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  1. Koay AS, Rohani MY, Cheong YM
    Med J Malaysia, 1997 Jun;52(2):158-60.
    PMID: 10968074
    Melioidosis is endemic in Malaysia. Emerging resistance with new and current antimicrobial agents has underscored the need to look further for new antimicrobial agents for the treatment of melioidosis. Hence, we evaluated the in-vitro susceptibility of fifty locally isolated strains of Burkholderia pseudomallei, the causative agent of melioidosis to cefoperazone-sulbactam combination using the method of NCCLS. All the fifty strains tested were susceptible in-vitro to cefoperazone-sulbactam. The MIC90 of the organism for cefoperazone-sulbactam was 4 mg/L. The results of our findings suggested that cefoperazone-sulbactam may be useful in the treatment of melioidosis.
    Matched MeSH terms: Burkholderia pseudomallei/drug effects*
  2. Podin Y, Sarovich DS, Price EP, Kaestli M, Mayo M, Hii K, et al.
    Antimicrob Agents Chemother, 2014;58(1):162-6.
    PMID: 24145517 DOI: 10.1128/AAC.01842-13
    Melioidosis is a potentially fatal disease caused by the saprophytic bacterium Burkholderia pseudomallei. Resistance to gentamicin is generally a hallmark of B. pseudomallei, and gentamicin is a selective agent in media used for diagnosis of melioidosis. In this study, we determined the prevalence and mechanism of gentamicin susceptibility found in B. pseudomallei isolates from Sarawak, Malaysian Borneo. We performed multilocus sequence typing and antibiotic susceptibility testing on 44 B. pseudomallei clinical isolates from melioidosis patients in Sarawak district hospitals. Whole-genome sequencing was used to identify the mechanism of gentamicin susceptibility. A novel allelic-specific PCR was designed to differentiate gentamicin-sensitive isolates from wild-type B. pseudomallei. A reversion assay was performed to confirm the involvement of this mechanism in gentamicin susceptibility. A substantial proportion (86%) of B. pseudomallei clinical isolates in Sarawak, Malaysian Borneo, were found to be susceptible to the aminoglycoside gentamicin, a rare occurrence in other regions where B. pseudomallei is endemic. Gentamicin sensitivity was restricted to genetically related strains belonging to sequence type 881 or its single-locus variant, sequence type 997. Whole-genome sequencing identified a novel nonsynonymous mutation within amrB, encoding an essential component of the AmrAB-OprA multidrug efflux pump. We confirmed the role of this mutation in conferring aminoglycoside and macrolide sensitivity by reversion of this mutation to the wild-type sequence. Our study demonstrates that alternative B. pseudomallei selective media without gentamicin are needed for accurate melioidosis laboratory diagnosis in Sarawak. This finding may also have implications for environmental sampling of other locations to test for B. pseudomallei endemicity.
    Matched MeSH terms: Burkholderia pseudomallei/drug effects*
  3. Hassan MR, Vijayalakshmi N, Pani SP, Peng NP, Mehenderkar R, Voralu K, et al.
    PMID: 24974653
    Burkholderia pseudomallei, the causative agent of melioidosis is an important cause of morbidity and mortality particularly among diabetics. We evaluated 228 isolates of B. pseudomallei for antimicrobial sensitivity during 2005-2010 using the disc diffusion technique, of which 144 were obtained from blood culture. More than 90% of the strains were susceptible to cefoperazone, ceftazidime, chloramphenicol and imipenem. Eighty-two percent of the isolates were susceptible to tetracycline and amoxicillin/clavulanate. The susceptibilities to ciprofloxacin was 78% and to trimethoprim-sulfamethoxezole was 47%. The susceptibilities to aminoglycoside antibiotics were low (21% to gentamicin and 6% to amikacin). The susceptibilities were similar between isolates from females and males, bacteremic and abacteremic cases, diabetics and non-diabetics, pneumonia and non-pneumonia cases and between those who died and those who survived. Our findings show antibiotic susceptibility patterns are not a major factor in determining outcomes of B. pseudomallei infection. Monitoring the drug susceptibilities among B. pseudomallei isolates needs to be conducted regularly to guide empiric therapy for melioidosis, as it causes high mortality, especially among diabetic cases.
    Matched MeSH terms: Burkholderia pseudomallei/drug effects*
  4. Chong CE, Lim BS, Nathan S, Mohamed R
    In Silico Biol. (Gedrukt), 2006;6(4):341-6.
    PMID: 16922696
    Recent advances in DNA sequencing technology have enabled elucidation of whole genome information from a plethora of organisms. In parallel with this technology, various bioinformatics tools have driven the comparative analysis of the genome sequences between species and within isolates. While drawing meaningful conclusions from a large amount of raw material, computer-aided identification of suitable targets for further experimental analysis and characterization, has also led to the prediction of non-human homologous essential genes in bacteria as promising candidates for novel drug discovery. Here, we present a comparative genomic analysis to identify essential genes in Burkholderia pseudomallei. Our in silico prediction has identified 312 essential genes which could also be potential drug candidates. These genes encode essential proteins to support the survival of B. pseudomallei including outer-inner membrane and surface structures, regulators, proteins involved in pathogenenicity, adaptation, chaperones as well as degradation of small and macromolecules, energy metabolism, information transfer, central/intermediate/miscellaneous metabolism pathways and some conserved hypothetical proteins of unknown function. Therefore, our in silico approach has enabled rapid screening and identification of potential drug targets for further characterization in the laboratory.
    Matched MeSH terms: Burkholderia pseudomallei/drug effects*
  5. Minassian MA, Gage A, Price E, Sefton AM
    Int J Antimicrob Agents, 1999 Aug;12(3):263-5.
    PMID: 10461846
    Melioidosis is a protean disease caused by Burkholderia pseudomallei. It is rare in the UK and is generally only seen in patients with a travel history to endemic areas such as Thailand, Singapore and Malaysia. Cases may present with disseminated bacteraemic, non-disseminated bacteraemic, multi-focal bacteraemic or localized disease. Subclinical infections also occur. Following acquisition of the organism a patient may remain asymptomatic for several years before infection becomes clinically apparent. Factors such as diabetes, renal failure or other causes for a decrease in host immunity may precipitate the appearance of overt disease. The current treatment choice for severe melioidosis is parenteral ceftazidime followed by oral amoxycillin-clavulanic acid or a combination of co-trimoxazole, doxycycline and chloramphenicol. We report a case of melioidosis in a 59-year-old male diabetic from Bangladesh who initially responded to piperacillin-tazobactam but was changed to ceftazidime when a definitive diagnosis was made. His condition deteriorated on the latter antibiotic. He subsequently responded to imipenem. The patient's long-term outcome is still not known.
    Matched MeSH terms: Burkholderia pseudomallei/drug effects
  6. Raja NS
    J Microbiol Immunol Infect, 2008 Apr;41(2):174-9.
    PMID: 18473106
    Melioidosis is an infectious disease caused by Burkholderia pseudomallei that is endemic in Southeast Asia and northern Australia and has also been reported from non-endemic areas of the world. Little is known about the antimicrobial susceptibility pattern and the demography of melioidosis patients in Malaysia.
    Matched MeSH terms: Burkholderia pseudomallei/drug effects*
  7. Karunakaran R, Puthucheary SD
    Scand. J. Infect. Dis., 2007;39(10):858-61.
    PMID: 17852912
    The treatment of melioidosis currently involves the use of antimicrobials such as ceftazidime, trimethoprim-sulfamethoxazole, amoxicillin-clavulanate and doxycycline. Evaluation of other antimicrobials with activity against the organism continues to be pursued, however, as the causative organism, B. pseudomallei, may not always be susceptible to the above antimicrobials. This study aimed to test the susceptibility of Malaysian isolates of B. pseudomallei against imipenem, meropenem, ertapenem, moxifloxacin and azithromycin. 80 previously stocked clinical isolates collected between 1978 and 2003 from the UMMC, Kuala Lumpur were tested for in vitro susceptibility to these antimicrobials using the E-test minimum inhibitory concentration method. 100% of isolates were sensitive to imipenem and meropenem, 97.5% were sensitive to trimethoprim-sulfamethozaxole, 37.5% to moxifloxacin, and only a minority was sensitive to ertapenem (7.5%). Using breakpoints for Staphylococcus and Haemophilus, 5.0%-6.3% of isolates were sensitive to azithromycin. In conclusion, our findings support the in vitro efficacy of imipenem, meropenem and trimethoprim-sulfamethoxazole against B. pseudomallei. Moxifloxacin, ertapenem and azithromycin cannot be recommended for the treatment of melioidosis; however, further studies are needed to test the efficacy of azithromycin in combination with quinolones.
    Matched MeSH terms: Burkholderia pseudomallei/drug effects*
  8. How HS, Ng KH, Yeo HB, Tee HP, Shah A
    J Microbiol Immunol Infect, 2005 Oct;38(5):314-9.
    PMID: 16211138
    Melioidosis is much less common in children than in adults. This study investigated the incidence, demographic characteristics, presenting symptoms and outcome of pediatric melioidosis in Pahang, Malaysia. This retrospective study included patients < or =18 years old with positive body fluid cultures for Burkholderia pseudomallei from January 2000 to June 2003. Data on culture results were obtained from 2 referral hospitals. The incidence of pediatric melioidosis was 0.68/100,000 population per year. Of the 13 patients identified during the study period, 10 were male; 9 were Malays, 2 were Indians and 2 were aborigines. The mean age of these patients was 9.5 +/- 5.4 years. None of the patients had a previous history of confirmed melioidosis or predisposing factors for infection. Localized melioidosis was the most common presentation (46.2%) followed by melioidosis with septic shock (38.4%). Among patients with localized melioidosis, head and neck involvement (83.3%) was the most common presentation (2 patients with cervical abscesses, 1 with submandibular abscesses and 2 with acute suppurative parotitis) and another patient had right axillary abscess. All of the patients with septic shock had pneumonia and 2 of them had multi-organ involvement. The mortality among patients with septic shock was 80% and death occurred within 24 h of admission in all cases. In contrast, no complications or death occurred among patients with localized melioidosis. Melioidosis with septic shock is less common than localized melioidosis in pediatric patients, but is associated with very high mortality.
    Matched MeSH terms: Burkholderia pseudomallei/drug effects
  9. Raja NS
    J Pak Med Assoc, 2003 Aug;53(8):373-4.
    PMID: 14558747
    Matched MeSH terms: Burkholderia pseudomallei/drug effects
  10. Radu S, Lihan S, Idris A, Ling OW, Al-Haddawi MH, Rusul G
    PMID: 10928372
    Seven isolates of Burkholderia pseudomallei from cases of melioidosis in human (2 isolates) and animal (2 isolates), cat (one isolate) and from soil samples (2 isolates) were examined for in vitro sensitivity to 14 antimicrobial agents and for presence of plasmid DNA. Randomly amplified polymorphic DNA (RAPD) analysis was used to type the isolates, using two arbitrary primers. All isolates were sensitive to chloramphenicol, kanamycin, carbenicillin, rifampicin, enrofloxacin, tetracycline and sulfamethoxazole-trimethoprim. No plasmid was detected in all the isolates tested. RADP fingerprinting demonstrated genomic relationship between isolates, which provides an effective method to study the epidemiology of the isolates examined.
    Matched MeSH terms: Burkholderia pseudomallei/drug effects*
  11. Radua S, Ling OW, Srimontree S, Lulitanond A, Hin WF, Yuherman, et al.
    Diagn Microbiol Infect Dis, 2000 Nov;38(3):141-5.
    PMID: 11109011
    A total of 35 Burkholderia pseudomallei isolates from Thailand (16 clinical and eight soil isolates) and Malaysia (seven animal, two isolate each from clinical and soil) were investigated by their antimicrobial resistance, plasmid profiles and were typed by randomly amplified polymorphic DNA analysis. All isolates were found to be resistant to six or more of the 12 antimicrobial agents tested. Only two small plasmids of 1.8 and 2.4 megadalton were detected in two clinical isolates from Thailand. RAPD analysis with primer GEN2-60-09 resulted in the identification of 35 RAPD-types among the 35 isolates. The constructed dendrogram differentiated the 35 isolates into two main clusters and a single isolate. The wide genetic biodiversity among the 35 isolates indicate that RAPD-PCR can be a useful method to differentiate unrelated B. pseudomallei in epidemiological investigation.
    Matched MeSH terms: Burkholderia pseudomallei/drug effects
  12. Al-Maleki AR, Vellasamy KM, Mariappan V, Venkatraman G, Tay ST, Vadivelu J
    Genomics, 2020 01;112(1):501-512.
    PMID: 30980902 DOI: 10.1016/j.ygeno.2019.04.002
    Differences in expression of potential virulence and survival genes were associated with B. pseudomallei colony morphology variants. Microarray was used to investigate B. pseudomallei transcriptome alterations among the wild type and small colony variant (SCV) pre- and post-exposed to A549 cells. SCV pre- and post-exposed have lower metabolic requirements and consume lesser energy than the wild type pre- and post-exposed to A549. However, both the wild type and SCV limit their metabolic activities post- infection of A549 cells and this is indicated by the down-regulation of genes implicated in the metabolism of amino acids, carbohydrate, lipid, and other amino acids. Many well-known virulence and survival factors, including T3SS, fimbriae, capsular polysaccharides and stress response were up-regulated in both the wild type and SCV pre- and post-exposed to A549 cells. Microarray analysis demonstrated essential differences in bacterial response associated with virulence and survival pre- and post-exposed to A549 cells.
    Matched MeSH terms: Burkholderia pseudomallei/drug effects
  13. Khosravi Y, Vellasamy KM, Mariappan V, Ng SL, Vadivelu J
    ScientificWorldJournal, 2014;2014:132971.
    PMID: 25379514 DOI: 10.1155/2014/132971
    Burkholderia pseudomallei, the causative agent of melioidosis, is intrinsically resistant to many antibiotics. Ceftazidime (CAZ), the synthetic β-lactam, is normally used as the first-line antibiotic therapy for treatment of melioidosis. However, acquired CAZ resistance can develop in vivo during treatment with CAZ, leading to mortality if therapy is not switched to a different antibiotic(s) in a timely manner. In this study, susceptibilities of 81 B. pseudomallei isolates to nine different antimicrobial agents were determined using the disk diffusion method, broth microdilution test and Etest. Highest percentage of susceptibility was demonstrated to CAZ, amoxicillin/clavulanic acid, meropenem, imipenem, and trimethoprim/sulfamethoxazole. Although these drugs demonstrated the highest percentage of susceptibility in B. pseudomallei, the overall results underline the importance of the emergence of resistance in this organism. PCR results showed that, of the 81 B. pseudomallei, six multidrug resistant (MDR) isolates carried bpeB, amrB, and BPSS1119 and penA genes. Genotyping of the isolates using random amplified polymorphic DNA analysis showed six different PCR fingerprinting patterns generated from the six MDR isolates clusters (A) and eight PCR fingerprinting patterns generated for the remaining 75 non-MDR isolates clusters (B).
    Matched MeSH terms: Burkholderia pseudomallei/drug effects*
  14. Liew FY, Tay ST, Puthucheary SD
    Trop Biomed, 2011 Dec;28(3):646-50.
    PMID: 22433895 MyJurnal
    Ciprofloxacin, a quinolone with good intracellular penetration may possibly be used for treatment of melioidosis caused by Burkholderia pseudomallei, but problems with resistance may be encountered. Amino acid substitutions in gyrA/gyrB have given rise to fluoroquinolone resistance in various microorganisms. Using published primers for gyrA and gyrB, PCR was performed on 11 isolates of B. pseudomallei with varying degrees of sensitivity to ciprofloxacin, followed by DNA sequencing to detect possible mutations. Results showed an absence of any point mutation in either gene. Local isolates have yet to develop full resistance to ciprofloxacin and probably other mechanisms of resistance may have been involved in the decreased sensitivity to ciprofloxacin.
    Matched MeSH terms: Burkholderia pseudomallei/drug effects*
  15. Mariappan V, Thavagnanam S, Vellasamy KM, Teh CJS, Atiya N, Ponnampalavanar S, et al.
    BMC Infect Dis, 2018 Sep 05;18(1):455.
    PMID: 30185168 DOI: 10.1186/s12879-018-3371-7
    BACKGROUND: Burkholderia pseudomallei is the causative agent of melioidosis, which is a potentially life threatening disease endemic in Southeast Asian countries. In Malaysia, cystic fibrosis (CF) is an uncommon condition. The association between CF and B.pseudomallei infections has been reported previously. However, this is the first case report of a pediatric melioidosis relapse and co-infection with other Gram-negative bacteria in Malaysia.

    CASE PRESENTATION: A 14-year-old Chinese Malaysian boy presented with a history of recurrent pneumonia, poor growth and steatorrhoea since childhood, and was diagnosed with CF. B. pseudomallei was cultured from his sputum during three different admissions between 2013 and 2016. However, the patient succumbed to end stage of respiratory failure in 2017 despite antibiotics treatment against B.pseudomallei. The isolates were compared using multilocus-sequence typing and repetitive-element polymerase chain reaction (PCR), and confirmed that two of the isolates were of same sequence type, which may indicate relapse.

    CONCLUSIONS: CF patients should be aware of melioidosis in endemic regions, as it is an emerging infectious disease, especially when persistent or recurrent respiratory symptoms and signs of infection occur. The high prevalence rates of melioidosis in Malaysia warrants better management options to improve quality of life, and life expectancy in patients with CF. Travel activities to endemic regions should also be given more consideration, as this would be crucial to identify and initiate appropriate empiric treatment.

    Matched MeSH terms: Burkholderia pseudomallei/drug effects
  16. Sam IC, See KH, Puthucheary SD
    J Clin Microbiol, 2009 May;47(5):1556-8.
    PMID: 19297597 DOI: 10.1128/JCM.01657-08
    A patient with a clonal infection of Burkholderia pseudomallei had subpopulations with ceftazidime and amoxicillin-clavulanate susceptibilities that differed among the clinical specimens. Resistance was associated with a novel Cys69Tyr substitution in the Ambler class A beta-lactamase. Susceptibility testing of multiple colony variants from different sites should be performed for patients with culture-confirmed melioidosis.
    Matched MeSH terms: Burkholderia pseudomallei/drug effects*
  17. Yuen CW, Ong EB, Mohamad S, Manaf UA, Najimudin N
    J Microbiol Biotechnol, 2012 Oct;22(10):1336-42.
    PMID: 23075783
    In Burkholderia pseudomallei, the pathogen that causes melioidosis, the gene cluster encoding the capsular polysaccharide, is located on chromosome 1. Among the 19 capsular genes in this cluster, wzm has not been thoroughly studied. To study the function of wzm, we generated a deletion mutant and compared it with the wild-type strain. The mutant produced less biofilm in minimal media and was more sensitive to desiccation and oxidative stress compared with the wild-type strain, indicating that wzm is involved in biofilm formation and membrane integrity. Scanning electron microscopy showed that the bacterial cells of the mutant strain have more defined surfaces with indentations, whereas cells of the wild-type strain do not.
    Matched MeSH terms: Burkholderia pseudomallei/drug effects
  18. Ramli NS, Eng Guan C, Nathan S, Vadivelu J
    PLoS One, 2012;7(9):e44104.
    PMID: 22970167 DOI: 10.1371/journal.pone.0044104
    Burkholderia pseudomallei, a Gram-negative saprophytic bacterium, is the causative agent of the potentially fatal melioidosis disease in humans. In this study, environmental parameters including temperature, nutrient content, pH and the presence of glucose were shown to play a role in in vitro biofilm formation by 28 B. pseudomallei clinical isolates, including four isolates with large colony variants (LCVs) and small colony variants (SCVs) morphotypes. Enhanced biofilm formation was observed when the isolates were tested in LB medium, at 30 °C, at pH 7.2, and in the presence of as little as 2 mM glucose respectively. It was also shown that all SVCs displayed significantly greater capacity to form biofilms than the corresponding LCVs when cultured in LB at 37 °C. In addition, octanoyl-homoserine lactone (C(8)-HSL), a quorum sensing molecule, was identified by mass spectrometry analysis in bacterial isolates referred to as LCV CTH, LCV VIT, SCV TOM, SCV CTH, 1 and 3, and the presence of other AHL's with higher masses; decanoyl-homoserine lactone (C(10)-HSL) and dodecanoyl-homoserine lactone (C(12)-HSL) were also found in all tested strain in this study. Last but not least, we had successfully acquired two Bacillus sp. soil isolates, termed KW and SA respectively, which possessed strong AHLs degradation activity. Biofilm formation of B. pseudomallei isolates was significantly decreased after treated with culture supernatants of KW and SA strains, demonstrating that AHLs may play a role in B. pseudomallei biofilm formation.
    Matched MeSH terms: Burkholderia pseudomallei/drug effects
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