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厄他培南在体外对肠球菌的活性和耐药机制。

In vitro activity of eravacycline and mechanisms of resistance in enterococci.

机构信息

CHU de Rennes, Service de Bactériologie-Hygiène hospitalière, Rennes, France.

CHU de Rennes, Service de Bactériologie-Hygiène hospitalière, Rennes, France; Université de Rennes 1, Unité Inserm U1230, Rennes, France.

出版信息

Int J Antimicrob Agents. 2020 Dec;56(6):106215. doi: 10.1016/j.ijantimicag.2020.106215. Epub 2020 Oct 27.

DOI:10.1016/j.ijantimicag.2020.106215
PMID:33122095
Abstract

Eravacycline (ERC), the first fluorocycline, is a new tetracycline with superior activity to tigecycline (TGC) against many bacterial species. This work aimed to determine the in vitro activity of ERC compared with other tetracyclines against enterococcal clinical isolates and to analyse corresponding resistance mechanisms. A collection of 60 enterococcal strains was studied: 54 epidemiologically unrelated clinical isolates (46 Enterococcus faecium and 8 Enterococcus faecalis) including 42 vancomycin-resistant enterococci (VRE) (33 vanA and 9 vanB), 3 in vitro TGC-resistant mutants (E. faecium AusTig, HMtig1 and HMtig2) and 3 reference wild-type strains (E. faecium Aus0004 and HM1070, E. faecalis ATCC 29212). In vitro susceptibility was determined using Etest strips (for ERC) or by broth microdilution (for TGC, doxycycline, minocycline and tetracycline). Resistance genes [tet(M), tet(L), tet(O) and tet(S)] were screened by PCR for TGC- and/or ERC-resistant strains as well as sequencing of the rpsJ gene (encoding ribosomal protein S10). MIC values were 0.016/0.08, ≤0.03/0.5, 4/32, 8/16 and 32/>32 mg/L for ERC, TGC, doxycycline, minocycline and tetracycline, respectively. According to EUCAST guidelines, nine strains were categorised as resistant to TGC (MIC, 0.5-8 mg/L), including four E. faecium vanA(+) strains also resistant to ERC (MIC, 0.19-1.5 mg/L). These four strains all possessed at least one mutation in rpsJ and two tet determinants: tet(M) + tet(L) (n = 2); and tet(M) + tet(S) (n = 2). Although ERC has excellent in vitro activity against enterococci (including VRE), emergence of resistance is possible due to combined mechanisms (rpsJ mutations + tet genes).

摘要

依拉环素(ERC)是首个氟环素,是一种新型四环素,其对许多细菌的活性优于替加环素(TGC)。本研究旨在比较 ERC 与其他四环素类药物对肠球菌临床分离株的体外活性,并分析相应的耐药机制。研究了 60 株肠球菌菌株:54 株无流行病学相关性的临床分离株(46 株屎肠球菌和 8 株粪肠球菌),包括 42 株万古霉素耐药肠球菌(VRE)(33 株 vanA 和 9 株 vanB),3 株体外 TGC 耐药突变株(屎肠球菌 AusTig、HMtig1 和 HMtig2)和 3 株参考野生型菌株(屎肠球菌 Aus0004 和 HM1070、粪肠球菌 ATCC 29212)。采用 Etest 条(用于 ERC)或肉汤微量稀释法(用于 TGC、多西环素、米诺环素和四环素)测定体外药敏性。对于 TGC 和/或 ERC 耐药株以及核糖体蛋白 S10 编码基因 rpsJ 的测序,筛选耐药基因[tet(M)、tet(L)、tet(O)和 tet(S)]。ERC、TGC、多西环素、米诺环素和四环素的 MIC 值分别为 0.016/0.08、≤0.03/0.5、4/32、8/16 和 32/>32mg/L。根据 EUCAST 指南,9 株菌株被归类为 TGC 耐药(MIC,0.5-8mg/L),包括 4 株屎肠球菌 vanA(+)株,也对 ERC 耐药(MIC,0.19-1.5mg/L)。这 4 株菌均至少有 1 个 rpsJ 突变和 2 个 tet 决定簇:tet(M) + tet(L)(n=2);tet(M) + tet(S)(n=2)。尽管 ERC 对肠球菌(包括 VRE)具有极好的体外活性,但由于联合机制(rpsJ 突变+tet 基因),耐药性的出现是可能的。

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