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Abstract：
BACKGROUND: Aztreonam-avibactam (ATM-AVI) combination shows promising effectiveness on most carbapenemase-producing Gram-negatives, yet standardized antibiotic susceptibility testing (AST) methods for evaluating the combination in clinical laboratories is lacking. We aimed to evaluate different ATM-AVI AST approaches.
METHODS: 96 characterized carbapenem-resistant clinical isolates belonging to 9 Enterobacterales (EB; n = 80) and P. aeruginosa (PA; n = 16) species, including 90 carbapenemase producers and 72 strains resistant to both CAZ-AVI and ATM, were tested. Paper disk elution (DE; Bio-Rad) and E-test gradient strips stacking (SS; bioMérieux) were performed for the ATM + CAZ-AVI combination. MIC Test Strip (MTS; Liofilchem) was evaluated for ATM-AVI MIC determination. Results were interpreted applying ATM clinical breakpoints of the EUCAST guidelines and compared to the broth microdilution method (Sensititre, Thermofisher).
RESULTS: According to broth microdilution method, 93% of EB and 69% of PA were tested susceptible to ATM-AVI. The synergistic effect of ATM-AVI was of 95% for EB, but of only 17% for PA. The MTS method yielded higher categorical and essential agreement (CA/EA) rates for both EB (89%/91%) and PA (94%/94%) compared to SS, where the rates were 87%/83% for EB and 81%/81% for PA. MTS and SS yielded 2 and 3 major discrepancies, respectively, while 3 very major discrepancies each were observed for both methods. Concerning the DE method, CA reached 91% for EB and 81% for PA, but high number of very major discrepancies were observed for EB (n = 6; 8%) and for PA (n = 3; 19%).
CONCLUSIONS: The ATM-AVI association displayed excellent in vitro activity against highly resistant clinical Enterobacterales strains. MTS method offers accurate ATM-AVI AST results, while the SS method might serve as better alternative then DE method in assessing the efficacy of ATM + CAZ-AVI combination. However, further investigation is needed to confirm the methods\' ability to detect ATM-AVI resistance.
METHODS: 96 characterized carbapenem-resistant clinical isolates belonging to 9 Enterobacterales (EB; n = 80) and P. aeruginosa (PA; n = 16) species, including 90 carbapenemase producers and 72 strains resistant to both CAZ-AVI and ATM, were tested. Paper disk elution (DE; Bio-Rad) and E-test gradient strips stacking (SS; bioMérieux) were performed for the ATM + CAZ-AVI combination. MIC Test Strip (MTS; Liofilchem) was evaluated for ATM-AVI MIC determination. Results were interpreted applying ATM clinical breakpoints of the EUCAST guidelines and compared to the broth microdilution method (Sensititre, Thermofisher).
RESULTS: According to broth microdilution method, 93% of EB and 69% of PA were tested susceptible to ATM-AVI. The synergistic effect of ATM-AVI was of 95% for EB, but of only 17% for PA. The MTS method yielded higher categorical and essential agreement (CA/EA) rates for both EB (89%/91%) and PA (94%/94%) compared to SS, where the rates were 87%/83% for EB and 81%/81% for PA. MTS and SS yielded 2 and 3 major discrepancies, respectively, while 3 very major discrepancies each were observed for both methods. Concerning the DE method, CA reached 91% for EB and 81% for PA, but high number of very major discrepancies were observed for EB (n = 6; 8%) and for PA (n = 3; 19%).
CONCLUSIONS: The ATM-AVI association displayed excellent in vitro activity against highly resistant clinical Enterobacterales strains. MTS method offers accurate ATM-AVI AST results, while the SS method might serve as better alternative then DE method in assessing the efficacy of ATM + CAZ-AVI combination. However, further investigation is needed to confirm the methods\' ability to detect ATM-AVI resistance.
摘要：
背景：氨曲南-阿维巴坦（ATM-AVI）组合对大多数产生碳青霉烯酶的革兰氏阴性药物显示出有希望的有效性，然而,目前还缺乏用于临床实验室评估联合用药的标准化抗生素药敏试验(AST)方法.我们旨在评估不同的ATM-AVIAST方法。
方法：96个特征为耐碳青霉烯的临床分离株，属于9个肠杆菌（EB；n=80）和铜绿假单胞菌（PA；n=16），包括90个碳青霉烯酶生产者和72个对CAZ-AVI和ATM均具有抗性的菌株，进行了测试。对ATM+CAZ-AVI组合进行纸盘洗脱(DE;Bio-Rad)和E-测试梯度条堆叠(SS;bioMérieux)。评估MIC测试条(MTS;Liofilchem)用于ATM-AVIMIC测定。应用EUCAST指南的ATM临床断点对结果进行了解释，并与肉汤微量稀释法进行了比较（Sensitte，Thermofisher）。
结果：根据肉汤微量稀释法，测试了93%的EB和69%的PA对ATM-AVI敏感。ATM-AVI对EB的协同作用为95%,但PA只有17%。与SS相比，MTS方法对EB（89％/91％）和PA（94％/94％）产生了更高的分类和基本协议（CA/EA）率，其中EB率为87%/83%，PA率为81%/81%。MTS和SS产生了2和3个主要差异，分别,而两种方法各有3个非常大的差异。关于DE方法，EB的CA达到91%，PA达到81%，但是对于EB（n=6;8％）和PA（n=3;19％）观察到大量非常重大的差异。
结论：ATM-AVI联合对高耐药临床肠杆菌菌株表现出优异的体外活性。MTS方法提供准确的ATM-AVIAST结果，而SS方法在评估ATM+CAZ-AVI组合的疗效方面可能比DE方法更好。然而,需要进一步研究以确认方法检测ATM-AVI耐药性的能力.
方法：96个特征为耐碳青霉烯的临床分离株，属于9个肠杆菌（EB；n=80）和铜绿假单胞菌（PA；n=16），包括90个碳青霉烯酶生产者和72个对CAZ-AVI和ATM均具有抗性的菌株，进行了测试。对ATM+CAZ-AVI组合进行纸盘洗脱(DE;Bio-Rad)和E-测试梯度条堆叠(SS;bioMérieux)。评估MIC测试条(MTS;Liofilchem)用于ATM-AVIMIC测定。应用EUCAST指南的ATM临床断点对结果进行了解释，并与肉汤微量稀释法进行了比较（Sensitte，Thermofisher）。
结果：根据肉汤微量稀释法，测试了93%的EB和69%的PA对ATM-AVI敏感。ATM-AVI对EB的协同作用为95%,但PA只有17%。与SS相比，MTS方法对EB（89％/91％）和PA（94％/94％）产生了更高的分类和基本协议（CA/EA）率，其中EB率为87%/83%，PA率为81%/81%。MTS和SS产生了2和3个主要差异，分别,而两种方法各有3个非常大的差异。关于DE方法，EB的CA达到91%，PA达到81%，但是对于EB（n=6;8％）和PA（n=3;19％）观察到大量非常重大的差异。
结论：ATM-AVI联合对高耐药临床肠杆菌菌株表现出优异的体外活性。MTS方法提供准确的ATM-AVIAST结果，而SS方法在评估ATM+CAZ-AVI组合的疗效方面可能比DE方法更好。然而,需要进一步研究以确认方法检测ATM-AVI耐药性的能力.
