Mourad Ahmad, Parsons Joshua B, Skalla Lesley A, Holland Thomas L, Jenkins Timothy C
Department of Medicine, Division of Infectious Diseases, Duke University Medical Center, Durham, NC, USA.
Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA.
JAC Antimicrob Resist. 2025 Jun 17;7(3):dlaf101. doi: 10.1093/jacamr/dlaf101. eCollection 2025 Jun.
Fosfomycin combination therapy for bacteraemia or endocarditis has been evaluated, but studies were limited by small sample sizes. We sought to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) to establish robust efficacy and safety estimates of fosfomycin combination therapy in this patient population.
MEDLINE, Embase, Cochrane Library and Web of Science databases were searched from inception through September 2024 (PROSPERO CRD42024583822).
RCTs comparing fosfomycin combination with standard-of-care antibiotics in patients with bacteraemia or endocarditis were included. Two independent reviewers screened studies for inclusion.
Risk of bias was assessed using the revised Cochrane RoB 2 tool.
Treatment effects were estimated with pooled risk ratios (RRs) using random effects meta-analysis. Heterogeneity between studies was assessed with Cochran's Q-statistic and test.
Of 437 articles identified, three RCTs met inclusion criteria. Primary outcome of treatment success or cure was not meta-analysed due to clinical heterogeneity. Combination therapy did not significantly improve mortality (RR 0.85; 95% CI, 0.28-2.52; = 27.8%) or persistent bacteraemia (RR 0.34; 95% CI, 0.04-2.59; = 0%). Participants receiving combination therapy had more adverse events leading to treatment discontinuation, but this was not statistically significant (RR 1.84; 95% CI, 0.36-9.36; = 18%).
In this meta-analysis of three RCTs, fosfomycin combination therapy for bacteraemia or endocarditis did not significantly improve patient outcomes and may be associated with higher rates of adverse events.
已对磷霉素联合疗法治疗菌血症或心内膜炎进行了评估，但研究受样本量小的限制。我们试图对随机对照试验（RCT）进行系统评价和荟萃分析，以确定该患者群体中磷霉素联合疗法的可靠疗效和安全性评估。
检索MEDLINE、Embase、Cochrane图书馆和Web of Science数据库，检索时间从建库至2024年9月（PROSPERO CRD42024583822）。
纳入比较磷霉素联合疗法与菌血症或心内膜炎患者标准护理抗生素的RCT。两名独立评审员筛选纳入研究。
使用修订后的Cochrane RoB 2工具评估偏倚风险。
采用随机效应荟萃分析，用合并风险比（RR）估计治疗效果。用Cochran's Q统计量和I²检验评估研究间的异质性。
在检索到的437篇文章中，三项RCT符合纳入标准。由于临床异质性，未对治疗成功或治愈的主要结局进行荟萃分析。联合疗法未显著改善死亡率（RR 0.85；95%CI，0.28 - 2.52；I² = 27.8%）或持续性菌血症（RR 0.34；95%CI，0.04 - 2.59；I² = 0%）。接受联合疗法的参与者有更多导致治疗中断的不良事件，但这无统计学意义（RR 1.84；95%CI，0.36 - 9.36；I² = 18%）。
在这项对三项RCT的荟萃分析中，磷霉素联合疗法治疗菌血症或心内膜炎未显著改善患者结局，且可能与更高的不良事件发生率相关。
