A broad-spectrum antimicrobial ointment containing Bi2O3 NPs for skin and soft tissue infections by multidrug-resistant bacteria

一种含有 Bi2O3 NP 的广谱抗菌软膏，用于治疗多重耐药菌引起的皮肤和软组织感染

• 批准号: 10648313
• 负责人: SONGPING D HUANG
• 金额: $ 8.92万
• 依托单位: KENT STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-19 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10648313
• 关键词: Anti-Bacterial Agents; Antibiotic Therapy; Antibiotics; Bacitracin; Bacteria; Bacterial Infections; Bismuth; Caring; Ciprofloxacin; Clinical; Collaborations; Communities; Coupled; Cream; Development; Drug Delivery Systems; Drug Prescriptions; Drug resistance; Drug resistant Pseudomonas aeruginosa; Effectiveness; Environmental Wind; Evaluation Studies; Fluoroquinolones; Formulation; Foundations; Fusidic Acid; Hospitals; In Vitro; Injectable; Life; Medical; Meropenem; Methicillin; Methicillin Resistance; Minor; Multiple Bacterial Drug Resistance; Mupirocin; Neomycin; Ointments; Oral; Oxides; Penetration; Persons; Pharmaceutical Preparations; Play; Polymyxin B; Preparation; Research; Research Project Grants; Resistance; Role; Skin; Skin Tissue; Skin injury; Soft Tissue Infections; Staphylococcus aureus; Superbug; Systemic infection; Techniques; Time; Topical Antibiotic; Treatment outcome; Wound Infection; antimicrobial; base; burn therapy; combat; delivery vehicle; drug resistance development; drug-sensitive; effectiveness study; experience; help-seeking behavior; improved; in vivo; methicillin resistant Staphylococcus aureus; multidrug-resistant Pseudomonas aeruginosa; nanomaterials; nanoparticle; prevent; prophylactic; response; success

SUMMARY Gone with the wind is the time when skin and soft tissue infections (SSTIs) were once readily treatable bacterial infections with over-the-counter ointments consisting of topical antibiotics such as bacitracin, neomycin and polymyxin B. With the emergence of methicillin-resistant Staphylococcus aureus (MRSA), the so-called “superbug” and multidrug-resistant Pseudomonas aeruginosa (MDPA), coupled with the dwindling number of available broad-spectrum topical antibiotics, treatment of SSTIs has become increasingly problematic. Currently, only three prescription-only topical antibiotics are still effective in the treatment of SSTIs caused by multi-drug resistant bacteria. These include mupirocin (Bactroban®) and fusidic acid (not approved for clinical use in the US yet) effective against MRSA, and polymyxin B (prescription-strength) effective against MDPA. To improve treatment outcomes, a broad-spectrum oral or injectable fluoroquinolone antibiotic (e.g., ciprofloxacin) is often prescribed in combination with one of these topical antibiotics. Such practice inadvertently contributes to the overuse and misuse of antibiotics. Many experts believe that there are now few clinical circumstances in which prescription of topical antibiotics is still appropriate and may not be a feasible treatment option at all for SSTIs by the end of this decade. In response to the urgent medical need in the treatment of SSTIs caused by multidrug-resistant bacteria, we propose to develop a new broad-spectrum topical antimicrobial ointment incorporating bismuth oxide nanoparticles (Bi2O3 NPs) as an over-the-counter medication in place of conventional topical, oral or injectable antibiotics. Additionally, this new antimicrobial ointment has an extremely low likelihood of developing Bi resistance. As the result, it may have potential for widespread use in a variety of situations ranging from the prophylactic care of minor skin injuries to the treatment of burn wound infections. Our broad and long-term objectives of this proposal are: (1) to perform extensive formulation studies to reach the optimal conditions for the incorporation of Bi2O3 NPs into an appropriate ointment base; and (2) to select three best ointments identified from the in vitro effectiveness studies for the evaluation of their in vivo efficacy. Therefore, the specific aims of this research include: (1) formulating Bi2O3 NPs into topical antimicrobial ointments (Aim 1); and (2) evaluating the in vivo efficacy of Bi2O3 NP ointments (Aim 2). The completion of these two specific aims will lead to the development of a new broad-spectrum topical antimicrobial ointment incorporating Bi2O3 NPs to combat SSTIs caused by multidrug-resistant bacteria in place of conventional topical, oral or injectable antibiotics, thus impacting the landscape of antibiotic stewardship.

概括 皮肤和软组织感染 (SSTI) 曾经很容易治疗的时代已成为过去 使用含有局部抗生素（如杆菌肽、新霉素）的非处方药膏治疗细菌感染 和多粘菌素 B。随着耐甲氧西林金黄色葡萄球菌 (MRSA) 的出现，所谓的 “超级细菌”和多重耐药铜绿假单胞菌（MDPA），再加上细菌数量的减少 目前，由于可用广谱外用抗生素，SSTI 的治疗变得越来越困难。 只有三种处方外用抗生素仍能有效治疗由多种药物引起的 SSTI 这些包括莫匹罗星 (Bactroban®) 和夫西地酸（未批准用于临床） 美国尚未）对 MRSA 有效，多粘菌素 B（处方强度）对 MDPA 有效。 为了达到治疗效果，通常需要使用广谱口服或注射氟喹诺酮抗生素（例如环丙沙星） 与其中一种外用抗生素联合使用，这种做法无意中会导致这种情况。 许多专家认为，目前临床上很少有过度使用和滥用抗生素的情况。 对于 SSTI 来说，局部使用抗生素处方仍然是合适的，但可能根本不是可行的治疗选择 到本十年末。 针对多重耐药菌引起的SSTI治疗的迫切医疗需求，我们 提议开发一种含有氧化铋的新型广谱外用抗菌软膏 纳米颗粒（Bi2O3 NPs）作为非处方药替代传统的外用、口服或注射药物 此外，这种新型抗菌软膏产生 Bi 的可能性极低。 因此，它可能具有在各种情况下广泛使用的潜力。 我们对轻微皮肤损伤进行预防性护理，以治疗烧伤伤口感染。 该提案的目标是：(1) 进行广泛的配方研究，以达到最佳条件 将 Bi2O3 纳米颗粒掺入适当的软膏基质中；(2) 选择三种最佳的软膏； 因此，从体外有效性研究来评估其体内功效。 该研究包括：(1) 将 Bi2O3 NP 配制为外用抗菌软膏（目标 1）；以及 (2) 评估 Bi2O3 NP 软膏的体内功效（目标 2）。 这两个具体目标的完成将导致新的广谱主题的开发 含有 Bi2O3 NP 的抗菌软膏，可对抗由多重耐药细菌引起的 SSTI 传统的外用、口服或注射抗生素的使用，从而影响抗生素管理的格局。