Kalpana Sriram, Lin Wan-Ying, Wang Yu-Chiang, Fu Yiwen, Wang Hsin-Yao
Department of Laboratory Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan.
Department of Medicine, University of California San Diego, San Diego, CA 92093, USA.
Diagnostics (Basel). 2023 Jul 26;13(15):2490. doi: 10.3390/diagnostics13152490.
New antimicrobial approaches are essential to counter antimicrobial resistance. The drug development pipeline is exhausted with the emergence of resistance, resulting in unsuccessful trials. The lack of an effective drug developed from the conventional drug portfolio has mandated the introspection into the list of potentially effective unconventional alternate antimicrobial molecules. Alternate therapies with clinically explicable forms include monoclonal antibodies, antimicrobial peptides, aptamers, and phages. Clinical diagnostics optimize the drug delivery. In the era of diagnostic-based applications, it is logical to draw diagnostic-based treatment for infectious diseases. Selection criteria of alternate therapeutics in infectious diseases include detection, monitoring of response, and resistance mechanism identification. Integrating these diagnostic applications is disruptive to the traditional therapeutic development. The challenges and mitigation methods need to be noted. Applying the goals of clinical pharmacokinetics that include enhancing efficacy and decreasing toxicity of drug therapy, this review analyses the strong correlation of alternate antimicrobial therapeutics in infectious diseases. The relationship between drug concentration and the resulting effect defined by the pharmacodynamic parameters are also analyzed. This review analyzes the perspectives of aligning diagnostic initiatives with the use of alternate therapeutics, with a particular focus on companion diagnostic applications in infectious diseases.
新的抗菌方法对于应对抗菌药物耐药性至关重要。随着耐药性的出现，药物研发渠道已枯竭，导致试验失败。传统药物组合中缺乏有效的药物，这就要求对潜在有效的非传统替代抗菌分子清单进行反思。具有临床可解释形式的替代疗法包括单克隆抗体、抗菌肽、适体和噬菌体。临床诊断可优化药物递送。在基于诊断的应用时代，对传染病进行基于诊断的治疗是合乎逻辑的。传染病替代疗法的选择标准包括检测、反应监测和耐药机制识别。整合这些诊断应用对传统治疗开发具有颠覆性。需要注意挑战和缓解方法。应用临床药代动力学的目标，包括提高药物治疗的疗效和降低毒性，本综述分析了传染病中替代抗菌疗法的强相关性。还分析了药物浓度与药效学参数所定义的结果效应之间的关系。本综述分析了将诊断举措与替代疗法的使用相结合的观点，特别关注传染病中的伴随诊断应用。
