Suchartlikitwong Pintip, Saninjuk Kritsakorn, Tirapattanun Aschana, Kongsai Jindaporn, Benjatikun Watcharin, Wongsurawat Thidathip, Chirakul Sunisa
Department of Microbiology, Division of Bacteriology, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand; Department of Pediatrics, Center of Excellence for Pediatric Infectious Diseases and Vaccines, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
School of Science, Mae Fah Luang University, Chiang Rai, Thailand; Microbial Products and Innovation Research Group, Mae Fah Luang University, Chiang Rai, Thailand.
J Glob Antimicrob Resist. 2025 Jun;43:319-326. doi: 10.1016/j.jgar.2025.05.006. Epub 2025 May 12.
This study aimed to characterize the clinical, phenotypic, and genomic attributes of Burkholderia pseudomallei isolates before and after the development of decreased susceptibility to β-lactam antibiotics during therapy.
Paired B. pseudomallei isolates collected before (SCBP001) and 23 days after intravenous ceftazidime (CAZ) therapy (SCBP007) were evaluated. Minimal inhibitory concentrations (MICs) for CAZ and meropenem (MEM) were initially determined using Etest and subsequently confirmed by broth microdilution (BMD). Whole-genome sequencing (WGS) was performed to identify genetic mutations associated with resistance.
A 12-year-old boy presented with acute pyelonephritis and kidney injury. MICs showed decreased susceptibility to CAZ and MEM, although the value remained within the susceptible range according to Clinical and Laboratory Standards Institute (CLSI) breakpoint criteria. MICs increased from 1 µg/mL for both CAZ and MEM in SCBP001 to 8 µg/mL for CAZ and 3 µg/mL for MEM in SCBP007. BMD confirmed a further increase in CAZ MIC to 32 µg/mL in SCBP007. WGS revealed no known CAZ-resistance mutations in penA coding sequences but identified a G(-78)A mutation upstream of penA, associated with increased promoter activity and β-lactam resistance. Multi-locus sequence typing (MLST) confirmed both isolates as sequence type 99, originating from the same clone. Phenotypic evaluation on Ashdown's agar showed consistent morphotype I characteristics for both isolates.
This case highlights the potential for B. pseudomallei to develop resistance during therapy. Early detection of decreased susceptibility, even within the susceptible range, using rapid molecular diagnostics is critical for timely antibiotic adjustments and improved patient outcomes.
本研究旨在描述在治疗期间对β-内酰胺类抗生素敏感性降低前后的伯克霍尔德菌分离株的临床、表型和基因组特征。
对静脉注射头孢他啶（CAZ）治疗前（SCBP001）和治疗23天后（SCBP007）收集的成对伯克霍尔德菌分离株进行评估。最初使用Etest测定CAZ和美罗培南（MEM）的最低抑菌浓度（MIC），随后通过肉汤微量稀释法（BMD）进行确认。进行全基因组测序（WGS）以鉴定与耐药性相关的基因突变。
一名12岁男孩出现急性肾盂肾炎和肾损伤。MIC显示对CAZ和MEM的敏感性降低，尽管根据临床和实验室标准协会（CLSI）的断点标准，该值仍在敏感范围内。MIC从SCBP001中CAZ和MEM的1μg/mL增加到SCBP007中CAZ的8μg/mL和MEM的3μg/mL。BMD证实SCBP007中CAZ的MIC进一步增加至32μg/mL。WGS显示penA编码序列中没有已知的CAZ耐药突变，但在penA上游鉴定出一个G（-78）A突变，与启动子活性增加和β-内酰胺耐药性相关。多位点序列分型（MLST）证实这两个分离株均为序列型99，源自同一克隆。在阿什当琼脂上的表型评估显示两个分离株均具有一致的I型形态特征。
该病例突出了伯克霍尔德菌在治疗期间产生耐药性的可能性。使用快速分子诊断方法早期检测敏感性降低，即使在敏感范围内，对于及时调整抗生素和改善患者预后至关重要。
