Grooters Susan V, Mollenkopf Dixie F, Ballash Gregory A, Wittum Thomas E
Department of Veterinary Preventive Medicine, The Ohio State University, Columbus, Ohio, USA.
Access Microbiol. 2025 Jun 26;7(6). doi: 10.1099/acmi.0.000972.v4. eCollection 2025.
Antibiotic-resistant infections cause an estimated 2.8 million illnesses and 35,900 deaths annually in the USA. Carbapenems are a class of antibiotics that are generally reserved to treat life-threatening invasive infections including sepsis. Accurate diagnosis of carbapenem-resistant infections is critical for early and appropriate treatment. encodes bacterial production of the IMP metallo-beta-lactamase (MBL), which can confer resistance to all the beta-lactams including carbapenems. Zinc is an essential co-factor in the IMP MBL enzymatic hydrolysis of carbapenems. Tests for the presence of IMP carbapenemase, such as the Carba NP, include zinc sulphate (ZnSO) although broth dilution methods for determining MIC for carbapenems may vary. We hypothesized that ZnSO availability would improve the accuracy of carbapenem MIC determination for bacteria expressing . Thus, the objective of this study was to determine if supplemental ZnSO affects the carbapenem MICs of , and expressing . Isolates utilized for this study were originally recovered from environmental samples collected at farms, wastewater treatment plants and surface water. They were selected based on phenotypic non-susceptibility to carbapenems and genetic confirmation of bacterial carriage of . Cation-adjusted Mueller-Hinton broth suspensions of each isolate standardized to a 0.5 MacFarland standard were tested with and without ZnSO added at 0.1 mmol l concentration to determine MICs using standard extended-spectrum beta-lactamase microbroth dilution MIC panels. Although we observed that imipenem MICs were higher (<0.001) than those from other bacteria harbouring , the inclusion of supplemental ZnSO did not influence carbapenem MIC. This suggests that supplemental ZnSO will not improve the accuracy of carbapenem MICs in environmental bacteria expressing IMP carbapenemase. Additional research will be required to identify important factors that may influence the expression of carbapenemase including IMP and the accurate determination of clinical MICs, which is critical to appropriate therapeutic decision-making.
在美国，抗生素耐药性感染每年估计导致280万例疾病和35900人死亡。碳青霉烯类抗生素是一类通常用于治疗包括败血症在内的危及生命的侵袭性感染的抗生素。准确诊断碳青霉烯类耐药感染对于早期和适当治疗至关重要。 编码IMP金属β-内酰胺酶（MBL）的细菌产生，该酶可赋予对包括碳青霉烯类在内的所有β-内酰胺类抗生素的耐药性。锌是IMP MBL对碳青霉烯类进行酶促水解的必需辅助因子。检测IMP碳青霉烯酶的方法，如Carba NP试验，包括硫酸锌（ZnSO），尽管用于确定碳青霉烯类抗生素最低抑菌浓度（MIC）的肉汤稀释方法可能有所不同。我们假设硫酸锌的可用性将提高表达 的细菌对碳青霉烯类抗生素MIC测定的准确性。因此，本研究的目的是确定补充硫酸锌是否会影响表达 的 、 和 的碳青霉烯类抗生素MIC。本研究使用的分离株最初从农场、污水处理厂和地表水采集的环境样本中分离得到。它们是根据对碳青霉烯类抗生素的表型不敏感性以及细菌携带 的基因确认而选择的。使用标准的超广谱β-内酰胺酶微量肉汤稀释MIC板，对每个标准化至0.5麦氏标准的分离株的阳离子调整后的 Mueller-Hinton肉汤悬液，在添加和不添加浓度为0.1 mmol/L的硫酸锌的情况下进行测试，以确定MIC。尽管我们观察到 亚胺培南的MIC高于携带 的其他细菌（<0.001），但补充硫酸锌并未影响碳青霉烯类抗生素的MIC。这表明补充硫酸锌不会提高表达IMP碳青霉烯酶的环境细菌中碳青霉烯类抗生素MIC的准确性。需要进一步的研究来确定可能影响碳青霉烯酶表达（包括IMP）的重要因素以及临床MIC的准确测定，这对于适当的治疗决策至关重要。
