Abstract：
BACKGROUND: Current guidelines recommend adjunctive gentamicin for the treatment of Enterococcus faecalis infective endocarditis (EFIE) despite a risk of toxicity. We sought to revisit the evidence for adjunctive therapy in EFIE and to synthesize the comparative safety and effectiveness of adjunctive use of the aminoglycosides versus ceftriaxone by systematic review and meta-analysis.
METHODS: For historical context, we reviewed the seminal case series and in vitro studies informing the evolution from penicillin monotherapy to modern-day regimens for EFIE. Next, we searched MEDLINE and Embase from inception to January 16, 2024 for studies of EFIE comparing 1) adjunctive aminoglycosides versus ceftriaxone or 2) adjunctive therapy versus monotherapy. Where possible, clinical outcomes were compared between regimens by random-effects meta-analysis. Otherwise, data were narratively summarized.
RESULTS: Results for the systematic review and meta-analysis were limited to 10 observational studies totaling 911 patients. All studies were at high risk of bias. Relative to adjunctive ceftriaxone, gentamicin had similar all-cause mortality (Risk Difference [RD]=-0.8%, 95% Confidence interval [95%CI]=-5.0, 3.5), relapse (RD=-0.1%, 95%CI=-2.4, 2.3), and treatment failure (RD=1.1%, 95%CI=-1.6, 3.7), but higher discontinuation due to toxicity (RD=26.3%, 95%CI=19.8, 32.7). The 3 studies comparing adjunctive therapy to monotherapy included only 30 monotherapy patients and heterogeneity precluded meta-analysis.
CONCLUSIONS: Adjunctive therapy with ceftriaxone appeared to be equally effective and less toxic than gentamicin for the treatment of EFIE. The existing evidence does not clearly establish the superiority of either adjunctive therapy or monotherapy. Pending randomized evidence, if adjunctive therapy is to be used, ceftriaxone appears to be a reasonable option.
METHODS: For historical context, we reviewed the seminal case series and in vitro studies informing the evolution from penicillin monotherapy to modern-day regimens for EFIE. Next, we searched MEDLINE and Embase from inception to January 16, 2024 for studies of EFIE comparing 1) adjunctive aminoglycosides versus ceftriaxone or 2) adjunctive therapy versus monotherapy. Where possible, clinical outcomes were compared between regimens by random-effects meta-analysis. Otherwise, data were narratively summarized.
RESULTS: Results for the systematic review and meta-analysis were limited to 10 observational studies totaling 911 patients. All studies were at high risk of bias. Relative to adjunctive ceftriaxone, gentamicin had similar all-cause mortality (Risk Difference [RD]=-0.8%, 95% Confidence interval [95%CI]=-5.0, 3.5), relapse (RD=-0.1%, 95%CI=-2.4, 2.3), and treatment failure (RD=1.1%, 95%CI=-1.6, 3.7), but higher discontinuation due to toxicity (RD=26.3%, 95%CI=19.8, 32.7). The 3 studies comparing adjunctive therapy to monotherapy included only 30 monotherapy patients and heterogeneity precluded meta-analysis.
CONCLUSIONS: Adjunctive therapy with ceftriaxone appeared to be equally effective and less toxic than gentamicin for the treatment of EFIE. The existing evidence does not clearly establish the superiority of either adjunctive therapy or monotherapy. Pending randomized evidence, if adjunctive therapy is to be used, ceftriaxone appears to be a reasonable option.
摘要：
背景：目前的指南推荐使用庆大霉素治疗粪肠球菌感染性心内膜炎（EFIE），尽管存在毒性风险。我们试图重新审视EFIE辅助治疗的证据，并通过系统评价和荟萃分析综合氨基糖苷类与头孢曲松的辅助使用的安全性和有效性。
方法：对于历史背景，我们回顾了开创性病例系列和体外研究,这些研究揭示了从青霉素单药治疗到现代EFIE治疗方案的演变过程.接下来,我们检索了MEDLINE和Embase从开始至2024年1月16日的EFIE研究,比较了1)辅助氨基糖苷类与头孢曲松或2)辅助治疗与单药治疗.在可能的情况下,通过随机效应荟萃分析比较了两种治疗方案的临床结局.否则,数据进行了叙述性总结。
结果：系统评价和荟萃分析的结果仅限于10项观察性研究，共911例患者。所有研究都存在高偏倚风险。相对于辅助头孢曲松,庆大霉素的全因死亡率相似(风险差异[RD]=-0.8%，95%置信区间[95CI]=-5.0,3.5),复发（RD=-0.1%，95CI=-2.4,2.3),治疗失败(RD=1.1%，95CI=-1.6,3.7),但由于毒性而停药率较高(RD=26.3%，95CI=19.8，32.7）。3项比较辅助治疗与单药治疗的研究仅包括30名单药治疗患者，异质性排除了荟萃分析。
结论：与庆大霉素相比，头孢曲松的辅助治疗似乎同样有效且毒性较小。现有证据并没有明确证明辅助治疗或单一治疗的优越性。有待随机证据，如果要使用辅助治疗，头孢曲松似乎是一个合理的选择。
方法：对于历史背景，我们回顾了开创性病例系列和体外研究,这些研究揭示了从青霉素单药治疗到现代EFIE治疗方案的演变过程.接下来,我们检索了MEDLINE和Embase从开始至2024年1月16日的EFIE研究,比较了1)辅助氨基糖苷类与头孢曲松或2)辅助治疗与单药治疗.在可能的情况下,通过随机效应荟萃分析比较了两种治疗方案的临床结局.否则,数据进行了叙述性总结。
结果：系统评价和荟萃分析的结果仅限于10项观察性研究，共911例患者。所有研究都存在高偏倚风险。相对于辅助头孢曲松,庆大霉素的全因死亡率相似(风险差异[RD]=-0.8%，95%置信区间[95CI]=-5.0,3.5),复发（RD=-0.1%，95CI=-2.4,2.3),治疗失败(RD=1.1%，95CI=-1.6,3.7),但由于毒性而停药率较高(RD=26.3%，95CI=19.8，32.7）。3项比较辅助治疗与单药治疗的研究仅包括30名单药治疗患者，异质性排除了荟萃分析。
结论：与庆大霉素相比，头孢曲松的辅助治疗似乎同样有效且毒性较小。现有证据并没有明确证明辅助治疗或单一治疗的优越性。有待随机证据，如果要使用辅助治疗，头孢曲松似乎是一个合理的选择。
