Melioidosis

 The

facultative intracellular gramnegative 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 α 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% IgG Sense 100%

Spec 88% 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 amoxicillinclavulanate  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 19892002 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