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

总结 皮肤和软组织感染（SSTI）曾经很容易治疗，但随着时间的推移， 使用由局部抗生素（如杆菌肽、新霉素）组成的非处方软膏的细菌感染 和多粘菌素B。随着耐甲氧西林金黄色葡萄球菌（MRSA）的出现， “超级细菌”和多重耐药铜绿假单胞菌（MDPA），加上越来越少的 由于可用的广谱局部抗生素，SSTI的治疗已变得越来越成问题。目前， 只有三种处方外用抗生素在治疗由多种药物引起的SSTI中仍然有效， 耐药细菌这些包括莫匹罗星（Bactroban®）和夫西地酸（未被批准用于临床应用）。 US）有效对抗MRSA，多粘菌素B（处方强度）有效对抗MDPA。提高 治疗结果，广谱口服或注射氟喹诺酮抗生素（例如，环丙沙星）通常 与这些局部抗生素联合使用。这种做法无意中助长了 滥用和滥用抗生素。许多专家认为，现在很少有临床情况下， 局部抗生素处方仍然是适当的，对于SSTI可能根本不是可行的治疗选择 到这个十年结束的时候。 为了应对治疗由多重耐药细菌引起的SSTI的迫切医疗需求，我们 建议开发一种新的广谱局部抗菌软膏， 纳米颗粒（Bi 2 O3 NPs）作为非处方药，代替传统的局部、口服或注射 抗生素此外，这种新的抗菌软膏具有极低的可能性， 阻力因此，它可能具有广泛用于各种情况的潜力， 轻微皮肤损伤的预防性护理到烧伤创面感染的治疗。我们广泛而长期的 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Bi 2 O3纳米颗粒掺入适当的软膏基质中;以及（2）选择三种经鉴定的最佳软膏 用于评价其体内疗效的体外有效性研究。因此， 该研究包括：（1）将Bi 2 O3纳米颗粒配制成局部抗菌软膏（目的1）;和（2）评价 Bi 2 O3 NP软膏的体内功效（目的2）。 这两个具体目标的完成将导致一个新的广谱专题的发展 含有Bi 2 O3纳米颗粒的抗微生物软膏，用于对抗由多重耐药细菌引起的SSTI 传统的局部、口服或注射抗生素，从而影响抗生素管理的前景。

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.