis was revisited to look for alternative causes of chronic lung infection. Endotracheal aspirate and pleural fluid were sent for cultures again which showed growth of Gram-negative bacilli with safety pin appearance and wrinkled colonies on MacConkey agar and Ashdown media produced haemolysis on 5% sheep blood agar plate suggestive of Burkholderia pseudomallei (figure 2A–D). The isolate was oxidase positive (figure 3A) motile, reduced nitrate to nitrite, dihydrolysed arginine (figure 3B), and resistant to polymyxin B 300 and gentamicin (figure 3C) thus preliminarily identified as B. pseudomallei. The identification was confirmed using the automated Vitek 2 system (Biomerieux, USA) giving a probability score of 95% (confidence level stated as very good identification).

Figure 2.

Microbiology: (A) microscopic ‘safety pin’ appearance of the Gram-negative bacilli on Gram’s stain (100 X oil immersion); (B) Dry wrinkled colonies on Ashdown Agar; (C) non-lactose fermenting colonies on MacConkey agar; (D) haemolysis on 5% sheep blood agar.

Figure 3.

Microbiology (A) purple colour change of the test organism inoculum on the dry oxidase paper along with control spots shows a positive oxidase test; (B) amino acid utilisation test with lysine, ornithine, and arginine along with the control tube showing deep purple colour in the tube with arginine indicating dihydrolysis and red colour in the last tube indicating positive nitrate reduction test; (C) Mueller-Hinton agar plate with lawn culture of the organism showing resistance to polymyxin B 300 and gentamicin discs.

Treatment

A diagnosis of melioidosis was made and he was continued on intravenous meropenem after which the patient gradually improved and was extubated after 4 days of mechanical ventilation. The intercostal drain was removed once the air leak ceased. After 2 weeks of meropenem, he was switched to oral cotrimoxazole which was continued for 3 months.

Outcome and follow-up

On follow-up at 3 months, he had complete symptomatic relief with chest radiograph showing resolution of alveolar opacities with persistent thin-walled cavities in the left upper and midzone (figure 1B).

Discussion

Melioidosis is caused by Gram-negative bacteria, Bu. pseudomallei which is an environmental saprophyte found in stagnant water, wet soil and rice paddy fields. It is an emerging infection with endemicity in northern Australia and Southeast Asia.¹ Sporadic cases have been reported from India and the geographic distribution of the disease is expanding probably due to increased global movement. Though the exact prevalence remains unknown, multiple case series have been reported from India.² The presence of a conducive environment with a predominantly rural population and the burgeoning epidemic of diabetes mellitus has led to the postulation that the estimated prevalence is much higher than is being reported.³ Besides, gross under-reporting could be attributed to a lack of awareness and laboratory facilities required to confirm the diagnosis.

The predominant route of infection in humans includes percutaneous inoculation of open wounds in contact with infected water or soil. Ingestion of contaminated potable water has also led to outbreaks.⁴ During extreme weather conditions like cyclones, heavy rainfall and tsunami, there may be a shift to inhalation as the principal route of infection causing pneumonic and septicaemic illness.⁵ The presence of diabetes mellitus, alcohol abuse, chronic lung diseases, chronic kidney disease, malignancy and immunosuppression are recognised underlying risk factors for infection.⁶ Given the ease of dissemination and the associated high mortality, melioidosis is being perceived as a potential weapon for biological warfare.⁷

Once infected, the clinical manifestation ranges from subclinical disease with asymptomatic seroconversion and localised cutaneous lesions to life-threatening pneumonia and sepsis, based on the underlying risk factors and route of infection.⁸ While acute presentation with pneumonia and sepsis carries a high mortality rate, the chronic form of this disease presents with non-healing ulcers and pulmonary involvement mimicking tuberculosis. The similarities with tuberculosis include clinical features of fever, cough with or without haemoptysis, weight loss, radiological presence of upper lobe predominant cavitating infiltrates and possible latent infection with reactivation and acute deterioration with septicaemia.⁸ With all the above features, it comes as no surprise that many cases are misdiagnosed especially in tuberculosis endemic countries like India.⁹

Pneumonia is the most common presenting feature in both acute and chronic disease forms.^{2 6} Radiological features include upper lobe or extensive unilateral consolidation and diffuse bilateral nodular infiltrates that may coalesce and cavitate.⁸ Other presentations include cutaneous ulcers and abscesses, encephalomyelitis with predominant brainstem involvement, septic arthritis, osteomyelitis and abscesses in kidneys, liver, prostate and parotids. Hence abdominal imaging is advised routinely in patients with melioidosis to rule out occult abscesses.

The diagnosis of melioidosis is confirmed by isolating the organism on culture. Gram-negative bacilli with characteristic bipolar staining yield the ‘safety pin’ appearance owing to the presence of a vacuole in the centre of the cell. Cultures show dry wrinkled colonies on MacConkey and Ashdown media. Identification in the lab is challenging due to many oxidase-positive non-fermenters resembling B. pseudomallei often isolated from respiratory samples. Adding to this, the organism grows slowly sometimes taking >72 hours, and also might be scanty.¹⁰ Manual biochemical methods along with the use of automated systems such as the Vitek 2 system giving a high probability score helps in final identification in labs where molecular tests are not done routinely.¹¹ Diagnosing melioidosis assumes importance since the organism is resistant to many of the routinely used antibiotics and requires a longer duration of therapy. B. pseudomallei is intrinsically resistant to antibiotics like penicillin, ampicillin, first-generation and second-generation cephalosporins, macrolides, few aminoglycosides and polymyxins.⁸

Treatment of melioidosis is in two phases—initial intensive phase and subsequent eradication phase.¹² The intensive phase is usually with intravenous ceftazidime (2 g, 6 hourly) or meropenem (1 g, 8 hourly) given for 2 weeks with longer duration (4–8 weeks) required for more extensive disease, internal organ abscesses, osteomyelitis and central nervous system infections.¹³ Meropenem is the preferred agent in septicaemic patients owing to better results compared with ceftazidime. This is followed by the eradication phase to prevent relapse and is usually achieved by administering trimethoprim–sulfamethoxazole (240+1200 mg, 12 hourly) for 3 months. Alternative agents include amoxicillin–clavulanate or doxycycline.⁸

Our patient was unique since he had no specific risk factors predisposing him to melioidosis, he did not recall exposure to either infected soil or water and was misdiagnosed as tuberculosis given the clinico-radiological profile. However, the clinical and radiological worsening despite ATT triggered repeated sampling of the tracheobronchial tree. This, coupled with the timely identification of the organism helped clinch the diagnosis, initiate appropriate treatment and avoid mortality.

Learning points.

• Our case highlights the importance of having a high index of suspicion even in non-endemic areas and in patients with no underlying risk factors.

• The importance of liaison with microbiologists in obtaining the diagnosis cannot be overemphasised.

• In patients with acute septicaemia and chronic infections alike, lack of adequate response to traditional therapy should prompt revisiting the diagnosis.