Stefanovic Aleksandra, Gowland Leah, Ritchie Gordon, Lee Colin, Chorlton Sam, Matic Nancy, Leung Victor, Payne Michael, Lowe Christopher F, Romney Marc G
Division of Medical Microbiology and Virology, St. Paul's Hospital, Providence Health Care, Vancouver, British Columbia, Canada.
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Microbiol Spectr. 2025 Mar 4;13(3):e0100624. doi: 10.1128/spectrum.01006-24. Epub 2025 Feb 7.
We performed phenotypic susceptibility testing and whole-genome sequencing to investigate mecillinam activity against multidrug-resistant (MDR) . Ninety-five isolates (53 [56%] and 42 [44%] ) were included. The MIC and MIC were 1 and 2 µg/mL, respectively, by agar dilution, and all zone diameters were ≥15 mm by disc diffusion testing. No known clinically relevant mecillinam resistance mutations (including B) were detected. The favorable MIC profile and absence of resistance markers make pivmecillinam an agent worth considering for the treatment of infections caused by MDR . Clinically feasible susceptibility testing methods and standardized interpretations for mecillinam and spp. are needed to guide therapy.
Rapidly emerging resistance in species leaves few antibiotic treatment options. The World Health Organization recommends pivmecillinam, a prodrug of mecillinam, for the treatment of infections. However, little is known about the susceptibility of spp. to mecillinam in North America. We performed mecillinam susceptibility testing on our collection of resistant isolates and investigated genetic mechanisms of resistance using whole-genome sequencing. We observed a favorable mecillinam susceptibility profile and a lack of known genetic mechanisms of resistance. However, in the absence of standardized laboratory guidelines for mecillinam susceptibility testing, interpreting susceptibility test results is challenging. We propose that further studies are needed to correlate susceptibility testing data with clinical outcomes, with the aim of establishing standardized clinical breakpoints for spp. and mecillinam.
我们进行了表型药敏试验和全基因组测序，以研究美西林对多重耐药（MDR）的活性。纳入了95株分离株（53株[56%]和42株[44%]）。通过琼脂稀释法测得的MIC和MIC分别为1和2μg/mL，通过纸片扩散试验测得的所有抑菌圈直径均≥15mm。未检测到已知的临床相关美西林耐药突变（包括B）。良好的MIC谱和无耐药标志物使匹美西林成为治疗由MDR引起的感染值得考虑的药物。需要临床可行的美西林药敏试验方法以及美西林和[具体菌种]的标准化解释来指导治疗。
[具体菌种]中迅速出现的耐药性使得抗生素治疗选择很少。世界卫生组织推荐匹美西林（美西林的前体药物）用于治疗[具体菌种]感染。然而，在北美，关于[具体菌种]对美西林的敏感性知之甚少。我们对收集的耐药[具体菌种]分离株进行了美西林药敏试验，并使用全基因组测序研究了耐药的遗传机制。我们观察到美西林药敏谱良好且缺乏已知的耐药遗传机制。然而，在缺乏美西林药敏试验标准化实验室指南的情况下，解释药敏试验结果具有挑战性。我们建议需要进一步研究将药敏试验数据与临床结果相关联，目的是为[具体菌种]和美西林建立标准化的临床断点。
