Abstract：
OBJECTIVE: Carbapenem resistant Pseudomonas aeruginosa (CR-PA) is escalating worldwide and leaves clinicians few therapeutic options in recent years, β-lactam/β-lactamase inhibitor combinations (ceftolozane-tazobactam, ceftazidime-avibactam) and a new siderophore cephalosporin (cefiderocol) have been approved for the treatment of P. aeruginosa infection and have shown potent activity against isolates defined as carbapenem resistant. The aim of this study was to determine the phenotypic profile of these agents against CR-PA in the emerging setting of carbapenemases.
METHODS: CR-PA clinical isolates were collected from three teaching hospitals in different geographical regions between January 2017-December 2021. All isolates were subjected to phenotypic carbapenemase testing using modified carbapenem inactivation method. MICs were determined by reference broth microdilution and evaluated according to EUCAST standards, while genotypic profiling was determined using PCR methods.
RESULTS: 244 CR-PA sourced most frequently from the respiratory tract (32.2%), blood (20.4%) and urine (17.5%) were evaluated. Of all isolates, 32 (13.1%) were phenotypically and 38 (15.6%) were genotypically defined as carbapenemase-positive. The most common carbapenemase was GES (63.1%), followed by VIM (15.8%). The MIC50/90(S%) of ceftazidime/avibactam, ceftolozane/tazobactam and cefiderocol in all CR-PA isolates were 4 and 32 (80%), 1 and > 64 (69%) and 0.25 and 1 mg/L (96%), respectively. Cefiderocol was also the most active agent in carbapenemase-positive isolates (90%).
CONCLUSIONS: While ceftolozane/tazobactam and ceftazidime/avibactam remained highly active against CR-PA devoid of carbapenemases, cefiderocol provided potent in vitro activity irrespective of carbapenemase production. When considering the potential clinical utility of newer agents against CR-PA, regional variations in carbapenemase prevalence must be considered.
METHODS: CR-PA clinical isolates were collected from three teaching hospitals in different geographical regions between January 2017-December 2021. All isolates were subjected to phenotypic carbapenemase testing using modified carbapenem inactivation method. MICs were determined by reference broth microdilution and evaluated according to EUCAST standards, while genotypic profiling was determined using PCR methods.
RESULTS: 244 CR-PA sourced most frequently from the respiratory tract (32.2%), blood (20.4%) and urine (17.5%) were evaluated. Of all isolates, 32 (13.1%) were phenotypically and 38 (15.6%) were genotypically defined as carbapenemase-positive. The most common carbapenemase was GES (63.1%), followed by VIM (15.8%). The MIC50/90(S%) of ceftazidime/avibactam, ceftolozane/tazobactam and cefiderocol in all CR-PA isolates were 4 and 32 (80%), 1 and > 64 (69%) and 0.25 and 1 mg/L (96%), respectively. Cefiderocol was also the most active agent in carbapenemase-positive isolates (90%).
CONCLUSIONS: While ceftolozane/tazobactam and ceftazidime/avibactam remained highly active against CR-PA devoid of carbapenemases, cefiderocol provided potent in vitro activity irrespective of carbapenemase production. When considering the potential clinical utility of newer agents against CR-PA, regional variations in carbapenemase prevalence must be considered.
摘要：
目的：耐碳青霉烯类铜绿假单胞菌（CR-PA）在全球范围内不断升级，近年来临床医生的治疗选择很少，β-内酰胺/β-内酰胺酶抑制剂组合（头孢特洛扎-他唑巴坦，头孢他啶-阿维巴坦）和一种新的铁载体头孢菌素（头孢地洛）已被批准用于治疗铜绿假单胞菌感染，并已显示出对碳青霉烯耐药的分离株的有效活性。这项研究的目的是确定这些药物在碳青霉烯酶新兴环境中针对CR-PA的表型特征。
方法：CR-PA临床分离株来自2017年1月至2021年12月不同地理区域的三家教学医院。使用改良的碳青霉烯灭活法对所有分离物进行表型碳青霉烯酶测试。通过参考肉汤微量稀释测定MIC，并根据EUCAST标准进行评估。而基因型分析是使用PCR方法确定的。
结果：244CR-PA最常见的来源是呼吸道（32.2％），评估了血液（20.4％）和尿液（17.5％）。在所有分离物中，32（13.1％）的表型和38（15.6％）的基因型定义为碳青霉烯酶阳性。最常见的碳青霉烯酶是GES（63.1%），其次是VIM（15.8%）。头孢他啶/阿维巴坦的MIC50/90(S%),头孢洛赞/他唑巴坦和头孢地洛在所有CR-PA分离株中分别为4和32(80%)，1和>64（69％）以及0.25和1mg/L（96％），分别。头孢地洛也是碳青霉烯酶阳性分离株中最具活性的药物(90%)。
结论：虽然头孢洛赞/他唑巴坦和头孢他啶/阿维巴坦对缺乏碳青霉烯酶的CR-PA保持高度活性，头孢地洛可提供有效的体外活性，而与碳青霉烯酶的产生无关。当考虑针对CR-PA的新型药物的潜在临床效用时，必须考虑碳青霉烯酶流行的区域差异。
方法：CR-PA临床分离株来自2017年1月至2021年12月不同地理区域的三家教学医院。使用改良的碳青霉烯灭活法对所有分离物进行表型碳青霉烯酶测试。通过参考肉汤微量稀释测定MIC，并根据EUCAST标准进行评估。而基因型分析是使用PCR方法确定的。
结果：244CR-PA最常见的来源是呼吸道（32.2％），评估了血液（20.4％）和尿液（17.5％）。在所有分离物中，32（13.1％）的表型和38（15.6％）的基因型定义为碳青霉烯酶阳性。最常见的碳青霉烯酶是GES（63.1%），其次是VIM（15.8%）。头孢他啶/阿维巴坦的MIC50/90(S%),头孢洛赞/他唑巴坦和头孢地洛在所有CR-PA分离株中分别为4和32(80%)，1和>64（69％）以及0.25和1mg/L（96％），分别。头孢地洛也是碳青霉烯酶阳性分离株中最具活性的药物(90%)。
结论：虽然头孢洛赞/他唑巴坦和头孢他啶/阿维巴坦对缺乏碳青霉烯酶的CR-PA保持高度活性，头孢地洛可提供有效的体外活性，而与碳青霉烯酶的产生无关。当考虑针对CR-PA的新型药物的潜在临床效用时，必须考虑碳青霉烯酶流行的区域差异。
