PDF(Pubmed)
Abstract：
BACKGROUND: The prolonged β-lactam antibiotics infusion has been an attractive strategy in severe infections, because it provides a more stable free drug concentration and a longer duration of free drug concentration above the minimum inhibitory concentration (MIC). We conducted this systematic review of randomized clinical trials (RCTs) with meta-analysis and trial sequential analysis (TSA) to compare the effects of prolonged vs intermittent intravenous infusion of β-lactam antibiotics for patients with sepsis.
METHODS: This study was prospectively registered on PROSPERO database (CRD42023447692). We searched EMBASE, PubMed, and Cochrane Library to identify eligible studies (up to July 6, 2023). Any study meeting the inclusion and exclusion criteria would be included. The primary outcome was all-cause mortality within 30 days. Two authors independently screened studies and extracted data. When the I2 values < 50%, we used fixed-effect mode. Otherwise, the random effects model was used. TSA was also performed to search for the possibility of false-positive (type I error) or false-negative (type II error) results.
RESULTS: A total of 4355 studies were identified in our search, and nine studies with 1762 patients were finally included. The pooled results showed that, compared with intermittent intravenous infusion, prolonged intravenous infusion of beta-lactam antibiotics resulted in a significant reduction in all-cause mortality within 30 days in patients with sepsis (RR 0.82; 95%CI 0.70-0.96; P = 0.01; TSA-adjusted CI 0.62-1.07). However, the certainty of the evidence was rated as low, and the TSA results suggested that more studies were needed to further confirm our conclusion. In addition, it is associated with lower hospital mortality, ICU mortality, and higher clinical cure. No significant reduction in 90-day mortality or the emergence of resistance bacteria was detected between the two groups.
CONCLUSIONS: Prolonged intravenous infusion of beta-lactam antibiotics in patients with sepsis was associated with short-term survival benefits and higher clinical cure. However, the TSA results suggested that more studies are needed to reach a definitive conclusion. In terms of long-term survival benefits, we could not show an improvement.
METHODS: This study was prospectively registered on PROSPERO database (CRD42023447692). We searched EMBASE, PubMed, and Cochrane Library to identify eligible studies (up to July 6, 2023). Any study meeting the inclusion and exclusion criteria would be included. The primary outcome was all-cause mortality within 30 days. Two authors independently screened studies and extracted data. When the I2 values < 50%, we used fixed-effect mode. Otherwise, the random effects model was used. TSA was also performed to search for the possibility of false-positive (type I error) or false-negative (type II error) results.
RESULTS: A total of 4355 studies were identified in our search, and nine studies with 1762 patients were finally included. The pooled results showed that, compared with intermittent intravenous infusion, prolonged intravenous infusion of beta-lactam antibiotics resulted in a significant reduction in all-cause mortality within 30 days in patients with sepsis (RR 0.82; 95%CI 0.70-0.96; P = 0.01; TSA-adjusted CI 0.62-1.07). However, the certainty of the evidence was rated as low, and the TSA results suggested that more studies were needed to further confirm our conclusion. In addition, it is associated with lower hospital mortality, ICU mortality, and higher clinical cure. No significant reduction in 90-day mortality or the emergence of resistance bacteria was detected between the two groups.
CONCLUSIONS: Prolonged intravenous infusion of beta-lactam antibiotics in patients with sepsis was associated with short-term survival benefits and higher clinical cure. However, the TSA results suggested that more studies are needed to reach a definitive conclusion. In terms of long-term survival benefits, we could not show an improvement.
摘要：
背景：延长β-内酰胺抗生素输注已成为严重感染的一种有吸引力的策略，因为它提供了更稳定的游离药物浓度和高于最小抑制浓度（MIC）的更长持续时间的游离药物浓度。我们对随机临床试验（RCTs）进行了系统评价，包括荟萃分析和试验序贯分析（TSA），以比较长期静脉输注β-内酰胺类抗生素与间歇性静脉输注对脓毒症患者的影响。
方法：本研究在PROSPERO数据库（CRD42023447692）上进行了前瞻性注册。我们搜索了EMBASE,PubMed,和Cochrane图书馆确定合格的研究（截至2023年7月6日）。符合纳入和排除标准的任何研究都将包括在内。主要结果是30天内的全因死亡率。两位作者独立筛选研究并提取数据。当I2值<50%时,我们使用了固定效果模式。否则,采用随机效应模型。还进行TSA以搜索假阳性(I型错误)或假阴性(II型错误)结果的可能性。
结果：在我们的搜索中确定了总共4355项研究，最终纳入了9项包含1762名患者的研究.汇总结果显示,与间歇静脉输液相比，长期静脉输注β-内酰胺类抗生素可显著降低脓毒症患者30天内的全因死亡率(RR0.82;95CI0.70~0.96;P=0.01;TSA-adjustedCI0.62~1.07).然而,证据的确定性被评为低，TSA结果提示需要更多的研究来进一步证实我们的结论.此外,它与较低的医院死亡率有关，ICU死亡率，和更高的临床治愈。两组间90天死亡率或耐药菌的出现没有显著降低。
结论：脓毒症患者长期静脉输注β-内酰胺类抗生素与短期生存获益和更高的临床治愈率相关。然而,TSA结果提示需要更多的研究才能得出明确的结论.在长期生存方面，我们无法表现出改善。
方法：本研究在PROSPERO数据库（CRD42023447692）上进行了前瞻性注册。我们搜索了EMBASE,PubMed,和Cochrane图书馆确定合格的研究（截至2023年7月6日）。符合纳入和排除标准的任何研究都将包括在内。主要结果是30天内的全因死亡率。两位作者独立筛选研究并提取数据。当I2值<50%时,我们使用了固定效果模式。否则,采用随机效应模型。还进行TSA以搜索假阳性(I型错误)或假阴性(II型错误)结果的可能性。
结果：在我们的搜索中确定了总共4355项研究，最终纳入了9项包含1762名患者的研究.汇总结果显示,与间歇静脉输液相比，长期静脉输注β-内酰胺类抗生素可显著降低脓毒症患者30天内的全因死亡率(RR0.82;95CI0.70~0.96;P=0.01;TSA-adjustedCI0.62~1.07).然而,证据的确定性被评为低，TSA结果提示需要更多的研究来进一步证实我们的结论.此外,它与较低的医院死亡率有关，ICU死亡率，和更高的临床治愈。两组间90天死亡率或耐药菌的出现没有显著降低。
结论：脓毒症患者长期静脉输注β-内酰胺类抗生素与短期生存获益和更高的临床治愈率相关。然而,TSA结果提示需要更多的研究才能得出明确的结论.在长期生存方面，我们无法表现出改善。
