Service de Bactériologie-Virologie, INSERM U914 Emerging Resistance to Antibiotics, Hôpital de Bicêtre, 94275 Le Kremlin-Bicêtre, Assistance Publique/Hôpitaux de Paris, Faculté de Médecine Paris-Sud, France.
Int J Antimicrob Agents. 2010 Mar;35(3):265-8. doi: 10.1016/j.ijantimicag.2009.10.021.
Four Klebsiella pneumoniae isolates (KP1-4) were recovered sequentially from an infected patient. Whilst KP1-3 were resistant to all beta-lactams except carbapenems, KP4 recovered after 24 days of imipenem-containing treatment showed additional resistance to carbapenems. No carbapenem hydrolysis could be identified in KP4. Molecular characterisation revealed that KP1-4 were indistinguishable by pulsed-field gel electrophoresis, contained a 95-kb self-transferable plasmid harbouring bla(CTXM-15) and bla(TEM-1) genes and a 65-kb plasmid that was not transferred by conjugation into Escherichia coli, and harboured the plasmid-mediated bla(DHA-1) AmpC beta-lactamase gene. In addition, KP4 failed to express OmpK36 owing to a point mutation leading to a premature stop of the protein. This study demonstrates development of carbapenem resistance related to loss of OmpK36 expression in a K. pneumoniae isolate harbouring extended-spectrum beta-lactamase and plasmid-mediated cephalosporinase genes following prolonged imipenem exposure.
从一名感染患者身上连续分离到 4 株肺炎克雷伯菌（KP1-4）。尽管 KP1-3 对除碳青霉烯类以外的所有β-内酰胺类药物均具有耐药性，但在使用亚胺培南治疗 24 天后分离得到的 KP4 显示出对碳青霉烯类药物的额外耐药性。在 KP4 中未发现碳青霉烯水解酶。分子特征表明，KP1-4 通过脉冲场凝胶电泳无法区分，均含有携带 bla(CTXM-15)和 bla(TEM-1)基因的 95kb 可自我转移质粒和不能通过接合转移到大肠杆菌中的 65kb 质粒，且均携带质粒介导的 bla(DHA-1)AmpC β-内酰胺酶基因。此外，由于点突变导致蛋白过早终止，KP4 未能表达 OmpK36。本研究表明，在一株携带超广谱β-内酰胺酶和质粒介导头孢菌素酶基因的肺炎克雷伯菌中，由于长时间暴露于亚胺培南，导致 OmpK36 表达缺失，从而产生了碳青霉烯类耐药性。
