Kufel Wesley D, Zeineddine Nabil, Fouad Aliaa, Roenfanz Hanna F, Shields Ryan K, Kline Ellen G, Warner Jameson, Hanrahan Kathleen, Kuti Joseph L
Department of Pharmacy Practice, State University of New York at Binghamton School of Pharmacy and Pharmaceutical Sciences, Binghamton, New York, USA.
Deparment of Pharmacy, State University of New York Upstate University Hospital, Syracuse, New York, USA.
Pharmacotherapy. 2025 Jul;45(7):396-402. doi: 10.1002/phar.70027. Epub 2025 May 15.
Drug databases currently do not provide dosing guidance for sulbactam-durlobactam in continuous renal replacement therapy. Herein, we present the first in vivo pharmacokinetic (PK) evaluation of sulbactam-durlobactam during continuous venovenous hemofiltration (CVVH) in a patient with carbapenem-resistant Acinetobacter baumannii-calcoaceticus complex (CRAB) bacteremia and ventilator-associated bacterial pneumonia (VABP).
A 59-year-old critically ill patient (body mass index 60 kg/m) required CVVH and developed CRAB bacteremia secondary to VABP. Sulbactam-durlobactam 2 g every 4 h infused over 3 h was initiated based on previous ex vivo data and the effluent rate of 6 L/h. The sulbactam-durlobactam minimum inhibitory concentration (MIC) was determined by reference broth microdilution, and whole genome sequencing (WGS) was performed. Steady-state pre-filter blood, post-filter blood, and effluent samples were collected on three different dosing intervals to characterize plasma exposure and estimate the sieving coefficient (SC).
The sulbactam-durlobactam MIC was 4/4 mcg/mL (susceptible). WGS revealed penicillin-binding protein (PBP)-1b and PBP-3 mutations. The selected dose exceeded sulbactam and durlobactam PK/pharmacodynamic (PD) targets with 100% free time above MIC (fT > MIC) and the ratio of area under the unbound concentration-time curve to MIC (fAUC/MIC) = 139, respectively. The SC for sulbactam and durlobactam was 0.68 and 0.67, respectively, and protein binding was 54% and 51%, respectively. Sulbactam-durlobactam monotherapy resulted in initial microbiological clearance for CRAB bacteremia but recurred later in hospitalization 11 days after sulbactam-durlobactam treatment. The patient was ultimately transitioned to comfort care.
Sulbactam-durlobactam monotherapy dosed at 2 g every 4 h (3-h infusion) in CVVH achieved PD targets for this CRAB isolate with a MIC of 4/4 mcg/ml. Although sulbactam-durlobactam monotherapy resulted in initial microbiological clearance for the CRAB bacteremia, recurrence occurred, and the patient ultimately died.
目前药物数据库未提供在连续性肾脏替代治疗中舒巴坦-杜洛巴坦的给药指导。在此，我们首次对一名患有耐碳青霉烯鲍曼不动杆菌-醋酸钙复合菌（CRAB）菌血症和呼吸机相关性细菌性肺炎（VABP）的患者在持续静静脉血液滤过（CVVH）期间进行舒巴坦-杜洛巴坦的体内药代动力学（PK）评估。
一名59岁的重症患者（体重指数60kg/m）需要进行CVVH，继发于VABP出现CRAB菌血症。根据先前的体外数据和6L/h的滤出液速率，开始每4小时静脉输注2g舒巴坦-杜洛巴坦，输注时间为3小时。通过参考肉汤微量稀释法测定舒巴坦-杜洛巴坦的最低抑菌浓度（MIC），并进行全基因组测序（WGS）。在三个不同的给药间隔采集稳态滤前血、滤后血和滤出液样本，以表征血浆暴露情况并估算筛滤系数（SC）。
舒巴坦-杜洛巴坦的MIC为4/4mcg/mL（敏感）。WGS显示青霉素结合蛋白（PBP）-1b和PBP-3突变。所选剂量超过了舒巴坦和杜洛巴坦的PK/药效学（PD）目标，游离时间高于MIC的比例为100%（fT＞MIC），未结合浓度-时间曲线下面积与MIC的比值（fAUC/MIC）分别为139。舒巴坦和杜洛巴坦的SC分别为0.68和0.67，蛋白结合率分别为54%和51%。舒巴坦-杜洛巴坦单药治疗使CRAB菌血症最初获得微生物清除，但在舒巴坦-杜洛巴坦治疗11天后住院期间病情复发。该患者最终转为舒适护理。
在CVVH中每4小时（3小时输注）给予2g舒巴坦-杜洛巴坦单药治疗，对于该MIC为4/4mcg/ml的CRAB分离株达到了PD目标。尽管舒巴坦-杜洛巴坦单药治疗使CRAB菌血症最初获得微生物清除，但病情复发，患者最终死亡。
