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.

摘要 《乱世佳人》是皮肤和软组织感染(SSTI)曾经很容易治愈的时代 非处方药软膏中含有杆菌素、新霉素等外用抗生素的细菌感染 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 “超级细菌”和多重耐药的铜绿假单胞菌(MDPA)，再加上数量的减少 由于有广谱的外用抗生素，SSTI的治疗变得越来越困难。目前， 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 耐药细菌。这些药物包括莫匹罗星(巴曲班®)和呋西地酸(未获批准在 多粘菌素B(处方强度)对MDPA有效。为了提高 治疗结果，广谱口服或注射氟喹诺酮类抗生素(如环丙沙星)通常 与这些外用抗生素中的一种结合开出的处方。这种做法不经意间导致了 过度使用和滥用抗生素。许多专家认为，现在很少有临床情况 局部抗生素的处方仍然是合适的，可能根本不是SSTI的可行治疗选择 到本十年末。 为回应治疗由多重耐药细菌引起的性传播感染的迫切医疗需要，我们 建议开发一种新的含有氧化铋的广谱局部抗菌软膏 纳米Bi2O3作为非处方药替代传统的外用、口服或注射用药 抗生素。此外，这种新的抗菌软膏发生胆红素的可能性极低。 抵抗。因此，它可能有潜力在各种情况下广泛使用，从 预防护理轻微皮肤损伤，治疗烧伤创面感染。我们广泛而长期的 这项建议的目标是：(1)进行广泛的配方研究，以达到以下最佳条件 将Bi2O3NPs加入到适当的软膏基质中；以及(2)选择三种经鉴定的最佳软膏 从体外药效研究中评价其体内疗效。因此，该计划的具体目标 这项研究包括：(1)将Bi2O3纳米颗粒制成局部抗菌软膏(目标1)；以及(2)评价 Bi2O3NP软膏的体内疗效(目标2)。 这两个具体目标的完成将导致新的广谱专题的发展 含有Bi2O3纳米粒子的抗菌软膏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，从而影响了抗生素管理的格局。