Dataset Information

Bone and Joint Tissue Penetration of the Staphylococcus-Selective Antibiotic Afabicin in Patients Undergoing Elective Hip Replacement Surgery.

ABSTRACT: Afabicin (formerly Debio 1450, AFN-1720) is a prodrug of afabicin desphosphono (Debio 1452, AFN-1252), a novel antibiotic in development which targets the staphylococcal enoyl-acyl carrier protein reductase (FabI) and exhibits selective potent antibacterial activity against staphylococcal species, including methicillin-resistant Staphylococcus aureus As part of clinical development in bone and joint infections, a distribution study in bone was performed in 17 patients who underwent elective hip replacement surgery. Patients received 3 doses of 240?mg afabicin orally (every 12?h) at various time points before surgery. Afabicin desphosphono concentrations were measured by liquid chromatography-tandem mass spectrometry in plasma, cortical bone, cancellous bone, bone marrow, soft tissue, and synovial fluid collected during surgery at 2, 4, 6, or 12?h after the third afabicin dose. The study showed good penetration of afabicin desphosphono into bone tissues, with mean area under the curve ratios for cortical bone-, cancellous bone-, bone marrow-, soft tissue-, and synovial fluid-to-total plasma concentrations of 0.21, 0.40, 0.32, 0.35, and 0.61, respectively. When accounting for the free fraction in plasma (2%) and synovial fluid (9.4%), the mean ratio was 2.88, which is indicative of excellent penetration and which showed that the afabicin desphosphono concentration was beyond the MIC90 of S. aureus over the complete dosing interval. These findings, along with preclinical efficacy data, clinical efficacy data for skin and soft tissue staphylococcal infection, the availability of both intravenous and oral formulations, and potential advantages over broad-spectrum antibiotics for the treatment of staphylococcal bone or joint infections, support the clinical development of afabicin for bone and joint infections. (This study has been registered at ClinicalTrials.gov under identifier NCT02726438.).

SUBMITTER: Menetrey A

PROVIDER: S-EPMC6395911 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Publications

Bone and Joint Tissue Penetration of the <i>Staphylococcus</i>-Selective Antibiotic Afabicin in Patients Undergoing Elective Hip Replacement Surgery.

Menetrey Annick A Janin Annick A Pullman John J Overcash J Scott JS Haouala Amina A Leylavergne François F Turbe Laurent L Wittke Frederick F Nicolas-Métral Valérie V

Antimicrobial agents and chemotherapy 20190226 3

Afabicin (formerly Debio 1450, AFN-1720) is a prodrug of afabicin desphosphono (Debio 1452, AFN-1252), a novel antibiotic in development which targets the staphylococcal enoyl-acyl carrier protein reductase (FabI) and exhibits selective potent antibacterial activity against staphylococcal species, including methicillin-resistant <i>Staphylococcus aureus</i> As part of clinical development in bone and joint infections, a distribution study in bone was performed in 17 patients who underwent electi ...[more]

PMID: 30559136

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Project description:BackgroundAn ageing population has resulted in a rise in the number of hip and knee replacement surgeries in the UK. The pre-operative pathway is plagued with issues causing long delays and cancellations. Virtual healthcare technologies have a growing evidence base to help solve these issues. One problem of implementing these technologies is the resistance to change mentality from healthcare professionals. By getting their opinions on the place of these technologies within the pre-operative pathway, a united front can be formed to help deliver change.MethodsSixteen semi-structured interviews were conducted with key stakeholders within the orthopaedic pre-operative pathway at Imperial College Healthcare NHS Trust. General topics included the different technologies that could be used within the pathway, their uses and associated benefits and problems. Interviews were audio-recorded, before being manually transcribed and then analysed to form categories and themes.ResultsVarious uses, benefits and problems were identified by healthcare professionals for each modality of technology. E-forms were seen as a high reward, low-risk intervention. Remote patient monitoring and teleconsultations had their bonuses, but feasibility was a primary concern. Web-based interventions were seen as an intervention of the past, whereas virtual reality was seen as perhaps being ahead of its time. M-health was very positively viewed due to its all-encompassing nature. Digital illiteracy emerged as a consistent problem for most technologies.ConclusionsCurrent literature, the results from this study and technology trends within society highlight both M-health and E-forms as the 2 most promising virtual healthcare technologies for use in the pre-operative pathway for orthopaedics. Areas such as pre-operative assessment, triaging and prehabilitation are prime candidates for virtual intervention. Future research should also consider including patient opinions on any proposed interventions, as well as taking into account barriers to implementation.

Dataset Information

Bone and Joint Tissue Penetration of the Staphylococcus-Selective Antibiotic Afabicin in Patients Undergoing Elective Hip Replacement Surgery.

Publications

Bone and Joint Tissue Penetration of the <i>Staphylococcus</i>-Selective Antibiotic Afabicin in Patients Undergoing Elective Hip Replacement Surgery.

Similar Datasets

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