國家衛生研究院 NHRI:Item 3990099045/16274
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    题名: Acquired bla(CfxA-3) carried by a conjugative transposon or duplicated intrinsic bla(CME-3) mediates cefiderocol resistance in Elizabethkingia anophelis clinical isolates
    作者: Yang, YS;Lee, YL;Liu, YM;Kuo, CF;Tan, MC;Huang, WC;Hsu, SY;Chang, YY;Shang, HS;Kuo, SC
    贡献者: National Institute of Infectious Diseases and Vaccinology;Institute of Population Health Sciences
    摘要: OBJECTIVES: Elizabethkingia spp. are resistant to multiple antibiotics. This study aimed to determine in vitro and in vivo activities of cefiderocol against Elizabethkingia spp. and to investigate resistance mechanisms. METHODS: Bloodstream isolates were collected from four hospitals. In vitro and in vivo activities were determined using broth microdilution and the wax moth model, respectively. Genome comparison and gene editing were used to confirm the contribution of target genes. Conjugation experiments and serial passage were used to determine transferability and stability, respectively. A MIC of ≤ 4 mg/L was designated as the susceptibility breakpoint. RESULTS: Among 228 non-duplicated isolates, 226 exhibited a MIC of ≤ 4 mg/L with MIC(50/90) of 1/2 mg/L. Two isolates had a MIC of 128 mg/L; both source patients had multiple comorbidities, were ventilator-dependent, and had not received cefiderocol previously. Resistance was attributable to acquisition of bla(CfxA-3), carried by a conjugative transposon from Prevotella jejuni, and duplication of intrinsic bla(CME-3), which led to its overexpression. tetQ coexisted with bla(CfxA-3) in this conjugative transposon and minocycline facilitated its transfer among E. anophelis. Antibiotics prescribed for source patients did not induce bla(CME-3) duplication. The stabilities of bla(CfxA-3) and double bla(CME-3) were 100% and > 90%, respectively, after 10-day serial passage. Cefiderocol failed to rescue moth larvae infected with resistant strains, but removal of resistance mechanisms restored in vivo efficacy. CONCLUSIONS: Cefiderocol was in vitro and in vivo active against Elizabethkingia spp. but resistance may emerge due to the availability, transferability, and/or stability of resistance mechanisms.
    日期: 2024-11-05
    關聯: International Journal of Antimicrobial Agents. 2024 Nov 05;Article in Press.
    Link to: http://dx.doi.org/10.1016/j.ijantimicag.2024.107378
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0924-8579&DestApp=IC2JCR
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