Zhou Yingjie, Zhang Jing, Chen Yuancheng, Wu Jufang, Guo Beining, Wu Xiaojie, Zhang Yingyuan, Wang Minggui, Ya Ru, Huang Hao
Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai 200040, China.
Key Laboratory of Clinical Pharmacology of Antibiotics, National Health Commission, Shanghai 200040, China.
Antibiotics (Basel). 2022 May 23;11(5):703. doi: 10.3390/antibiotics11050703.
Cefoperazone/sulbactam (CPZ/SUL) is a β-lactam and β-lactamase inhibitor combination therapy for the treatment of respiratory tract infections. Using data from a prospective, multiple-center, open-label clinical trial in 54 patients with hospital-acquired pneumonia or ventilator-associated pneumonia caused by multidrug-resistant Acinetobacter baumannii (Ab), we showed that a combined PK/PD index %(T > MICcpz*T > MICsul) is a more appropriate PK/PD index against Ab, compared to the PK/PD index (%T > MIC) for a single drug. For a 2 h infusion, the PK/PD cutoff of CPZ/SUL (2 g/1 g, q8h) for clinical and microbiological efficacy was 4/2 and 1/0.5 mg/L, respectively. The corresponding cumulative fraction of response was 46.5% and 25.3%, respectively. Results based on the combined PK/PD index were quite similar to that based on the joint probability of target attainment. The two drugs have interaction from the viewpoint of PK/PD. When the dose of one drug was too high, the PK/PD cutoff was often determined by another drug in which the dose was maintained. In most cases, sulbactam exerted the main effect against infection by Ab in the complex CPZ/SUL, which was similar to the literature reports. When the MIC of CPZ was 8, 16, or 32 mg/L, a CPZ/SUL 2 g/1 g (q8h), 2 g/2 g (q8h), or 2 g/2 g (q6h) (infusion was all 3 h) was recommended, respectively. A clinical efficacy and safety study to confirm simulation results is warranted.
头孢哌酮/舒巴坦（CPZ/SUL）是一种用于治疗呼吸道感染的β-内酰胺类与β-内酰胺酶抑制剂联合疗法。利用一项针对54例由多重耐药鲍曼不动杆菌（Ab）引起的医院获得性肺炎或呼吸机相关性肺炎患者的前瞻性、多中心、开放标签临床试验数据，我们发现，与单一药物的药代动力学/药效学指标（%T > MIC）相比，联合药代动力学/药效学指标%（T > MICcpz*T > MICsul）是针对Ab更合适的药代动力学/药效学指标。对于2小时输注，CPZ/SUL（2 g/1 g，q8h）临床和微生物学疗效的药代动力学/药效学临界值分别为4/2和1/0.5 mg/L。相应的累积反应分数分别为46.5%和25.3%。基于联合药代动力学/药效学指标的结果与基于目标达成联合概率的结果非常相似。从药代动力学/药效学角度来看，这两种药物存在相互作用。当一种药物剂量过高时，药代动力学/药效学临界值通常由维持剂量的另一种药物决定。在大多数情况下，舒巴坦在复合制剂CPZ/SUL中对Ab感染发挥主要作用，这与文献报道相似。当CPZ的MIC为8、16或32 mg/L时，分别推荐CPZ/SUL 2 g/1 g（q8h）、2 g/2 g（q8h）或2 g/2 g（q6h）（输注均为3小时）。有必要开展一项临床疗效和安全性研究以证实模拟结果。
