Abstract:
: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 microg/ml) and meropenem (up to 16 microg/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 oxyimino-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 MIC, 4 microg/ml, increasing to 16 microg/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.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Martínez-Martínez L,Pascual A,Hernández-Allés S,Alvarez-Díaz D,Suárez AI,Tran J,Benedí VJ,Jacoby GAdoi
10.1128/AAC.43.7.1669subject
Has Abstractpub_date
1999-07-01 00:00:00pages
1669-73issue
7eissn
0066-4804issn
1098-6596journal_volume
43pub_type
杂志文章abstract::The 2-year follow-up results for a randomized placebo-controlled study of 47 patients with multidrug-resistant pulmonary tuberculosis treated with either the new diarylquinoline TMC207, recently renamed bedaquiline, or placebo, added to the first 8 weeks of a background regimen, are presented. Bedaquiline significantl...
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abstract::The biosynthetic gene cluster of lankamycin (LM), a 14-member macrolide antibiotic, is encoded on the 210-kb linear plasmid pSLA2-L in Streptomyces rochei 7434AN4. LM contains a 3-hydroxy-2-butyl group at the C-13 position, which is different from an ethyl group in erythromycin. The following two possibilities could b...
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