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The facultative intracellular gram-

negative bacterium

Burkholderia pseudomallei
A widely distributed environmental
saprophyte in soil and fresh surface
water in endemic regions
Southeast Asia, especially in Thailand,
Malaysia, Singapore

Northern Australia
South Asia
China
Inhalation
Percutaneous
inoculation
Analysis from rainfall
data and clinical
presentations

During severe weather events
(tropical storms and cyclones),
there may be a shift from
inoculation to inhalation
Unproven : Ingestion ,
sexual transmission
Person-to-person :
unusual
Iatrogenic infection
Zoonotic infection (case
report)
Diabetes
Excessive alcohol ingestion
Chronic renal disease
Chronic lung disease
Thalassemia
Kava consumption
Disseminated septicemic melioidosis
› Septicemia with multiple organs infection
› Usually death in 48 hours
Non-disseminated septicemic melioidosis

Septicemia
› No specific organ infection
Localized melioidosis
› 1-2 organs infection
Transient bacteremic melioidosis
› Transient septicemia
› Clinical improve even though no treatment
Probable melioidosis
› Clinical-like but culture negative for B. pseudomallei
Subclinical melioidosis
› Serology postitive for B. pseudomallei but no clinical
Pneumonia
› Most common
› Acute presentation : high fever, cough,
sputum, chills, rigors, respiratory distress w/ or w/o
shock
› Subacute or chronic presentation : cough,
purulent sputum production, hemoptysis and
night sweats
Encephalomyelitis
› Usually results from brainstem encephalitis

CSF
• Elevated WBC counts 30-775 per
microL
• Mononuclear cells predominant
• Elevated protein
• Normal or slightly decrease glucose
Melioidosis: Case series in Maharaj
Nakorn Chiang Mai Hospital

Chaiwarith R, et al. J Infect Dis Antimicrob Agents 2005; 22: 45-51


Appropriate clinical samples
› Blood

Sputum
› Urine
› Swab of an ulcer or skin lesion
› Abscess fluid
› Throat swab
› Rectal swab
Bacteriology
› Gram : GNB, bipolar staining [Enterobacteriaceae,
Klebsiella, E. coli, and
Pasteurella pestis], sense 55%
› C/S
› Latex agglutination [LA]
Poly/monoclonal Ab to LPS and exopolysaccharide of
organisms blood culture
Sense 96-100% Spec 100%
› Direct immunofluorescence [DIF]
Polyclonal Ab to LPS of organisms sputum, urine, pus

Sense 73% Spec 99%


Immunology
› Indirect haemagglutination [IHA]
cut off titer area
1:80-1:320
Ab not related to severity of disease
› ELISA
Sense 93% Spec 97%
› Gold blot detection IgM specific Ab
IgM Sense 87.5% Spec 88%
IgG Sense 100% Spec 91%
› Specific Ag by ELISA Sense 90%
Culture : Ashdown’s selective media
(crystal violet, glycerol, neutral red,
gentamicin)
Microscopy
› Gram-negative bacilli
› Bipolar staining with a “safety pin” appearance
Serology
› Indirect hemagglutination test (IHAT)
False negative
Positive antibody to B. pseudomallei occur in healthy
individuals in endemic areas
› ELISA-based rapid immunochromogenic test kit
IgM
IgG : traveler
Imaging
› Chest radiography

CT and MRI
Intensive therapy
Eradication therapy
Ceftazidime
› 50 mg/kg up to 2 g IV q 6 hours

Meropenem
› 25 mg/kg up to 1 g IV q 8 hours

Imipenem
› 25 mg/kg up to 1 g IV q 6 hours
Addition of TMP-SMX
› Intracellular activity
› Decreasing the emergence of antimicrobial
resistance
› In vitro time-kill studies have shown that adding TMP-
SMX had no effect on the action of ceftazidime

› the addition of TMP-SMX provides further benefit in


mortality reduction compared to monotherapy with
ceftazidime was addressed in two randomized
controlled trials of 449
patients with severe melioidosis in Thailand
Chierakul, W, Anunnatsiri, S, Short, JM, et al. Clin

Infect Dis 2005; 41:1105.


Despite the lack of proven benefit, TMP-
SMX is still routinely added to ceftazidime
or a carbapenem in some
centers
TMP-SMX 320 mg/1600 mg IV or PO twice daily
Alternative agents
› cefoperazone-sulbactam plus TMP-SMX
› high-dose intravenous amoxicillin-
clavulanate
Duration
› At least 14 days
› Critically ill (extensive pulmonary disease, deep
seated collections or organ abscess, osteomelitis,
septic arthritis or neurologic mellioidosis)

4-6 weeks
Adjunctive therapy
› Abscess drainage

Recombinant G-CSF
A retrospective study using historical controls examined the
mortality rates before and after the introduction of G-CSF therapy
during the period of 1989-2002 in 42 patients with septic shock and
culture-confirmed melioidosis.

Mortality in patients treated with G-CSF was dramatically


lower (10 compared to 95 percent in historical controls without G-CSF
therapy)
Cheng, AC, Stephens, DP, Anstey, NM, Currie, BJ. Adjunctive granulocyte colony-stimulating factor for
treatment of septic shock due to melioidosis. Clin Infect Dis 2004; 38:32.
Preventing recrudescence or later
relapse of melioidosis

Duration
› At least 3 months
› Osteomyelitis or neurologic melioidosis :
recommended 6 months
Choice of agents
› “Conventional”
TMP-SMX (8 mg/kg trimethoprim - 40 mg/kg sulfamethoxazole up to two double-
strength tablets [320 mg/1600 mg] twice daily)

with or without doxycycline (2.5 mg/kg up to 100 mg


twice daily)
With or without chloramphenicol 40 mg/kg/day, qid
in first 4 weeks
› Amoxicillin-clavulanate +/- azithromycin
Amoxicillin 60 mg/kg/day + clavulanic acid 15
mg/kg/d
Devide in three or four times per day
Recommend : Pregnancy, younger children
Risk of relapse
› Poor compliance
› Duration of eradication
› Sever disease
Treatment
› Re-initiation of intravenous intensive
therapy
› Followed by eradication therapy
› Antimicrobial susceptibility testing
Bacteremia
Respiratory failure
Renal failure

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