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.
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.