Destiny Pharma Plc, Brighton, United Kingdom.
Front Cell Infect Microbiol. 2023 Oct 11;13:1264456. doi: 10.3389/fcimb.2023.1264456. eCollection 2023.
XF-73 (exeporfinium chloride) is a synthetic, di-cationic porphyrin derivative with rapid, potent bactericidal properties and a low propensity for engendering bacterial resistance. It is being developed clinically for the decolonization of in the nasal cavity to prevent post-operative staphylococcal infections. This study reports the minimum inhibitory concentration (MIC) of XF-73 in comparison to 22 antibiotics against a panel of >2,500 clinical isolates composed of 16 different Coagulase-positive and -negative species from 33 countries. XF-73 was found to be effective against all isolates tested, with MICs ranging between ≤0.12 - 4 µg/ml (MIC and MIC values of 0.5 and 1 µg/ml respectively). XF-73 was found to be equally effective against antibiotic resistant isolates as antibiotic sensitive isolates, with no impact of pre-existing antibiotic resistance mechanisms to cell wall synthesis inhibitors (β-lactams, carbapenems, glycopeptides and cephalosporins), protein synthesis inhibitors (oxazolidinones, macrolides and tetracyclines), DNA synthesis inhibitors (fluoroquinolones) and a folate synthesis inhibitor. The panel selected also included examples of multidrug-resistant isolates and, in all cases, the XF-73 MIC ranges were found to be similar against each of these groups. This dataset expands the knowledge of the breadth of activity of this novel antibacterial against a wide range of global isolates and supports the potential utility of XF-73 for the treatment of patients who are nasal carriers. Similar results were also obtained for multidrug-resistant isolates of other included in the study and collectively support the continued clinical development of XF-73 as an effective anti-staphylococcal drug.
XF-73（氯化外啡因）是一种合成的二阳离子卟啉衍生物，具有快速、强效的杀菌特性，不易产生细菌耐药性。它正在临床上开发用于鼻腔的去定植，以预防术后葡萄球菌感染。本研究报告了 XF-73 的最低抑菌浓度（MIC）与 22 种抗生素相比，针对由来自 33 个国家的 16 种不同凝固酶阳性和阴性葡萄球菌物种组成的>2500 个临床分离株的药敏试验板。研究发现，XF-73 对所有测试的分离株均有效，MIC 范围在≤0.12-4μg/ml（MIC 和 MIC 值分别为 0.5 和 1μg/ml）之间。研究发现，XF-73 对耐药和敏感的分离株均有效，对细胞壁合成抑制剂（β-内酰胺类、碳青霉烯类、糖肽类和头孢菌素类）、蛋白合成抑制剂（唑烷酮类、大环内酯类和四环素类）、DNA 合成抑制剂（氟喹诺酮类）和叶酸合成抑制剂无预先存在的耐药机制的影响。所选的药敏试验板还包括多药耐药的葡萄球菌分离株的实例，在所有情况下，XF-73 的 MIC 范围对这些组中的每一组都相似。该数据集扩展了对这种新型抗菌剂对广泛的全球葡萄球菌分离株的活性范围的认识，并支持 XF-73 用于治疗定植有葡萄球菌的患者的潜在应用。在研究中包括的其他葡萄球菌的多药耐药分离株也得到了类似的结果，这共同支持了 XF-73 作为一种有效的抗葡萄球菌药物的持续临床开发。
