Abstract：
BACKGROUND: Cefiderocol is a last resort option for carbapenem-resistant (CR) Gram-negative bacteria, especially metallo-β-lactamase-producing Pseudomonas aeruginosa and CR Acinetobacter baumannii. Monitoring global levels of cefiderocol non-susceptibility (CFDC-NS) is important.
OBJECTIVE: To systematically collate and examine studies investigating in vitro CFDC-NS and estimate the global prevalence of CFDC-NS against major Gram-negative pathogens.
METHODS: PubMed and Scopus, up to May 2023.
METHODS: Eligible were studies reporting CFDC-NS in Enterobacterales, P. aeruginosa, A. baumannii, or Stenotrophomonas maltophilia clinical isolates.
UNASSIGNED: Two independent reviewers extracted study data and assessed the risk of bias on the population, setting, and measurement (susceptibility testing) domains.
RESULTS: Binomial-Normal mixed-effects models were applied to estimate CFDC-NS prevalence by species, coresistance phenotype, and breakpoint definition (EUCAST, CLSI, and FDA). Sources of heterogeneity were investigated by subgroup and meta-regression analyses.
RESULTS: In all, 78 studies reporting 82 035 clinical isolates were analysed (87% published between 2020 and 2023). CFDC-NS prevalence (EUCAST breakpoints) was low overall but varied by species (S. maltophilia 0.4% [95% CI 0.2-0.7%], Enterobacterales 3.0% [95% CI 1.5-6.0%], P. aeruginosa 1.4% [95% CI 0.5-4.0%]) and was highest for A. baumannii (8.8%, 95% CI 4.9-15.2%). CFDC-NS was much higher in CR Enterobacterales (12.4%, 95% CI 7.3-20.0%) and CR A. baumannii (13.2%, 95% CI 7.8-21.5%), but relatively low for CR P. aeruginosa (3.5%, 95% CI 1.6-7.8%). CFDC-NS was exceedingly high in New Delhi metallo-β-lactamase-producing Enterobacterales (38.8%, 95% CI 22.6-58.0%), New Delhi metallo-β-lactamase-producing A. baumannii (44.7%, 95% CI 34.5-55.4%), and ceftazidime/avibactam-resistant Enterobacterales (36.6%, 95% CI 22.7-53.1%). CFDC-NS varied considerably with breakpoint definition, predominantly among CR bacteria. Additional sources of heterogeneity were single-centre investigations and geographical regions.
CONCLUSIONS: CFDC-NS prevalence is low overall, but alarmingly high for specific CR phenotypes circulating in some institutions or regions. Continuous surveillance and updating of global CFDC-NS estimates are imperative while cefiderocol is increasingly introduced into clinical practice. The need to harmonize EUCAST and CLSI breakpoints was evident.
OBJECTIVE: To systematically collate and examine studies investigating in vitro CFDC-NS and estimate the global prevalence of CFDC-NS against major Gram-negative pathogens.
METHODS: PubMed and Scopus, up to May 2023.
METHODS: Eligible were studies reporting CFDC-NS in Enterobacterales, P. aeruginosa, A. baumannii, or Stenotrophomonas maltophilia clinical isolates.
UNASSIGNED: Two independent reviewers extracted study data and assessed the risk of bias on the population, setting, and measurement (susceptibility testing) domains.
RESULTS: Binomial-Normal mixed-effects models were applied to estimate CFDC-NS prevalence by species, coresistance phenotype, and breakpoint definition (EUCAST, CLSI, and FDA). Sources of heterogeneity were investigated by subgroup and meta-regression analyses.
RESULTS: In all, 78 studies reporting 82 035 clinical isolates were analysed (87% published between 2020 and 2023). CFDC-NS prevalence (EUCAST breakpoints) was low overall but varied by species (S. maltophilia 0.4% [95% CI 0.2-0.7%], Enterobacterales 3.0% [95% CI 1.5-6.0%], P. aeruginosa 1.4% [95% CI 0.5-4.0%]) and was highest for A. baumannii (8.8%, 95% CI 4.9-15.2%). CFDC-NS was much higher in CR Enterobacterales (12.4%, 95% CI 7.3-20.0%) and CR A. baumannii (13.2%, 95% CI 7.8-21.5%), but relatively low for CR P. aeruginosa (3.5%, 95% CI 1.6-7.8%). CFDC-NS was exceedingly high in New Delhi metallo-β-lactamase-producing Enterobacterales (38.8%, 95% CI 22.6-58.0%), New Delhi metallo-β-lactamase-producing A. baumannii (44.7%, 95% CI 34.5-55.4%), and ceftazidime/avibactam-resistant Enterobacterales (36.6%, 95% CI 22.7-53.1%). CFDC-NS varied considerably with breakpoint definition, predominantly among CR bacteria. Additional sources of heterogeneity were single-centre investigations and geographical regions.
CONCLUSIONS: CFDC-NS prevalence is low overall, but alarmingly high for specific CR phenotypes circulating in some institutions or regions. Continuous surveillance and updating of global CFDC-NS estimates are imperative while cefiderocol is increasingly introduced into clinical practice. The need to harmonize EUCAST and CLSI breakpoints was evident.
摘要：
背景：头孢地洛是耐碳青霉烯（CR）革兰氏阴性菌的最后选择，尤其是产生金属β-内酰胺酶（MBL）的铜绿假单胞菌和CR鲍曼不动杆菌。监测头孢地洛非敏感性（CFDC-NS）的全球水平很重要。
目的：系统地整理和检查体外CFDC-NS的研究，并评估CFDC-NS对主要革兰氏阴性病原体的全球流行率。
方法：PubMed和Scopus，到2023年5月。
方法：符合条件的研究报告了肠杆菌中的CFDC-NS，铜绿假单胞菌,A.鲍曼尼,或嗜麦芽窄食单胞菌临床分离株。
方法：两名独立评审员提取研究数据并评估人群偏倚风险，设置和测量（敏感性测试）领域。二项-正常混合效应模型用于估计按物种划分的CFDC-NS患病率，共抗性表型和断点定义(EUCAST，CLSI,FDA）。通过亚组和荟萃回归分析调查异质性的来源。
结果：总而言之，对78项报告82035种临床分离株的研究进行了分析（87%在2020年至2023年之间发表）。CFDC-NS患病率(EUCAST断点)总体较低，但因物种而异[S.嗜麦芽癖0.4%（95CI0.2-0.7%），肠杆菌3.0%（95CI1.5-6.0%），铜绿假单胞菌1.4%（95CI0.5-4.0%）]，鲍曼不动杆菌最高（8.8%，95CI4.9-15.2%）。CFDC-NS在CR肠杆菌中高得多(12.4%，95CI7.3-20.0%）和CRA.鲍曼不动杆菌（13.2%，95CI7.8-21.5%），但铜绿假单胞菌的CR相对较低(3.5%，95CI1.6-7.8%）。CFDC-NS在产生NDM的肠杆菌中非常高(38.8%，95CI22.6-58.0%），生产NDM的鲍曼不动杆菌（44.7%，95CI34.5-55.4%），和头孢他啶/阿维巴坦耐药肠杆菌(36.6%，95CI22.7-53.1%）。CFDC-NS与断点定义有很大不同，主要在CR细菌中。异质性的其他来源是单中心调查和地理区域。
结论：CFDC-NS总体患病率较低，但对于某些机构或地区流行的特定CR表型来说，高得惊人。不断监测和更新全球CFDC-NS估计值是必要的，而头孢多罗被越来越多地引入临床实践。显然需要协调EUCAST和CLSI断点。
目的：系统地整理和检查体外CFDC-NS的研究，并评估CFDC-NS对主要革兰氏阴性病原体的全球流行率。
方法：PubMed和Scopus，到2023年5月。
方法：符合条件的研究报告了肠杆菌中的CFDC-NS，铜绿假单胞菌,A.鲍曼尼,或嗜麦芽窄食单胞菌临床分离株。
方法：两名独立评审员提取研究数据并评估人群偏倚风险，设置和测量（敏感性测试）领域。二项-正常混合效应模型用于估计按物种划分的CFDC-NS患病率，共抗性表型和断点定义(EUCAST，CLSI,FDA）。通过亚组和荟萃回归分析调查异质性的来源。
结果：总而言之，对78项报告82035种临床分离株的研究进行了分析（87%在2020年至2023年之间发表）。CFDC-NS患病率(EUCAST断点)总体较低，但因物种而异[S.嗜麦芽癖0.4%（95CI0.2-0.7%），肠杆菌3.0%（95CI1.5-6.0%），铜绿假单胞菌1.4%（95CI0.5-4.0%）]，鲍曼不动杆菌最高（8.8%，95CI4.9-15.2%）。CFDC-NS在CR肠杆菌中高得多(12.4%，95CI7.3-20.0%）和CRA.鲍曼不动杆菌（13.2%，95CI7.8-21.5%），但铜绿假单胞菌的CR相对较低(3.5%，95CI1.6-7.8%）。CFDC-NS在产生NDM的肠杆菌中非常高(38.8%，95CI22.6-58.0%），生产NDM的鲍曼不动杆菌（44.7%，95CI34.5-55.4%），和头孢他啶/阿维巴坦耐药肠杆菌(36.6%，95CI22.7-53.1%）。CFDC-NS与断点定义有很大不同，主要在CR细菌中。异质性的其他来源是单中心调查和地理区域。
结论：CFDC-NS总体患病率较低，但对于某些机构或地区流行的特定CR表型来说，高得惊人。不断监测和更新全球CFDC-NS估计值是必要的，而头孢多罗被越来越多地引入临床实践。显然需要协调EUCAST和CLSI断点。
