School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western, Australia.
Department of Microbiology, PathWest Laboratory Medicine, Nedlands, Western, Australia.
Lett Appl Microbiol. 2022 Sep;75(3):526-536. doi: 10.1111/lam.13664. Epub 2022 Feb 11.
Clostridium (Clostridioides) difficile infection (CDI) remains an urgent threat to patients in health systems worldwide. Recurrent CDI occurs in up to 30% of cases due to sustained dysbiosis of the gut microbiota which normally protects against CDI. Associated costs of initial and recurrent episodes of CDI impose heavy financial burdens on health systems. Vancomycin and metronidazole have been the mainstay of therapy for CDI for many years; however, these agents continue to cause significant disruption to the gut microbiota and thus carry a high risk of recurrence for CDI patients. Treatment regimens are now turning towards novel narrow spectrum antimicrobial agents which target C. difficile while conserving the commensal gut microbiota, thus significantly reducing risk of recurrence. One such agent, fidaxomicin, has been in therapeutic use for several years and is now recommended as a first-line treatment for CDI, as it is superior to vancomycin in reducing risk of recurrence. Another narrow spectrum agent, ridnilazole, was recently developed and is undergoing evaluation of its potential clinical utility. This review aimed to summarize experimental reports of ridinilazole and assess its potential as a first-line agent for treatment of CDI. Reported results from in vitro assessments, and from hamster models of CDI, show potent activity against C. difficile, non-inferiority to vancomycin for clinical cure and non-susceptibility among most gut commensal bacteria. Phase I and II clinical trials have been completed with ridinilazole showing high tolerability and efficacy in treatment of CDI, and superiority over vancomycin in reducing recurrence of CDI within 30 days of treatment completion. Phase III trials are currently underway, the results of which may prove its potential to reduce recurrent CDI and lessen the heavy health and financial burden C. difficile imposes on patients and healthcare systems.
艰难梭菌(梭状芽胞杆菌)感染(CDI)仍然是全球卫生系统中患者面临的紧迫威胁。由于肠道微生物群落的持续失调,正常情况下可预防 CDI,多达 30%的病例会出现复发性 CDI。初始和复发性 CDI 的相关成本给卫生系统带来了沉重的经济负担。万古霉素和甲硝唑多年来一直是 CDI 的主要治疗药物;然而,这些药物仍然会对肠道微生物群落造成严重破坏,因此 CDI 患者复发的风险很高。治疗方案现在转向针对艰难梭菌的新型窄谱抗菌药物,同时保留共生肠道微生物群落,从而显著降低 CDI 患者的复发风险。一种此类药物,非达霉素,已在治疗中使用了数年,现在被推荐作为 CDI 的一线治疗药物,因为它在降低复发风险方面优于万古霉素。另一种窄谱药物,利奈唑胺,最近开发出来,并正在评估其潜在的临床应用。本综述旨在总结利奈唑胺的实验报告,并评估其作为治疗 CDI 的一线药物的潜力。来自体外评估和 CDI 仓鼠模型的报告结果显示,它对艰难梭菌具有强大的活性,在临床治愈率方面与万古霉素相当,而对大多数肠道共生菌具有非耐药性。利奈唑胺的 I 期和 II 期临床试验已经完成,结果显示其在治疗 CDI 方面具有高耐受性和疗效,并且在治疗完成后 30 天内降低 CDI 复发的效果优于万古霉素。目前正在进行 III 期临床试验,其结果可能证明其具有降低复发性 CDI 的潜力,并减轻艰难梭菌对患者和医疗保健系统造成的沉重健康和经济负担。