Infectious Diseases Laboratory, 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece.
University General Hospital 'ATTIKON', Chaidari, Athens, Greece.
J Antimicrob Chemother. 2020 Aug 1;75(8):2164-2172. doi: 10.1093/jac/dkaa160.
We evaluated the in vitro activity of ceftolozane/tazobactam and comparator agents against MDR non-MBL Pseudomonas aeruginosa isolates collected from nine Greek hospitals and we assessed the potential synergistic interaction between ceftolozane/tazobactam and amikacin.
A total of 160 non-MBL P. aeruginosa isolates collected in 2016 were tested for susceptibility to ceftolozane/tazobactam and seven comparator agents including ceftazidime/avibactam. Time-kill assays were performed for synergy testing using ceftolozane/tazobactam 60 or 7.5 mg/L, corresponding to the peak and trough concentrations of a 1.5 g q8h dose, respectively, in combination with 69 mg/L amikacin, corresponding to the free peak plasma concentration. Synergy was defined as a ≥2 log10 cfu/mL reduction compared with the most active agent.
Overall, ceftolozane/tazobactam inhibited 64.4% of the P. aeruginosa strains at ≤4 mg/L. Colistin was the most active agent (MIC50/90, 0.5/2 mg/L; 96.3% susceptible) followed by ceftazidime/avibactam (MIC50/90, 4/16 mg/L; 80.6% susceptible). GES-type enzymes were predominantly responsible for ceftolozane/tazobactam resistance; 81.6% of the non-producers were susceptible. MICs for the P. aeruginosa isolates selected for synergy testing were 2-32 mg/L ceftolozane/tazobactam and 2-128 mg/L amikacin. The combination of ceftolozane/tazobactam with amikacin was synergistic against 85.0% of all the isolates tested and against 75.0% of the GES producers. No antagonistic interactions were observed.
Ceftolozane/tazobactam demonstrated good in vitro activity against MDR/XDR P. aeruginosa clinical isolates, including strains with co-resistance to other antipseudomonal drugs. In combination with amikacin, a synergistic interaction at 24 h was observed against 85.0% of P. aeruginosa strains tested, including isolates with ceftolozane/tazobactam MICs of 32 mg/L or GES producers.
我们评估了头孢洛扎/他唑巴坦和比较剂对从希腊 9 家医院收集的 MDR 非 MBL 铜绿假单胞菌分离株的体外活性，并评估了头孢洛扎/他唑巴坦与阿米卡星之间潜在的协同相互作用。
对 2016 年收集的 160 株非 MBL 铜绿假单胞菌分离株进行了头孢洛扎/他唑巴坦和 7 种比较剂（包括头孢他啶/阿维巴坦）的药敏试验。使用头孢洛扎/他唑巴坦 60 或 7.5mg/L（分别对应于 1.5g q8h 剂量的峰和谷浓度）和 69mg/L 阿米卡星（对应于游离峰血浆浓度）进行时间杀伤试验以检测协同作用。协同作用定义为与最有效的药物相比，减少≥2log10cfu/mL。
总体而言，头孢洛扎/他唑巴坦在≤4mg/L 时抑制了 64.4%的铜绿假单胞菌菌株。多粘菌素是最有效的药物（MIC50/90，0.5/2mg/L；96.3%敏感），其次是头孢他啶/阿维巴坦（MIC50/90，4/16mg/L；80.6%敏感）。GES 型酶主要导致头孢洛扎/他唑巴坦耐药；81.6%的非产酶者敏感。用于协同作用测试的铜绿假单胞菌分离株的 MIC 值为 2-32mg/L 头孢洛扎/他唑巴坦和 2-128mg/L 阿米卡星。头孢洛扎/他唑巴坦与阿米卡星联合使用对 85.0%的测试分离株和 75.0%的 GES 产生者具有协同作用。未观察到拮抗相互作用。
头孢洛扎/他唑巴坦对 MDR/XDR 铜绿假单胞菌临床分离株具有良好的体外活性，包括对其他抗假单胞菌药物耐药的菌株。与阿米卡星联合使用时，在 24 小时时观察到 85.0%的铜绿假单胞菌分离株具有协同作用，包括头孢洛扎/他唑巴坦 MIC 为 32mg/L 或 GES 产生者的分离株。
