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Published Date: 2017-06-28 11:51:38
Subject: PRO/EDR> Melioidosis - Belgium: ex Southeast Asia
Archive Number: 20170628.5137064
A ProMED-mail post
ProMED-mail is a program of the
International Society for Infectious Diseases

Date: Wed 28 Jun 2017
From: Caroline Theunissen <ctheunissen@itg.be> [edited]

On [Fri 16 Jun 2017], a 71-year old male patient presented at the University Hospital of Antwerp (UZA), Belgium, with an eight weeks history of spiking fever (up to 42 C [107.6 F]), dyspnea, tachypnea, cough, swelling of the right knee, severe swelling and pain of the left wrist, chest and back pain. Medical history included inguinal hernia repair, laparoscopic resection of the rectum and sigmoid for a pT3N0 colon cancer (September 2014), arthroscopy of the right knee (October 2014) and bilateral cataract surgery (July 2016).

The man was born in Belgium but had been living in Pattaya, Thailand for over 10 years and had travelled to Cambodia twice in the past year [2016]. In April 2016 he visited Phnom Penh and Ankor Wat (Siem Reap) for 9 days, during which he developed diarrhea and fever. He was diagnosed with acute gastroenteritis in a Bangkok hospital and was sent home. Despite a course of antibacterials, fever persisted and the patient was readmitted. Amoebic liver abscess was diagnosed and treated with surgical drainage. In May 2017, the high grade fever recurred after a 9 - day trip to Phnom Penh and the patient returned to Belgium for further medical care. He was 1st admitted in the regional hospital of Geel before being referred the same day to the department of Tropical Medicine at the UZA.

Upon admission his temperature was 38.8 C [101.8 F], oxygen saturation 88 percent and respiratory rate 40 per minute. Blood pressure was 160/87 mmHg and pulse was 90 beats per minute. Clinical examination revealed audible crepitation on the right lung basis and a subcutaneous abscess on the right knee. Laboratory tests revealed leucocytosis of 19000/microL and a C-Reactive Protein (CRP) level of 289 mg/dL. A CT-scan of the chest and abdomen revealed multiple abscesses in lung and liver. IV ceftazidime was started for a presumptive clinical diagnosis of melioidosis. The solitary liver abscess of 8.3 cm [3.26 inches] diameter was drained percutaneously, as well as the cutaneous abscess on the patient's knee. Within 24 hours, cultures of blood, liver abscess and skin became positive for Gram-negative rods and ceftazidime was switched into IV meropenem for optimal Gram-negative coverage. The isolates were subsequently identified as _Burkholderia pseudomallei_.

On the 3rd day of hospitalization, trimethoprim/sulfamethoxazole was added because of limited clinical improvement. During the following days, the patient improved clinically and CRP and leucocytosis declined. On day 8 of hospitalization, the patient developed visual hallucinations and intermittent confusion. A brain MRI revealed abscesses in the left parietal and occipital cortex which were drained subsequently.

Melioidosis is an infection caused by _Burkholderia pseudomallei_, a facultative intracellular Gram-negative bacterium, present in soil and fresh water. The disease is endemic in large parts of the world, especially in South and South-East Asia and tropical Australia. Its incidence is estimated around 165 000 cases per year, of which more than 50 percent are fatal. Infection occurs after exposure to environmental sources such as contaminated soil or fresh water (i.e. dust, paddy field, flooding during the rainy season) and presents particularly in patients with comorbidities such as diabetes mellitus, chronic lung, liver or kidney disease and alcoholism.

Although our patient is not known with any of these specific conditions, we presume a decreased immunity because of his older age and history of colon cancer. The clinical presentation of melioidosis varies by age and geographic region. In children the most common presentation includes localized skin infection, with lower fatality rates. In adults, clinical manifestations include pneumonia, bacteremia, (deep) abscesses of the skin, muscles, and organs such as liver, brain, spleen and lungs; arthritis, spondylodiscitis and encephalitis. Infection can be latent, with subsequent reactivation, as in tuberculosis. Probably, the "amoebic" abscess of our patient one year earlier was a 1st episode, partially treated by surgical drainage. Differential diagnosis depends on the initial presentation but is generally wide, including community acquired pneumonia, Gram negative blood stream infection, tuberculosis, pyogenic abscesses, etc. _B. pseudomallei_ is inherently resistant to ampicillin, ceftriaxone, fluoroquinolones and aminoglycosides, thus compromising the adequacy of most empiric antibacterial treatments. Beside surgical drainage of abscesses, the optimal treatment regimen consists of an initial intensive phase with ceftazidime or meropenem with or without cotrimoxazole, during 2-8 weeks, followed by a maintenance phase with cotrimoxazole during 3 to 6 months. There is a significant risk for infection relapse, especially when disease is severe, or treatment incomplete.

This case of melioidosis with a typical clinical presentation (blood stream infection with multiple organ and skin abscesses, pneumonia and arthritis) in a patient residing and travelling in an hyper endemic region, emphasizes the importance of its recognition as a potentially life threatening imported infection in returning travelers.

Caroline Theunissen
Leander Depuysseleyr
Erika Vlieghe
Department of Internal Medicine, Infectious Diseases and Tropical Medicine
University Hospital Antwerp
Department of Clinical Sciences
Institute of Tropical Medicine
Antwerp, Belgium

[ProMED thanks Dr Theunissen and colleagues for this 1st hand contribution.

Melioidosis is a disease of the rainy season in its endemic areas. It mainly affects people who have direct contact with soil and water. Many have an underlying predisposing condition such as diabetes (commonest risk factor), renal disease, cirrhosis, thalassemia, alcohol dependence, immunosuppressive therapy, chronic obstructive lung disease, cystic fibrosis, and excess kava consumption. Kava is an herbal member of the pepper family that can be associated with chronic liver disease.

Melioidosis may present at any age, but peaks in the 4th and 5th decades of life, affecting men more than women. In addition, although severe fulminating infection can and does occur in healthy individuals, severe disease and fatalities are much less common in those without risk factors.

The most commonly recognized presentation of melioidosis is pneumonia, associated with high fever, significant muscle aches, chest pain, and -- although the cough can be nonproductive -- respiratory secretions can be purulent, significant in quantity, and associated with on-and-off bright, red blood. The lung infection can be rapidly fatal -- with bacteremia and shock -- or somewhat more indolent.

Acute melioidosis septicemia is the most severe complication of the infection. It presents as a typical sepsis syndrome with hypotension, high cardiac output, and low systemic vascular resistance. In many cases, a primary focus in the soft tissues or lung can be found. The syndrome, usually in patients with risk factor comorbidities, is characteristically associated with multiple abscesses involving the cutaneous tissues, the lung, the liver, and spleen, and a very high mortality rate of 80 to 95 percent. With prompt optimal therapy, the case fatality rate can be decreased to 40 to 50 percent.

The melioidosis bacillus is intrinsically insensitive to many antimicrobials. It should be noted that bioterrorism strains may be engineered to be even more resistant. _Burkholderia pseudomallei_ is usually inhibited by tetracyclines, chloramphenicol, trimethoprim-sulfamethoxazole (SXT), antipseudomonal penicillins, carbapenems, ceftazidime, and amoxicillin/clavulanate or ampicillin/sulbactam. Ceftriaxone and cefotaxime have good in vitro activity but poor efficacy; and cefepime did not appear, as well, to be equivalent to ceftazidime in a mouse model. The unusual antimicrobial profile of resistance to colistin and polymyxin B and the aminoglycosides but sensitivity to amoxicillin/clavulanate is a useful tool to consider in treatment of infection with the organism.

The randomized and quasi-randomized trials comparing melioidosis treatment have been reviewed, and it was found that the formerly standard therapy of chloramphenicol, doxycycline, and SXT combination had a higher mortality rate than therapy with ceftazidime, imipenem/cilastatin, or amoxicillin/clavulanate (or ampicillin/sulbactam). The betalactam-betalactamase inhibitor therapy, however, seemed to have a higher failure rate.

Source: Tolaney P, Lutwick LI: Melioidosis. In: Lutwick LI, Lutwick SM (eds). Bioterror: the weaponization of infectious diseases. Totowa NJ: Humana Press, 2008 pp 145-58.

For the microbiologists among our readers, a new (and 5th) member of the _B. pseudomallei_ complex has been described, _B. humptydooensis_ , from the Northern Territory of Australia and named after the small town of Humpty Doo near to where the isolate was found (Tuanyok A, Mayo M, Scholz H, et al: _Burkholderia humptydooensis_ sp. nov., a new species related to _Burkholderia thailandensis_ and the fifth member of the _Burkholderia pseudomallei_ complex. App Environ Microbiol 2017; 83(5): e02802-16; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5311406/. - Mod.LL

A HealthMap/ProMED-mail map can be accessed at: http://healthmap.org/promed/p/99.]

See Also

Melioidosis - Australia (04): (NT) 20170412.4965903
Melioidosis - Australia (03): (NT) fatality 20170210.4830367
Melioidosis - Australia (02): (NT) 20170113.4760582
Melioidosis - Australia: (NT) 20170107.4749013
Melioidosis - Peru 20161114.4624371
Melioidosis - Viet Nam: (TH) 20161019.4570856
Melioidosis - Malaysia: (SK) 20160213.4018880
Melioidosis: worldwide burden 20160112.39303002014
Melioidosis - Malaysia: (PH) 20150310.3218685
Melioidosis - Australia: (NT) 20141224.3051783
Melioidosis - Madagascar: 2012-2013 20141010.2850487
Melioidosis - Worldwide: western hemisphere cases 20140402.2370033
Melioidosis, 2011 - Thailand: drinking water source 20140112.2164773
Melioidosis - Belgium ex Madagascar 20130503.1687746
Melioidosis - Belgium ex Thailand (02): cutaneous, travel-assoc. 20121016.1345407
Melioidosis: travel-associated, background 20121009.1331658
Melioidosis: Belgium ex Thailand: cutaneous, travel-assoc. 20121007.1329106

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