biostudies-literatureFen SHYDeutscher Akademischer AustauschdienstNIAID NIH HHSThailand Research FundHHS | NIH | National Institute of Allergy and Infectious DiseasesWellcome TrustAAC.02230-20https://www.ebi.ac.uk/biostudies/studies/S-EPMC8092913biostudies-literatureUnknown95(5)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.Antimicrobial agents and chemotherapyAntibiotic susceptibility of clinical <i>Burkholderia pseudomallei</i> isolates in northeast Thailand during 2015-2018 and the genomic characterization of β-lactam-resistant isolates.PMC8092913MRG6280226U01AI115520U01 AI115520107376/Z/15/Z216457/Z/19/Z91716082Saiprom NChantratita NTanwisaid KDay NPJWest TEChaisuksant SChetchotisakd PEkchariyawat PChantratita WLertmemongkolchai GPhunpang RHompleum TTandhavanant SChayangsu SThiansukhon EChuananont SSangsa NFen SHYSeng RChewapreecha CSilakun WBuasi NMorakot CfalseAntibiotic susceptibility of clinical <i>Burkholderia pseudomallei</i> isolates in northeast Thailand during 2015-2018 and the genomic characterization of β-lactam-resistant isolates.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.2023-01-01T00:00:00Z2023 May2026-05-08T02:16:17.901Z2025-04-06T00:00:18.51ZS-EPMC80929133359384210.1128/AAC.02230-20