Bouvier Maxime, Freire Samanta, Findlay Jacqueline, Nordmann Patrice
Medical and Molecular Microbiology, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland.
Swiss National Reference Center for Emerging Antibiotic Resistance (NARA), University of Fribourg, Fribourg, Switzerland.
Microb Drug Resist. 2025 Jan;31(1):16-20. doi: 10.1089/mdr.2024.0104. Epub 2024 Nov 25.
Carbapenenemase producers, particularly the metallo-β-lactamase (MBL) types in , have emerged as an urgent threat in health care settings. MBLs require zinc at their catalytic site and can be inhibited by dimercaptosuccinic acid (DMSA), a metal chelator known for the treatment of lead and mercury intoxication. Isogenic strains of wild-type and OprD-deleted PA14, were constructed, producing the MBLs VIM-2, NDM-1, SPM-1, IMP-1, and AIM-1, or the non-MBL carbapenemases, GES-5 and KPC-2. In addition, 59 previously characterized clinical isolates of producing different ß-lactamases (including carbapenemases), and with known outer-membrane porin OprD status, were utilized. Minimal inhibitory concentrations values of imipenem and meropenem, and DMSA combinations were determined, and time-kill assays were performed with PA14 expressing VIM-2. Results indicated a significant additive effect of DMSA (most effective at 3 mM) and carbapenems in recombinant and clinical strains of expressing MBLs, in particular against VIM producers, which are the most prevalent carbapenemases in . This effect was best evidenced with meropenem and in strains without OprD modification. DMSA shows promising efficacy, particularly in combination therapy with meropenem, for treating infections caused by MBL-producing .
产碳青霉烯酶的细菌，尤其是其中的金属β-内酰胺酶（MBL）类型，已成为医疗机构中的一个紧迫威胁。MBL在其催化位点需要锌，并且可被二巯基琥珀酸（DMSA）抑制，DMSA是一种用于治疗铅和汞中毒的金属螯合剂。构建了野生型和缺失OprD的PA14的同基因菌株，它们分别产生MBL VIM-2、NDM-1、SPM-1、IMP-1和AIM-1，或非MBL碳青霉烯酶GES-5和KPC-2。此外，还利用了59株先前已鉴定的临床分离株，这些分离株产生不同的β-内酰胺酶（包括碳青霉烯酶），且外膜孔蛋白OprD状态已知。测定了亚胺培南、美罗培南及DMSA组合的最低抑菌浓度值，并对表达VIM-2的PA14进行了时间杀菌试验。结果表明，在表达MBL的重组菌株和临床菌株中，DMSA（在3 mM时最有效）与碳青霉烯类药物有显著的相加作用，特别是对VIM产生菌，VIM产生菌是[具体地点未给出]中最常见的碳青霉烯酶。这种作用在美罗培南及未修饰OprD的菌株中最为明显。DMSA显示出有前景的疗效，特别是与美罗培南联合治疗由产MBL的[细菌名称未给出]引起的感染时。
