Abstract：
BACKGROUND: Bloodstream infections (BSIs), or bacteremia, are responsible for considerable disease burden. Increasing rates of antibiotic resistance and delays in selection of appropriate treatment lead to increased morbidity, mortality, and costs. Due to limitations of current standard treatments, especially for bacteremia caused by resistant pathogens, a systematic literature review (SLR) was conducted to understand the utilization of ceftolozane/tazobactam (C/T) in bacteremia.
METHODS: Electronic database searches of EMBASE®, MEDLINE®, CCTR and Northern Lights, as well as hand searches of conference proceedings from the last two annual meetings (i.e., 2018, 2019) of the European Congress of Clinical Microbiological and Infectious Diseases (ECCMID) and the Infectious Diseases Society of America\'s annual meeting (IDWeek) were conducted. A total of 23 studies reporting on patients with bacteremia receiving C/T were included in the review.
RESULTS: Most studies were observational (k = 20 studies), though few interventional studies were also identified (k = 3). Heterogeneity was ubiquitous with respect to source of bacteremia (i.e., primary or secondary), source of infection (for secondary bacteremia), pathogen type, antibiotic resistance, C/T dose, and outcome definitions. This heterogeneity, along with limited data, and small sample sizes (n = 1 to 31) made it difficult to draw any substantial conclusions, though overall results were favorable to C/T with respect to the outcomes of interest. Nineteen studies reported clinical cure or success (primary bacteremia: k = 6, reported range: 33.3% to 100%; secondary bacteremia: k = 8, 60% to 100%; mixed/unspecified bacteremia: k = 10, 50% to 91.7%). Eight studies reported microbiological cure or eradication rates (primary: k = 3, all reporting 100%; secondary: k = 4, 68% to 80%; mixed/unspecified: k = 5, 60% to 80%). Thirteen studies reported mortality (primary: k = 4, 0% to 14%; secondary: k = 7, 0% to 100%; or mixed/unspecified bacteremia: k = 7, 0% to 51.6%). One study each also reported composite clinical response, relapse, hospital re-admission, and hospital length of stay.
CONCLUSIONS: Although the available evidence and observed trends for C/T in bacteremia should be interpreted with caution, the direction of effect would support the utilization of C/T for these difficult to treat infections. Future research should supplement the existing evidence by considering the impact of key treatment effect modifiers without contributing to the observed heterogeneity.
METHODS: Electronic database searches of EMBASE®, MEDLINE®, CCTR and Northern Lights, as well as hand searches of conference proceedings from the last two annual meetings (i.e., 2018, 2019) of the European Congress of Clinical Microbiological and Infectious Diseases (ECCMID) and the Infectious Diseases Society of America\'s annual meeting (IDWeek) were conducted. A total of 23 studies reporting on patients with bacteremia receiving C/T were included in the review.
RESULTS: Most studies were observational (k = 20 studies), though few interventional studies were also identified (k = 3). Heterogeneity was ubiquitous with respect to source of bacteremia (i.e., primary or secondary), source of infection (for secondary bacteremia), pathogen type, antibiotic resistance, C/T dose, and outcome definitions. This heterogeneity, along with limited data, and small sample sizes (n = 1 to 31) made it difficult to draw any substantial conclusions, though overall results were favorable to C/T with respect to the outcomes of interest. Nineteen studies reported clinical cure or success (primary bacteremia: k = 6, reported range: 33.3% to 100%; secondary bacteremia: k = 8, 60% to 100%; mixed/unspecified bacteremia: k = 10, 50% to 91.7%). Eight studies reported microbiological cure or eradication rates (primary: k = 3, all reporting 100%; secondary: k = 4, 68% to 80%; mixed/unspecified: k = 5, 60% to 80%). Thirteen studies reported mortality (primary: k = 4, 0% to 14%; secondary: k = 7, 0% to 100%; or mixed/unspecified bacteremia: k = 7, 0% to 51.6%). One study each also reported composite clinical response, relapse, hospital re-admission, and hospital length of stay.
CONCLUSIONS: Although the available evidence and observed trends for C/T in bacteremia should be interpreted with caution, the direction of effect would support the utilization of C/T for these difficult to treat infections. Future research should supplement the existing evidence by considering the impact of key treatment effect modifiers without contributing to the observed heterogeneity.
摘要：
背景：血流感染（BSI），或者菌血症,造成相当大的疾病负担。抗生素耐药性的增加和选择适当治疗的延迟导致发病率增加。死亡率,和成本。由于目前标准治疗的局限性，特别是由耐药病原体引起的菌血症，我们进行了系统文献综述(SLR),以了解头孢洛赞/他唑巴坦(C/T)在菌血症中的应用.
方法：EMBASE®的电子数据库搜索，MEDLINE®,CCTR和北极光，以及对最近两次年度会议的会议记录的手工搜索(即，2018年，2019年）欧洲临床微生物和传染病大会（ECCMID）和美国传染病学会年会（IDWeek）举行。共有23项研究报告了接受C/T的菌血症患者。
结果：大多数研究是观察性的（k=20项研究），尽管很少进行干预研究（k=3）。就菌血症的来源而言，异质性是普遍存在的(即，主要或次要)，感染源（继发菌血症），病原体类型,抗生素耐药性,C/T剂量，和结果定义。这种异质性，加上有限的数据，小样本量(n=1到31)使得很难得出任何实质性结论，尽管就感兴趣的结果而言，总体结果有利于C/T。19项研究报告了临床治愈或成功（原发性菌血症：k=6，报告范围：33.3％至100％；继发性菌血症：k=8，60％至100％；混合/未指定菌血症：k=10，50％至91.7％）。8项研究报告了微生物治愈率或根除率（主要：k=3，全部报告100％；次要：k=4，68％至80％；混合/未指定：k=5，60％至80％）。13项研究报告了死亡率（主要：k=4，0%至14%；次要：k=7，0%至100%；或混合/未指明菌血症：k=7，0%至51.6%）。一项研究还报道了复合临床反应，复发,再次入院,和住院时间。
结论：尽管菌血症中C/T的现有证据和观察到的趋势应谨慎解释，效果的方向将支持C/T对这些难以治疗的感染的利用。未来的研究应通过考虑关键治疗效果调节剂的影响来补充现有证据，而不会导致观察到的异质性。
方法：EMBASE®的电子数据库搜索，MEDLINE®,CCTR和北极光，以及对最近两次年度会议的会议记录的手工搜索(即，2018年，2019年）欧洲临床微生物和传染病大会（ECCMID）和美国传染病学会年会（IDWeek）举行。共有23项研究报告了接受C/T的菌血症患者。
结果：大多数研究是观察性的（k=20项研究），尽管很少进行干预研究（k=3）。就菌血症的来源而言，异质性是普遍存在的(即，主要或次要)，感染源（继发菌血症），病原体类型,抗生素耐药性,C/T剂量，和结果定义。这种异质性，加上有限的数据，小样本量(n=1到31)使得很难得出任何实质性结论，尽管就感兴趣的结果而言，总体结果有利于C/T。19项研究报告了临床治愈或成功（原发性菌血症：k=6，报告范围：33.3％至100％；继发性菌血症：k=8，60％至100％；混合/未指定菌血症：k=10，50％至91.7％）。8项研究报告了微生物治愈率或根除率（主要：k=3，全部报告100％；次要：k=4，68％至80％；混合/未指定：k=5，60％至80％）。13项研究报告了死亡率（主要：k=4，0%至14%；次要：k=7，0%至100%；或混合/未指明菌血症：k=7，0%至51.6%）。一项研究还报道了复合临床反应，复发,再次入院,和住院时间。
结论：尽管菌血症中C/T的现有证据和观察到的趋势应谨慎解释，效果的方向将支持C/T对这些难以治疗的感染的利用。未来的研究应通过考虑关键治疗效果调节剂的影响来补充现有证据，而不会导致观察到的异质性。
