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依拉环素在免疫功能低下患者中的应用:及时起始与延迟起始对临床结局影响的多中心评估

Eravacycline use in immunocompromised patients: multicenter evaluation of timely versus late initiation on clinical outcomes.

作者信息

Kunz Coyne Ashlan J, Alosaimy Sara, Lucas Kristen, Morrisette Taylor, Molina Kyle C, DeKerlegand Alaina, Schrack Melanie Rae, Kang-Birken S Lena, Hobbs Athena L V, Agee Jazmin, Perkins Nicholson B, Biagi Mark, Pierce Michael, Truong James, Andrade Justin, Bouchard Jeannette, Gore Tristan, King Madeline A, Pullinger Benjamin M, Claeys Kimberly C, Herbin Shelbye, Cosimi Reese, Tart Serina, Veve Michael P, Jones Bruce M, Rojas Leonor M, Feehan Amy K, Zhao Jing J, Witucki Paige, Rybak Michael J

机构信息

Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA.

Department of Emergency Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA.

出版信息

Microbiol Spectr. 2025 Aug 26:e0056525. doi: 10.1128/spectrum.00565-25.

Abstract

Infections from multidrug-resistant (MDR) bacteria lead to worse outcomes in immunocompromised patients. Eravacycline (ERV) is effective against MDR gram-negative and gram-positive bacteria, but its effects in immunocompromised populations remain unstudied. We aimed to evaluate clinical end points of immunocompromised patients receiving timely versus late ERV therapy. This multicenter, retrospective, observational study (October 2018 to September 2022) included adult immunocompromised patients hospitalized and treated with ERV for ≥72 h. The primary outcome was a composite of all-cause 30-day mortality, failure to improve clinically while on ERV, and/or microbial recurrence within 30 days of ERV initiation. Inverse probability of treatment weighting (IPTW) and Kaplan-Meier analyzes were used. Eighty-two patients from 17 US centers were included (median age 62 years; 59% male; intensive care unit admissions 57%). In the unadjusted cohort, timely ERV significantly reduced odds of clinical treatment failure (odds ratio [OR]: 0.321, 95% confidence interval [CI]: 0.129-0.800, = 0.012) and microbial recurrence (OR: 0.545, 95% CI: 0.326-0.913, = 0.034) compared to late ERV; in the IPTW-adjusted cohort, these associations remained significant with ORs of 0.675 (95% CI: 0.465-0.979, = 0.029) for treatment failure and 0.384 (95% CI: 0.142-0.943, = 0.041) for recurrence. Kaplan-Meier analysis showed a higher cumulative proportion of clinical treatment failure in the late ERV group (57%) compared to the timely ERV group (30%, = 0.013), with a significantly longer time to clinical treatment failure in the timely ERV group (log-rank = 0.034). Timely initiation of ERV in immunocompromised patients may improve clinical outcomes by reducing treatment failure and microbial recurrence compared to later initiation.IMPORTANCEThis multicenter, retrospective study evaluates the impact of timely versus late initiation of eravacycline (ERV) in immunocompromised patients with multidrug-resistant (MDR) bacterial infections. Immunocompromised patients face heightened risks of severe infections due to weakened immune defenses and limited treatment options, yet data on ERV use in this population are scarce. Our findings demonstrate that timely ERV initiation ≤72 h from index culture collection) significantly reduces clinical treatment failure and microbial recurrence compared to late initiation, with inverse probability of treatment weighting-adjusted odds ratios of 0.675 ( = 0.029) for treatment failure and 0.384 ( = 0.041) for recurrence. Kaplan-Meier analysis further confirms that delayed ERV therapy is associated with a higher cumulative incidence of clinical failure (57% vs 30%, = 0.013). These results highlight the importance of early ERV initiation in optimizing outcomes for immunocompromised patients and addressing the growing challenge of MDR infections, emphasizing the need for further prospective studies to confirm these findings.

摘要

多重耐药(MDR)菌感染在免疫功能低下患者中会导致更差的预后。依拉环素(ERV)对MDR革兰氏阴性菌和革兰氏阳性菌有效,但其在免疫功能低下人群中的作用仍未得到研究。我们旨在评估接受及时与延迟ERV治疗的免疫功能低下患者的临床终点。这项多中心、回顾性、观察性研究(2018年10月至2022年9月)纳入了住院并接受ERV治疗≥72小时的成年免疫功能低下患者。主要结局是30天全因死亡率、在接受ERV治疗期间临床未改善和/或在开始使用ERV后30天内微生物复发的综合情况。采用治疗权重逆概率(IPTW)分析和Kaplan-Meier分析。纳入了来自美国17个中心的82例患者(中位年龄62岁;59%为男性;57%入住重症监护病房)。在未调整的队列中,与延迟使用ERV相比,及时使用ERV显著降低了临床治疗失败的几率(优势比[OR]:0.321,95%置信区间[CI]:0.129 - 0.800,P = 0.012)和微生物复发几率(OR:0.545,95% CI:0.326 - 0.913,P = 0.034);在IPTW调整后的队列中,这些关联仍然显著,治疗失败的OR为0.675(95% CI:0.465 - 0.979,P = 0.029),复发的OR为0.384(95% CI:0.142 - 0.943,P = 0.041)。Kaplan-Meier分析显示,延迟使用ERV组的临床治疗失败累积比例(57%)高于及时使用ERV组(30%,P = 0.013),及时使用ERV组达到临床治疗失败的时间显著更长(对数秩检验P = 0.034)。与延迟开始治疗相比,免疫功能低下患者及时开始使用ERV可能通过减少治疗失败和微生物复发来改善临床结局。

重要性

这项多中心回顾性研究评估了在免疫功能低下的多重耐药(MDR)菌感染患者中及时与延迟开始使用依拉环素(ERV)的影响。免疫功能低下患者由于免疫防御减弱和治疗选择有限,面临严重感染的风险增加,但关于该人群使用ERV的数据很少。我们的研究结果表明,与延迟开始治疗相比,从首次培养采集起≤72小时及时开始使用ERV显著降低了临床治疗失败和微生物复发,治疗失败的IPTW调整后优势比为0.675(P = 0.029),复发的优势比为0.384(P = 0.041)。Kaplan-Meier分析进一步证实,延迟ERV治疗与更高的临床失败累积发生率相关(57%对30%,P = 0.013)。这些结果凸显了早期开始使用ERV对优化免疫功能低下患者的结局以及应对日益严峻的MDR感染挑战的重要性,强调需要进一步的前瞻性研究来证实这些发现。

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