Fatal deep venous thrombosis and pulmonary embolism secondary to melioidosis in China: case report and literature review
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Burkholderia pseudomallei is a gram-negative bacterium and the causative pathogen of melioidosis, which manifests a variety ranges of infection symptoms. However, deep venous thrombosis (DVT) and pulmonary embolism (PE) secondary to bacteremic melioidosis are rarely documented in the literature. Herein, we reported a fatal case of melioidosis combined with DVT and PE.
A 54-year-old male construction worker and farmer with a history of diabetes was febrile, painful in left thigh, swelling in left lower limb, with chest tightness and shortness of breath for 4 days. He was later diagnosed as DVT of left lower extremity and PE. The culture of his blood, sputum and bone marrow samples grew B. pseudomallei. The subject was administrated with antibiotics (levofloxacin, cefoperazone/tazobactam, and imipenem) according to antimicrobial susceptibility testing and low molecular heparin for venous thrombosis. However, even after appropriate treatment, the patient deteriorated rapidly, and died 2 weeks after admission.
This study enhanced awareness of the risk of B. pseudomallei bloodstream infection in those with diabetes. If a patient has predisposing factors of melioidosis, when DVT is suspected, active investigation and multiple therapeutic interventions should be implemented immediately to reduce mortality rate.
KeywordsBurkholderia pseudomallei Melioidosis Deep venous thrombosis Pulmonary embolism
Antimicrobial susceptibility testing
Deep venous thrombosis
Multilocus sequence typing
Burkholderia pseudomallei, a gram-negative bacterium commonly found in soil and water, is the infective pathogen of melioidosis in southeast Asia and northern Australia [1, 2]. Southern China has been in the expanded endemic zone of melioidosis [3, 4, 5]. Melioidosis involves almost any part of the body, with its clinical manifestation ranging from acute septicemia, respiratory tract infection, to chronic cutaneous infection. It is also called the great mimicker, as its pathogenesis and clinical features might present like tuberculosis or brucellosis [6, 7].
Furthermore, there are some predisposing risk factors for melioidosis, including smoking, diabetes, occupation, and history of exposure to contaminated soil or water prior to their illness [3, 8, 9]. Deep venous thrombosis (DVT) and pulmonary embolism (PE) caused by B. pseudomallei will reinforce the high mortality rate associated with this infection, but rarely documented in the literature [10, 11]. Herein, we reported a fetal case of DVT and PE secondary to bacteremic melioidosis in a diabetic farmer in mainland China alongside a literature review of B. pseudomallei-caused venous thrombosis.
His coagulation results were normal except for the elevated fibrinogen level (4.17 g/L, normal rang 2~4 g/L). Blood examination demonstrated hyperglycemia (blood glucose7.98 mmol/L, normal range 3.89~6.11 mmol/L) and hyperlipemia (triglyceride 2.59 mmol/L, normal range 0.33~1.69 mmol/L), but antibody examinations for human immune deficiency virus, hepatitis B virus and hepatitis C virus were all negative. Expectorated sputum smear revealed a large amount of polymorphonuclear leucocytes and gram-negative bacilli. On July18 to 22, his blood, sputum and bone marrow grew B. pseudomallei, respectively. Antimicrobial susceptibility testing (AST) showed that the strain was susceptible to all antimicrobial agents with breakpoint value in CLSI.
On July 20, the patient began receiving antimicrobial therapy of imipenem. However, 4 days later, his condition dramatically deteriorated, and presented as heart failure, renal failure and persistent high fever (up to 40.1 °C). On July 25, his family members received the medical crisis notice of life-threatening respiratory and circulatory failure. Considering the low probability of his survival, his family decided to take him home in accordance to the local customs of not dying in hospital. Without proper treatment the patient died 3 days later after he was discharged.
Identification by 16S rRNA sequencing and multilocus sequence typing (MLST) of BP86
To genetically characterize the isolate, the 16S rRNA sequencing was conducted. Sequence analysis of the 1385 bp-segment of 16S rRNA gene of BP86 demonstrated an identity of 99.93% with B. pseudomallei K96243 (GenBank accession no. NC_006351.1). The whole genome of the pathogen was also sequenced using a whole-genome shotgun strategy based on the Illumina HiSeq platform. The selected optimal assembly results were compared with the seven housekeeping genes of B. pseudomallei for MLST by reference to https://pubmlst.org/bpseudomallei/, and the determined sequence type of BP86 was ST 46.
Discussion and conclusions
B. pseudomallei is the pathogen of melioidosis, an infectious disease involving almost every system all over the body with complicated clinical characteristics. Melioidosis is generally thought to be epidemic in tropical and sub-tropical zone, but recently, it is speculated that it is distributed more widely beyond the tropics based on increased case reports and predictive modelling studies . Southern China, especially Hainan province, is one of the additional endemic areas [1, 5]. As reported by Zheng X et al., there are approximately 20 to 30 culture-confirmed melioidosis cases in Hainan General Hospital . Between 2002 and 2013, in another research in Hainan province, not including the cases in Hainan General Hospital, 170 cases of melioidosis were documented, and the most common presentations were pneumonia and bacteremia .
B. pseudomallei is found in soil and stagnant water in endemic regions, and it usually invades the epithelial cells of the mucosal surface or skin and then spread to others [12, 13, 14, 15, 16]. Diabetes mellitus is the most common predisposing factor of melioidosis, and more than 50% of the world’s melioidosis patients are diabetic [8, 9]. In the present study, our patient was a diabetic construction worker and farmer living in the endemic area, and therefore, the most possible way of being infected might be via percutaneous inoculation or inhalation of contaminated soil or water in the environment .
Literature review of melioidosis thrombosis cases with summary of predisposing factors, clinical presentation, treatment and outcome
diabetes, mild alcoholic cirrhosis
fever, headache, left hemiparesis, focal seizure, increased intracranial pressure
fever, seizures, altered conscious level and neck stiffness,
diplopia, decreased hearing
fever, rigor, abdominal pain, loss of appetite, weight loss
fever with chills, palpitations and an unproductive cough.
febrile, icteric, dehydrated
febrile, painful in left thigh with left lower limb swelling, chest tightness, shortness of breath
superior sagittal sinus
dural venous sinus
splenic vein, right portion of the portal vein
left portal vein
left lower extremity
brain tissue biopsy
blood, pancreas, lung, spleen, liver
blood, sputum, bone marrow
ceftazidime, amoxicillin-clavulanic acid, doxycycline, co-trimoxazole
ceftazidime, meropenem, co-trimoxazole, amoxicillin-clavulanic acid,
ceftazidime, amoxicillin-clavulanic acid
levofloxacin, cefoperazone/tazobactam, imipenem
antiepileptic drug and anticoagulant
craniectomy and drainage of the abscess
no other therapy
anticoagulant (low molecular heparin)
Five of six reported and our case B. pseudomallei strains were isolated from blood culture, and in an Indian young male, the microorganism was recovered from brain tissue biopsy . Furthermore, in our case, bone marrow also grew B. pseudomallei. Melioidosis has a case-fatality rate as high as 40% [3, 25], and the prognosis may be worse if combined with DVT/PE. However, to our surprise, in line with our review, five cases in literature with DVT/PE recovered and discharged home and one remained unchanged. Unfortunately, our patien was complicated with PE, and died afterwards, even timely anticoagulation and susceptible antibiotics were used.
In summary, to the best of our knowledge, this is the first report of PE/DVT secondary to B. pseudomallei infection. Physicians and laboratories in endemic areas should be aware of this potentially emerging disease. DVT/PE or other thrombosis should be taken into account when patients have predisposing factors or culture-confirmed melioidosis, especially if the patient has pain and swelling in the limb and chest pain.
We are grateful to Dr. Xiao Zhanxiang, director of Vascular Surgery Department, Hainan General Hospital, for his generous help to this study.
HW, DH, BW, and MP isolated bacteria and performed the laboratory measurements. HW and BL made substantial contributions to conception and design, and drafted the manuscript. All authors read and approved the final manuscript.
We gratefully acknowledge funding from National Key Research and Development Program of China (Grant No. 2018YFC1200102), Key Research and Development Program of Hainan Province (Grant No. ZDYF2018113), and Beijing Municipal Science & Technology Commission, PR China (No. Z171100001017118). The funding bodies had no role in the design of the study or collection, analysis, processing or interpretation of data or in writing the manuscript.
Ethics approval and consent to participate
The institutional review boards at the Hainan general hospital approved the study protocol.
Consent for publication
Written informed consent was obtained from the patient’s direct relative for publication of this study. A copy of the written consent is available for review by the Editor of this journal.
The authors declare that they have no competing interests.
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