辅助β-内酰胺治疗金黄色葡萄球菌菌血症:叙述性回顾。

IF 3.4 Q2 INFECTIOUS DISEASES
Therapeutic Advances in Infectious Disease Pub Date : 2025-06-14 eCollection Date: 2025-01-01 DOI:10.1177/20499361251343969
Daniel B Chastain, Bryan P White, Andrés F Henao-Martínez, Patrick J Tu, Christopher M Bland, Rachel A Foster, David B Cluck
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引用次数: 0

摘要

金黄色葡萄球菌菌血症(SAB)仍然是一个主要的临床挑战,尽管抗菌治疗取得了进展,但死亡率仍然很高。以社区获得性感染增加、留置医疗器械使用增加以及转移性并发症负担增加为特征的SAB流行病学的演变增加了其复杂性。鉴于这些挑战,辅助β-内酰胺治疗已被提出作为增强杀菌活性和改善患者预后的策略。β-内酰胺与其他抗葡萄球菌药物联合使用时,可能通过饱和多种青霉素结合蛋白并修饰细菌细胞壁结构,从而增加对宿主免疫反应的易感性,从而发挥协同作用。辅助β-内酰胺治疗的早期证据来自回顾性研究和“计划外协同作用”的偶然观察,这表明细菌清除率提高。随后的随机对照试验对这种方法进行了探索,其中一些试验显示可以减少菌血症持续时间。然而,生存获益一直不一致,对急性肾损伤(AKI)的担忧降低了人们的热情。然而,最近的研究表明,明智的β-内酰胺选择和有针对性的患者选择可以减轻AKI风险。许多评估SAB联合治疗的随机对照试验的局限性是采用了统一的治疗方案,未能考虑到患者的异质性。这种方法可能会限制研究结果的普遍性,并模糊特定患者亚组的潜在益处。相反,回顾性分析表明,高风险患者,包括血培养快速阳性、源控制不充分、显著合并症和转移性疾病的患者,可能从早期联合治疗中获益最大。优化SAB管理需要一个多方面的策略,包括患者特定的临床因素、精细的风险分层和创新的评估框架。诸如结果排序可取性(DOOR)和抗生素风险持续时间反应调整(RADAR)等方法能够全面评估治疗疗效和安全性,并考虑到患者的整体体验。未来的研究应优先考虑个性化的治疗策略,利用生物标志物和精细的风险分层,以确定最有可能从辅助β-内酰胺治疗中获益的患者,同时最大限度地减少不良事件。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Adjunctive β-lactams for Staphylococcus aureus bacteremia: a narrative review.

Staphylococcus aureus bacteremia (SAB) remains a major clinical challenge, with persistently high mortality despite advancements in antimicrobial therapy. The evolving epidemiology of SAB, characterized by a rise in community-acquired infections, increased use of indwelling medical devices, and a growing burden of metastatic complications, adds to its complexity. Given these challenges, adjunctive β-lactam therapy has been proposed as a strategy to enhance bactericidal activity and improve patient outcomes. β-lactams may exert synergistic effects when combined with other antistaphylococcal agents by saturating multiple penicillin-binding proteins and modifying bacterial cell wall structure, thereby increasing susceptibility to host immune responses. Early evidence for adjunctive β-lactam therapy emerged from retrospective studies and incidental observations of "unplanned synergy," which suggested improved bacterial clearance. Subsequent randomized controlled trials have explored this approach, with some demonstrating reductions in bacteremia duration. However, survival benefits have been inconsistent, and concerns regarding acute kidney injury (AKI) have tempered enthusiasm. Recent investigations, however, suggest that judicious β-lactam selection and targeted patient selection can mitigate AKI risk. A limitation of many randomized controlled trials evaluating combination therapy for SAB is the adoption of uniform treatment protocols that fail to account for patient heterogeneity. This approach may limit the generalizability of findings and obscure potential benefits in specific patient subgroups. Conversely, retrospective analyses suggest that high-risk patients, including those with rapid blood culture positivity, inadequate source control, significant comorbidities, and metastatic disease, may derive the greatest benefit from early combination therapy. Optimizing SAB management necessitates a multifaceted strategy that incorporates patient-specific clinical factors, refined risk stratification, and innovative assessment frameworks. Approaches such as the Desirability of Outcome Ranking (DOOR) and Response Adjusted for Duration of Antibiotic Risk (RADAR) enable holistic evaluations of treatment efficacy and safety, accounting for the overall patient experience. Future research should prioritize individualized treatment strategies, leveraging biomarkers and refined risk stratification to identify patients most likely to benefit from adjunct β-lactam therapy while minimizing adverse events.

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来源期刊
CiteScore
5.30
自引率
8.80%
发文量
64
审稿时长
9 weeks
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