Roles of β-lactamases and porins is activities of carbapenems and cephalosporins against Klebsiella pneumoniae
Roles of β-lactamases and porins is activities of carbapenems and cephalosporins against Klebsiella pneumoniae
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DOI：
10.1128/aac.43.7.1669
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发表时间：
1999-07-01
影响因子：
4.9
通讯作者：
Jacoby, GA
中科院分区：
文献类型：
--
作者：
Martínez-Martínez, L;Pascual, A;Jacoby, GA
两株产广谱β -内酰胺酶（ESBL）的肺炎克雷伯菌对亚胺培南的敏感性低于预期。两者都缺少作为抗生素进入通道的外膜蛋白。通过消除原始ESBL并引入编码各种ESBL和AmpC β -内酰胺酶类型的质粒，研究增加接种量的效果，以及评估与β -内酰胺酶抑制剂的相互作用，研究了β -内酰胺酶在耐药性中的作用。通过在质粒上恢复一个功能性的ompK36基因，研究了孔蛋白缺乏的贡献。在缺乏孔蛋白的菌株中，编码ampc型β -内酰胺酶的质粒对亚胺培南（高达64 μ g/ml）和美罗培南（高达16 μ g/ml）具有抗性。碳青霉烯耐药表现出很小的接种效应，不受克拉维酸盐的影响，但被BRL 42715阻断，如果恢复OmpK36孔蛋白，则抗性减弱，编码TEM-和shv型ESBLs的质粒使其对头孢吡肟和头孢匹罗以及早期的酰亚胺- β -内酰胺产生抗性。这种抗性随着接种量的增加而增强，被克拉维酸阻断，并通过修复OmpK36孔蛋白而降低。此外，当孔蛋白缺失时，SHV-2 β -内酰胺酶对碳青霉烯类耐药（亚胺培南MIG为4 μ g/ml，随着接种量的增加而增加到16 μ g/ml）的影响较小。因此，在肺炎克雷伯菌中，孔蛋白丢失可增强TEM或shv型ESBLs或质粒介导的AmpC酶（包括最新的氧亚胺- β -内酰胺类和碳青霉烯类）提供的耐药性。
Two clinical isolates of extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae were noted to be less susceptible than expected to imipenem. Both were missing outer membrane proteins that serve as channels for antibiotic entry. The role of beta-lactamase in resistance was investigated by eliminating the original ESBL and introducing plasmids encoding various ESBLs and AmpC beta-lactamase types, by studying the effect of an increased inoculum, and by evaluating interactions with beta-lactamase inhibitors. The contribution of porin deficiency was investigated by restoring a functional ompK36 gene on a plasmid. Plasmids encoding AmpC-type beta-lactamases provided resistance to imipenem (up to 64 mu g/ml) and meropenem (up to 16 mu g/ml) in strains deficient in porins. Carbapenem resistance showed little inoculum effect, was not affected by clavulanate but was blocked by BRL 42715, and was diminished if OmpK36 porin was restored, Plasmids encoding TEM- and SHV-type ESBLs conferred resistance to cefepime and cefpirome, as well as to earlier onyimino-beta-lactams. This resistance was magnified with an increased inoculum, was blocked by clavulanate, and was also lowered by OmpK36 porin restoration. In addition, SHV-2 beta-lactamase had a small effect on carbapenem resistance (imipenem MIG, 4 mu g/ml, increasing to 16 mu g/ml with a higher inoculum) when porins were absent. In K. pneumoniae porin loss can thus augment resistance provided either by TEM- or SHV-type ESBLs or by plasmid-mediated AmpC enzymes to include the latest oxyimino-beta-lactams and carbapenems.