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Exploring disparities in HIV-1 pretreatment and acquired drug resistance in China from 2003 to 2022. 探索 2003 至 2022 年中国 HIV-1 预处理和获得性耐药性的差异。
IF 3.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-01 DOI: 10.1093/jac/dkae260
Zhaoquan Wang, He Jiang, Xianwu Pang, Jianjun Li, Shujia Liang, Jinghua Huang, Dejian Li, Wenxuan Hou, Ni Chen, Guanghua Lan

Objectives: To investigate the epidemic patterns of pretreatment drug resistance (PDR) and acquired drug resistance (ADR) in HIV-1 sequences from China.

Methods: HIV-1 pol sequences and associated epidemiological data were collected from the Los Alamos HIV Sequence Database, NCBI, HIV Gene Sequence Database and PubMed. Genotypic resistance and subtypes were identified using the Stanford HIV Drug Resistance Database.

Results: A total of 36 263 sequences from ART-naïve individuals and 1548 sequences from ART-experienced individuals with virological failure were evaluated. PDR prevalence was 6.64%, initially decreasing and then increasing to 7.84% (2018-22) due to NNRTI. Pooled ADR prevalence (44.96%) increased, with NNRTI and NRTI aligning with the overall trend. The percentage of multidrug resistance was more than that of single-drug resistance in PDR and especially ADR annually. PDR was most prevalent in Central China followed by Southwest and North. ADR prevalence was highest in North China followed by Northwest and Southwest. In ADR sequences, high-level resistance was more common, especially in NRTI. PDR sequences exhibited low-level or intermediate resistance, especially PI. Drug resistance mutations revealed distinct patterns in PDR and ADR. CRF01_AE, the predominant subtype in China, exhibited the highest proportions among most ART drugs and drug resistance mutations, with a few exceptions where CRF07_BC (prominent in the Northwest), CRF55_01B and CRF08_BC (prominent in the Southwest) showed the highest proportions.

Conclusions: HIV-1 PDR and ADR prevalence in China exhibited diverse epidemiological characteristics, underscoring the importance of ongoing national monitoring of PDR, ADR and subtype; patient education on adherence; and personalized regimens.

目的:研究中国 HIV-1 序列中治疗前耐药性(PDR)和获得性耐药性(ADR)的流行模式:方法:从洛斯阿拉莫斯HIV序列数据库、NCBI、HIV基因序列数据库和PubMed收集HIV-1 pol序列和相关流行病学数据。利用斯坦福大学艾滋病毒耐药性数据库确定基因型耐药性和亚型:结果:共评估了 36 263 个来自抗逆转录病毒疗法无效者的序列和 1548 个来自抗逆转录病毒疗法有经验者的序列。PDR发生率为6.64%,最初有所下降,后因NNRTI而上升至7.84%(2018-22年)。汇总的 ADR 患病率(44.96%)有所增加,其中 NNRTI 和 NRTI 与总体趋势一致。在PDR中,多药耐药的比例高于单药耐药的比例,尤其是每年的ADR。PDR 在华中地区最为普遍,其次是西南和华北地区。华北地区的 ADR 发生率最高,其次是西北和西南地区。在 ADR 序列中,高水平耐药更为常见,尤其是 NRTI。PDR序列表现出低水平或中等水平的耐药性,尤其是PI。耐药性突变在 PDR 和 ADR 中显示出不同的模式。CRF01_AE是中国的主要亚型,在大多数抗逆转录病毒疗法药物和耐药突变中的比例最高,但也有少数例外,CRF07_BC(西北地区突出)、CRF55_01B和CRF08_BC(西南地区突出)的比例最高:结论:中国的HIV-1 PDR和ADR流行呈现出不同的流行病学特征,强调了对PDR、ADR和亚型进行持续的全国性监测、患者依从性教育和个性化治疗方案的重要性。
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引用次数: 0
Redefining cross-resistance, co-resistance and co-selection: beyond confusion? 重新定义交叉阻力、共同阻力和共同选择:超越混淆?
IF 3.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-01 DOI: 10.1093/jac/dkae304
Shabbir Simjee, J Scott Weese, Ruby Singh, Darren J Trott, Sabiha Essack, Rungtip Chuanchuen, Shubhi Mehrotra

The similarity of current definitions of 'cross-resistance' and 'co-resistance' continues to cause confusion both in the scientific community as well as in understanding policies and in particular when looking at resistance from a risk assessment perspective. Further, lack of harmonized definitions of these terms in the regulatory space is challenging for interpretation. The purpose of this article is to: (i) provide an overview of the ambiguity in existing terminology related to cross-resistance, co-resistance and co-selection; (ii) emphasize the challenges created by the use of poor terminology in research and scientific literature; and (iii) propose a clear set of harmonized definitions that could be put into use through international regulatory agencies and institutions, such as the World Health Organization, Food and Drug Administration, European Medicines Agency, Center for Disease Control, Committee for Veterinary Medicinal Products, World Organization for Animal Health/Office International des Epizooties and the Food and Agriculture Organization of the United Nations.

目前,"交叉抗药性 "和 "共同抗药性 "的定义相似,这继续在科学界和政策理解方面造成混乱,特别是从风险评估的角度看待抗药性时更是如此。此外,监管领域缺乏对这些术语的统一定义,也给解释工作带来了挑战。本文旨在(i) 概述与交叉抗药性、共同抗药性和共同选择相关的现有术语的模糊性;(ii) 强调研究和科学文献中使用不恰当术语所带来的挑战;(iii) 提出一套明确的统一定义,供世界卫生组织、美国食品药品管理局、欧洲药品管理局、疾病控制中心、兽药产品委员会、世界动物卫生组织/国际兽疫局和联合国粮食及农业组织等国际监管机构和组织使用。
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引用次数: 0
Correction to: Use of teicoplanin monotherapy for the treatment of enterococcal infective endocarditis: a retrospective and comparative study at a referral centre. 更正:使用替考拉宁单药治疗肠球菌感染性心内膜炎:一家转诊中心的回顾性比较研究。
IF 3.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-01 DOI: 10.1093/jac/dkae317
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引用次数: 0
EUCAST ciprofloxacin area of technical uncertainty in Escherichia coli and Klebsiella pneumoniae using BD Phoenix™ and VITEK® 2 automated susceptibility systems. 使用 BD Phoenix™ 和 VITEK® 2 自动药敏系统对大肠埃希菌和肺炎克雷伯菌进行的 EUCAST 环丙沙星技术不确定性分析。
IF 3.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-01 DOI: 10.1093/jac/dkae245
T J Harryvan, E Schaftenaar, B T Franssens, D C Melles, R J Rentenaar
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引用次数: 0
Investigating the treatment shortening potential of a combination of bedaquiline, delamanid and moxifloxacin with and without sutezolid, in a murine tuberculosis model with confirmed drug exposures. 在一个已确认药物暴露的小鼠结核病模型中,研究贝达喹啉、地拉那米德和莫西沙星与或不与沙特唑烷的复方制剂缩短治疗时间的潜力。
IF 3.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-01 DOI: 10.1093/jac/dkae266
Kerstin Walter, Lindsey H M Te Brake, Ann-Kathrin Lemm, Michael Hoelscher, Elin M Svensson, Christoph Hölscher, Norbert Heinrich

Background: New and shorter regimens against multi-drug resistant tuberculosis (TB) remain urgently needed. To inform treatment duration in clinical trials, this study aimed to identify human pharmacokinetic equivalent doses, antimycobacterial and sterilizing activity of a novel regimen, containing bedaquiline, delamanid, moxifloxacin and sutezolid (BDMU), in the standard mouse model (BALB/c) of Mycobacterium tuberculosis (Mtb) infection.

Methods: Treatment of mice with B25D0.6M200U200, B25D0.6M200, B25D0.6M200(U2003) or H10R10Z150E100 (isoniazid, rifampicin, pyrazinamide, ethambutol, HRZE), started 3 weeks after Mtb infection. Bactericidal activity was assessed after 1, 2, 3 and 4 months of treatment and relapse rates were assessed 3 months after completing treatment durations of 2, 3 and 4 months.

Results: B25D0.6M200U200 generated human equivalent exposures in uninfected BALB/c mice. After 1 month of treatment, a higher bactericidal activity was observed for the B25D0.6M200U200 and the B25D0.6M200 regimen compared to the standard H10R10Z150E100 regimen. Furthermore, 3 months of therapy with both BDM-based regimens resulted in negative lung cultures, whereas all H10R10Z150E100 treated mice were still culture positive. After 3 months of therapy 7% and 13% of mice relapsed receiving B25D0.6M200U200 and B25D0.6M200, respectively, compared to 40% for H10R10Z150E100 treatment showing an increased sterilizing activity of both BDM-based regimens.

Conclusions: BDM-based regimens, with and without sutezolid, have a higher efficacy than the HRZE regimen in the BALB/c model of TB, with some improvement by adding sutezolid. By translating these results to TB patients, this novel BDMU regimen should be able to reduce treatment duration by 25% compared to HRZE therapy.

背景:治疗耐多药结核病(TB)仍然迫切需要新的、更短的治疗方案。为了在临床试验中为治疗持续时间提供依据,本研究旨在确定在结核分枝杆菌(Mtb)感染的标准小鼠模型(BALB/c)中,包含贝达喹啉、地拉马尼、莫西沙星和沙替唑胺(BDMU)的新型治疗方案的人体药代动力学等效剂量、抗结核和杀菌活性:方法:在小鼠感染 Mtb 3 周后开始用 B25D0.6M200U200、B25D0.6M200、B25D0.6M200(U2003) 或 H10R10Z150E100(异烟肼、利福平、吡嗪酰胺、乙胺丁醇、HRZE)治疗。在治疗 1、2、3 和 4 个月后评估杀菌活性,在完成 2、3 和 4 个月的治疗后 3 个月评估复发率:结果:B25D0.6M200U200在未感染的BALB/c小鼠体内产生了与人类相当的暴露量。治疗 1 个月后,观察到 B25D0.6M200U200 和 B25D0.6M200 方案的杀菌活性高于 H10R10Z150E100 标准方案。此外,使用这两种基于 BDM 的方案治疗 3 个月后,肺培养结果均为阴性,而所有接受 H10R10Z150E100 治疗的小鼠培养结果仍为阳性。治疗 3 个月后,分别有 7% 和 13% 的小鼠在接受 B25D0.6M200U200 和 B25D0.6M200 治疗后复发,而接受 H10R10Z150E100 治疗的小鼠复发率为 40%:结论:在 BALB/c 结核病模型中,使用或不使用沙特唑烷的 BDM 方案比 HRZE 方案具有更高的疗效,使用沙特唑烷还能提高疗效。将这些结果应用于肺结核患者,与HRZE疗法相比,这种新型的BDMU疗法应能将治疗时间缩短25%。
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引用次数: 0
Evaluation of several routine methods for fosfomycin and mecillinam susceptibility testing of Enterobacterales urine isolates. 对检测肠杆菌尿液分离物的磷霉素和美西林敏感性的几种常规方法进行评估。
IF 3.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-01 DOI: 10.1093/jac/dkae271
C Massip, L Feletti, C V Chagneau, Y Dumont, E Maurin, A Muggeo, M Pichon, M Pompilio, F Buchler, D Halimi, D Dubois

Objectives: Performance evaluation of routine laboratory methods to determine the susceptibility of Enterobacterales urinary isolates to fosfomycin (oral administration) and mecillinam.

Methods: We collected 347 Enterobacterales isolates from monomicrobial midstream urine samples from women with significant bacteriuria and leukocyturia. Mostly non-Escherichia coli isolates (i.e. Klebsiella spp., Citrobacter koseri, Enterobacter cloacae complex and Proteus mirabilis) were included (n = 298). Performance of VITEK®2, ETEST®, and disc diffusion to determine fosfomycin and mecillinam susceptibility was evaluated following International Organization for Standardization (ISO) 20776-2:2021 (or 20776-2:2007 for disc diffusion) in comparison with the agar dilution reference method.

Results: For fosfomycin testing, VITEK®2 and ETEST® were close to reaching ISO requirements (essential agreement  ≥ 90%; bias  ±30%) for C. koseri, E. coli and P. mirabilis. Categorical agreement (CA) and major error rates were acceptable for disc diffusion. Fosfomycin displayed lower activity against E. cloacae complex and Klebsiella spp., with MIC50 (minimum inhibitory concentration required to inhibit the growth of 50% of tested isolates) equal to the E. coli EUCAST breakpoint (8 mg/L). For these species, the three alternative techniques overestimated MICs and resistance, and did not meet performance criteria. For mecillinam testing of Enterobacterales isolates, apart from P. mirabilis, ETEST® nearly fulfilled ISO requirements, and CA rates were acceptable for disc diffusion. ISO criteria were reached for C. koseri and E. coli testing with VITEK®2, apart from too high rates of very major errors. For P. mirabilis, performances were unacceptable, whatever the routine method used.

Conclusions: Commercially available tests may serve as alternatives to agar dilution to assess fosfomycin (oral) and mecillinam susceptibility of Enterobacterales urinary isolates, with important interspecies variabilities. Additional studies comprising more fosfomycin- and mecillinam-resistant isolates are needed to strengthen our conclusions.

目的:对常规实验室方法进行性能评估,以确定肠杆菌对磷霉素(口服)和美西林的敏感性:对常规实验室方法进行性能评估,以确定尿液中分离出的肠杆菌对磷霉素(口服)和美西林的敏感性:我们从有明显菌尿和白细胞尿的妇女的单菌中段尿液样本中收集了 347 株肠杆菌。其中大部分为非大肠埃希菌分离物(即克雷伯氏菌属、柯氏柠檬杆菌、复合泄殖腔肠杆菌和奇异变形杆菌)(n = 298)。根据国际标准化组织 (ISO) 20776-2:2021(或 20776-2:2007,用于圆盘扩散法)与琼脂稀释参考方法进行比较,评估了 VITEK®2、ETEST® 和圆盘扩散法测定磷霉素和美西林敏感性的性能:结果:对于磷霉素检测,VITEK®2和ETEST®接近ISO要求(基本一致度≥90%;偏差±30%)。盘扩散法的分类一致率(CA)和主要误差率均可接受。福斯霉素对复合物大肠杆菌和克雷伯氏菌的活性较低,其 MIC50(抑制 50%受试分离菌生长所需的最低抑菌浓度)与大肠杆菌 EUCAST 分界点(8 毫克/升)相同。对于这些菌种,三种替代技术都高估了 MIC 和耐药性,不符合性能标准。对于肠杆菌科分离菌株的美西林检测,除了奇异变形杆菌外,ETEST® 几乎达到了 ISO 的要求,CA 率在盘扩散法中也是可以接受的。使用 VITEK®2 对科氏菌和大肠杆菌进行检测时,除重大错误率过高外,均达到了 ISO 标准。对于奇异变形杆菌,无论使用哪种常规方法,其结果都是不可接受的:结论:市售检验可替代琼脂稀释法评估肠杆菌科尿液分离物对磷霉素(口服)和美西林的敏感性,但种间差异很大。为了加强我们的结论,还需要进行更多的研究,其中包括更多对磷霉素和美西林耐药的分离物。
{"title":"Evaluation of several routine methods for fosfomycin and mecillinam susceptibility testing of Enterobacterales urine isolates.","authors":"C Massip, L Feletti, C V Chagneau, Y Dumont, E Maurin, A Muggeo, M Pichon, M Pompilio, F Buchler, D Halimi, D Dubois","doi":"10.1093/jac/dkae271","DOIUrl":"10.1093/jac/dkae271","url":null,"abstract":"<p><strong>Objectives: </strong>Performance evaluation of routine laboratory methods to determine the susceptibility of Enterobacterales urinary isolates to fosfomycin (oral administration) and mecillinam.</p><p><strong>Methods: </strong>We collected 347 Enterobacterales isolates from monomicrobial midstream urine samples from women with significant bacteriuria and leukocyturia. Mostly non-Escherichia coli isolates (i.e. Klebsiella spp., Citrobacter koseri, Enterobacter cloacae complex and Proteus mirabilis) were included (n = 298). Performance of VITEK®2, ETEST®, and disc diffusion to determine fosfomycin and mecillinam susceptibility was evaluated following International Organization for Standardization (ISO) 20776-2:2021 (or 20776-2:2007 for disc diffusion) in comparison with the agar dilution reference method.</p><p><strong>Results: </strong>For fosfomycin testing, VITEK®2 and ETEST® were close to reaching ISO requirements (essential agreement  ≥ 90%; bias  ±30%) for C. koseri, E. coli and P. mirabilis. Categorical agreement (CA) and major error rates were acceptable for disc diffusion. Fosfomycin displayed lower activity against E. cloacae complex and Klebsiella spp., with MIC50 (minimum inhibitory concentration required to inhibit the growth of 50% of tested isolates) equal to the E. coli EUCAST breakpoint (8 mg/L). For these species, the three alternative techniques overestimated MICs and resistance, and did not meet performance criteria. For mecillinam testing of Enterobacterales isolates, apart from P. mirabilis, ETEST® nearly fulfilled ISO requirements, and CA rates were acceptable for disc diffusion. ISO criteria were reached for C. koseri and E. coli testing with VITEK®2, apart from too high rates of very major errors. For P. mirabilis, performances were unacceptable, whatever the routine method used.</p><p><strong>Conclusions: </strong>Commercially available tests may serve as alternatives to agar dilution to assess fosfomycin (oral) and mecillinam susceptibility of Enterobacterales urinary isolates, with important interspecies variabilities. Additional studies comprising more fosfomycin- and mecillinam-resistant isolates are needed to strengthen our conclusions.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11441990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Biliary pharmacokinetic/pharmacodynamic analysis of continuous infusion meropenem/vaborbactam in a case series of orthotopic liver transplant recipients. 连续输注美罗培南/伐硼巴坦在肝移植受者中的胆汁药代动力学/药效学分析。
IF 3.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-01 DOI: 10.1093/jac/dkae261
Milo Gatti, Matteo Rinaldi, Cristiana Laici, Simone Ambretti, Antonio Siniscalchi, Pierluigi Viale, Federico Pea

Objective: To analyse the biliary pharmacokinetics/pharmacodynamics (PK/PD) of continuous infusion (CI) meropenem-vaborbactam (MEM-VBM) in a case series of orthotopic liver transplant (OLT) recipients being treated for Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) related biliary tract infections (BTIs) or as preemptive therapy of KPC-Kp rectal colonization.

Methods: Critical OLT recipients receiving CI MEM-VBM (2 g/2 g q8h over 8 h) because of KPC-Kp related BTIs or as preemptive therapy of KPC-Kp rectal colonization, having Kehr's tube positioned and undergoing simultaneous therapeutic drug monitoring of MEM and VBM in plasma and bile were retrospectively assessed. Bile-to-plasma ratio of free steady-state concentrations (fCss) of MEM and VBM was used for assessing biliary penetration. Optimal joint MEM-VBM PK/PD target attainment was defined as MEM fCss/MIC ratio >4 coupled with VBM free area under time-concentration curve (fAUC)/threshold concentration (CT) ratio >24.

Results: Overall, four critical OLT recipients were included. Median bile-to-plasma ratio was 0.32 for MEM (range 0.21-0.79) and 0.40 for VBM (range 0.20-0.77). Biliary MEM-VBM joint PK/PD target attainment was optimal in 3/4 OLT recipients and quasi-optimal in the other one.

Conclusions: The 1:1 proportion between MEM and VBM concentrations was maintained unchanged in the bile, allowing us to assume that the efficacy of MEM-VBM may be appropriate even in the treatment of BTIs. CI administration was an effective strategy for attaining aggressive biliary joint PK/PD targets against pathogens with an MIC up to 2 mg/L.

目的分析连续输注(CI)美罗培南-伐硼巴坦(MEM-VBM)的胆汁药代动力学/药效学(PK/PD),该连续输注(CI)美罗培南-伐硼巴坦(MEM-VBM)在因产碳青霉烯酶肺炎克雷伯菌(KPC-Kp)相关胆道感染(BTIs)而接受治疗或作为 KPC-Kp 直肠定植的抢先治疗的正位肝移植(OLT)受者中的病例系列:因 KPC-Kp 相关胆道感染或作为 KPC-Kp 直肠定植的预防性治疗而接受 CI MEM-VBM (2 克/2 克,q8h,8 小时)治疗的危重 OLT 受试者均已放置 Kehr 管,并同时接受血浆和胆汁中 MEM 和 VBM 的治疗药物监测。MEM 和 VBM 的游离稳态浓度(fCss)的胆汁与血浆比值用于评估胆汁渗透。MEM-VBM联合PK/PD目标的最佳实现定义为:MEM fCss/MIC比值大于4,VBM游离时间-浓度曲线下面积(fAUC)/阈值浓度(CT)比值大于24:共纳入了四名危重的 OLT 受试者。MEM 的胆汁与血浆比值中位数为 0.32(范围为 0.21-0.79),VBM 的胆汁与血浆比值中位数为 0.40(范围为 0.20-0.77)。胆汁MEM-VBM联合PK/PD目标在3/4的OLT受者中达到最佳,在另一个受者中达到准最佳:胆汁中 MEM 和 VBM 浓度 1:1 的比例保持不变,因此我们认为 MEM-VBM 的疗效即使在治疗 BTI 时也是合适的。CI 给药是一种有效的策略,可实现积极的胆汁联合 PK/PD 目标,以对抗 MIC 高达 2 mg/L 的病原体。
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引用次数: 0
In vitro activity of olorofim against 507 filamentous fungi including antifungal drug-resistant strains at a tertiary laboratory in Australia: 2020-2023. 奥罗芬对 507 种丝状真菌(包括澳大利亚一家三级实验室的抗真菌药物耐药菌株)的体外活性:2020-2023 年。
IF 3.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-01 DOI: 10.1093/jac/dkae267
Catriona L Halliday, Enoch Tay, Wendy Green, Derek Law, Ronald Lopez, Silvia Faris, Lauren Meehan, Emma Harvey, Mike Birch, Sharon C A Chen

Background: New antifungal agents are required to mitigate against azole-resistant Aspergillus and drug-resistant non-Aspergillus moulds. The novel orotomide, olorofim (F2G, Manchester, UK), has potent fungicidal activity against Aspergillus including azole-resistant Aspergillus fumigatus, Lomentospora prolificans and Scedosporium spp. Development of olorofim-specific clinical breakpoints/epidemiological cut-off values requires reliable MIC data.

Objectives: Determine the in vitro activity of olorofim compared with standard antifungals against mould pathogens at an Australian hospital.

Materials and methods: Olorofim MICs were determined for 507 clinical mould isolates using the CLSI M38-A3 standard. MICs of amphotericin B, anidulafungin, posaconazole, voriconazole and isavuconazole were obtained using Sensititre™ YeastOne YO10 and AUSNMRCI panels (Thermo-Fisher Scientific).

Results: A. fumigatus sensu stricto was the commonest species (33.3%) followed by L. prolificans (18.3%), Scedosporium (11.4%) and Fusarium (6%) species. Olorofim modal MICs were ≤0.25 mg/L (MIC90 0.25 mg/L) for all Aspergillus except Aspergillus Section Usti (1 mg/L); MICs for nine azole-resistant/non-wild-type A. fumigatus ranged from 0.008 to 0.125 mg/L. The MIC90 of olorofim for L. prolificans was 0.5 mg/L, 0.25-0.5 mg/L for Scedosporium spp. and 8 mg/L for the F. solani complex but with modal MICs of 0.25 and 0.008 mg/L for F. oxysporum and F. proliferatum complexes, respectively. For Verruconis gallopava (n = 10), the olorofim MIC90 was 0.06 mg/L (voriconazole MIC90 2 mg/L, isavuconazole MICs of 4->8 mg/L). Olorofim had little activity against other dematiaceous moulds including Exophiala species.

Conclusions: Olorofim was highly active against Aspergillus spp. including azole-resistant A. fumigatus, L. prolificans, Scedosporium spp. and some Fusarium species with the new finding of potent activity against V. gallopava.

背景:需要新的抗真菌剂来减轻对唑类耐药曲霉菌和非曲霉菌的耐药性。新型奥罗托咪唑--奥罗非姆(F2G,英国曼彻斯特)对曲霉菌(包括耐唑曲霉菌、多孔菌和头孢菌属)具有很强的杀真菌活性,但开发奥罗非姆特异性临床断点/流行病学临界值需要可靠的 MIC 数据:在澳大利亚的一家医院中,与标准抗真菌药相比,确定奥罗芬对霉菌病原体的体外活性:采用 CLSI M38-A3 标准测定了 507 个临床霉菌分离株的奥罗芬 MIC。使用 Sensititre™ YeastOne YO10 和 AUSNMRCI 面板(Thermo-Fisher Scientific)测定两性霉素 B、阿尼妥芬、泊沙康唑、伏立康唑和异武康唑的 MIC:结果:严格意义上的烟曲霉是最常见的菌种(33.3%),其次是增殖酵母菌(18.3%)、Scedosporium(11.4%)和镰刀菌(6%)。除乌斯季曲霉(1 毫克/升)外,奥罗芬对所有曲霉的 MIC 值均小于 0.25 毫克/升(MIC90 为 0.25 毫克/升);对 9 种抗唑/非野生型烟曲霉的 MIC 值介于 0.008 至 0.125 毫克/升之间。Olorofim 对 L. prolificans 的 MIC90 为 0.5 毫克/升,对 Scedosporium 属的 MIC90 为 0.25-0.5 毫克/升,对 F. solani 复合物的 MIC90 为 8 毫克/升,但对 F. oxysporum 和 F. proliferatum 复合物的模式 MIC 分别为 0.25 和 0.008 毫克/升。对于 Verruconis gallopava(n = 10),Olorofim 的 MIC90 为 0.06 mg/L(伏立康唑的 MIC90 为 2 mg/L,异戊唑的 MIC 为 4->8 mg/L)。Olorofim 对包括 Exophiala 菌在内的其他脱霉菌几乎没有活性:结论:Olorofim 对曲霉菌属(包括耐唑曲霉菌属)、L. prolificans、Scedosporium 菌属和一些镰刀菌属具有很高的活性,对 V. gallopava 菌属也有很强的活性。
{"title":"In vitro activity of olorofim against 507 filamentous fungi including antifungal drug-resistant strains at a tertiary laboratory in Australia: 2020-2023.","authors":"Catriona L Halliday, Enoch Tay, Wendy Green, Derek Law, Ronald Lopez, Silvia Faris, Lauren Meehan, Emma Harvey, Mike Birch, Sharon C A Chen","doi":"10.1093/jac/dkae267","DOIUrl":"10.1093/jac/dkae267","url":null,"abstract":"<p><strong>Background: </strong>New antifungal agents are required to mitigate against azole-resistant Aspergillus and drug-resistant non-Aspergillus moulds. The novel orotomide, olorofim (F2G, Manchester, UK), has potent fungicidal activity against Aspergillus including azole-resistant Aspergillus fumigatus, Lomentospora prolificans and Scedosporium spp. Development of olorofim-specific clinical breakpoints/epidemiological cut-off values requires reliable MIC data.</p><p><strong>Objectives: </strong>Determine the in vitro activity of olorofim compared with standard antifungals against mould pathogens at an Australian hospital.</p><p><strong>Materials and methods: </strong>Olorofim MICs were determined for 507 clinical mould isolates using the CLSI M38-A3 standard. MICs of amphotericin B, anidulafungin, posaconazole, voriconazole and isavuconazole were obtained using Sensititre™ YeastOne YO10 and AUSNMRCI panels (Thermo-Fisher Scientific).</p><p><strong>Results: </strong>A. fumigatus sensu stricto was the commonest species (33.3%) followed by L. prolificans (18.3%), Scedosporium (11.4%) and Fusarium (6%) species. Olorofim modal MICs were ≤0.25 mg/L (MIC90 0.25 mg/L) for all Aspergillus except Aspergillus Section Usti (1 mg/L); MICs for nine azole-resistant/non-wild-type A. fumigatus ranged from 0.008 to 0.125 mg/L. The MIC90 of olorofim for L. prolificans was 0.5 mg/L, 0.25-0.5 mg/L for Scedosporium spp. and 8 mg/L for the F. solani complex but with modal MICs of 0.25 and 0.008 mg/L for F. oxysporum and F. proliferatum complexes, respectively. For Verruconis gallopava (n = 10), the olorofim MIC90 was 0.06 mg/L (voriconazole MIC90 2 mg/L, isavuconazole MICs of 4->8 mg/L). Olorofim had little activity against other dematiaceous moulds including Exophiala species.</p><p><strong>Conclusions: </strong>Olorofim was highly active against Aspergillus spp. including azole-resistant A. fumigatus, L. prolificans, Scedosporium spp. and some Fusarium species with the new finding of potent activity against V. gallopava.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Novel optrA-carrying integrative and conjugative element in a porcine Streptococcus suis, Italy. 意大利猪链球菌中携带 optrA 的新型整合和共轭元件。
IF 3.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-01 DOI: 10.1093/jac/dkae354
Sonia Nina Coccitto, Francesca Romana Massacci, Marzia Cinthi, Elisa Albini, Lucilla Cucco, Marta Paniccià, Giovanni Pezzotti, Silvia Di Lodovico, Mara Di Giulio, Xiang-Dang Du, Chiara Francesca Magistrali, Andrea Brenciani, Eleonora Giovanetti
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引用次数: 0
Optimal dosing regimen of caspofungin in adolescents with allogeneic haematopoietic stem cell transplantation. 同种异体造血干细胞移植青少年使用卡泊芬净的最佳剂量方案。
IF 3.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-01 DOI: 10.1093/jac/dkae276
Bin Du, Wei Zhang, Yang Wang, Yue-E Wu, Ya-Hui Zhang, John van den Anker, Guo-Xiang Hao, Wei Zhao

Objectives: The optimal dosing regimen of caspofungin in adolescents undergoing allogeneic haematopoietic stem cell transplantation against Candida spp. is unknown. The study aimed to compare body surface area (BSA)-based and fixed dosing regimens through population pharmacokinetic (PPK) analysis and to optimize dosing regimens likely to achieve therapeutic exposures.

Methods: Opportunistic sampling was used to collect plasma concentrations through a prospective observational pharmacokinetic study. PPK analysis and Monte Carlo simulations (n = 1000) were performed using NONMEM.

Results: A total of 86 samples of 30 adolescents (12-17 years old) were best described by a two-compartment pharmacokinetic model. BSA is the only covariate on clearance and central volume of distribution. For Candida glabrata and Candida albicans, a standard dosing regimen could achieve at least a 90% probability of target attainment for the indicator of AUC0-24/MIC90. Dosing regimen simulations identified a BSA cut-off value of 1.3 m2, where a fixed loading dose (LD) is preferred when BSA ≥ 1.3 m2 and a BSA-based LD is preferred when BSA < 1.3 m2. For maintenance dose (MD), however, the BSA-based dose was proposed, regardless of BSA. The current maximum dosing regimen of LD 70 mg/day and MD 70 mg/day could not result in sufficient antifungal exposure for Candida parapsilosis with MIC90 of 1 mg/L. Furthermore, an LD of 70 mg/day and MD of 60 mg/m2/day rendered 90.4% steady-state trough concentration (Ctrough) over 1 mg/L in the virtual population.

Conclusions: Our study proposed optimized dosing regimens of caspofungin based on AUC0-24/MIC90 or Ctrough, which may support further individualized treatment.

目的:对于接受异体造血干细胞移植的青少年,抗念珠菌的卡泊芬净最佳给药方案尚不清楚。该研究旨在通过群体药代动力学(PPK)分析,比较基于体表面积(BSA)的给药方案和固定给药方案,并优化可能达到治疗暴露的给药方案:方法:通过一项前瞻性观察药代动力学研究,采用机会取样法收集血浆浓度。采用 NONMEM 进行 PPK 分析和蒙特卡罗模拟(n = 1000):结果:30 名青少年(12-17 岁)的 86 份样本用两室药代动力学模型进行了最佳描述。BSA 是清除率和中心分布容积的唯一协变量。对于白色念珠菌和白色念珠菌,标准给药方案至少有 90% 的概率达到 AUC0-24/MIC90 指标。用药方案模拟确定 BSA 临界值为 1.3 m2,当 BSA ≥ 1.3 m2 时,首选固定负荷剂量 (LD),当 BSA 结论时,首选基于 BSA 的 LD:我们的研究提出了基于 AUC0-24/MIC90 或 Ctrough 的卡泊芬净优化给药方案,这可能有助于进一步的个体化治疗。
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Journal of Antimicrobial Chemotherapy
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