Li Mingliang, Zhu Donglin, Diao Qiuyue, Liu Xiaoyun, Bi Xiaogang, Dong Jianwen, Sun Jian, Xi Yun, Zhang Kouxing
Department of General ICU, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China.
Department of Clinical Laboratory, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China.
J Fungi (Basel). 2024 Nov 22;10(12):812. doi: 10.3390/jof10120812.
Pythiosis, a rare and formidable infectious disease caused by , is characterized by profound uncertainties in achieving definitive diagnoses, suboptimal outcomes, and an exceptionally high mortality rate. Here, we present a rare case of human spinal pythiosis in southern China. With advanced metagenomic sequencing technology, was pinpointed as the causative pathogen. We discovered that the inoculation of either tissue fragments or homogenate yielded more successful results and enabled a moderate extension of the culture duration to 5-10 days through an exhaustive comparison of diverse inoculation and culture conditions for general clinical specimens. A pronounced genetic affinity of the isolated strain towards the strain MCC 13 was detected after a comprehensive whole-genome sequencing analysis. Antifungal agents exhibited negligible sensitivity towards in an antimicrobial susceptibility test. Conversely, antibacterial agents such as oxazolidinones, tetracyclines, macrolides, and amphenicols demonstrated varying degrees of sensitivity, albeit with most of their minimum inhibitory concentrations (MICs) substantially surpassing the safe concentration ranges for effective clinical treatment. Notably, tigecycline stood out as a promising candidate, exhibiting favorable therapeutic effects at moderate concentrations, making it a potential drug of choice for the control of pythiosis. A combined susceptibility test suggested that combinations of tetracyclines with macrolides, oxazolidinones, and amphenicols exhibited synergistic antibacterial effects, with the combination of doxycycline and trimethoprim-sulfamethoxazole (TMP-SMX) in particular playing a pivotal role. To our surprise, the MICs of iron chelators, specifically deferiprone and deferoxamine, against the strain were exceedingly low, which led to the speculation that exogenous iron chelators may have competitively inhibited the iron-chelating enzymes of the strain. The research derived from this single, rare case has certain limitations, but considering that there are currently no reports of invasive infections of deep organs in humans caused by , the above findings can offer novel insights into the treatment of invasive pythiosis. Combination therapy based on tetracyclines, especially tigecycline, the use of TMP-SMX, and the adjunctive use of iron chelators, represent promising approaches to tackle the clinical challenges in the treatment of invasive pythiosis. However, further studies, including similar cases of spinal pythiosis and in vivo trials, are still needed to validate them. In addition, while paying attention to the therapeutic potentials of the above plans, we should also closely monitor the risks and side effects that may arise from excessive MICs or the expanded use of related drugs during the treatment process.
腐皮病是一种由[病原体名称未给出]引起的罕见且严重的传染病,其特点是在实现明确诊断方面存在很大不确定性、治疗效果欠佳以及死亡率极高。在此,我们报告中国南方一例罕见的人类脊柱腐皮病病例。借助先进的宏基因组测序技术,[病原体名称未给出]被确定为致病病原体。通过对一般临床标本的多种接种和培养条件进行详尽比较,我们发现接种组织碎片或匀浆能取得更成功的结果,并能将培养时间适度延长至5 - 10天。经过全面的全基因组测序分析,检测到分离菌株与[菌株名称未给出]菌株MCC 13具有显著的遗传亲缘关系。在抗菌药敏试验中,抗真菌药物对[病原体名称未给出]的敏感性可忽略不计。相反,恶唑烷酮类、四环素类、大环内酯类和氯霉素类等抗菌药物表现出不同程度的敏感性,尽管它们的大多数最低抑菌浓度(MIC)大大超过有效临床治疗的安全浓度范围。值得注意的是,替加环素是一个有前景的候选药物,在中等浓度下表现出良好的治疗效果,使其成为控制腐皮病的潜在首选药物。联合药敏试验表明,四环素类与大环内酯类、恶唑烷酮类和氯霉素类的联合使用具有协同抗菌作用,尤其是多西环素与甲氧苄啶 - 磺胺甲恶唑(TMP - SMX)的联合发挥了关键作用。令我们惊讶的是,铁螯合剂,特别是去铁酮和去铁胺,对该菌株的MIC极低,这引发了一种推测,即外源性铁螯合剂可能竞争性抑制了该菌株的铁螯合酶。源于这一罕见单病例的研究有一定局限性,但鉴于目前尚无[病原体名称未给出]引起人类深部器官侵袭性感染的报道,上述发现可为侵袭性腐皮病的治疗提供新的见解。基于四环素类,特别是替加环素、TMP - SMX的使用以及铁螯合剂的辅助使用的联合治疗,是应对侵袭性腐皮病临床挑战的有前景的方法。然而,仍需要进一步的研究,包括类似的脊柱腐皮病病例和体内试验来验证它们。此外,在关注上述方案治疗潜力的同时,我们还应密切监测治疗过程中因MIC过高或相关药物使用范围扩大可能产生的风险和副作用。