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。
Evolution of GES β-Lactamases Driven by Ceftazidime/Avibactam Treatment of Pseudomonas aeruginosa Infections.
机构信息
Servicio de Microbiología and Unidad de Investigación, Hospital Universitario Son Espases, Instituto de Investigación Sanitaria Illes Balears (IdISBa), Palma de Mallorca, Spain.
Servicio de Microbiología, Hospital Universitario Central de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain.
出版信息
Antimicrob Agents Chemother. 2021 Aug 17;65(9):e0098621. doi: 10.1128/AAC.00986-21.
Abstract
The mechanisms underlying an switch in the resistance phenotype of P. aeruginosa after ceftazidime-avibactam treatment was investigated. The initial isolate (a blood culture) was resistant to meropenem but remained susceptible to antipseudomonal cephalosporins and combinations with β-lactamase inhibitors. One week after ceftazidime-avibactam therapy, a subsequent isolate (a rectal swab) recovered from the same patient showed the opposite phenotype. Whole-genome sequence analysis revealed a single SNP difference between both (ST235) isolates, leading to a P162S change in , creating . Thus, , , and were cloned and expressed in the wild-type strain PAO1. Susceptibility profiles confirmed the P162S substitution reverted the carbapenemase phenotype determined by the G170S change of GES-5 back into the ESBL phenotype of GES-1.
摘要
本研究旨在探究铜绿假单胞菌对头孢他啶-阿维巴坦耐药表型转变的机制。初始分离株（血培养）对美罗培南耐药，但对抗假单胞菌头孢菌素和β-内酰胺酶抑制剂复合制剂仍保持敏感。在头孢他啶-阿维巴坦治疗 1 周后，从同一患者中分离出的后续分离株（直肠拭子）表现出相反的表型。全基因组序列分析显示，两株（ST235）分离株之间仅有一个 SNP 差异，导致 中的 P162S 发生改变，形成 。因此，将 、 、 和 克隆并在野生型 PAO1 菌株中表达。药敏谱证实，P162S 取代使由 GES-5 的 G170S 变化决定的碳青霉烯酶表型恢复为 GES-1 的 ESBL 表型。
相似文献
1
Evolution of GES β-Lactamases Driven by Ceftazidime/Avibactam Treatment of Pseudomonas aeruginosa Infections.
Antimicrob Agents Chemother. 2021 Aug 17;65(9):e0098621. doi: 10.1128/AAC.00986-21.
2
Antimicrobial Activity of Ceftolozane-Tazobactam, Ceftazidime-Avibactam, and Cefiderocol against Multidrug-Resistant Pseudomonas aeruginosa Recovered at a German University Hospital.
Microbiol Spectr. 2022 Oct 26;10(5):e0169722. doi: 10.1128/spectrum.01697-22. Epub 2022 Oct 3.
3
Selection of AmpC β-Lactamase Variants and Metallo-β-Lactamases Leading to Ceftolozane/Tazobactam and Ceftazidime/Avibactam Resistance during Treatment of MDR/XDR Pseudomonas aeruginosa Infections.
Antimicrob Agents Chemother. 2022 Feb 15;66(2):e0206721. doi: 10.1128/AAC.02067-21. Epub 2021 Dec 20.
4
Within-host transition to GES-55 during a GES-6-producing Serratia marcescens outbreak: Emergence of ceftazidime-avibactam resistance and increased susceptibility to carbapenems.
Int J Antimicrob Agents. 2024 Aug;64(2):107257. doi: 10.1016/j.ijantimicag.2024.107257. Epub 2024 Jun 23.
5
Acquisition of Extended-Spectrum β-Lactamase GES-6 Leading to Resistance to Ceftolozane-Tazobactam Combination in .
Antimicrob Agents Chemother. 2018 Dec 21;63(1). doi: 10.1128/AAC.01809-18. Print 2019 Jan.
6
ESBLs and resistance to ceftazidime/avibactam and ceftolozane/tazobactam combinations in Escherichia coli and Pseudomonas aeruginosa.
J Antimicrob Chemother. 2019 Jul 1;74(7):1934-1939. doi: 10.1093/jac/dkz149.
7
Molecular mechanisms driving the in vivo development of OXA-10-mediated resistance to ceftolozane/tazobactam and ceftazidime/avibactam during treatment of XDR Pseudomonas aeruginosa infections.
J Antimicrob Chemother. 2021 Jan 1;76(1):91-100. doi: 10.1093/jac/dkaa396.
8
Assessing the in vivo efficacy of rational antibiotics and combinations against difficult-to-treat Pseudomonas aeruginosa producing GES β-lactamases.
J Antimicrob Chemother. 2023 Aug 2;78(8):1843-1847. doi: 10.1093/jac/dkad098.
9
Emergence of KPC-31, a KPC-3 Variant Associated with Ceftazidime-Avibactam Resistance, in an Extensively Drug-Resistant ST235 Pseudomonas aeruginosa Clinical Isolate.
Antimicrob Agents Chemother. 2022 Nov 15;66(11):e0064822. doi: 10.1128/aac.00648-22. Epub 2022 Oct 26.
10
Challenging Antimicrobial Susceptibility and Evolution of Resistance (OXA-681) during Treatment of a Long-Term Nosocomial Infection Caused by a Pseudomonas aeruginosa ST175 Clone.
Antimicrob Agents Chemother. 2019 Sep 23;63(10). doi: 10.1128/AAC.01110-19. Print 2019 Oct.
引用本文的文献
1
Spectrum of cefepime-taniborbactam coverage against 190 β-lactamases defined in engineered isogenic strains.
Antimicrob Agents Chemother. 2025 May 7;69(5):e0169924. doi: 10.1128/aac.01699-24. Epub 2025 Apr 1.
2
Mechanisms leading to ceftazidime/avibactam resistance development during treatment of GES-5-producing infections.
Antimicrob Agents Chemother. 2024 Nov 6;68(11):e0116424. doi: 10.1128/aac.01164-24. Epub 2024 Oct 21.
3
Not all carbapenem-resistant Pseudomonas aeruginosa strains are alike: tailoring antibiotic therapy based on resistance mechanisms.
Curr Opin Infect Dis. 2024 Dec 1;37(6):594-601. doi: 10.1097/QCO.0000000000001044. Epub 2024 Sep 18.
4
Impact of chromosomally encoded resistance mechanisms and transferable β-lactamases on the activity of cefiderocol and innovative β-lactam/β-lactamase inhibitor combinations against Pseudomonas aeruginosa.
J Antimicrob Chemother. 2024 Oct 1;79(10):2591-2597. doi: 10.1093/jac/dkae263.
5
Genomic epidemiology and ceftazidime-avibactam high-level resistance mechanisms of in China from 2010 to 2022.
Emerg Microbes Infect. 2024 Dec;13(1):2324068. doi: 10.1080/22221751.2024.2324068. Epub 2024 Mar 11.
6
Phenotypic and genotypic profile of ceftolozane/tazobactam-non-susceptible, carbapenem-resistant Pseudomonas aeruginosa.
J Antimicrob Chemother. 2022 Dec 23;78(1):252-256. doi: 10.1093/jac/dkac385.
7
Emergence of KPC-31, a KPC-3 Variant Associated with Ceftazidime-Avibactam Resistance, in an Extensively Drug-Resistant ST235 Pseudomonas aeruginosa Clinical Isolate.
Antimicrob Agents Chemother. 2022 Nov 15;66(11):e0064822. doi: 10.1128/aac.00648-22. Epub 2022 Oct 26.
8
Role of the multi-drug efflux systems on the baseline susceptibility to ceftazidime/avibactam and ceftolozane/tazobactam in clinical isolates of non-carbapenemase-producing carbapenem-resistant .
Front Pharmacol. 2022 Oct 3;13:1007162. doi: 10.3389/fphar.2022.1007162. eCollection 2022.
9
Role of Enzymatic Activity in the Biological Cost Associated with the Production of AmpC β-Lactamases in Pseudomonas aeruginosa.
Microbiol Spectr. 2022 Oct 26;10(5):e0270022. doi: 10.1128/spectrum.02700-22. Epub 2022 Oct 10.
10
Antimicrobial Activity of Ceftolozane-Tazobactam, Ceftazidime-Avibactam, and Cefiderocol against Multidrug-Resistant Pseudomonas aeruginosa Recovered at a German University Hospital.
Microbiol Spectr. 2022 Oct 26;10(5):e0169722. doi: 10.1128/spectrum.01697-22. Epub 2022 Oct 3.
本文引用的文献
1
New β-Lactam-β-Lactamase Inhibitor Combinations.
Clin Microbiol Rev. 2020 Nov 11;34(1). doi: 10.1128/CMR.00115-20. Print 2020 Dec 16.
2
Molecular mechanisms driving the in vivo development of OXA-10-mediated resistance to ceftolozane/tazobactam and ceftazidime/avibactam during treatment of XDR Pseudomonas aeruginosa infections.
J Antimicrob Chemother. 2021 Jan 1;76(1):91-100. doi: 10.1093/jac/dkaa396.
3
Pseudomonas aeruginosa epidemic high-risk clones and their association with horizontally-acquired β-lactamases: 2020 update.
Int J Antimicrob Agents. 2020 Dec;56(6):106196. doi: 10.1016/j.ijantimicag.2020.106196. Epub 2020 Oct 9.
4
Molecular and biochemical insights into the in vivo evolution of AmpC-mediated resistance to ceftolozane/tazobactam during treatment of an MDR Pseudomonas aeruginosa infection.
J Antimicrob Chemother. 2020 Nov 1;75(11):3209-3217. doi: 10.1093/jac/dkaa291.
5
Adding Insult to Injury: Mechanistic Basis for How AmpC Mutations Allow Pseudomonas aeruginosa To Accelerate Cephalosporin Hydrolysis and Evade Avibactam.
Antimicrob Agents Chemother. 2020 Aug 20;64(9). doi: 10.1128/AAC.00894-20.
6
Epidemiology and Treatment of Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa Infections.
Clin Microbiol Rev. 2019 Aug 28;32(4). doi: 10.1128/CMR.00031-19. Print 2019 Sep 18.
7
ESBLs and resistance to ceftazidime/avibactam and ceftolozane/tazobactam combinations in Escherichia coli and Pseudomonas aeruginosa.
J Antimicrob Chemother. 2019 Jul 1;74(7):1934-1939. doi: 10.1093/jac/dkz149.
8
Deciphering the Evolution of Cephalosporin Resistance to Ceftolozane-Tazobactam in Pseudomonas aeruginosa.
mBio. 2018 Dec 11;9(6):e02085-18. doi: 10.1128/mBio.02085-18.
9
The Versatile Mutational Resistome of .
Front Microbiol. 2018 Apr 6;9:685. doi: 10.3389/fmicb.2018.00685. eCollection 2018.
10
Mechanisms leading to in vivo ceftolozane/tazobactam resistance development during the treatment of infections caused by MDR Pseudomonas aeruginosa.
J Antimicrob Chemother. 2018 Mar 1;73(3):658-663. doi: 10.1093/jac/dkx424.
Zotero 插件