Kotsaki Antigone, Tziolos Nikolaos, Kontopoulou Theano, Koutelidakis Ioannis M, Symbardi Styliani, Reed Vaughan, O'Hare Miriam, Alexiou Zoi, Sambatakou Helen, Toutouzas Konstantinos, Akinosoglou Karolina, Lada Malvina, Giamarellos-Bourboulis Evangelos J, MacGowan Alasdair
4th Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Hellenic Institute for the Study of Sepsis, Athens, Greece.
EClinicalMedicine. 2022 Dec 26;56:101790. doi: 10.1016/j.eclinm.2022.101790. eCollection 2023 Feb.
The need for oral, cost-effective treatment for complicated skin and skin structure infections (cSSSIs) due to methicillin-resistant (MRSA) was addressed by the non-inferiority comparisons of oral minocycline plus rifampicin with linezolid.
In the AIDA multicenter, open label, randomized, controlled clinical trial, hospitalized adults with cSSSI and documented MRSA were randomly assigned at a 2:1 ratio to either oral 600 mg rifampicin qd plus 100 mg minocycline bid or oral 600 mg linezolid bid for 10 days. The primary endpoint was the clinical cure rate in the clinically evaluable (CE) population at the test-of-cure visit (14 days). Non-inferiority was confirmed if the lower confidence limit (CI) did not fall below the accepted error margin of 15%. The study is registered with EudraCT number 2014-001276-56.
123 patients recruited between November 2014 and January 2017 were randomly assigned to treatment (81 patients to minocycline plus rifampicin and 42 patients to linezolid). Cure rates were 78.% (46/59, 90% CI 67.3-86.5) and 68.6% (24/35, 90% CI 53.4-81.3), respectively ( = 0.337). The percent difference in cure rates was 9.4% (90% CI -7.2 to 26.8%). Minocycline plus rifampicin combination was deemed non-inferior to linezolid as the lower CI was -7.2% i.e. smaller than the accepted error margin of -15%. Although statistically not significant, the overall rate of adverse events was higher in the linezolid group (47.6%, 20/42 versus 38.3%, 31/81).
Oral minocycline plus rifampicin was non-inferior to oral linezolid treatment providing alternative oral treatment for cSSSI.
The EU Seventh Research Framework Programme.
通过口服米诺环素联合利福平与利奈唑胺的非劣效性比较，解决了耐甲氧西林金黄色葡萄球菌（MRSA）所致复杂皮肤及皮肤结构感染（cSSSIs）对口服、经济高效治疗的需求。
在AIDA多中心、开放标签、随机对照临床试验中，将患有cSSSI且记录有MRSA的住院成人按2:1的比例随机分配，分别接受每日一次口服600mg利福平加每日两次口服100mg米诺环素或每日两次口服600mg利奈唑胺治疗10天。主要终点是在治疗评估访视（14天）时临床可评估（CE）人群中的临床治愈率。如果下限置信区间（CI）不低于15%的可接受误差范围，则确认非劣效性。该研究已在欧洲临床试验数据库（EudraCT）注册，编号为2014 - 001276 - 56。
2014年11月至2017年1月招募的123例患者被随机分配接受治疗（81例接受米诺环素加利福平治疗，42例接受利奈唑胺治疗）。治愈率分别为78.%（46/59，90%CI 67.3 - 86.5）和68.6%（24/35，90%CI 53.4 - 81.3）（P = 0.337）。治愈率的百分比差异为9.4%（90%CI -7.2至26.8%）。米诺环素加利福平联合用药被认为不劣于利奈唑胺，因为下限CI为-7.2%，即小于-15%的可接受误差范围。尽管在统计学上无显著差异，但利奈唑胺组的总体不良事件发生率更高（47.6%，20/42对比38.3%，31/81）。
口服米诺环素加利福平不劣于口服利奈唑胺治疗，为cSSSI提供了另一种口服治疗方案。
欧盟第七研究框架计划。
