Abstract：
METHODS: These ESCMID guidelines address the targeted antibiotic treatment of third-generation cephalosporin-resistant Enterobacterales (3GCephRE) and carbapenem-resistant Gram-negative bacteria, focusing on the effectiveness of individual antibiotics and on combination versus monotherapy.
METHODS: An expert panel was convened by ESCMID. A systematic review was performed including randomized controlled trials and observational studies, examining different antibiotic treatment regimens for the targeted treatment of infections caused by the 3GCephRE, carbapenem-resistant Enterobacterales, carbapenem-resistant Pseudomonas aeruginosa and carbapenem-resistant Acinetobacter baumannii. Treatments were classified as head-to-head comparisons between individual antibiotics and between monotherapy and combination therapy regimens, including defined monotherapy and combination regimens only. The primary outcome was all-cause mortality, preferably at 30 days and secondary outcomes included clinical failure, microbiological failure, development of resistance, relapse/recurrence, adverse events and length of hospital stay. The last search of all databases was conducted in December 2019, followed by a focused search for relevant studies up until ECCMID 2021. Data were summarized narratively. The certainty of the evidence for each comparison between antibiotics and between monotherapy and combination therapy regimens was classified by the GRADE recommendations. The strength of the recommendations for or against treatments was classified as strong or conditional (weak).
CONCLUSIONS: The guideline panel reviewed the evidence per pathogen, preferably per site of infection, critically appraising the existing studies. Many of the comparisons were addressed in small observational studies at high risk of bias only. Notably, there was very little evidence on the effects of the new, recently approved, β-lactam/β-lactamase inhibitors on infections caused by carbapenem-resistant Gram-negative bacteria. Most recommendations are based on very-low- and low-certainty evidence. A high value was placed on antibiotic stewardship considerations in all recommendations, searching for carbapenem-sparing options for 3GCephRE and limiting the recommendations of the new antibiotics for severe infections, as defined by the sepsis-3 criteria. Research needs are addressed.
METHODS: An expert panel was convened by ESCMID. A systematic review was performed including randomized controlled trials and observational studies, examining different antibiotic treatment regimens for the targeted treatment of infections caused by the 3GCephRE, carbapenem-resistant Enterobacterales, carbapenem-resistant Pseudomonas aeruginosa and carbapenem-resistant Acinetobacter baumannii. Treatments were classified as head-to-head comparisons between individual antibiotics and between monotherapy and combination therapy regimens, including defined monotherapy and combination regimens only. The primary outcome was all-cause mortality, preferably at 30 days and secondary outcomes included clinical failure, microbiological failure, development of resistance, relapse/recurrence, adverse events and length of hospital stay. The last search of all databases was conducted in December 2019, followed by a focused search for relevant studies up until ECCMID 2021. Data were summarized narratively. The certainty of the evidence for each comparison between antibiotics and between monotherapy and combination therapy regimens was classified by the GRADE recommendations. The strength of the recommendations for or against treatments was classified as strong or conditional (weak).
CONCLUSIONS: The guideline panel reviewed the evidence per pathogen, preferably per site of infection, critically appraising the existing studies. Many of the comparisons were addressed in small observational studies at high risk of bias only. Notably, there was very little evidence on the effects of the new, recently approved, β-lactam/β-lactamase inhibitors on infections caused by carbapenem-resistant Gram-negative bacteria. Most recommendations are based on very-low- and low-certainty evidence. A high value was placed on antibiotic stewardship considerations in all recommendations, searching for carbapenem-sparing options for 3GCephRE and limiting the recommendations of the new antibiotics for severe infections, as defined by the sepsis-3 criteria. Research needs are addressed.
摘要：
方法：这些ESCMID指南针对第三代头孢菌素耐药肠杆菌（3GCephRE）和碳青霉烯耐药革兰氏阴性菌的靶向抗生素治疗，重点关注单独抗生素的有效性以及联合治疗与单一治疗。
方法：ESCMID召集了一个专家小组。进行了系统评价，包括随机对照试验和观察性研究，检查不同的抗生素治疗方案，以靶向治疗由3GCephRE引起的感染，耐碳青霉烯类肠杆菌,耐碳青霉烯类铜绿假单胞菌和耐碳青霉烯类鲍曼不动杆菌。治疗分为单独抗生素之间的头对头比较和单药治疗和联合治疗方案之间的比较。仅包括定义的单一治疗和联合治疗方案。主要结果是全因死亡率，优选在30天，次要结果包括临床失败，微生物失败，抗性的发展，复发/复发，不良事件和住院时间。所有数据库的最后一次搜索是在2019年12月进行的，随后重点搜索了相关研究，直到ECCMID2021年。数据进行了叙述性总结。根据GRADE建议对抗生素之间以及单药治疗和联合治疗方案之间的每个比较的证据的确定性进行分类。支持或反对治疗的建议的强度被分类为强或有条件(弱)。
结论：指南小组审查了每种病原体的证据，最好是每个感染部位，批判性地评价现有的研究。许多比较仅在偏倚高风险的小型观察性研究中得到解决。值得注意的是,几乎没有证据表明新的效果，最近批准,β-内酰胺/β-内酰胺酶抑制剂对碳青霉烯类耐药革兰阴性菌感染的影响.大多数建议是基于非常低和低确定性的证据。所有建议都高度重视抗生素管理方面的考虑，为3GCephRE寻找碳青霉烯保留的选择，并限制新抗生素对严重感染的建议，由脓毒症-3标准定义。研究需要得到解决。
方法：ESCMID召集了一个专家小组。进行了系统评价，包括随机对照试验和观察性研究，检查不同的抗生素治疗方案，以靶向治疗由3GCephRE引起的感染，耐碳青霉烯类肠杆菌,耐碳青霉烯类铜绿假单胞菌和耐碳青霉烯类鲍曼不动杆菌。治疗分为单独抗生素之间的头对头比较和单药治疗和联合治疗方案之间的比较。仅包括定义的单一治疗和联合治疗方案。主要结果是全因死亡率，优选在30天，次要结果包括临床失败，微生物失败，抗性的发展，复发/复发，不良事件和住院时间。所有数据库的最后一次搜索是在2019年12月进行的，随后重点搜索了相关研究，直到ECCMID2021年。数据进行了叙述性总结。根据GRADE建议对抗生素之间以及单药治疗和联合治疗方案之间的每个比较的证据的确定性进行分类。支持或反对治疗的建议的强度被分类为强或有条件(弱)。
结论：指南小组审查了每种病原体的证据，最好是每个感染部位，批判性地评价现有的研究。许多比较仅在偏倚高风险的小型观察性研究中得到解决。值得注意的是,几乎没有证据表明新的效果，最近批准,β-内酰胺/β-内酰胺酶抑制剂对碳青霉烯类耐药革兰阴性菌感染的影响.大多数建议是基于非常低和低确定性的证据。所有建议都高度重视抗生素管理方面的考虑，为3GCephRE寻找碳青霉烯保留的选择，并限制新抗生素对严重感染的建议，由脓毒症-3标准定义。研究需要得到解决。
