Melioidosis: the great mimicker presenting as spondylodiscitis

Abstract

Melioidosis, a syndrome with protean clinical manifestations, is caused by Gram-negative soil saprophyte Burkholderiapseudomallei. Among its diverse clinical presentations, the involvement of spine is a rare phenomenon and can mimic tuberculosis on presentation. A 65-year-old female with a known case of diabetes presented with fever with lower back pain. Blood culture grew Staphylococcus aureus, and as per sensitivity report, clindamycin and cefazolin were started. X-ray and MRI lumbosacral spine showed spondylodiscitis (likely Koch’s). Decompression and biopsy were done, and a sample was sent for microbiological investigations that showed no growth of any significant pathogen; furthermore, all tests for tuberculosis diagnosis also remained negative. Active Melioidosis Detect Lateral Flow Assay was used on the tissue sample, which was positive for B. pseudomallei Capsular Polysaccharide (CPS) antigen; the case was confirmed by typethree secretion system 1 PCR for melioidosis. Antibiotics were changed to parenteral ceftazidime for 2 weeks followed by oral cotrimoxazole. A dedicated team of microbiologists and physicians is required to identify and treat the disease.

Background

Melioidosis caused by Gram-negative intracellular pathogen Burkholderia pseudomallei encompasses varied clinical manifestations ranging from suppurative localised skin infection to fatal septicaemia.¹ While the disease is known to be highly endemic in Thailand and Northern Australia, the recent evidence of the upsurge in the number of cases in published literature suggests the possibility of melioidosis to be endemic in South Asian countries such as India, Sri Lanka and Bangladesh.^2–4 Although the clinical presentation of the disease is very diverse, melioidotic spondylodiscitis is one of the rarest manifestations.^{5 6} We present a case of melioidotic spondylodiscitis with an aim to outline the presentation of melioidosis related to the spine and create awareness among healthcare practitioners to consider melioidosis as an important differential diagnosis in such type of presentations. The presentation was similar to tuberculosis as suggested by histopathological examination initially, which might have led to inappropriate treatment unless diagnosed accurately in microbiology setup. These types of unique cases remain undiagnosed, most often due to lack of expertise and laboratory infrastructure and need to be highlighted to create awareness.

Case presentation

A 65-year-old female from southern part of Karnataka, housewife by occupation, was admitted with fever and lower back pain, which led to difficulty in sitting in the past 5 days. She has a known case of type 2 diabetes mellitus in the past 5 years. Continuous fever of 101°F/38.3°C with no diurnal variation was not relieved with antipyretics. Lower back pain was sudden in onset, progressive in nature and radiating to left hip leading to difficulty in sitting and walking. There was no history of a cough, expectoration or haemoptysis.

On local examination of the lower back, tenderness was present over L5-S1 spine with associated paravertebral spasm and bilateral planter flexor with no ankle clonus. The sensation was intact with power 4+/5 and reflexes 1+. Perirectal examination showed normal superficial and deep anal sensation without laxity in muscle tone. There was no associated lymphadenopathy.

Investigations

On admission to a secondary care hospital, the initial haematological workup showed Erythrocyte Sedimentation Rate (ESR) as 70 mm/hour, C reactive protein as 81.5 mg/L and total white cell count count as 12 000/µL with an absolute neutrophil count of 8700/µL. Furthermore, HbA1c of 12.7% and random blood sugar of 231 mg/dL suggest the long-standing undiagnosed diabetic status of the patient. All other routine blood tests were normal. X-ray lumbar spine and MRI lumbosacral spine was done, which showed spondylodiscitis (likely Koch’s) involving L3, L5 and S1 vertebral bodies and L4-L5 and L5-S1 discs with anterior epidural and prevertebral and paravertebral collections (figure 1). As the blood was collected for culture on day 1, it showed the growth of methicillin-sensitive Staphylococcus aureus (MSSA) in both the bottles. The empirical treatment with cefoperazone-sulbactum injection was changed to clindamycin and cefazolin as per the sensitivity report. In view of persistent lower back pain, the patient was referred to our tertiary care hospital for orthopaedic consultation.

Figure 1.

MRI lumbosacral spine showing spondylodiscitis involving L3, L5 and S1 vertebral bodies and L4-L5 and L5-S1 discs with anterior epidural and prevertebral and paravertebral collections.

In our setting, decompression was done, and the biopsy specimen was sent for histopathological and microbiological investigations. Histopathology report was consistent with spondylodiscitis as it showed fragments of degenerated cartilage with loss of basophilia, and fibrillation along with adjacent fibrocollagenous stroma and dense neutrophilic infiltrate focally extending into cartilage. Gram stain of the biopsy specimen showed moderate pus cells without any evidence of bacteria. Disc material and soft tissue were negative for Gene Xpert (Cepheid) and PCR (IS6110) for Mycobacterium tuberculosis. There was no evidence of MSSA bacteraemia in repeat culture, and the patient was discharged in stable condition with oral cotrimoxazole for 6 weeks. However, the patient revisited the Out Patient Deaprtment after 7 days as her back pain did recur, and now, she had difficulty walking also. There was pus discharge from the wound over surgical site as well. The patient was readmitted for further investigation.

On second admission in our setting, debridement and laminectomy were done, and vancomycin dipped gel foam was applied. Tissue was sent to the bacterial culture that showed no growth. Furthermore, AMD LFA (Active Melioidosis Detect Lateral Flow Assay, InBios International, Seattle, Washington, USA) for melioidosis was used on the pus sample, which gave a positive band.⁷ The final confirmation was made by performing type three secretion system 1 (TTSS1) PCR for B. pseudomallei.⁸

Differential diagnosis

Melioidosis should be suspected in patients presenting with spondylodiscitis with paravertebral and prevertebral collection apart from tuberculosis, especially in patients with associated risk factors.

Treatment

Antibiotics were changed to parenteral ceftazidime (2 g every 8 hours intravenously) as intensive phase for 2 weeks. On completion, her clinical condition improved, and she was discharged on oral cotrimoxazole (32/1600; ie, two double strength tablets) for 14 weeks. It is a well-established fact that B. pseudomallei is intrinsically resistant to a wide range of antibiotics. According to Centers for Disease Control and Prevention guidelines, the treatment regimen includes an intravenous antimicrobial therapy of meropenem or ceftazidime for 14 days followed by 3–6 months of oral antibiotics consisting of cotrimoxazole or doxycycline (https://www.cdc.gov/melioidosis/treatment/index.html). Ceftazidime and cotrimoxazole are the drugs of choice in the resource-poor countries like India due to its overall availability and affordability. The susceptibility of the organism against these two drugs can be tested in vitro (CLSI M-45) for positive cultures.

Outcome and follow-up

Her diabetic status was under control. The patient was followed at regular intervals with complete blood count and renal and liver function tests. Repeat X-ray lumbar spine had not shown any evidence of local or distant recurrence of the disease.

Discussion

Melioidosis is a disease comprising diverse clinical presentations. Transmission of B. pseudomallei occurs primarily through percutaneous inoculation, inhalation/aspiration and very less commonly ingestion. Haematogenous spread from the site of inoculation via the vascular or lumbar venous plexus is considered to be the most common route of transmission in bone and joint infection.^9–11 In the present case, it could be a possibility that the pathogen seeded into the spine after spreading through haematogenous route from the site of inoculation.

Patients with underlying risk factors and exposure to soil are prone to infection. This patient was a housewife performing the gardening activity at her house and was also a patient of long-standing diabetes, which was uncontrolled. There are evidence that exposure of soil with B. pseudomallei in endemic region may give rise to infection by inoculation and long-standing diabetes in patients with reduced immunity are prone to have infection.¹ In absence of any other positive microbiological findings and presence of the aforementioned risk factors, melioidosis was suspected in the patient.

A review of the similar presentation of melioidosis in India showed that all the patients were male and the majority were in the fifth decade of their life (table 1). Spondylodiscitis is more common in men with increased age being one of the predisposing factors. All the cases were chronic and suspected to be tuberculosis initially based on radiological and histopathological findings. The lumbar region is the most common site involved. All the patients grew B. pseudomallei from drained pus or aspirate from the infected site and were cured following specific therapy. Our case is a 65-year-old female patient with long-standing uncontrolled diabetes mellitus as a major risk factor for melioidosis. Spondylodiscitis with paravertebral and prevertebral collection was suspected to be tuberculosis based on radiological findings only, since there was no microbiological evidence. In India, most of these cases, if not all, are treated as tuberculosis and designated as ‘smear-negative tuberculosis’. However, the outcome is invariably not satisfactory. The patient was treated with oral cotrimoxazole for some duration. It is not sure if this could be the possible reason for the failure of growth in culture for B. pseudomallei. Such cases can be easily missed due to lack of awareness and may lead to reactivation of the infection from latent foci in absence of correct treatment with appropriate antibiotics at right dosage and duration.

Table 1.

Review of cases reported

Case	Country	Age/gender	Risk factors	Clinical presentation	Duration	Location	Clinical suspicion	Initial treatment	Final diagnosis	Final treatment	Outcome
Tungsanga et al16	Thailand	57/male	Controlled diabetes mellitus, chronic alcoholism	Chronic low back pain for 1 year and intermittent fever, psoas abscess	1 year	T12/L1	Tubercular spondylodiscitis	Isoniazid, rifampin, ethambutol and pyrazinamide	Drainage from psoas abscess grew Burkholderia pseudomallei	Cotrimoxazole (15 mg/kg/day of trimethoprim) and intravenous ceftazidime (120 mg/kg/day) for 18 days followed by oral cotrimoxazole for 6 months	Cured
Arockiaraj et al17	India	58/male	Uncontrolled diabetes mellitus	Low back pain, discharging sinus, multiple subcutaneous abscesses around 11th and 12th rib.	6 months	L3	Tubercular spondylodiscitis	ATT	Aspirate from local subcutaneous abscess grew B. pseudomallei	Ceftazidime (2 g every 8 hours for 2 weeks) followed by cotrimoxazole
		58/male	Uncontrolled diabetes mellitus	Mid and low backache, psoas abscess, splenic abscess	8 months	D12, L1		ATT	Ultrasound-guided drainage of the abscess send to culture grew B. pseudomallei	Ceftazidime (2 g every 8 hours for 2 weeks) followed by cotrimoxazole
		65/male	Uncontrolled diabetes mellitus	A low backache	7 months	L5, S1	Tuberculosis	ATT	CT-guided biopsy of the lesion was sent to culture that grew B. pseudomallei	Ceftazidime (2 g every 8 hours for 2 weeks) followed by cotrimoxazole
		58/male	Uncontrolled diabetes mellitus	A low backache and swelling in the lower back	2 years	S3	Tuberculosis	ATT	Ultrasound-guided drainage of psoas abscess	Ceftazidime (2 g every 8 hours for 2 weeks) followed by cotrimoxazole
Vidyalakshmi etal12	India	41/male	None	Chronic spondylitis, psoas abscess	6 months		Tuberculosis	ATT	Ultrasound-guided abscess drainage grew B. pseudomallei	Ceftazidime (40 mg/kg) intravenous every 8 hours (14 days) followed by cotrimoxazole (10 mg and 50 mg/kg/day)	cured

ATT, antitubercular treatment.

B. pseudomallei being an intracellular pathogen can well mimic M. tuberculosis in case of chronic suppurative infection affecting various tissues including the bone and joint.¹² Host response in both the infection are similar and dominated by interferon signalling that may produce similar clinical manifestations. The routine laboratory findings were also not conclusive to rule out tuberculosis as the ESR rate was high and the patient had intermittent fever. PCR has an upper hand in detecting B. pseudomallei from clinical samples when compared with conventional culture techniques that have low sensitivity (60%). The negative predictive value of culture was also reported to be less suggestive as it poses to be an imperfect gold standard for diagnosing melioidosis.¹³ Hence, a rapid and accurate point of care diagnostic assay is a prime requisite. The advent of AMD LFA has brought a new avenue for early detection of B. pseudomallei antigen directly from the patient’s sample.¹⁴ The test can be helpful for presumptive diagnosis of the disease and institution of an early specific therapy. In view of its rapidity and ease of testing, the assay can be used for screening melioidosis among patients with high clinical suspicion, especially in those from endemic areas, where standard laboratory facilities are not available.

In a country like India where tuberculosis is endemic, misdiagnosis or underdiagnosis of melioidosis can be a common consequence. With increasing number of cases being reported from different parts of the country, it is evident that the disease is highly endemic.^{4 15} Only early suspicion and prompt diagnosis may avoid fatal consequences of the disease. Rapid point of care diagnostic assays are required to strengthen the microbiological facilities in the resource-poor settings.

Learning points.

• It is a well-established fact that India is endemic for melioidosis, but there are very few centres that have suitable diagnostic facilities to detect the cases.

• High clinical suspicion and microbiological expertise are essential for early detection of disease.

• Infection can go unrecognised if culture is used as a gold standard; rapid and accurate diagnostic POC assays such as the Active Melioidosis Detect Lateral Flow Assay can be a substitute for culture in early screening in resource-poor settings.