{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Fen SHY"],"funding":["Deutscher Akademischer Austauschdienst","NIAID NIH HHS","Thailand Research Fund","HHS | NIH | National Institute of Allergy and Infectious Diseases","Wellcome Trust"],"pagination":["AAC.02230-20"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8092913"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["95(5)"],"pubmed_abstract":["Melioidosis is an often fatal infection in tropical regions caused by an environmental bacterium, <i>Burkholderia pseudomallei</i> Current recommended melioidosis treatment requires intravenous β-lactam antibiotics such as ceftazidime (CAZ), meropenem (MEM) or amoxicillin-clavulanic acid (AMC) and oral trimethoprim-sulfamethoxazole. Emerging antibiotic resistance could lead to therapy failure and high mortality. We performed a prospective multicentre study in northeast Thailand during 2015-2018 to evaluate antibiotic susceptibility and characterize β-lactam resistance in clinical <i>B. pseudomallei</i> isolates. Collection of 1,317 <i>B. pseudomallei</i> isolates from patients with primary and relapse infections were evaluated for susceptibility to CAZ, imipenem (IPM), MEM and AMC. β-lactam resistant isolates were confirmed by broth microdilution method and characterized by whole genome sequence analysis, <i>penA</i> expression and β-lactamase activity. The resistant phenotype was verified via <i>penA</i> mutagenesis. All primary isolates were IPM-susceptible but we observed two CAZ-resistant and one CAZ-intermediate resistant isolates, two MEM-less susceptible isolates, one AMC-resistant and two AMC-intermediate resistant isolates. One of 13 relapse isolates was resistant to both CAZ and AMC. Two isolates were MEM-less susceptible. Strains DR10212A (primary) and DR50054E (relapse) were multi-drug resistant. Genomic and mutagenesis analyses supplemented with gene expression and β-lactamase analyses demonstrated that CAZ-resistant phenotype was caused by PenA variants: P167S (N=2) and <i>penA</i> amplification (N=1). Despite the high mortality rate in melioidosis, our study revealed that <i>B. pseudomallei</i> isolates had a low frequency of β-lactam resistance caused by <i>penA</i> alterations. Clinical data suggest that resistant variants may emerge in patients during antibiotic therapy and be associated with poor response to treatment."],"journal":["Antimicrobial agents and chemotherapy"],"pubmed_title":["Antibiotic susceptibility of clinical <i>Burkholderia pseudomallei</i> isolates in northeast Thailand during 2015-2018 and the genomic characterization of β-lactam-resistant isolates."],"pmcid":["PMC8092913"],"funding_grant_id":["MRG6280226","U01AI115520","U01 AI115520","107376/Z/15/Z","216457/Z/19/Z","91716082"],"pubmed_authors":["Saiprom N","Chantratita N","Tanwisaid K","Day NPJ","West TE","Chaisuksant S","Chetchotisakd P","Ekchariyawat P","Chantratita W","Lertmemongkolchai G","Phunpang R","Hompleum T","Tandhavanant S","Chayangsu S","Thiansukhon E","Chuananont S","Sangsa N","Fen SHY","Seng R","Chewapreecha C","Silakun W","Buasi N","Morakot C"],"additional_accession":[]},"is_claimable":false,"name":"Antibiotic susceptibility of clinical <i>Burkholderia pseudomallei</i> isolates in northeast Thailand during 2015-2018 and the genomic characterization of β-lactam-resistant isolates.","description":"Melioidosis is an often fatal infection in tropical regions caused by an environmental bacterium, <i>Burkholderia pseudomallei</i> Current recommended melioidosis treatment requires intravenous β-lactam antibiotics such as ceftazidime (CAZ), meropenem (MEM) or amoxicillin-clavulanic acid (AMC) and oral trimethoprim-sulfamethoxazole. Emerging antibiotic resistance could lead to therapy failure and high mortality. We performed a prospective multicentre study in northeast Thailand during 2015-2018 to evaluate antibiotic susceptibility and characterize β-lactam resistance in clinical <i>B. pseudomallei</i> isolates. Collection of 1,317 <i>B. pseudomallei</i> isolates from patients with primary and relapse infections were evaluated for susceptibility to CAZ, imipenem (IPM), MEM and AMC. β-lactam resistant isolates were confirmed by broth microdilution method and characterized by whole genome sequence analysis, <i>penA</i> expression and β-lactamase activity. The resistant phenotype was verified via <i>penA</i> mutagenesis. All primary isolates were IPM-susceptible but we observed two CAZ-resistant and one CAZ-intermediate resistant isolates, two MEM-less susceptible isolates, one AMC-resistant and two AMC-intermediate resistant isolates. One of 13 relapse isolates was resistant to both CAZ and AMC. Two isolates were MEM-less susceptible. Strains DR10212A (primary) and DR50054E (relapse) were multi-drug resistant. Genomic and mutagenesis analyses supplemented with gene expression and β-lactamase analyses demonstrated that CAZ-resistant phenotype was caused by PenA variants: P167S (N=2) and <i>penA</i> amplification (N=1). Despite the high mortality rate in melioidosis, our study revealed that <i>B. pseudomallei</i> isolates had a low frequency of β-lactam resistance caused by <i>penA</i> alterations. Clinical data suggest that resistant variants may emerge in patients during antibiotic therapy and be associated with poor response to treatment.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 May","modification":"2026-05-08T02:16:17.901Z","creation":"2025-04-06T00:00:18.51Z"},"accession":"S-EPMC8092913","cross_references":{"pubmed":["33593842"],"doi":["10.1128/AAC.02230-20"]}}