Bone and joint infections due to melioidosis; diagnostic and management strategies to optimise outcomes.

BACKGROUND: Melioidosis, a life-threatening infection caused by the gram negative bacterium Burkholderia pseudomallei, can involve almost any organ. Bone and joint infections (BJI) are a recognised, but incompletely defined, manifestation of melioidosis that are associated with significant morbidity and mortality in resource-limited settings. METHODOLOGY/PRINCIPAL FINDINGS: We identified all individuals with BJI due to B. pseudomallei managed at Cairns Hospital in tropical Australia between January 1998 and June 2023. The patients' demographics, their clinical findings and their treatment were correlated with their subsequent course. Of 477 culture-confirmed cases of melioidosis managed at the hospital during the study period, 39 (8%) had confirmed BJI; predisposing risk factors for melioidosis were present in 37/39 (95%). However, in multivariable analysis only diabetes mellitus was independently associated with the presence of BJI (odds ratio (95% confidence interval): 4.04 (1.81-9.00), p = 0.001). BJI was frequently only one component of multi-organ involvement: 29/39 (74%) had infection involving other organs and bacteraemia was present in 31/39 (79%). Of the 39 individuals with BJI, 14 (36%) had osteomyelitis, 8 (20%) had septic arthritis and 17 (44%) had both osteomyelitis and septic arthritis; in 32/39 (83%) the lower limb was involved. Surgery was performed in 30/39 (77%). Readmission after the initial hospitalisation was necessary in 11/39 (28%), 5/39 (13%) had disease recrudescence and 3/39 (8%) had relapse; 4/39 (10%) developed pathological fractures. ICU admission was necessary in 11/39 (28%) but all 11 of these patients survived. Only 1/39 (3%) died, 138 days after admission, due to his significant underlying comorbidity. CONCLUSIONS: The case-fatality rate from melioidosis BJI in Australia's well-resourced health system is very low. However, recrudescence, relapse and orthopaedic complications are relatively common and emphasise the importance of collaborative multidisciplinary care that includes early surgical review, aggressive source control, prolonged antibiotic therapy, and thorough, extended follow-up.

A case of pulmonary melioidosis in Germany: a rare differential diagnosis in returning travelers from South-East Asia.

BACKGROUND: Melioidosis is a bacterial infection associated with high mortality. The diagnostic approach to this rare disease in Europe is challenging, especially because pulmonary manifestation of melioidosis can mimic pulmonary tuberculosis (TB). Antibiotic therapy of melioidosis consists of an initial intensive phase of 2-8 weeks followed by an eradication therapy of 3-6 months. CASE PRESENTATION: We present the case of a 46-year-old female patient with pulmonary melioidosis in Germany. The patient showed chronic cough, a pulmonary mass and a cavitary lesion, which led to the initial suspicion of pulmonary TB. Melioidosis was considered due to a long-term stay in Thailand with recurrent exposure to rice fields. RESULTS: Microbiologic results were negative for TB. Histopathology of an endobronchial tumor showed marked chronic granulation tissue and fibrinous inflammation. Melioidosis was diagnosed via polymerase chain reaction by detection of Burkholderia pseudomallei/mallei target from mediastinal lymph-node tissue. CONCLUSION: This case report emphasizes that melioidosis is an important differential diagnosis in patients with suspected pulmonary tuberculosis and recent travel to South-East Asia.

Melioidosis masquerading as malignancy in tropical Australia; lessons for clinicians and implications for clinical management.

Melioidosis is a life-threatening, emerging infectious disease caused by the environmental bacterium Burkholderia pseudomallei. Melioidosis is hyperendemic in tropical Australia and southeast Asia, however the disease is increasingly encountered beyond these regions. Early diagnosis is essential as the infection has a case-fatality rate of up to 50 %. Melioidosis most commonly involves the lungs, although almost any organ can be affected. Most patients present acutely but an insidious presentation over weeks to months is also well described. We present a case series of 7 patients from tropical Australia whom local clinicians initially believed to have cancer ‒ most commonly lung cancer ‒ only for further investigation to establish a diagnosis of melioidosis. All 7 patients had comorbidities that predisposed them to developing melioidosis and all survived, but their delayed diagnosis resulted in 3 receiving anti-cancer therapies that resulted in significant morbidity. The study emphasises the importance of thorough diagnostic evaluation and repeated collection of microbiological samples. It is hoped that our experience will encourage other clinicians ‒ in the appropriate clinical context ‒ to consider melioidosis as a potential explanation for a patient's presentation, expediting its diagnosis and the initiation of potentially life-saving therapy.

Nasopharyngeal melioidosis: a case report.

A 12-year-old boy was admitted after 11 days of fever and 2 days of nasal obstruction as well as swelling of a right cervical lymph node. Nasal endoscopy and computed tomography of the neck showed a nasopharyngeal mass occupying the entire nasopharynx, extending into the nasal cavity, and obliterating the fossa of Rosenmuller. Abdominal ultrasonography revealed a small solitary splenic abscess. Although a nasopharyngeal tumor or malignancy was initially considered, biopsy of the mass showed only suppurative granulomatous inflammation, and bacterial culture from the enlarged cervical lymph node yielded Burkholderia pseudomallei. The symptoms, nasopharyngeal mass, and cervical lymph node enlargement resolved with melioidosis-directed antibiotic therapy. Although rarely reported, the nasopharynx may be an important primary site of infection in melioidosis patients, especially in pediatric patients.

Coinfection of Melioidosis and Tuberculosis Causing Infective Lumbar Spondylodiscitis: A Rare Case Report.

CASE: A 63-year-old farmer who is a known diabetic and chronic alcoholic presented with lower back pain and neurological weakness of lower limbs present for the past 3 months. His acute phase reactants were very high, and magnetic resonance imaging displayed L4-L5 vertebral involvement with epidural, paravertebral, and bilateral psoas abscesses. Cultures of an ultrasound-guided aspiration from the psoas were positive for Burkholderia pseudomallei, and a nucleic acid amplification test also detected Mycobacterium tuberculosis. He underwent posterior decompression and fixation, and intraoperative biopsy confirmed a granulomatous reaction. He received appropriate antibiotics for both diseases. At 1 year, he showed healing on radiographic imaging, with independent ambulation status. CONCLUSION: The coexistence of melioidosis and tuberculosis is rare, and as far as we know, a case of infective spondylodiscitis has not been reported. In patients with infective spondylodiscitis, every attempt should be made to confirm the diagnosis before starting empirical antitubercular treatment (ATT).

Travel-associated melioidosis: a narrative review.

BACKGROUND: Melioidosis, caused by Burkholderia pseudomallei, may be considered a neglected tropical disease that remains underdiagnosed in many geographical areas. Travellers can act as the sentinels of disease activity, and data from imported cases may help complete the global map of melioidosis. METHODS: A literature search for imported melioidosis for the period 2016-22 was performed in PubMed and Google Scholar. RESULTS: In total, 137 reports of melioidosis associated with travel were identified. The majority were males (71%) and associated with exposure in Asia (77%) (mainly Thailand, 41%, and India, 9%). A minority acquired the infection in the Americas-Caribbean area (6%), Africa (5%) and Oceania (2%). The most frequent comorbidity was diabetes mellitus (25%) followed by underlying pulmonary, liver or renal disease (8, 5 and 3%, respectively). Alcohol/tobacco use were noted for seven and six patients, respectively (5%). Five patients (4%) had associated non-human immunodeficiency virus (HIV)-related immunosuppression, and three patients (2%) had HIV infection. One patient (0.8%) had concomitant coronavirus disease 19. A proportion (27%) had no underlying diseases. The most frequent clinical presentations included pneumonia (35%), sepsis (30%) and skin/soft tissue infections (14%). Most developed symptoms <1 week after return (55%), and 29% developed symptoms >12 weeks after. Ceftazidime and meropenem were the main treatments used during the intensive intravenous phase (52 and 41% of patients, respectively) and the majority (82%) received co-trimoxazole alone/combination, for the eradication phase. Most patients had a favourable outcome/survived (87%). The search also retrieved cases in imported animals or cases secondary to imported commercial products. CONCLUSIONS: As post-pandemic travel soars, health professionals should be aware of the possibility of imported melioidosis with its diverse presentations. Currently, no licensed vaccine is available, so prevention in travellers should focus on protective measures (avoiding contact with soil/stagnant water in endemic areas). Biological samples from suspected cases require processing in biosafety level 3 facilities.

Case Report: Burkholderia pseudomallei-Caused Sclerokeratitis.

This report is on a 45-year-old male patient without underlying disease who presented with a Burkholderia pseudomallei-caused keratoscleritis in his right eye. Slit-lamp examination revealed multiple, indistinct corneal infiltrations with subconjunctival/scleral abscesses. Corneal tissue culture was positive for B. pseudomallei and confirmed by mass spectrometry. The patient was treated with fortified ceftazidime, fortified gentamicin eyedrops, and intravenous ceftazidime injection. Penetrating keratoplasty, including intracameral ceftazidime injections, was undertaken due to corneal lesion worsening. Scleral debridement with subconjunctival ceftazidime injections were undertaken due to the progression of the scleral abscess. After 2 months, the corneal and scleral lesions were inactive, and the systemic and topical antibiotics were tapered. This is the first case report of B. pseudomallei-caused keratoscleritis with photography. The patient was seen in an endemic geographical area with multiple corneal infiltrations and subconjunctival/scleral abscess. Systemic and topical antibiotics accompanied with surgery should be considered.

A rare case of melioidosis presenting as myositis in Sri Lanka.

BACKGROUND: Melioidosis caused by Burkholderia pseudomallei is an emerging infection in Sri Lanka with a high case fatality rate. The disease usually manifests as pneumonia, however multisystem involvement is common. Myositis is an extremely rare occurrence and this is the only documented case where the initial presentation of melioidosis has been myositis and later complicated to myonecrosis. CASE PRESENTATION: A 45-year-old gentleman with pre-existing diabetes presented with a tender, right thigh lump for 1 week duration without any history of trauma or infection. Investigations revealed neutrophil leukocytosis, high erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels whilst ultrasonography showed focal myositis of right quadriceps. The patient went into sepsis amidst antibacterial treatment which warranted urgent surgery. At surgery, a large intramuscular abscess with myonecrosis was observed within vastus medialis which was completely drained and pus was taken for culture which eventually isolated Burkholderia pseudomallei. Melioidosis was diagnosed and intravenous meropenem was prescribed for 3 weeks. Following complete recovery, the patient was discharged on doxycycline and trimethoprim sulfamethoxazole for 3 months. CONCLUSIONS: Melioidosis, an endemic disease in south east Asia and northern Australia, is an emerging infection in Sri Lanka. Myositis is a rare presentation of the disease that can lead to myonecrosis and abscess formation which can cause rapid disease escalation and sepsis. Early surgical intervention may be life-saving in such cases where antibiotic therapy alone may not suffice.

CNS Melioidosis: A Diagnostic Challenge.

Melioidosis is an emerging tropical disease. Central nervous system (CNS) melioidosis may present as a brain abscess or encephalomyelitis mimics tuberculosis. Early diagnosis and management decreases mortality as well as morbidity. This case of brain abscess and encephalomyelitis in a young man with no known comorbidities was a diagnostic challenge. The surgery helped in debulking as well as isolating the causative organism. Appropriate antibiotic therapy for melioidosis was lifesaving and prevented further complications.

Melioidosis con endocarditis de válvula protésica / Prosthetic valve endocarditis in melioidosis: case report

Resumen La melioidosis es endémica en varias regiones, con predominio en el Sudeste Asiático, norte de Australia, sur de Asia, China y Taiwán. En Sudamérica, Colombia ocupa el segundo lugar de casos de melioidosis, después de Brasil. Su manifestación clínica es variable, desde una infección asintomática hasta un compromiso multiorgánico con formación de abscesos múltiples y choque séptico. El compromiso cardiaco es inusual, con una incidencia menor del 1%. Se presenta el caso de un varón de 51 años, colombiano, con antecedente de una valvula aórtica mecánica, quien presentó un absceso en la pierna derecha y en la válvula cardiaca protésica, aislándose Burkholderia pseudomallei en hemocultivos y en el cultivo de secreción de la pierna. Fue tratado con meropenem y cotrimoxazol, con una adecuada respuesta clínica, requiriendo un reemplazo valvular aórtico.

Abstract Melioidosis is an endemic disease to several regions and occurs predominantly in Southern Asia, Northern Australia, China and Taiwan. In South America, Colombia is second after Brazil in number of melioidosis cases reported. Clinical manifestation varies from asymptomatic infection to multiorgan compromise involving multiple abscesses and septic shock. Cardiac compromise is infrequent, with an incidence of <1%. We report the case of a 51-year-old patient from Colombia with a mechanical aortic valve who had an abscess in right leg and in the prosthetic valve. Burkholderia pseudomallei was isolated in blood cultures and drained pus from the leg cultures. Patient was treated with meropenem and cotrimoxazole and required aortic valve replacement, resulting in adequate improvement in clinical symptoms.

Fine-needle aspiration to improve diagnosis of melioidosis of the head and neck in children: a study from Sarawak, Malaysia.

BACKGROUND: Melioidosis, the infection caused by Burkholderia pseudomallei, is associated with a high case fatality rate, due in part to difficulties in clinical recognition and diagnostic confirmation of the disease. Although head and neck involvement is common in children, specific disease manifestations differ between geographic regions. The aim of this study was to provide a detailed description of melioidosis of the head and neck among children in Sarawak, Malaysia, and determine if fine-needle aspiration of suspected head or neck lesions could improve melioidosis diagnosis. METHODS: We conducted a retrospective descriptive study of all children aged < 12 years with culture-confirmed melioidosis presenting with head and neck manifestations and admitted to Bintulu Hospital in Sarawak, Malaysia, from January 2011 until December 2020. Fine-needle aspiration of head and neck lesions suspected to be due to melioidosis with inoculation in blood culture bottles (FNA + BCB) was used from the beginning of 2016. RESULTS: Of 34 children with culture-confirmed melioidosis, 20 (59%) had an infection involving one or more sites in the head and neck. Of these, 17 (85%) were diagnosed in or after 2016. Cervical lymph nodes were the most common organ or site affected, involved in 19 (95%) children. Clinical presentations of B. pseudomallei lymph node infections were highly variable. Five (25%) children had salivary gland involvement. Lacrimal gland involvement (dacryocystitis) and skin or soft tissue infection (scalp abscess) were less frequent. B. pseudomallei was isolated from the head or neck using FNA + BCB in 15 (75%) children and by standard culture methods of direct plating of pus on agar following incision and drainage in only 2 (10%) children. B. pseudomallei was isolated from non-head or neck specimens or blood in 3 (15%) children. CONCLUSIONS: Manifestations of pediatric head and neck melioidosis in Sarawak, Malaysia, differ from those of other regions. Fine-needle aspiration, mainly of affected cervical lymph nodes, facilitates B. pseudomallei detection and enables confirmation of melioidosis infections.

Leg ulceration due to cutaneous melioidosis in a returning traveller.

A 26-year-old man, returned to the UK having travelled extensively in Asia. He was referred with a 3-month history of distal leg ulceration following an insect bite while in Thailand. Despite multiple courses of oral antibiotics, he developed two adjacent ulcers. A wound swab isolated an organism identified as Burkholderia thailandensis The histology of the skin biopsy was non-specific. A diagnosis of cutaneous melioidosis was made, based on clinical and microbiological grounds. The ulcers re-epithelialised on completion of intravenous ceftazidime followed by 3 months of high dose co-trimoxazole and wound care. Many clinical microbiology laboratories have limited diagnostics for security-related organisms, with the result that B. pseudomallei, the causative bacterium of melioidosis, may be misidentified. This case highlights the importance of maintaining high levels of clinical suspicion and close microbiological liaison in individuals returning from South-East Asia and northern Australia with such symptoms.

A 2-Biomarker Model Augments Clinical Prediction of Mortality in Melioidosis.

BACKGROUND: Melioidosis, infection caused by Burkholderia pseudomallei, is a common cause of sepsis with high associated mortality in Southeast Asia. Identification of patients at high likelihood of clinical deterioration is important for guiding decisions about resource allocation and management. We sought to develop a biomarker-based model for 28-day mortality prediction in melioidosis. METHODS: In a derivation set (N = 113) of prospectively enrolled, hospitalized Thai patients with melioidosis, we measured concentrations of interferon-γ, interleukin-1ß, interleukin-6, interleukin-8, interleukin-10, tumor necrosis factor-ɑ, granulocyte-colony stimulating factor, and interleukin-17A. We used least absolute shrinkage and selection operator (LASSO) regression to identify a subset of predictive biomarkers and performed logistic regression and receiver operating characteristic curve analysis to evaluate biomarker-based prediction of 28-day mortality compared with clinical variables. We repeated select analyses in an internal validation set (N = 78) and in a prospectively enrolled external validation set (N = 161) of hospitalized adults with melioidosis. RESULTS: All 8 cytokines were positively associated with 28-day mortality. Of these, interleukin-6 and interleukin-8 were selected by LASSO regression. A model consisting of interleukin-6, interleukin-8, and clinical variables significantly improved 28-day mortality prediction over a model of only clinical variables [AUC (95% confidence interval [CI]): 0.86 (.79-.92) vs 0.78 (.69-.87); P = .01]. In both the internal validation set (0.91 [0.84-0.97]) and the external validation set (0.81 [0.74-0.88]), the combined model including biomarkers significantly improved 28-day mortality prediction over a model limited to clinical variables. CONCLUSIONS: A 2-biomarker model augments clinical prediction of 28-day mortality in melioidosis.

Utility of endobronchial ultrasound guided trans-bronchial needle aspiration in diagnosis of melioidosis - case series and review of literature.

Endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) is routinely performed for diagnostic evaluation of mediastinal lymphadenopathy due to various etiologies with excellent sensitivity and specificity. Melioidosis can have atypical features like isolated mediastinal lymphadenopathy mimicking as tuberculosis or lymphoma. Differentiation of such atypical melioidosis presentation become difficult due to similar clinical, radiological and even similar EBUS lymph node characteristics. Role of EBUS TBNA in diagnosing melioidosis is under investigated and sparsely reported. We describe two cases of melioidosis diagnosed by point of care rapid lateral flow immunoassay antigen testing and culture of EBUS-TBNA samples from necrotic mediastinal lymph nodes.

Adapting Microarray Gene Expression Signatures for Early Melioidosis Diagnosis.

Melioidosis is caused by Burkholderia pseudomallei and is predominantly seen in tropical regions. The clinical signs and symptoms of the disease are nonspecific and often result in misdiagnosis, failure of treatment, and poor clinical outcome. Septicemia with septic shock is the most common cause of death, with mortality rates above 40%. Bacterial culture is the gold standard for diagnosis, but it has low sensitivity and takes days to produce definitive results. Early laboratory diagnosis can help guide physicians to provide treatment specific to B. pseudomallei In our study, we adapted host gene expression signatures obtained from microarray data of B. pseudomallei-infected cases to develop a real-time PCR diagnostic test using two differentially expressed genes, AIM2 (absent in melanoma 2) and FAM26F (family with sequence similarity 26, member F). We tested blood from 33 patients with B. pseudomallei infections and 29 patients with other bacterial infections to validate the test and determine cutoff values for use in a cascading diagnostic algorithm. Differentiation of septicemic melioidosis from other sepsis cases had a sensitivity of 82%, specificity of 93%, and negative and positive predictive values (NPV and PPV) of 82% and 93%, respectively. Separation of cases likely to be melioidosis from those unlikely to be melioidosis in nonbacteremic situations showed a sensitivity of 40%, specificity of 54%, and NPV and PPV of 44% and 50%, respectively. We suggest that our AIM2 and FAM26F expression combination algorithm could be beneficial for early melioidosis diagnosis, offering a result within 24 h of admission.

Burkholderia pseudomallei was Identified in a Melioidosis Aneurysm using Polymerase Chain Reaction Targeting 23S rRNA.

Melioidosis abdominal aortic aneurysm and splenic abscesses lead to poor prognosis and high mortality rate as high as 50% due to delayed/missed diagnosis. We describe an attempt to identify Burkholderia pseudomallei immediately, which was confirmed by polymerase chain reaction (PCR) and gene sequence analysis of 23S rRNA gene. PCR is not only an unambiguous identification of B. pseudomallei but also a rapid detection because B. pseudomallei may not be readily isolated. For patients of melioidosis abdominal aortic aneurysm with spleen abscess, prolonged antibiotic therapy, splenectomy and artificial vessel replacement provided an excellent result in our study. The progression, roentgenographic findings and histopathology character of melioidosis are similar to those of tuberculosis disease. PCR is useful to differentiate B. pseudomallei from Mycobacterium tuberculosis.

Selective media and real-time PCR improves diagnosis of melioidosis in community-acquired pneumonia in a low-incidence setting in Kuala Lumpur, Malaysia.

Introduction. Burkholderia pseudomallei (melioidosis) is an important cause of community-acquired pneumonia (CAP) in the tropics. Selective medium is recommended for laboratory diagnosis with non-sterile respiratory samples, while PCR is not routinely used due to variable reported performance. The effectiveness of these diagnostic modalities varies by site.Aim. To compare selective media and real-time PCR (qPCR) with routine media in detecting B. pseudomallei in CAP respiratory samples in a low-incidence setting in Kuala Lumpur, Malaysia.Methodology. Respiratory samples were routinely cultured on blood, chocolate and MacConkey agar (RESP-ROUTINE), and compared to culture on selective Ashdown medium (RESP-SELECTIVE) and qPCR. The gold standard was routine culture of B. pseudomallei from any site (ALL-ROUTINE).Results. B. pseudomallei was detected in 8/204 (3.9 %) samples. Overall sensitivity rates differed (P=0.03) for qPCR (100%), RESP-SELECTIVE (87.5%) and RESP-ROUTINE (50%). There was a trend towards lower median days to positive culture for RESP-SELECTIVE (1 day) compared to RESP-ROUTINE (2 days, P=0.08) and ALL-ROUTINE (2 days, P=0.06). Reagent costs for each additional detection were USD59 for RESP-SELECTIVE and USD354 for PCR.Conclusions. In a low-incidence setting, selective culture of respiratory samples on Ashdown was more sensitive and allowed quicker identification than routine media, at reasonable cost. Blood cultures are critical, confirming four cases missed by routine respiratory culture. Selective medium is useful in early pneumonia (pre-sepsis) and resource-limited settings where blood cultures are infrequently done. Real-time PCR is costly, but highly sensitive and useful for high-risk patients with diabetes, cancer or immunosuppressants, or requiring ventilation or intensive care.