Yang Ya-Sung, Lee Yu-Lin, Liu Yuag-Meng, Kuo Chen-Feng, Tan Mei-Chen, Huang Wei-Cheng, Hsu Shu-Yuan, Chang Yea-Yuan, Shang Hung-Sheng, Kuo Shu-Chen
Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Institute of Preventive Medicine, National Defense Medical Center, Taipei, Taiwan.
Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan.
Int J Antimicrob Agents. 2024 Dec;64(6):107378. doi: 10.1016/j.ijantimicag.2024.107378. Epub 2024 Nov 5.
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.
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.
Among 228 non-duplicated isolates, 226 exhibited a MIC of ≤4 mg/L with MIC of 1/2 mg/L. Two isolates had a MIC of 128 mg/L; both patients had multiple comorbidities, were ventilator-dependent and had not received cefiderocol previously. Resistance was attributable to acquisition of bla, carried by a conjugative transposon from Prevotella jejuni, and duplication of intrinsic bla, which led to its overexpression. tetQ coexisted with bla in this conjugative transposon and minocycline facilitated its transfer among E. anophelis. Antibiotics prescribed for source patients did not induce bla duplication. The stabilities of bla and double bla 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.
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.
伊丽莎白菌属对多种抗生素耐药。本研究旨在确定头孢地尔对伊丽莎白菌属的体外和体内活性，并研究其耐药机制。
从四家医院收集血流感染分离株。分别采用肉汤微量稀释法和蜡螟模型测定体外和体内活性。通过基因组比较和基因编辑来确认靶基因的作用。分别采用接合试验和连续传代来确定耐药性的可转移性和稳定性。将≤4mg/L的最低抑菌浓度（MIC）指定为敏感折点。
在228株非重复分离株中，226株的MIC≤4mg/L，MIC为1/2mg/L。两株分离株的MIC为128mg/L；这两名患者均有多种合并症，依赖呼吸机，且此前未接受过头孢地尔治疗。耐药性归因于从空肠普雷沃菌获得的携带bla的接合转座子，以及固有bla的复制，导致其过度表达。tetQ与bla共存于该接合转座子中，米诺环素促进其在嗜蚊伊氏菌之间转移。为源患者开具的抗生素未诱导bla复制。连续传代10天后，bla和双bla的稳定性分别为100%和>90%。头孢地尔未能挽救感染耐药菌株的蛾幼虫，但去除耐药机制可恢复体内疗效。
头孢地尔对伊丽莎白菌属具有体外和体内活性，但由于耐药机制的可获得性、可转移性和/或稳定性，可能会出现耐药性。
