Ahmed Babiker, Sarah Warner, Xiaobai Li, Emad A Chishti, Eltaib Saad, Bruce J Swihart, John P Dekker, Morgan Walker, Alexander Lawandi, Sameer S Kadri
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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 <em>Clostridium difficile</em> infection.<h3>Findings</h3>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] <em>vs</em> 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 <em>C difficile</em> infection risk (aRR 1·76 [95% CI 0·37 to 1·75]; p=0·29) were not statistically significantly different between the two groups.<h3>Interpretation</h3>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.<h3>Funding</h3>The Intramural Research Program of the US National Institutes of Health Clinical Center and the National Institute of Allergy and Infectious Disease.","PeriodicalId":49923,"journal":{"name":"Lancet Infectious Diseases","volume":"6 1","pages":""},"PeriodicalIF":36.4000,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Adjunctive linezolid versus clindamycin for toxin inhibition in β-lactam-treated patients with invasive group A streptococcal infections in 195 US hospitals from 2016 to 2021: a retrospective cohort study with target trial emulation\",\"authors\":\"Ahmed Babiker, Sarah Warner, Xiaobai Li, Emad A Chishti, Eltaib Saad, Bruce J Swihart, John P Dekker, Morgan Walker, Alexander Lawandi, Sameer S Kadri\",\"doi\":\"10.1016/s1473-3099(24)00507-3\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<h3>Background</h3>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. 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引用次数: 0
摘要
背景辅助使用克林霉素与侵袭性 A 组链球菌（GAS）感染的存活率有关，但 GAS 中克林霉素耐药性的增加使人们对其在这一适应症中的持久性产生了怀疑。方法我们利用 PINC AI 数据库，回顾性地模拟了一项目标多中心、非盲法、非劣效性试验，以评估 2016 年至 2021 年期间，在使用β-内酰胺类药物治疗侵袭性 A 组链球菌感染的成年住院患者中，与林可霉素相比，利奈唑胺辅助治疗的疗效。如果患者进行了单菌 GAS 培养，并在培养后 3 天内同时或在β-内酰胺类药物开始治疗后接受了辅助治疗，且完成了至少 3 天的β-内酰胺类药物治疗，则符合条件。主要结果是院内死亡率的调整风险比 (aRR)，采用倾向评分重叠加权法进行评估。在1095名接受过β-内酰胺治疗的GAS患者中，829人（76%）接受了克林霉素治疗，266人（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 aRR 的差异无统计学意义（利奈唑胺：9-8% [26/266] vs 克林霉素：7-0% [58/829]; aRR: 0-92 [95% CI 0-42 to 1-43]; p=0-76）。风险差异为-0-005（95% CI -0-05至0-04；P=0-81），在0-05的非劣效性范围内。在重要的亚组和敏感性分析中，主要分析结果是一致的。在幸存者中，两组的中位住院时间（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）在统计学上无显著差异。释义在这项针对使用β-内酰胺治疗的侵袭性GAS感染成人患者的模拟试验中，利奈唑胺的疗效似乎并不优于克林霉素，这表明利奈唑胺可作为辅助抗毒素治疗的替代药物。
Adjunctive linezolid versus clindamycin for toxin inhibition in β-lactam-treated patients with invasive group A streptococcal infections in 195 US hospitals from 2016 to 2021: a retrospective cohort study with target trial emulation
Background
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.
Methods
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.
Findings
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.
Interpretation
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.
Funding
The Intramural Research Program of the US National Institutes of Health Clinical Center and the National Institute of Allergy and Infectious Disease.
期刊介绍：
The Lancet Infectious Diseases was launched in August, 2001, and is a lively monthly journal of original research, review, opinion, and news covering international issues relevant to clinical infectious diseases specialists worldwide.The infectious diseases journal aims to be a world-leading publication, featuring original research that advocates change or sheds light on clinical practices related to infectious diseases. The journal prioritizes articles with the potential to impact clinical practice or influence perspectives. Content covers a wide range of topics, including anti-infective therapy and immunization, bacterial, viral, fungal, and parasitic infections, emerging infectious diseases, HIV/AIDS, malaria, tuberculosis, mycobacterial infections, infection control, infectious diseases epidemiology, neglected tropical diseases, and travel medicine. Informative reviews on any subject linked to infectious diseases and human health are also welcomed.
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