在治疗产 GES-5 的感染期间导致头孢他啶/阿维巴坦耐药性发展的机制。
Mechanisms leading to ceftazidime/avibactam resistance development during treatment of GES-5-producing infections.
机构信息
Servicio de Microbiología, Hospital Universitario La Princesa, Madrid, Spain.
Servicio de Microbiología and Unidad de Investigación, Hospital Universitario Son Espases, Instituto de Investigación Sanitaria Illes Balears (IdISBa), CIBERINFEC, Palma de Mallorca, Spain.
出版信息
Antimicrob Agents Chemother. 2024 Nov 6;68(11):e0116424. doi: 10.1128/aac.01164-24. Epub 2024 Oct 21.
Abstract
The mechanisms underlying ceftazidime/avibactam resistance development in four ceftazidime/avibactam susceptible/resistant pairs of GES-5-producing ST235 clinical isolates were investigated. In three of the cases, ceftazidime/avibactam resistance was driven by a single mutation leading to GES-27 (P162Q), GES-29 (P162A), or the novel GES-60 (N136S), as confirmed through cloning experiments. Moreover, these mutations were associated with increased cefiderocol MICs but reduced carbapenem, particularly imipenem/relebactam, resistance. Understanding the complexity of resistance mechanisms to the growing repertoire of antipseudomonal β-lactams is crucial to guide optimized treatments and antimicrobial stewardship measures.
摘要
研究了 4 对产 GES-5 的 ST235 临床分离株中头孢他啶/阿维巴坦敏感/耐药对中头孢他啶/阿维巴坦耐药发展的机制。在三种情况下，头孢他啶/阿维巴坦耐药是由单个突变驱动的，导致 GES-27（P162Q）、GES-29（P162A）或新型 GES-60（N136S），这通过克隆实验得到证实。此外，这些突变与增加的头孢地尔肟 MIC 相关，但降低了碳青霉烯类，特别是亚胺培南/雷巴他定的耐药性。了解对不断增加的抗假单胞菌β-内酰胺类药物的耐药机制的复杂性对于指导优化治疗和抗菌药物管理措施至关重要。
相似文献
1
Mechanisms leading to ceftazidime/avibactam resistance development during treatment of GES-5-producing infections.在治疗产 GES-5 的感染期间导致头孢他啶/阿维巴坦耐药性发展的机制。
Antimicrob Agents Chemother. 2024 Nov 6;68(11):e0116424. doi: 10.1128/aac.01164-24. Epub 2024 Oct 21.
2
Mutant prevention concentrations and phenotypic and genomic profiling of first-step resistance mechanisms to classical and novel β-lactams in .突变预防浓度以及对经典和新型β-内酰胺类药物第一步耐药机制的表型和基因组分析
Antimicrob Agents Chemother. 2025 Apr 2;69(4):e0194224. doi: 10.1128/aac.01942-24. Epub 2025 Mar 11.
3
In vitro activity of cefepime-zidebactam, ceftolozane-tazobactam, ceftazidime-avibactam, imipenem-relebactam, and other comparators against imipenem-non-susceptible Pseudomonas aeruginosa in Taiwan, 2022.2022年台湾地区头孢吡肟-他唑巴坦、头孢托罗-他唑巴坦、头孢他啶-阿维巴坦、亚胺培南-瑞来巴坦及其他对照药物对亚胺培南不敏感铜绿假单胞菌的体外活性
Int J Antimicrob Agents. 2025 Sep;66(3):107550. doi: 10.1016/j.ijantimicag.2025.107550. Epub 2025 Jun 4.
4
Mutant prevention concentrations, resistance evolution dynamics, and mechanisms of resistance to imipenem and imipenem/relebactam in carbapenem-susceptible isolates showing ceftazidime/avibactam resistance.对头孢他啶/阿维巴坦耐药的碳青霉烯敏感菌株中，亚胺培南及亚胺培南/瑞来巴坦的突变预防浓度、耐药性演变动态及耐药机制
Antimicrob Agents Chemother. 2024 Dec 5;68(12):e0112024. doi: 10.1128/aac.01120-24. Epub 2024 Nov 15.
5
Resistance to ceftazidime-avibactam and other new β-lactams in clinical isolates: a multi-center surveillance study.临床分离株对头孢他啶-阿维巴坦及其他新型β-内酰胺类药物的耐药性：一项多中心监测研究。
Microbiol Spectr. 2024 Aug 6;12(8):e0426623. doi: 10.1128/spectrum.04266-23. Epub 2024 Jun 27.
6
Activity of cefiderocol, imipenem/relebactam, cefepime/taniborbactam and cefepime/zidebactam against ceftolozane/tazobactam- and ceftazidime/avibactam-resistant Pseudomonas aeruginosa.头孢地尔肟、亚胺培南/雷巴他定、头孢吡肟/他唑巴坦和头孢吡肟/齐多夫定对头孢他啶/他唑巴坦和头孢噻肟/阿维巴坦耐药铜绿假单胞菌的活性。
J Antimicrob Chemother. 2022 Sep 30;77(10):2809-2815. doi: 10.1093/jac/dkac241.
7
Emergence of KPC-8-producing infection without prior exposure to ceftazidime/avibactam: the threat of infections by ceftazidime/avibactam-resistant KPC variants.在未预先接触头孢他啶/阿维巴坦的情况下出现产KPC-8感染：头孢他啶/阿维巴坦耐药KPC变体感染的威胁。
Antimicrob Agents Chemother. 2025 Jun 4;69(6):e0149424. doi: 10.1128/aac.01494-24. Epub 2025 Apr 22.
8
ARGONAUT-III and -V: susceptibility of carbapenem-resistant and multidrug-resistant to the bicyclic boronate β-lactamase inhibitor taniborbactam combined with cefepime.ARGONAUT-III 和 -V：碳青霉烯类耐药和多重耐药对双环硼酸β-内酰胺酶抑制剂替加环素与头孢吡肟联合用药的敏感性。
Antimicrob Agents Chemother. 2024 Sep 4;68(9):e0075124. doi: 10.1128/aac.00751-24. Epub 2024 Aug 12.
9
In vivo divergent evolution of cross-resistance to new β-lactam/β-lactamase inhibitor combinations in Pseudomonas aeruginosa following ceftazidime/avibactam treatment.在接受头孢他啶/阿维巴坦治疗后，铜绿假单胞菌对新型β-内酰胺/β-内酰胺酶抑制剂组合产生交叉耐药性的体内趋异进化。
Infection. 2025 Apr;53(2):635-647. doi: 10.1007/s15010-024-02432-5. Epub 2024 Nov 8.
10
Addressing carbapenemase-producing extensively drug-resistant Pseudomonas aeruginosa: the potential of cefiderocol and ceftazidime/avibactam plus aztreonam therapy.应对产碳青霉烯酶的广泛耐药铜绿假单胞菌：头孢地尔及头孢他啶/阿维巴坦联合氨曲南治疗的潜力
Eur J Clin Microbiol Infect Dis. 2025 May;44(5):1077-1087. doi: 10.1007/s10096-025-05061-4. Epub 2025 Feb 18.
本文引用的文献
1
Pseudomonasaeruginosa antimicrobial susceptibility profiles, resistance mechanisms and international clonal lineages: update from ESGARS-ESCMID/ISARPAE Group.铜绿假单胞菌抗菌药物敏感性谱、耐药机制及国际克隆谱系：ESGARS-ESCMID/ISARPAE 集团的最新研究进展。
Clin Microbiol Infect. 2024 Apr;30(4):469-480. doi: 10.1016/j.cmi.2023.12.026. Epub 2023 Dec 30.
2
In vitro activity of cefiderocol against a global collection of carbapenem-resistant Pseudomonas aeruginosa with a high level of carbapenemase diversity.头孢地尔罗对具有高度碳青霉烯酶多样性的全球碳青霉烯类耐药铜绿假单胞菌的体外活性。
J Antimicrob Chemother. 2024 Feb 1;79(2):412-416. doi: 10.1093/jac/dkad396.
3
antibiotic susceptibility profiles, genomic epidemiology and resistance mechanisms: a nation-wide five-year time lapse analysis.抗生素敏感性谱、基因组流行病学及耐药机制：一项全国范围的五年时间跨度分析
Lancet Reg Health Eur. 2023 Sep 19;34:100736. doi: 10.1016/j.lanepe.2023.100736. eCollection 2023 Nov.
4
Global epidemiology and clinical outcomes of carbapenem-resistant Pseudomonas aeruginosa and associated carbapenemases (POP): a prospective cohort study.碳青霉烯类耐药铜绿假单胞菌和相关碳青霉烯酶（POP）的全球流行病学和临床结局：一项前瞻性队列研究。
Lancet Microbe. 2023 Mar;4(3):e159-e170. doi: 10.1016/S2666-5247(22)00329-9. Epub 2023 Feb 9.
5
Cefiderocol resistance genomics in sequential chronic Pseudomonas aeruginosa isolates from cystic fibrosis patients.囊性纤维化患者连续分离出的铜绿假单胞菌中头孢地尔耐药性的基因组学研究
Clin Microbiol Infect. 2023 Apr;29(4):538.e7-538.e13. doi: 10.1016/j.cmi.2022.11.014. Epub 2022 Nov 24.
6
Emergence of KPC-31, a KPC-3 Variant Associated with Ceftazidime-Avibactam Resistance, in an Extensively Drug-Resistant ST235 Pseudomonas aeruginosa Clinical Isolate.产 KPC-31 碳青霉烯酶，一种与头孢他啶-阿维巴坦耐药相关的 KPC-3 变体，在广泛耐药的 ST235 铜绿假单胞菌临床分离株中出现。
Antimicrob Agents Chemother. 2022 Nov 15;66(11):e0064822. doi: 10.1128/aac.00648-22. Epub 2022 Oct 26.
7
Genomic Analysis of Ceftazidime/Avibactam-Resistant GES-Producing Sequence Type 235 Isolates.产GES的235型序列的头孢他啶/阿维巴坦耐药菌株的基因组分析
Antibiotics (Basel). 2022 Jun 28;11(7):871. doi: 10.3390/antibiotics11070871.
8
In vivo translational assessment of the GES genotype on the killing profile of ceftazidime, ceftazidime/avibactam and meropenem against Pseudomonas aeruginosa.体内评估 GES 基因型对头孢他啶、头孢他啶/阿维巴坦和美罗培南对铜绿假单胞菌杀伤作用的影响。
J Antimicrob Chemother. 2022 Sep 30;77(10):2803-2808. doi: 10.1093/jac/dkac232.
9
Susceptibility profiles and resistance genomics of Pseudomonas aeruginosa isolates from European ICUs participating in the ASPIRE-ICU trial.欧洲 ICU 参与 ASPIRE-ICU 试验的铜绿假单胞菌分离株的药敏谱和耐药基因组学。
J Antimicrob Chemother. 2022 Jun 29;77(7):1862-1872. doi: 10.1093/jac/dkac122.
10
Evolution of GES β-Lactamases Driven by Ceftazidime/Avibactam Treatment of Pseudomonas aeruginosa Infections.耐头孢他啶/阿维巴坦治疗铜绿假单胞菌感染的 GES β-内酰胺酶的演变。
Antimicrob Agents Chemother. 2021 Aug 17;65(9):e0098621. doi: 10.1128/AAC.00986-21.
Zotero 插件