Abstract：
BACKGROUND: Antimicrobial resistance is a global threat, which requires novel intervention strategies, for which priority pathogens and settings need to be determined.
OBJECTIVE: We evaluated pathogen-specific excess health burden of drug-resistant bloodstream infections (BSIs) in Europe.
METHODS: A systematic review and meta-analysis.
METHODS: MEDLINE, Embase, and grey literature for the period January 1990 to May 2022.
METHODS: Studies that reported burden data for six key drug-resistant pathogens: carbapenem-resistant (CR) Pseudomonas aeruginosa and Acinetobacter baumannii, third-generation cephalosporin or CR Escherichia coli and Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium. Excess health outcomes compared with drug-susceptible BSIs or uninfected patients. For MRSA and third-generation cephalosporin E. coli and K. pneumoniae BSIs, five or more European studies were identified. For all others, the search was extended to high-income countries.
METHODS: Paediatric and adult patients diagnosed with drug-resistant BSI.
METHODS: Not applicable.
UNASSIGNED: An adapted version of the Joanna-Briggs Institute assessment tool.
UNASSIGNED: Random-effect models were used to pool pathogen-specific burden estimates.
RESULTS: We screened 7154 titles, 1078 full-texts and found 56 studies on BSIs. Most studies compared outcomes of drug-resistant to drug-susceptible BSIs (46/56, 82.1%), and reported mortality (55/56 studies, 98.6%). The pooled crude estimate for excess all-cause mortality of drug-resistant versus drug-susceptible BSIs ranged from OR 1.31 (95% CI 1.03-1.68) for CR P. aeruginosa to OR 3.44 (95% CI 1.62-7.32) for CR K. pneumoniae. Pooled crude estimates comparing mortality to uninfected patients were available for vancomycin-resistant Enterococcus and MRSA BSIs (OR of 11.19 [95% CI 6.92-18.09] and OR 6.18 [95% CI 2.10-18.17], respectively).
CONCLUSIONS: Drug-resistant BSIs are associated with increased mortality, with the magnitude of the effect influenced by pathogen type and comparator. Future research should address crucial knowledge gaps in pathogen- and infection-specific burdens to guide development of novel interventions.
OBJECTIVE: We evaluated pathogen-specific excess health burden of drug-resistant bloodstream infections (BSIs) in Europe.
METHODS: A systematic review and meta-analysis.
METHODS: MEDLINE, Embase, and grey literature for the period January 1990 to May 2022.
METHODS: Studies that reported burden data for six key drug-resistant pathogens: carbapenem-resistant (CR) Pseudomonas aeruginosa and Acinetobacter baumannii, third-generation cephalosporin or CR Escherichia coli and Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium. Excess health outcomes compared with drug-susceptible BSIs or uninfected patients. For MRSA and third-generation cephalosporin E. coli and K. pneumoniae BSIs, five or more European studies were identified. For all others, the search was extended to high-income countries.
METHODS: Paediatric and adult patients diagnosed with drug-resistant BSI.
METHODS: Not applicable.
UNASSIGNED: An adapted version of the Joanna-Briggs Institute assessment tool.
UNASSIGNED: Random-effect models were used to pool pathogen-specific burden estimates.
RESULTS: We screened 7154 titles, 1078 full-texts and found 56 studies on BSIs. Most studies compared outcomes of drug-resistant to drug-susceptible BSIs (46/56, 82.1%), and reported mortality (55/56 studies, 98.6%). The pooled crude estimate for excess all-cause mortality of drug-resistant versus drug-susceptible BSIs ranged from OR 1.31 (95% CI 1.03-1.68) for CR P. aeruginosa to OR 3.44 (95% CI 1.62-7.32) for CR K. pneumoniae. Pooled crude estimates comparing mortality to uninfected patients were available for vancomycin-resistant Enterococcus and MRSA BSIs (OR of 11.19 [95% CI 6.92-18.09] and OR 6.18 [95% CI 2.10-18.17], respectively).
CONCLUSIONS: Drug-resistant BSIs are associated with increased mortality, with the magnitude of the effect influenced by pathogen type and comparator. Future research should address crucial knowledge gaps in pathogen- and infection-specific burdens to guide development of novel interventions.
摘要：
背景：抗菌素耐药性是一个全球性威胁，这需要新的干预策略，需要确定哪些优先病原体和设置。
目的：我们评估了欧洲耐药血流感染（BSIs）的病原体特异性超额健康负担。
方法：系统综述和荟萃分析。
方法：MEDLINE，Embase,1990年1月至2022年5月期间的灰色文献。
方法：研究报告了六种关键耐药病原体的负担数据：耐碳青霉烯（CR）铜绿假单胞菌和鲍曼不动杆菌，第三代头孢菌素或CR大肠杆菌和肺炎克雷伯菌，耐甲氧西林金黄色葡萄球菌（MRSA）和耐万古霉素屎肠球菌。与药物敏感的BSI或未感染患者相比，健康结果过多。对于MRSA和第三代头孢菌素大肠杆菌和肺炎克雷伯菌BSIs，确定了五项或更多的欧洲研究。对于所有其他人，搜索扩展到高收入国家。
方法：诊断为耐药BSI的儿科和成年患者。
方法：不适用。
■乔安娜-布里格斯研究所评估工具的改编版本。
■随机效应模型用于汇集病原体特异性负荷估计。
结果：我们筛选了7154个标题，1078个全文，发现56个关于BSIs的研究。大多数研究比较了耐药与药物敏感BSI的结果（46/56，82.1％），和报告的死亡率(55/56研究，98.6%）。耐药与敏感的BSI的全因死亡率的汇总粗估计值从CR铜绿假单胞菌的OR1.31（95％CI1.03-1.68）到CR肺炎克雷伯菌的OR3.44（95％CI1.62-7.32）。对万古霉素耐药肠球菌和MRSABSI的死亡率与未感染患者的死亡率进行汇总的粗略估计(OR为11.19[95%CI6.92-18.09]和OR为6.18[95%CI2.10-18.17],分别)。
结论：耐药BSI与死亡率增加相关，影响的大小受病原体类型和比较物的影响。未来的研究应解决病原体和感染特异性负担中的关键知识差距，以指导新型干预措施的开发。
目的：我们评估了欧洲耐药血流感染（BSIs）的病原体特异性超额健康负担。
方法：系统综述和荟萃分析。
方法：MEDLINE，Embase,1990年1月至2022年5月期间的灰色文献。
方法：研究报告了六种关键耐药病原体的负担数据：耐碳青霉烯（CR）铜绿假单胞菌和鲍曼不动杆菌，第三代头孢菌素或CR大肠杆菌和肺炎克雷伯菌，耐甲氧西林金黄色葡萄球菌（MRSA）和耐万古霉素屎肠球菌。与药物敏感的BSI或未感染患者相比，健康结果过多。对于MRSA和第三代头孢菌素大肠杆菌和肺炎克雷伯菌BSIs，确定了五项或更多的欧洲研究。对于所有其他人，搜索扩展到高收入国家。
方法：诊断为耐药BSI的儿科和成年患者。
方法：不适用。
■乔安娜-布里格斯研究所评估工具的改编版本。
■随机效应模型用于汇集病原体特异性负荷估计。
结果：我们筛选了7154个标题，1078个全文，发现56个关于BSIs的研究。大多数研究比较了耐药与药物敏感BSI的结果（46/56，82.1％），和报告的死亡率(55/56研究，98.6%）。耐药与敏感的BSI的全因死亡率的汇总粗估计值从CR铜绿假单胞菌的OR1.31（95％CI1.03-1.68）到CR肺炎克雷伯菌的OR3.44（95％CI1.62-7.32）。对万古霉素耐药肠球菌和MRSABSI的死亡率与未感染患者的死亡率进行汇总的粗略估计(OR为11.19[95%CI6.92-18.09]和OR为6.18[95%CI2.10-18.17],分别)。
结论：耐药BSI与死亡率增加相关，影响的大小受病原体类型和比较物的影响。未来的研究应解决病原体和感染特异性负担中的关键知识差距，以指导新型干预措施的开发。
