Department of Clinical Infectious Diseases, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan.
Department of Surgery, Toho University Sakura Medical Center, 564-1 Shimoshizu, Sakura, Chiba, 285-8741, Japan.
J Infect Chemother. 2022 Sep;28(9):1235-1241. doi: 10.1016/j.jiac.2022.04.027. Epub 2022 Jun 16.
The results from the phase 3 study that evaluated the efficacy and safety of tedizolid phosphate, an oxazolidinone drug, for the treatment of gram-positive ventilated hospital-acquired bacterial pneumonia (vHABP)/ventilator-associated bacterial pneumonia (VABP) compared with linezolid (VITAL study), have been previously reported. We conducted a subgroup analysis to report the data obtained from Japanese patients enrolled in this study.
Patients aged ≥18 years with vHABP/VABP likely to be caused by gram-positive cocci were randomized 1:1 to tedizolid phosphate 200 mg once daily for 7 days or linezolid 600 mg twice daily for 10 days. In both treatment groups, patients with concurrent gram-positive bacteremia were treated for 14 days. Primary efficacy endpoints were day 28 all-cause mortality (ACM) and investigator-assessed clinical response at test-of-cure (TOC) in the intention-to-treat population. Safety outcomes included assessment of treatment-emergent adverse events.
Fifty-three Japanese patients were randomized at received study drug (tedizolid, n = 28; linezolid, n = 25). Demographics and characteristics were generally similar between treatment groups. Rates of day 28 ACM were 10.7% and 20.0% with tedizolid and linezolid, respectively (difference, 9.3%; 95% CI, -10.1 to 28.7). Rates of investigator-assessed clinical cure at TOC were 78.6% and 72.0% with tedizolid and linezolid, respectively (difference, 6.6%; 95% CI, -16.7 to 29.8). Tedizolid phosphate was generally well tolerated and no new safety concerns were observed in the Japanese subgroup.
The results from this subgroup analysis suggest generally favorable efficacy and safety of tedizolid in adult Japanese patients with vHABP/VABP. (ClinicalTrials.gov identifier: NCT02019420).
先前已报道过评估磷替唑利（一种唑烷酮类药物）治疗革兰阳性需氧医院获得性细菌性肺炎（vHABP）/呼吸机相关性细菌性肺炎（VABP）的疗效和安全性的 3 期研究（VITAL 研究）的结果。我们进行了亚组分析，以报告该研究纳入的日本患者的数据。
年龄≥18 岁、患有可能由革兰阳性球菌引起的 vHABP/VABP 的患者按 1:1 比例随机分为替唑利磷酸盐 200mg 每日 1 次治疗 7 天或利奈唑胺 600mg 每日 2 次治疗 10 天组。在这两组治疗中，合并革兰阳性菌血症的患者治疗 14 天。主要疗效终点为第 28 天全因死亡率（ACM）和治疗结束时（TOC）的研究者评估临床反应。安全性结局包括评估治疗出现的不良事件。
53 名日本患者被随机分配至接受研究药物（替唑利组，n=28；利奈唑胺组，n=25）。治疗组间的人口统计学和特征通常相似。第 28 天 ACM 的发生率分别为替唑利组 10.7%和利奈唑胺组 20.0%（差异为 9.3%；95%CI，-10.1 至 28.7）。在 TOC 时，研究者评估的临床治愈率分别为替唑利组 78.6%和利奈唑胺组 72.0%（差异为 6.6%；95%CI，-16.7 至 29.8）。替唑利磷酸盐总体耐受性良好，在日本亚组中未观察到新的安全性问题。
这项亚组分析的结果表明替唑利在日本成年 vHABP/VABP 患者中的疗效和安全性总体良好。（临床试验注册号：NCT02019420）。
