School of Pharmacy, University of Wisconsin-Madison, La Jolla.
Department of Pediatrics, University of California-San Diego School of Medicine, La Jolla.
Clin Infect Dis. 2020 Jun 10;70(12):2634-2640. doi: 10.1093/cid/ciz686.
Patient interleukin (IL)-1β and IL-10 responses early in Staphylococcus aureus bacteremia (SaB) are associated with bacteremia duration and mortality. We hypothesized that these responses vary depending on antimicrobial therapy, with particular interest in whether the superiority of β-lactams links to key cytokine pathways.
Three medical centers included 59 patients with SaB (47 methicillin-resistant S. aureus [MRSA], 12 methicillin-sensitive S. aureus [MSSA]) from 2015-2017. In the first 48 hours, patients were treated with either a β-lactam (n = 24), including oxacillin, cefazolin, or ceftaroline, or a glyco-/lipopeptide (n = 35), that is, vancomycin or daptomycin. Patient sera from days 1, 3, and 7 were assayed for IL-1β and IL-10 by enzyme-linked immunosorbent assay and compared using the Mann-Whitney U test.
On presentation, IL-10 was elevated in mortality (P = .008) and persistent bacteremia (P = .034), while no difference occurred in IL-1β. Regarding treatment groups, IL-1β and IL-10 were similar prior to receiving antibiotic. Patients treated with β-lactam had higher IL-1β on days 3 (median +5.6 pg/mL; P = .007) and 7 (+10.9 pg/mL; P = .016). Ex vivo, addition of the IL-1 receptor antagonist anakinra to whole blood reduced staphylococcal killing, supporting an IL-1β functional significance in SaB clearance. β-lactam-treated patients had sharper declines in IL-10 than vancomycin or daptomycin -treated patients over 7 days.
These data underscore the importance of β-lactams for SaB, including consideration that the adjunctive role of β-lactams for MRSA in select patients helps elicit favorable host cytokine responses.
金黄色葡萄球菌菌血症（SaB）早期患者白细胞介素（IL）-1β和 IL-10 的反应与菌血症持续时间和死亡率相关。我们假设这些反应因抗菌治疗而异，特别关注β-内酰胺类药物的优势是否与关键细胞因子途径有关。
三家医疗中心纳入了 2015 年至 2017 年期间 59 例 SaB 患者（47 例耐甲氧西林金黄色葡萄球菌[MRSA]，12 例甲氧西林敏感金黄色葡萄球菌[MSSA]）。在最初的 48 小时内，患者接受了β-内酰胺（n=24），包括苯唑西林、头孢唑林或头孢替坦，或糖/脂肽（n=35），即万古霉素或达托霉素治疗。通过酶联免疫吸附试验检测患者第 1、3 和 7 天的血清中 IL-1β和 IL-10，并使用 Mann-Whitney U 检验进行比较。
在就诊时，IL-10 在死亡率（P=0.008）和持续性菌血症（P=0.034）中升高，而 IL-1β 则无差异。关于治疗组，在接受抗生素治疗之前，IL-1β 和 IL-10 相似。接受β-内酰胺治疗的患者在第 3 天（中位数+5.6 pg/mL；P=0.007）和第 7 天（中位数+10.9 pg/mL；P=0.016）时 IL-1β 水平更高。在体外，白细胞介素 1 受体拮抗剂 anakinra 加入全血后降低了金黄色葡萄球菌的杀伤作用，支持 IL-1β 在 SaB 清除中的功能意义。与万古霉素或达托霉素治疗的患者相比，接受β-内酰胺治疗的患者在 7 天内 IL-10 的下降更为明显。
这些数据强调了β-内酰胺类药物对 SaB 的重要性，包括考虑到在某些患者中，β-内酰胺类药物对 MRSA 的辅助作用有助于引发有利的宿主细胞因子反应。
