The primary purpose of this study is to assess the effect of renal impairment on the PK of afabicin desphosphono after a single oral 80 milligrams (mg) or intravenous (IV) 55 mg dose of afabicin.

开始日期2026-09-01

申办/合作机构

Debiopharm International SA

NCT03723551

/ Terminated临床2期

Randomized Open-label Active-controlled Study to Assess the Safety, Tolerability, and Efficacy of Afabicin IV/Oral in the Treatment of Patients With Bone or Joint Infection Due to Staphylococcus

This is a randomized, active-controlled, open-label study to assess the safety, tolerability and efficacy of Afabicin in the treatment of participants with bone or joint infection due to Staphylococcus aureus [both methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA)] and/or coagulase-negative staphylococci (CoNS) and to compare it to standard of care (SoC).

开始日期2019-02-20

申办/合作机构

Debiopharm International SA

NCT03209648

/ Completed临床1期

A Phase 1, Open-Label, Fixed Sequence Study to Investigate the Effect of Itraconazole on the Pharmacokinetics of Debio 1450 in Healthy Subjects

Debio 1450 is metabolised mainly by CYP3A4, therefore inhibitors of CYP3A4 have the potential to raise Debio 1450 plasma concentrations. Hence, it is important to determine the effect of CYP3A4 inhibition by itraconazole on the Pharmacokinetics of Debio 1450.

开始日期2017-06-14

申办/合作机构

Debiopharm International SA

100 项与 Afabicin diolamine 相关的临床结果

登录后查看更多信息

100 项与 Afabicin diolamine 相关的转化医学

登录后查看更多信息

100 项与 Afabicin diolamine 相关的专利（医药）

登录后查看更多信息

项与 Afabicin diolamine 相关的文献（医药）

2026-04-01·ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

Model-based quantification of immune response and anti-staphylococcal activity of afabicin in immunocompetent mouse thigh infections to enable predictions of clinical efficacy

Article

作者: Nielsen, Elisabet I. ; Nicolas-Métral, Valérie ; Cameron, David R. ; Menetrey, Annick ; Friberg, Lena E. ; Saporta, Raphaël

ABSTRACT:

This study aimed to describe the immune response and activity of the novel antibiotic afabicin against Staphylococcus aureus in an immunocompetent mouse thigh infection model using PKPD modeling and to predict the clinical efficacy of different afabicin dosing regimens in Staphylococcus -infected immunocompetent patients. Bacterial counts of five Staphylococcus aureus strains were determined over 74 h in an immunocompetent mouse thigh infection model. Afabicin doses of 0.011–150 mg/kg were administered intraperitoneally every 6 h. A PKPD model was developed to describe immune response and afabicin desphosphono (active moiety) activity. The model was used jointly with a human population PK model for afabicin to predict the efficacy of different clinical dosing regimens (intravenous 55 to 160 mg twice-daily or oral 80 to 240 mg twice-daily) in immunocompetent patients. The developed model included a saturable neutrophil-mediated phagocytosis process of bacteria. The afabicin desphosphono effect was characterized using a model structure previously developed based on in vitro time-kill and neutropenic mouse thigh infection data. A lower maximum killing rate constant (0.24 h −1 ) and an 82% lower EC 50 were estimated for immunocompetent animals compared to in vitro . Predictions indicated that all tested afabicin regimens would achieve bacterial killing in immunocompetent patients infected with S. aureus . Afabicin activity against five S. aureus strains was adequately quantified in immunocompetent animals by the developed PKPD model. Predictions supported the efficacy of afabicin 55 mg intravenously twice daily, followed by an 80 mg oral twice-daily regimen in humans, which is currently tested in a clinical trial in bone and joint infections.

2024-12-02·JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY

Model-based translation of results from in vitro to in vivo experiments for afabicin activity against Staphylococcus aureus

Article

作者: Nielsen, Elisabet I ; Menetrey, Annick ; Friberg, Lena E ; Nicolas-Metral, Valérie ; Cameron, David R ; Saporta, Raphaël

Abstract:

Background:

Translation of experimental data on antibiotic activity typically relies on pharmacokinetic/pharmacodynamic (PK/PD) indices. Model-based approaches, considering the full antibiotic killing time course, could be an alternative.

Objectives:

To develop a mechanism-based modelling framework to assess the in vitro and in vivo activity of the FabI inhibitor antibiotic afabicin, and explore the ability of a model built on in vitro data to predict in vivo outcome.

Methods:

A PK/PD model was built to describe bacterial counts from 162 static in vitro time–kill curves evaluating the effect of afabicin desphosphono, the active moiety of the prodrug afabicin, against 21 Staphylococcus aureus strains. Combined with a mouse PK model, outcomes of afabicin doses of 0.011–190 mg/kg q6h against nine S. aureus strains in a murine thigh infection model were predicted, and thereafter refined by estimating PD parameters.

Results:

A sigmoid Emax model, with EC50 scaled by the MIC described the afabicin desphosphono killing in vitro. This model predicted, without parameter re-estimation, the in vivo bacterial counts at 24 h within a ±1 log margin for most dosing groups. When parameters were allowed to be estimated, EC50 was 38%–45% lower in vivo, compared with in vitro, within the studied MIC range.

Conclusions:

The developed PK/PD model described the time course of afabicin activity across experimental conditions and bacterial strains. This model showed translational capacity as parameters estimated on in vitro time–kill data could well predict the in vivo outcome for a wide variety of doses in a mouse thigh infection model.

2023-08-02·The Journal of antimicrobial chemotherapy

Evaluation of the microbiota-sparing properties of the anti-staphylococcal antibiotic afabicin

Article

作者: Kühn, J ; Nicolas-Metral, V ; Le Vacon, F ; Nowakowska, J ; Wittke, F ; Le Fresne-Languille, S ; Vuagniaux, G ; Amouzou, Y ; Carton, T ; De Martino, A ; Leuillet, S ; Chaves, R L ; Cameron, D R

Abstract:

Background:

Antibiotic use is associated with collateral damage to the healthy microbiota. Afabicin is a first-in-class prodrug inhibitor of the FabI enzyme that, when converted to the pharmacologically active agent afabicin desphosphono, demonstrates a staphylococcal-specific spectrum of activity. An expected benefit of highly targeted antibiotics such as afabicin is microbiome preservation.

Objectives:

To compare the effects of oral treatment with afabicin and standard-of-care antibiotics upon the murine gut microbiota, and to assess the effects of oral afabicin treatment on the human gut microbiota.

Methods:

Gut microbiota effects of a 10 day oral course of afabicin treatment were monitored in mice and compared with clindamycin, linezolid and moxifloxacin at human-equivalent dose levels using 16S rDNA sequencing. Further, the gut microbiota of healthy volunteers was longitudinally assessed across 20 days of oral treatment with afabicin 240 mg twice daily.

Results:

Afabicin treatment did not significantly alter gut microbiota diversity (Shannon H index) or richness (rarefied Chao1) in mice. Only limited changes to taxonomic abundances were observed in afabicin-treated animals. In contrast, clindamycin, linezolid and moxifloxacin each caused extensive dysbiosis in the murine model. In humans, afabicin treatment was not associated with alterations in Shannon H or rarefied Chao1 indices, nor relative taxonomic abundances, supporting the findings from the animal model.

Conclusions:

Oral treatment with afabicin is associated with preservation of the gut microbiota in mice and healthy subjects.

项与 Afabicin diolamine 相关的新闻（医药）

2026-08-20

·腾讯网

张静萍/申川教授：铜绿假单胞菌耐药机制与头孢德罗在复杂感染中的临床应用

编者按：多重耐药革兰阴性菌（MDR-GNB），尤其是碳青霉烯耐药革兰阴性菌（CRO）感染仍是临床抗感染治疗的重大挑战，而铜绿假单胞菌因其先天与获得性耐药机制叠加，常导致复杂感染迁延难愈，尤其在骨关节感染、血管植入物感染以及其他深部感染中增加治疗难度。近年来，以头孢德罗为代表的新型抗菌药物凭借独特的“铁载体介导主动摄取”机制，为部分高度耐药铜绿假单胞菌感染提供了新的治疗选择。本文围绕铜绿假单胞菌的多层耐药机制，复杂感染治疗困境，并结合头孢德罗作用特点以及现有临床证据，探讨其在难治性感染管理中的应用价值。01.铜绿假单胞菌：天生高致病、高耐药的临床棘手致病菌铜绿假单胞菌是广泛分布在自然环境中的革兰阴性机会致病菌，可定植于人体表皮、呼吸道和尿道等部位[1]。2024年世界卫生组织（WHO）更新的全球威胁最大的耐药菌名单中，耐碳青霉烯铜绿假单胞菌（CRPA）被作为高优先级关注的病原体[2]。创伤相关性四肢骨髓炎是骨折相关感染最主要类型，一项覆盖中国21家医院、纳入3526例创伤后肢体骨髓炎患者的10年多中心队列研究显示，铜绿假单胞菌位列主要革兰阴性菌之首，占全部病原体的10.92%[3]。血管植入物相关感染中，铜绿假单胞菌是常见革兰阴性病原菌之一，部分研究显示其占感染病例的10%以上，并为该类感染中最常见的革兰阴性致病菌[4]。铜绿假单胞菌感染难治与其多重耐药机制及复杂致病特点密切相关。其可通过多种机制共同介导耐药，包括外膜屏障导致药物进入受限、外排泵系统促进药物排出、抗菌药物灭活酶降低药物活性，以及生物膜形成增强细菌耐受性等。此外，基因突变和水平基因转移可进一步促进耐药表型形成[2]。多重机制叠加使铜绿假单胞菌具有高度适应性和持续感染能力，导致深部感染迁延不愈，增加了临床治疗难度。02.两大高危铜绿感染困局，抗菌药治疗遇阻对于创伤后慢性骨髓炎或假体周围骨关节感染，铜绿假单胞菌常通过开放性骨折或医疗操作进入人体，在血供较差的骨组织或植入物表面定植并形成生物膜[5,6]。由于骨组织血供相对不足，且生物膜可降低抗菌药物渗透并增强细菌耐受，感染往往迁延难愈。在治疗选择方面，多黏菌素类虽对部分耐药株具有活性，药物因其肾毒性限制了其长疗程应用[7]；其他传统抗菌药如阿米卡星与毒性、耐药性增加相关，致其临床应用受限[8]。更为棘手的是，部分新型β-内酰胺/β-内酰胺酶抑制剂复方在常规体外药敏中可能表现为敏感，但在模拟感染微环境或动物模型中可能出现疗效下降甚至治疗失败，提示体外药敏与体内疗效之间存在脱节[9]。铜绿假单胞菌最常见碳青霉烯耐药模式为OprD孔蛋白下调与AmpC/A/D类β-内酰胺酶的产生，头孢德罗依靠铁转运系统主动跨膜入胞，可规避孔蛋白下调介导的耐药；同时其分子结构对A/B/C/D四类β-内酰胺酶高度稳定，不易被铜绿假单胞菌产AmpC酶水解失活[8]。不同动物感染模型结果均表明头孢德罗对铜绿假单胞菌菌株显示出有效的体内活性，APEKS-cUTI试验证实头孢德罗对临床分离的铜绿假单胞菌感染可实现可靠的细菌清除与临床治疗应答[8]。血管植入物相关感染的治疗同样面临挑战。铜绿假单胞菌可因术中器械污染或远期血行播散导致病原体定植于植入物表面，并在人工血管等植入物表面形成生物膜，限制抗菌药物渗透并屏蔽微生物免受宿主免疫防御，从而使感染迁延不愈，即使在系统性抗菌治疗下也常出现复发。一项系统性综述研究表明，在腔内移植物感染中，对于无法接受手术干预的患者，单纯抗菌药物治疗的预后较差[10]。一项回顾性队列研究显示，在不适合手术的假体血管移植物感染患者中，长期抑制性抗菌治疗（SAT）可在一定程度上控制感染，但存在较高的治疗失败和不良事件负担[11]。在这种困局下，临床亟需兼具对碳青霉烯耐药菌株强效活性、优异骨/软组织穿透、突出抗生物膜作用以及长疗程安全性的新型抗菌药物，以改善当前治疗困境。03.头孢德罗：突破铜绿耐药“城墙”的“特洛伊木马”铁载体主动转运机制绕开外膜通透性耐药通路头孢德罗是全球首款获批的铁载体头孢菌素，其独特之处在于利用细菌天然摄铁系统实现主动转运，即“特洛伊木马”机制。其C-3位侧链的氯代儿茶酚基团螯合三价铁离子，形成的复合物被铜绿假单胞菌的PiuA、大肠埃希菌的CirA/Fiu等TonB依赖性铁转运通道主动识别并转运进入周质间隙，区别于传统β内酰胺类药物主要依赖外膜通透性被动扩散进入的通路[12]。头孢德罗的构效关系及其对革兰氏阴性菌的作用机制[8,12]铁载体主动转运机制使其在一定程度上降低了外膜通透性下降和部分外排机制对药物活性的影响。研究表明，OprD缺失突变仅使头孢德罗MIC由0.12升至0.25mg/L（2倍变化），而亚胺培南MIC升高8倍；MexAB-OprM外排泵过表达对头孢德罗MIC的影响较小[8,13]，表明头孢德罗区别于传统β-内酰胺类药物受外膜通透性的限制，并对部分膜屏障缺陷型耐药菌株仍保持稳定抗菌活性。需指出的是，该机制并非完全“免疫”：当铁转运受体本身发生突变（如piuA缺失）时，头孢德罗MIC可升高16倍，这意味着其活性高度依赖于细菌摄铁系统的完整性[13]。大规模体外监测证实抗菌活性头孢德罗具有强效体外抗菌活性，对绝大多数多重耐药铜绿临床分离株保持优异抑制效果。依托2014-2017年北美、欧洲多国开展的SIDERO-WT全球常规革兰阴性菌监测，以及2014-2016年覆盖全球多地区的SIDERO-CR碳青霉烯耐药专项监测两项大型多中心研究，体外药敏数据显示，头孢德罗对铜绿假单胞菌整体MIC90=0.5mg/L，对MDR铜绿MIC90=1mg/L；而头孢他啶-阿维巴坦MIC90=8mg/L，头孢洛生-他唑巴坦在MDR及头孢他啶-阿维巴坦不敏感亚组中MIC90高达32-＞64mg/L。针对碳青霉烯耐药铜绿假单胞菌（CRPA）及产VIM的铜绿假单胞菌，头孢德罗MIC90仅为0.5-2mg/L，较上述新型复方制剂低2个数量级[8]。结果证实头孢德罗对普通、多重耐药、碳青霉烯耐药铜绿假单胞菌均具备较好的体外杀菌活性，是临床治疗难治铜绿感染的潜力药物。抗生物膜活性与多组织深度渗透能力头孢德罗单药在体外生物膜模型中对铜绿假单胞菌成熟生物膜的活菌减少率达93%（P＜0.0001），优于头孢洛生-他唑巴坦（81.2%）、头孢他啶-阿维巴坦（80%）等7种对照抗菌药（总体49%-82%）[14]。需要指出的是，这些发现主要来自体外模型，虽然提示头孢德罗具有降低生物膜菌负荷的潜力，但其在人体内对于植入物感染的临床获益仍有待更多临床研究验证。头孢德罗降低铜绿假单胞菌生物膜负荷的效果优于对照抗菌药[14]激光共聚焦荧光成像证实了头孢德罗的抗生物膜活性：菌株先培养24h使其形成成熟生物膜，随后分别采用8mg/mL头孢德罗持续处理48h（给药组）、等体积无菌生理盐水孵育（阳性对照组），镜下可见铜绿假单胞菌生物膜的胞外多糖基质（绿色荧光信号）与菌体总数量（红色荧光信号）下降幅度显著优于鲍曼不动杆菌及肺炎克雷伯菌，菌体残留量极少，生物膜结构破坏程度在三种受试多重耐药革兰阴性菌中最为明显[15]。生物膜成熟培养24h，头孢德罗持续处理48h后，不同菌种生物膜的激光共聚焦显微镜（CLSM）图像。采用GS-II偶联Alexa Fluor 488标记胞外基质多糖（绿色荧光），细菌菌体经染色呈红色，白色箭头指示胞外基质区域[15]在联合用药方面，体外试验证实，头孢德罗与多黏菌素联用可在部分碳青霉烯耐药铜绿假单胞菌中呈现协同杀菌效应，但该体外活性尚待大规模临床研究进一步确证其在真实世界的有效性[16-17]。另一项体外研究证实铋剂可显著放大头孢德罗抗生物膜效应，二者联用可大幅降低生物膜活菌负荷，共聚焦成像直观显示联用组生物膜厚度与完整度显著受损[18]。绿色荧光蛋白（GFP）标记铜绿假单胞菌生物膜共聚焦三维成像：空白对照、单用头孢德罗（CEF）、单用胶体枸橼酸铋（CBS）、CEF+CBS联用[18]另有一例病例报告显示，一例广泛耐药铜绿假单胞菌菌血症合并疑似骨髓炎的患者，按标准方案给药后骨组织中的头孢德罗浓度达到13.9mcg/g，皮下软组织浓度为35.9mcg/g[19]，提示其具备穿透至骨及深部软组织的潜力，但需注意这仅是基于单一个案报道，并非标准的药代动力学临床研究。2025ICM共识会议[20]亦提到，多项研究评估了新型抗菌药的骨穿透能力，包括达巴万星、奥利万星、Afabicin、Levonadifloxacin、头孢德罗。上述药物在骨与关节感染常见致病菌中，骨内药物浓度均可超过MIC。但需强调，不同研究间试验设计差异较大，无法得出这类新药骨穿透性能全面优于传统抗菌药的确切结论。临床选择需结合药敏结果、病灶局部条件等综合判断。04.循证探索：头孢德罗在骨与植入物感染救治中的临床潜力国际PROVE真实世界研究骨与关节感染亚组PROVE研究[21]是一项国际多中心回顾性真实世界研究，纳入了54例合并骨与关节感染（BJI）的患者进行亚组回顾性分析，其中64.8%为单一病原体感染，约三分之一的患者为混合感染。结果显示，在头孢德罗治疗结束时，BJI患者的整体临床治愈率为83.3%，临床应答率为88.9%；第14天和第30天的全因死亡率分别为3.7%和11.1%。其中，由假单胞菌属所致的单菌感染临床治愈率为88.9%（8/9例），混合感染的临床治愈率为72.2%（14/19例）。该研究提示，头孢德罗在骨与关节感染，尤其是耐药革兰阴性菌相关感染管理中具有一定临床应用价值，但其疗效仍需通过前瞻性研究进一步验证。PROVE研究中BJI患者不同病原体对应的临床结局（2020-2024年；样本量N=54）[21]法国全国多中心骨关节感染回顾性队列研究一项纳入45例患者的法国多中心研究[22]表明，在多重耐药革兰阴性菌所致的骨关节感染（其中44%为植入物相关，铜绿假单胞菌占38%）中，头孢德罗中位治疗时长为34天，89%的患者采用了联合治疗方案。治疗结束时，总体治疗失败率为49%，死亡率为22%。较高的治疗失败率根本原因在于：入组患者均为末线挽救人群；高龄、多重合并症；植入物相关感染占比高，混合感染多见；部分患者仅能保守清创、无法完整移除植入物，治疗失败更多与感染病灶生物膜、患者基础衰弱相关。因此，该研究结论认为，在治疗选择有限的MDR-GNB骨关节感染中，头孢德罗可作为一种潜在的挽救性替代方案。植入物感染临床挽救病例高危免疫抑制患者成功救治[23]：一例CAR-T治疗后出现重度中性粒细胞缺乏的患者，因广泛耐药铜绿假单胞菌导致坏死性筋膜炎和盆腔骨髓炎，在常规新型头孢复方治疗失败后，换用头孢德罗治疗12周，60天随访创面完全愈合，感染无复发。无法移除植入物患者的应用[24]：两例由于MDR革兰阴性菌（包括铜绿假单胞菌）引起的血管内异物感染（包括门静脉假体、左心室辅助装置），患者因无法移除植入物，采用含头孢德罗的联合方案后成功控制感染。门诊长程治疗方案[25]：一例由产金属β-内酰胺酶的多重耐药铜绿假单胞菌引起的创伤后骨髓炎患者，通过门诊肠外抗菌药治疗（OPAT）成功完成了头孢德罗长疗程治疗。脊柱内固定物感染的治疗[26]：1例高龄患者脊柱深部内固定感染，致病菌为泛耐药鲍曼不动杆菌合并全敏感铜绿假单胞菌，植入物无法取出，采用头孢德罗挽救治疗获得成功。手术切口感染合并深部骨髓炎的成功救治[27]：一例胫骨内固定术后泛耐药铜绿假单胞菌（产IMP型金属β-内酰胺酶）骨髓炎患者，因多黏菌素诱发严重肾损伤无法耐受，经清创取内固定、予头孢德罗同情用药联合环丙沙星治疗28天，感染治愈，远期骨修复与肢体功能恢复良好。05.指南证据：头孢德罗在耐药铜绿假单胞菌感染中的应用定位头孢德罗因其独特的主动转运机制和对产碳青霉烯酶菌株的活性，《IDSA 2026版耐药革兰阴性菌治疗指南》[28]将头孢德罗纳入相应治疗推荐中，为其在CRPA治疗中的应用提供了规范依据。IDSA指南明确，对于产金属酶的DTR-PA感染，首选治疗是头孢德罗。此外，头孢德罗首选用于治疗DTR-PA感染所致的复杂性尿路感染，同时也是治疗DTR-PA引起的尿路外感染的替代治疗选择。骨/植入物感染由于感染部位特殊、生物膜形成以及治疗周期较长，耐药演变和药物暴露不足风险进一步增加。《碳青霉烯耐药铜绿假单胞菌感染诊治指南（2026版）》[25]指南则强调了CRPA感染需要长疗程感染的患者中，MIC监测、抗菌药物TDM在此类感染管理中具有重要意义。《碳青霉烯耐药铜绿假单胞菌感染诊治指南（2026版）》[25]针对CRPA感染提出了多项治疗原则，可作为临床决策的基础框架。推荐3：建议在CRPA感染治疗过程中尽可能实施抗菌药物的药物敏感性（如MIC）监测，并据此调整治疗方案。尤其是疗程长、重症感染以及疗效不佳的患者更加建议进行药物敏感性监测。推荐4：建议在使用头孢洛生-他唑巴坦、头孢他啶-阿维巴坦、亚胺培南-西司他丁-瑞来巴坦、头孢德罗、多黏菌素类药物、头孢他啶、美罗培南和亚胺培南-西司他丁等药物治疗CRPA感染时，尤其是对于重症或需要长疗程治疗的患者，应尽可能进行抗菌药物TDM。06.总结多重耐药铜绿所致骨关节、血管植入物感染临床预后差，多层耐药屏障大幅削弱传统抗菌药疗效，现有药物难以兼顾深部组织穿透、生物膜清除与长期用药安全性，临床治疗缺口突出。头孢德罗依托独特转运通路规避膜屏障耐药，并对部分耐碳青霉烯铜绿假单胞菌保持良好体外活性。同时，已有研究显示其在体外生物膜模型及复杂感染场景中具有降低菌负荷和控制感染的潜在价值。多项国际真实世界研究及病例报道提示，头孢德罗可作为治疗选择有限的耐药铜绿假单胞菌感染中的重要治疗选择之一，且总体安全性可控。但耐药菌感染需外科干预、个体化联合用药综合管理。未来仍需更多前瞻性研究优化给药策略，完善分层诊疗体系，改善患者远期预后。参考文献[1] 郑远明, 姜冉冉, 周杰. 某三甲医院1548株铜绿假单胞菌临床分布、耐药性及流行病学分析[J]. 国外医药(抗生素分册), 2025, 46(5):333-338.[2] 郑远明, 姜冉冉, 周杰. 铜绿假单胞菌耐药的研究进展及潜在治疗策略[J]. 国外医药(抗生素分册), 2026, 47(3):215-220.[3] Ren Y, Liu L, Sun D, et al. Epidemiological updates of post-traumatic related limb osteomyelitis in china: a 10 years multicentre cohort study. Int J Surg. 2023;109(9):2721-2731.[4] Bandyk DF, Novotney ML, Back MR, Johnson BL, Schmacht DC. Expanded application of in situ replacement for prosthetic graft infection. J Vasc Surg. 2001;34(3):411-420.[5] Akcicek E, Mitterer JA, Achatz V, Szirmay T, Sebastian S, Hofstaetter JG. High failure rate in Pseudomonas aeruginosa-associated periprosthetic hip and knee joint infections. J Bone Jt Infect. 2026;11(1):83-94.[6] 乔林, 夏志林, 刘健, 等. 多中心创伤后慢性骨髓炎的细菌谱特点及药敏分析 [J] . 中华创伤骨科杂志, 2016, 18(9) : 769-774.[7] Wagenlehner F, Lucenteforte E, Pea F, et al. Systematic review on estimated rates of nephrotoxicity and neurotoxicity in patients treated with polymyxins. Clin Microbiol Infect. Published online January 6, 2021. S1198-743X(20)30764-3.[8] Zhanel GG, Golden AR, Zelenitsky S, et al. Cefiderocol: A Siderophore Cephalosporin with Activity Against Carbapenem-Resistant and Multidrug-Resistant Gram-Negative Bacilli. Drugs. 2019;79(3):271-289.[9] Lyons N, Wu W, Jin Y, Lamont IL, Pletzer D. Using host-mimicking conditions and a murine cutaneous abscess model to identify synergistic antibiotic combinations effective against Pseudomonas aeruginosa. Front Cell Infect Microbiol. 2024;14:1352339.[10] Argyriou C, Georgiadis GS, Lazarides MK, Georgakarakos E, Antoniou GA. Endograft Infection After Endovascular Abdominal Aortic Aneurysm Repair: A Systematic Review and Meta-analysis. J Endovasc Ther. 2017;24(5):688-697.[11] Imeneo A, Zaçe D, Oddi FM, et al. Long-Term Suppressive Antimicrobial Therapy in Prosthetic Vascular Graft Infection: A Retrospective Evaluation of a Cohort of Patients Enrolled at Tor Vergata Hospital in Rome. Open Forum Infect Dis. 2026;13(6):ofag327.[12] Sato T, Yamawaki K. Cefiderocol: Discovery, Chemistry, and In Vivo Profiles of a Novel Siderophore Cephalosporin. Clin Infect Dis. 2019;69(Suppl 7):S538-S543.[13] Ito A, Sato T, Ota M, et al. In Vitro Antibacterial Properties of Cefiderocol, a Novel Siderophore Cephalosporin, against Gram-Negative Bacteria. Antimicrob Agents Chemother. 2017;62(1):e01454-17.[14] Pybus CA, Felder-Scott C, Obuekwe V, Greenberg DE. Cefiderocol Retains Antibiofilm Activity in Multidrug-Resistant Gram-Negative Pathogens. Antimicrob Agents Chemother. 2021;65(2):e01194-20.[15] Díaz-Navarro M, Cercenado E, Visedo A, et al. Assessment of the Anti-Biofilm Effect of Cefiderocol Against 28 Clinical Strains of Multidrug-Resistant Gram-Negative Bacilli. Antibiotics (Basel). 2025;14(8):738.[16] Babidhan R, Lewis A, Atkins C, et al. Safety and efficacy of cefiderocol for off-label treatment indications: A systematic review. Pharmacotherapy. 2022;42(7):549-566.[17] Mataracı-Kara E, Özer B, Yilmaz M, Özbek-Çelik B. An assessment of cefiderocol's synergistic effects with eravacycline, colistin, meropenem, levofloxacin, ceftazidime/avibactam, and tobramycin against carbapenem-resistant and -susceptible Pseudomonasaeruginosa. Microb Pathog. 2025;204:107560.[18] Wang C, Xia Y, Wang R, et al. Metallo-sideromycin as a dual functional complex for combating antimicrobial resistance. Nat Commun. 2023;14(1):5311.[19] Mueller SW, Molina KC, Blass B, et al. Bone and Skin/Subcutaneous Tissue Concentrations of Cefiderocol During Treatment of Extensively Drug-Resistant Pseudomonas aeruginosa. J Burn Care Res. 2024;45(3):808-810.[20] Sadek FZ, Tevell S, Lora-Tamayo J, et al. 2025 ICM: Use of Newer Antibiotics and Fluoroquinolone-Resistance. J Arthroplasty. 2025;41(1S1):S196-S205.[21] K. Molina, A. Dinh, S.T. Nguyen, et al. Cefiderocol in clinical practice for bone and joint infections: insights from the PROVE study. ESCMID Global 2026. P1863.[22] Diarra A, Degrendel M, Eberl I, et al. Real-Life Cefiderocol Use in Bone and Joint Infection: A French National Cohort. Antibiotics (Basel). 2025;14(4):388.[23] P4814-Cefiderocol as a decisive rescue therapy in Fournier's gangrene caused by extensively drug-resistant Pseudomonas aeruginosa aft er CAR-T therapy.[24] Bodro M, Hernández-Meneses M, Ambrosioni J, et al. Salvage Treatment with Cefiderocol Regimens in Two Intravascular Foreign Body Infections by MDR Gram-Negative Pathogens, Involving Non-Removable Devices. Infect Dis Ther. 2021;10(1):575-581.[25] 中华医学会细菌感染与耐药防治分会, 等. 碳青霉烯耐药铜绿假单胞菌感染诊治指南（2026版）[J]. 中华医学杂志,2026,106(07)：601-617.[26] Cipko K, Kizny Gordon A, Adhikari S, Konecny P. Cefiderocol treatment of Pseudomonas aeruginosa and extensively drug-resistant Acinetobacter baumannii retained spinal hardware infection causing reversible acute interstitial nephritis: Recto: Cefiderocol causing acute interstitial nephritis. Int J Infect Dis. 2021;109:108-111.[27] Chavda A, Gilchrist M, Samarasinghe D. Education: A compassionate use of cefiderocol to treat osteomyelitis caused by an XDR Pseudomonas aeruginosa. JAC Antimicrob Resist. 2021;3(Suppl 1):i18-i20.[28] Tamma PD, Bonomo RA, Heil EL, Justo JA, Satlin MJ, Mathers AJ. Infectious Diseases Society of America 2026 Guidance on the Treatment of Antimicrobial-Resistant Gram-Negative Infections. Clin Infect Dis. Published online August 8, 2026.张静萍教授中国医科大学附属第一医院教授，主任医师，硕士生导师中国医科大学附属第一医院感染性疾病一科主任专业：细菌真菌感染，耐药菌、罕见真菌、免疫低下宿主感染诊治中华医学会感染病分会委员中国医师学会感染病分会委员兼细菌真菌学组副组长中国老年医学学会感染管理质量控制分会副主任委员国家细菌真菌感染诊治培训项目管理专委会委员国家感染预防与控制专家委员会委员中国医药教育学会感染性疾病专业委员会常务委员中国医药教育学会真菌病专业委员会委员中国医疗保健国际交流促进会临床微生物分会常务委员辽宁省医学会传染病与寄生虫学分会候任主任委员辽宁省院感质控中心主任辽宁省预防医学会感控分会副主任委员沈阳市细菌真菌感染临床医学研究中心主任申川教授河北医科大学第三医院感染一科副主任医学博士，副主任医师，副教授，硕士生导师中华医学会细菌感染与耐药防治分会委员中华医学会消化病学分会疑难重症疾病协作组委员中国医师协会感染科医师分会青年学组委员中华预防医学会感染性疾病防控分会青年委员中国医疗保健国际交流促进会临床微生物分会委员中国医药教育协会真菌病专业委员会委员、临床微生物学专业委员会委员中国医院管理协会抗微生物药物合理应用工作委员会委员河北省预防医学会医学寄生虫病分会副主任委员河北省医学会细菌感染与耐药防治分会常委河北省医师协会感染科医师分会委员兼秘书石家庄市医学会感染病学专业委员会常委兼秘书

2024-10-15

·debiopharm.com

Debiopharm to Showcase Research Results of Their First-In-Class Anti-Staphylococcal Program at IDWeek 2024 in Los Angeles

Share Debiopharm to present at the Rapid Fire session on Challenging Bacterial Infections, the latest data for afabicin, first-in-class, pathogen-specific FabI inhibitor antibiotic with clinically demonstrated activity against antibiotic-resistant staphylococcus infections and microbiome sparing potential. Lausanne, Switzerland – Debiopharm (www.debiopharm.com), a privately-owned, Swiss-based biopharmaceutical company aiming to establish tomorrow’s standard-of-care to cure cancer and infectious diseases, today announced preclinical and clinical data releases for the afabicin (Debio 1450) antibiotic program during the 2024 IDWeek summit in Los Angeles, California. “With the global demographic shift, healthcare practitioners are likely to experience more and more patients with bone and joint infections (BJIs), particularly involving prosthetic devices. Staphylococcus aureus is the most prevalent microorganism involved in BJIs and is notorious for its ability to become resistant to widely used antibiotics, including newer agents. With the phase 2 results I will be presenting, physicians may question themselves further on whether it’s still a smart choice to use wide-spectrum antibiotics.” – Dr. Alireza Shamaei-Tousi, Principal Clinical Scientist at Debiopharm Thu, October 17th Poster display: 12:15-12:45pm Rapid Fire Session: Challenging Bacterial Infections Results from A Phase 2 Clinical Trial for Treatment of Bone And Joint Infections with Afabicin, A First-in-Class Selective Anti-Staphylococcal Antibiotic Alireza Shamaei-Tousi, Principal Clinical Scientist Fri, October 18th Poster display: 12:15-1:30pm Poster Session: PK/PD Studies Assessment of Pharmacokinetic-Pharmacodynamic (PK-PD) Target Attainment for the Anti-Staphylococcal Antibiotic Afabicin David Cameron, Senior Scientist, Translational Pharmacology Sat, October 19th Poster display: 12:15-1:30pm Poster Session: Basic Science and Translational Studies The First-in-Class Anti-Staphylococcal Antibiotic Afabicin Desphosphono is Not Associated With Clostridioides difficile Infection in an in vitro Human Gut Model David Cameron, Senior Scientist, Translational Pharmacology Bone and joint infections are a group of diseases that include osteomyelitis, septic arthritis and prosthetic joint infections affecting over 30,000 people per year within the US, UK, France, Germany, Spain and Italy combined. These conditions are associated with significant global morbidity, and in certain circumstances, mortality. Staphylococci are the most common causative bacteria, identified in 30 to 70% of the cases. Debiopharm aims to develop innovative therapies that target high unmet medical needs in oncology and bacterial infections. Bridging the gap between disruptive discovery products and real-world patient reach, we identify high-potential compounds and technologies for in-licensing, clinically demonstrate their safety and efficacy, and then select large pharmaceutical commercialization partners to maximize patient access globally. For more information, please visit www.debiopharm.com We are on X. Follow us @DebiopharmNews at http://twitter.com/DebiopharmNews or on LinkedIn

临床2期临床结果合格传染病产品

2024-08-27

·Business Wire

Debiopharm Underlines Commitment to Eradicating Antimicrobial Resistance by Sponsoring the 8th Annual World AMR Conference

LAUSANNE, Switzerland--( BUSINESS WIRE )--Debiopharm ( www.debiopharm.com ), a Swiss-based, global biopharmaceutical company, aiming to establish tomorrow’s standard-of-care to cure cancer and infectious diseases, announced today their participation in the 2024 World AMR conference from September 5 th -6 th in Philadelphia, Pennsylvania, USA. For the last decade, Debiopharm has been committed to developing new antimicrobials for patients by conducting research on a novel class of antibiotics that target hard-to-treat infections, caused by WHO priority pathogens. Now in its third year of sponsoring World AMR, Debiopharm is proud to support the conference’s mission to unite key decision-makers in AMR from international government bodies, policy organizations, and the healthcare sector to meet, discuss, and formulate initiatives to tackle the emerging threat of AMR effectively. This year, Debiopharm’s Head of Global Value & Access, Jennifer Quinn, will present within the Impact, Policy and Awareness Track and lead a roundtable discussion on how to move the needle on fair reimbursement for antibiotics. Focused on actionable ways to leverage current reimbursement models, Jennifer’s presentation will outline a tangible framework for payer negotiations and discuss evidence needs for products that will reach the market before ‘pull incentives’ become available. “We’re looking forward to open discussions and networking opportunities with public organizations and other infectious disease industry experts to put into place practical solutions to combat the reimbursement challenged that help to fuel AMR.” – Jennifer Quinn, Head of Global Value & Access . World AMR 2023 Session details Congress agenda Speaker Presentation Sept. 5 th 11:20AM EST How can current reimbursement models be leveraged while waiting for 'pull incentives'? Jennifer Quinn, Head of Global Value & Access Roundtable discussion Sept. 5 th 01:30PM EST What data is needed to fit current payer evidence requirements and how can we generate it? Jennifer Quinn, Head of Global Value & Access About afabicin Afabicin (Debio 1450) is Debiopharm’s first-in-class FabI inhibitor , selectively targeting Staphylococcus ’ essential bacterial fatty acid biosynthesis pathway. Afabicin is active against Staphylococcus spp., of which methicillin-resistant Staphylococcus aureus (MRSA) strains are high on the WHO global priority pathogen list and deemed a “serious threat” by the CDC. Afabicin can be administered orally or intravenously. Promising results have been obtained in a comparative double-blind Phase 2 trial with afabicin in acute bacterial skin and skin structure infections. Currently, a global Phase 2 trial in bone and joint infections is being conducted, comparing afabicin to standard antibiotics. About Debio 1453 Analogous to afabicin, the preclinical compound Debio 1453 is a potential first-in-class pathogen-specific drug targeting the essential bacterial fatty acid biosynthesis pathway. Debio 1453 has been developed as an oral drug with activity against. Neisseria gonorrhoeae , the bacteria causing the sexually transmitted disease gonorrhea. Untreated gonorrhea can cause serious and permanent health issues including infertility, ectopic pregnancy, long-term pelvic/abdominal pain, blindness in newborns and in rare cases also have a lethal outcome. Debiopharm’s fight against antimicrobial resistance Debiopharm, an innovation-focused, Swiss biopharmaceutical company is one of the few privately owned companies developing novel class antibiotics to combat hard-to-treat infections. Through their unique partnership-based business model, the company is advancing pathogen-specific antibiotics from early stage through phase II clinical research with afabicin, specifically targeting staphylococci. As a result of high selectivity, FabI inhibitors specifically target selected pathogens, and potentially preserve intestinal microbiota. Debiopharm’s FabI inhibitors meet all four WHO 2020 innovation criteria: new chemical class, new target, new mode of action and no cross-resistance to other antibiotic classes. For more information, please visit www.debiopharm.com We are on X. Follow us @DebiopharmNews at http://twitter.com/DebiopharmNews Sources Antimicrobial Resistance Collaborators. (2022). Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. The Lancet; 399(10325): P629-655.

临床2期合格传染病产品

100 项与 Afabicin diolamine 相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB15268

研发状态

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
关节炎	临床2期	美国	Debiopharm International SA	2019-02-20
关节炎	临床2期	南非	Debiopharm International SA	2019-02-20
关节炎	临床2期	乌克兰	Debiopharm International SA	2019-02-20
骨和关节感染	临床2期	美国	Debiopharm International SA	2019-02-20
骨和关节感染	临床2期	南非	Debiopharm International SA	2019-02-20
骨和关节感染	临床2期	乌克兰	Debiopharm International SA	2019-02-20
细菌性皮肤疾病	临床2期	美国	Debiopharm International SA	2015-05-01
传染性皮肤病	临床2期	-	GSK Plc	-
软组织感染	临床2期	-	GSK Plc	-
感染性骨疾病	临床1期	美国	Debiopharm International SA	2016-04-01

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03723551 (CTgov)	临床2期	骨和关节感染 \| 关节炎	67	Afabicin (Part A: Afabicin: Cohort 1)	壓壓壓齋積構艱齋鏇願 = 網製窪淵餘構衊鹽繭壓築繭繭選襯襯壓壓艱鏇 (願艱糧範鏇醖醖鹽鹽鹽, 積願簾鬱願窪簾醖願鏇 ~ 鹽餘蓋築鹽膚簾網淵製) 更多	-	2026-09-09
				Afabicin (Part A: Afabicin: Cohort 2)	壓壓壓齋積構艱齋鏇願 = 廠簾餘鑰衊夢簾蓋繭淵築繭繭選襯襯壓壓艱鏇 (願艱糧範鏇醖醖鹽鹽鹽, 鏇鏇壓窪壓醖遞構齋廠 ~ 構餘廠艱簾鹽餘壓夢鏇) 更多
NCT02426918 (CTgov)	临床2期	细菌性皮肤疾病	330	Debio 1450 (Debio 1450 80 mg/120 mg BID)	繭壓鬱網窪選鹽網窪遞 = 餘繭淵衊鹹廠蓋製襯鹽鏇衊網淵蓋艱鏇膚鏇鏇 (齋壓蓋鏇選觸淵艱壓鑰, 製餘憲積願顧膚範選願 ~ 構顧鹹繭築艱夢鏇鬱廠) 更多	-	2019-11-13
				Debio 1450 (Debio 1450 160 mg/240 mg BID)	繭壓鬱網窪選鹽網窪遞 = 構觸鑰餘選鏇獵顧糧蓋鏇衊網淵蓋艱鏇膚鏇鏇 (齋壓蓋鏇選觸淵艱壓鑰, 廠糧繭醖願願簾蓋簾壓 ~ 襯鑰窪襯鑰鏇製獵築觸) 更多