Infections due to methicillin-resistant Staphylococcus aureus bacteremia (MRSAB) seriously threaten public health due to poor outcomes and high mortality. The objective of this study is to perform a systematic review and meta-analysis of the current evidence on adjuvant β-lactam (BL) therapy combined with vancomycin (VAN) or daptomycin (DAP) for MRSAB. PubMed, Embase, and Cochrane Library were systematically searched for publications reporting clinical outcomes of BLs+VAN or BLs+DAP for adult patients with MRSAB through 5 April 2020. Meta-analysis techniques were applied using random effects modeling. Three randomized controlled trials and 12 retrospective cohort studies were identified, totaling 2,594 patients. Combination treatment significantly reduced the risk of clinical failure (risk ratio [RR] = 0.80; 95% confidence interval [CI], 0.66 to 0.96; P = 0.02; I² = 39%), bacteremia recurrence (RR = 0.66; 95% CI, 0.50 to 0.86; P = 0.002; I² = 0%), and persistent bacteremia (RR = 0.65; 95% CI, 0.55 to 0.76; P < 0.00001; I² = 0%) and shortened the duration of bacteremia (standardized mean difference [SMD] = –0.37; 95% CI, –0.48 to –0.25; P < 0.00001; I² = 0%). There was no significant difference in the risk of crude mortality, nephrotoxicity, or thrombocytopenia between groups. Notably, combination treatment might nonsignificantly increase the risk of Clostridium difficile infection (CDI) (RR = 2.13; 95% CI, 0.98 to 4.63; P = 0.06; I² = 0%). Subgroup analysis suggested that DAP+BLs could reduce crude mortality (RR = 0.53; 95% CI, 0.28 to 0.98; P = 0.04; I² = 0%). The meta-analysis suggested that although combination therapy with BLs could improve some microbial outcomes, it could not reduce crude mortality but might increase the risk of CDI and should be applied very cautiously. Regarding mortality reduction, the combination of DAP+cephalosporins appears more promising.

中文翻译：

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β-内酰胺辅助疗法联合万古霉素或达托霉素治疗耐甲氧西林的金黄色葡萄球菌菌血症：系统评价和荟萃分析。

耐甲氧西林金黄色葡萄球菌引起的感染菌血症（MRSAB）由于不良结果和高死亡率而严重威胁公共健康。这项研究的目的是对MRSAB的佐剂β-内酰胺（BL）联合万古霉素（VAN）或达托霉素（DAP）联合治疗的现有证据进行系统的回顾和荟萃分析。系统地在PubMed，Embase和Cochrane库中搜索了报道到2020年4月5日成年MRSAB患者BLs + VAN或BLs + DAP的临床结果的出版物。采用随机效应模型应用荟萃分析技术。确定了三项随机对照试验和12项回顾性队列研究，总计2,594例患者。联合治疗显着降低了临床失败的风险（风险比[RR] = 0.80； 95％置信区间[CI]为0.66至0.96；P = 0.02； I² = 39％），菌血症复发（RR = 0.66; 95％CI，0.50至0.86; P = 0.002; I ² = 0％）和持续性菌血症（RR = 0.65; 95％CI，0.55至0.76; P < 0.00001； I ² = 0％）并缩短了菌血症的持续时间（标准化平均差[SMD] = –0.37； 95％CI，从–0.48到–0.25；P <0.00001； I ² = 0％）。两组之间的粗死亡率，肾毒性或血小板减少风险没有显着差异。值得注意的是，联合治疗可能会显着增加艰难梭菌感染（CDI）的风险（RR = 2.13； 95％CI，0.98至4.63；P = 0.06； I ²= 0％）。亚组分析表明，DAP + BLs可以降低粗死亡率（RR = 0.53； 95％CI，0.28至0.98；P = 0.04； I ² = 0％）。荟萃分析表明，尽管与BLs联合治疗可以改善某些微生物的预后，但不能降低粗死亡率，但可能增加CDI的风险，应谨慎使用。关于降低死亡率，DAP +头孢菌素的组合似乎更有希望。