Pragai Z, Nagy E
Department of Clinical Microbiology, Albert Szent-Györgyi Medical University, Hungary.
J Antimicrob Chemother. 1998 Dec;42(6):821-4. doi: 10.1093/jac/42.6.821.
We have evaluated the ability of imipenem and meropenem to select, in vitro, resistant mutants of two clinical isolates of Klebsiella pneumoniae producing both SHV and TEM beta-lactamases. Only meropenem selected mutants of both isolates for which the MICs of meropenem, but not imipenem, were markedly higher than those for the parent strains; the MICs of several other beta-lactam antibiotics, including beta-lactam/beta-lactamase inhibitor combinations, for these mutants were also higher than those for the parent strains. In contrast, the MICs for the imipenem-selected mutants were the same as, or similar to, those for the parent strains. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis analysis revealed that an outer membrane protein in both parent strains was absent in the meropenem-selected mutants, but not in the imipenem-selected mutants. This protein is likely to be a porin, the absence of which is presumably associated with impaired beta-lactam permeability and, therefore, the reduced susceptibilities to these antibiotics exhibited by the mutant strains. We believe that this is the first report of the in-vitro selection of porin-deficient mutants of K. pneumoniae following exposure to meropenem.
我们评估了亚胺培南和美罗培南在体外对两株产 SHV 和 TEM β-内酰胺酶的肺炎克雷伯菌临床分离株选择耐药突变体的能力。只有美罗培南选择出了两株分离株的突变体，这些突变体对美罗培南的最低抑菌浓度（MIC）显著高于亲本菌株，而对亚胺培南的 MIC 则不然；包括β-内酰胺/β-内酰胺酶抑制剂组合在内的其他几种β-内酰胺类抗生素对这些突变体的 MIC 也高于亲本菌株。相比之下，亚胺培南选择出的突变体的 MIC 与亲本菌株相同或相似。十二烷基硫酸钠-聚丙烯酰胺凝胶电泳分析显示，两种亲本菌株中的一种外膜蛋白在美罗培南选择出的突变体中缺失，但在亚胺培南选择出的突变体中未缺失。这种蛋白可能是一种孔蛋白，其缺失可能与β-内酰胺通透性受损有关，因此突变菌株对这些抗生素的敏感性降低。我们认为，这是首次报道肺炎克雷伯菌在体外暴露于美罗培南后选择出孔蛋白缺陷突变体的情况。
