Babiker Ahmed, Warner Sarah, Li Xiaobai, Chishti Emad A, Saad Eltaib, Swihart Bruce J, Dekker John P, Walker Morgan, Lawandi Alexander, Kadri Sameer S
Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Clinical Epidemiology Section, Critical Care Medicine Department, National Institutes of Health Clinical Center, Bethesda, MD, USA; Critical Care Medicine Branch, National Heart Lung and Blood Institute, Bethesda, MD, USA.
Lancet Infect Dis. 2025 Mar;25(3):265-275. doi: 10.1016/S1473-3099(24)00507-3. Epub 2024 Oct 10.
Adjunctive clindamycin use is associated with survival in invasive group A streptococcus (GAS) infections but increasing clindamycin resistance in GAS has called into question its durability for this indication. Linezolid also inhibits GAS toxin and virulence factor production, but clinical efficacy data remain sparse.
We retrospectively emulated a target multicentre, non-blinded, non-inferiority trial to assess the efficacy of adjunctive linezolid compared with clindamycin in adult inpatients with invasive GAS infection treated with a β-lactam using the PINC AI database between 2016 and 2021. Patients were eligible if they had a monomicrobial GAS culture and received adjunctive therapy within 3 days of culture either concurrently or after β-lactam initiation and completed at least 3 days of β-lactam therapy. The primary outcome was adjusted risk ratio (aRR) of in-hospital mortality assessed by overlap-weighting using propensity scores. Secondary outcomes were length of stay among survivors and Clostridium difficile infection.
Of 1095 β-lactam-treated patients with GAS, 829 (76%) received clindamycin and 266 (24%) received linezolid. In the overlap weighted cohort, the receipt of linezolid was not associated with a statistically significant different aRR of in-hospital mortality compared with clindamycin (linezolid: 9·8% [26/266] vs clindamycin: 7·0% [58/829]; aRR: 0·92 [95% CI 0·42 to 1·43]; p=0·76). The risk difference was -0·005 (95% CI -0·05 to 0·04; p=0·81) and fell within the non-inferiority margin of 0·05. The primary analysis results were consistent across important subgroups and sensitivity analyses. Among survivors, median length of stay (adjusted ratio 0·96 [95% CI 0·16 to 0·08]; p=0·47) and C difficile infection risk (aRR 1·76 [95% CI 0·37 to 1·75]; p=0·29) were not statistically significantly different between the two groups.
In this emulated trial of adult patients with invasive GAS infections treated with β-lactam, linezolid appeared non-inferior to clindamycin suggesting linezolid as an alternative for adjunctive antitoxin therapy.
The Intramural Research Program of the US National Institutes of Health Clinical Center and the National Institute of Allergy and Infectious Disease.
在侵袭性A组链球菌（GAS）感染中，联用克林霉素与生存率相关，但GAS中克林霉素耐药性的增加使其在此适应症中的持久性受到质疑。利奈唑胺也可抑制GAS毒素和毒力因子的产生，但临床疗效数据仍然稀少。
我们回顾性模拟了一项目标多中心、非盲、非劣效性试验，以评估在2016年至2021年期间使用PINC AI数据库接受β-内酰胺治疗的侵袭性GAS感染成年住院患者中，联用利奈唑胺与克林霉素的疗效。如果患者有单一微生物GAS培养物，且在培养后3天内同时或在开始使用β-内酰胺后接受辅助治疗，并完成至少3天的β-内酰胺治疗，则符合入选条件。主要结局是使用倾向评分通过重叠加权评估的院内死亡率调整风险比（aRR）。次要结局是幸存者的住院时间和艰难梭菌感染。
在1095例接受β-内酰胺治疗的GAS患者中，829例（76%）接受了克林霉素治疗，266例（24%）接受了利奈唑胺治疗。在重叠加权队列中，与克林霉素相比，接受利奈唑胺治疗与院内死亡率的aRR无统计学显著差异（利奈唑胺：9.8%[26/266] vs克林霉素：7.0%[58/829]；aRR：0.92[95%CI 0.42至1.43]；p=0.76）。风险差异为-0.005（95%CI -0.05至0.04；p=0.81），且在非劣效性边界0.05之内。主要分析结果在重要亚组和敏感性分析中保持一致。在幸存者中，两组之间的中位住院时间（调整比值0.96[95%CI 0.16至0.08]；p=0.47）和艰难梭菌感染风险（aRR 1.76[95%CI 0.37至1.75]；p=0.29）无统计学显著差异。
在这项对接受β-内酰胺治疗的侵袭性GAS感染成年患者的模拟试验中，利奈唑胺似乎不劣于克林霉素，这表明利奈唑胺可作为辅助抗毒素治疗的替代药物。
美国国立卫生研究院临床中心和国家过敏与传染病研究所的内部研究项目。
