Jingjing He, Nanyang Li, Xin Li, Yuancheng Chen, Jingjing Lin, Lei Yang, Jufang Wu, Xuehai Wu, Rui Li, Zhiping Liu, Yan Xu, Yangyi Dai, Wei Liu, Xu Zhu, Xiaofen Liu, Jin Hu, Gang Wu, Jing Zhang
Eravacycline achieved substantial pulmonary exposure in critically ill patients with HAP/VAP despite reduced plasma exposure, with acceptable safety and encouraging clinical responses. Notably, eravacycline's independent contribution to clinical outcomes cannot be determined due to concurrent antimicrobial use.
OBJECTIVES: To characterize the pulmonary pharmacokinetics (PK), safety, and exploratory efficacy of eravacycline in critically ill patients with hospital-acquired or ventilator-associated pneumonia (HAP/VAP) caused by carbapenem-resistant pathogens.
METHODS: In this prospective, single-center, open-label study, 16 critically ill adults with HAP/VAP caused by carbapenem-resistant Acinetobacter baumannii (CRAB) or carbapenem-resistant Enterobacterales (CRE) received intravenous eravacycline (1 mg/kg every 12 h) for 7-14 days. Plasma and epithelial lining fluid (ELF) PK were assessed at steady state. Pulmonary penetration was evaluated using the ELF-to-plasma AUC0-12h ratio. Safety and exploratory efficacy were assessed at end of therapy (EOT).
RESULTS: Sixteen patients were included (13/16 VAP, 3/16 HAP), with a median APACHE II score of 23 (IQR 18-25). Mean plasma AUC0-12h and fAUC0-12h were 2.35 ± 0.84 and 1.48 ± 0.54 μg·h/mL, respectively. ELF exposure was higher than plasma, with ELF-to-free plasma AUC0-12h ratios of 4.0. Eravacycline was well tolerated; treatment-related adverse events (TRAEs) occurred in 7/16 (43.8%) patients and were all mild to moderate, including rash (2/16, 12.5%), prolonged activated partial thromboplastin time (APTT, 2/16, 12.5%), prolonged thrombin time (TT, 1/16, 6.3%), diarrhea (1/16, 6.3%), and vomiting (1/16, 6.3%). All patients received eravacycline-based combination therapy. Clinical response at EOT was observed in 13/16 (81.2%, 95% CI: 54.4-95.9%) patients, and microbiological eradication in 10/16 (62.5%, 95% CI: 35.4-84.8%).
CONCLUSIONS: Eravacycline achieved substantial pulmonary exposure in critically ill patients with HAP/VAP despite reduced plasma exposure, with acceptable safety and encouraging clinical responses. Notably, eravacycline's independent contribution to clinical outcomes cannot be determined due to concurrent antimicrobial use.