Distribution of blaOXA genes among Malaysian Burkholderia pseudomallei isolates and correlation with patient outcome

• Published in: International journal of infectious diseases 2022-03, Vol.116, p.S1-S2
• Main Authors: Arushothy, R., Hashim, R., Cheng, S., Nathan, S.
• Format: Article
• Language: English
• ISSN: 1201-9712; 1878-3511
• DOI: 10.1016/j.ijid.2021.12.003

Melioidosis is endemic in Malaysia and is caused by the Gram-negative bacterium Burkholderia pseudomallei. Melioidosis manifests as either localized or disseminated, involving multiple organs of the body and is usually fatal if untreated. Treatment includes an intensive and maintenance phase, and carbapenems, such as ceftazidime, are usually the drugs of choice. However, despite displaying a sensitive susceptibility profile in vitro, there have been several reports of carbapenem treatment failure. In this study, we aim to correlate in vitro susceptibility with the type of Carbapenem-hydrolysing class D beta-lactamase (blaOXA) encoding genes and melioidosis patient outcome. Eighty-four B. pseudomallei isolates, obtained from patients confirmed with melioidosis, were used in this study. All isolates were isolated from blood and collected from all over Malaysia. The Minimum Inhibitory Concentrations (MIC) for amoxicillin-clavulanate, ceftazidime, imipenem, doxycycline, tetracycline and trimethoprim-sulfamethoxazole were determined using the E-test. Genomic DNA was extracted and subjected to whole genome sequencing using the Illumina HiSeq 2500 platform. The raw data was aligned, assembled and annotated using the bacterial bioinformatics database and analysis resource pipeline, PATRIC. The screen for blaOXA genes was performed using ResFinder 4.0. Principal Component Analysis was performed to visualise the correlation between the blaOXA genes content and patient outcome. Seventy-six (90.5%) isolates were sensitive to all the antimicrobials tested. All isolates were sensitive to ceftazidime (MIC90 range: 0.75 to 3.00μg/ml) and imipenem (MIC90 range: 0.19 to 1.00μg/ml). The distribution of blaOXA genes in all isolates was 65.5% blaOXA-59, 17.9% blaOXA-43 gene and 16.7% blaOXA-57. A biplot graph showed significant correlation between blaOXA-59 gene and patient outcome in those who succumbed to infection. All B. pseudomallei isolates were susceptible to carbapenems, however, the detection of beta-lactamase-encoding blaOXA genes suggests the possibility that patients died as a result of treatment failure. Further studies to assess the action of blaOXA genes in vivo is required.