High-Dose versus Standard-Dose Tigecycline Treatment of Secondary Bloodstream Infections Caused by Extensively Drug-Resistant Acinetobacter baumannii: An Observational Cohort Study

Hui Han,1,* Weidong Qin,1,* Yue Zheng,2– 5 Dongming Cao,6 Haining Lu,7 Lu Zhang,8 Yi Cui,1 Yuanyuan Hu,1 Wei Li,9 Haipeng Guo,1 Dawei Wu,7 Chen Li,1 Hao Wang,1,2,10 Yuguo Chen2– 5 1Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan, People’s Republic of China; 2Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Chest Pain Center, Qilu Hospital of Shandong University, Jinan, People’s Republic of China; 3Department of Emergency Medicine, Qilu Hospital of Shandong University, Jinan, People’s Republic of China; 4Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Qilu Hospital of Shandong University, Jinan, People’s Republic of China; 5The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, People’s Republic of China; 6Department of Critical Care Medicine, Liaocheng People’s Hospital Affiliated with Shandong First Medical University, Liaocheng, People’s Republic of China; 7Department of Critical Care Medicine, Qilu Hospital of Shandong University (Qingdao), Qingdao, People’s Republic of China; 8Department of Critical Care Medicine, The Second Hospital of Shandong University, Jinan, People’s Republic of China; 9Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, People’s Republic of China; 10Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hao WangDepartment of Critical Care Medicine, Qilu Hospital of Shandong University, 107 Wenhua-xi Road, Jinan, 250012, People’s Republic of ChinaTel +86 18560081013Email wanghao34@126.comYuguo ChenDepartment of Emergency Medicine, Qilu Hospital of Shandong University, 107 Wenhua-xi Road, Jinan, 250012, People’s Republic of ChinaTel +86 0531-8216 6843Email chen919085@sdu.edu.cnBackground: Extensively drug-resistant Acinetobacter baumannii (XDR-AB) infections have become difficult to treat and are associated with a high mortality rate. Tigecycline is one of the most effective agents used to treat XDR-AB infections, but data from treating bloodstream infection (BSI) in standard dose do not look promising, because of its low plasma concentration. Secondary BSI with primary infection source may indicate tigecycline treatment with a higher dose. Currently, little is known about the application of high-dose tigecycline among patients with secondary BSI caused by XDR-AB. We aimed to investigate the outcomes for high-dose (HD) tigecycline treatment versus standard-dose (SD) treatment of these patients.Methods: An observational cohort study was conducted at four university affiliated hospitals in mainland China. Adult inpatients who were confirmed as having secondary BSI caused by XDR-AB and received definitive tigecycline treatment were consecutively included. Patients who were treated with 50 mg every 12 h were defined as the SD group, and a twice dose was defined as the HD group.Results: Of the enrolled patients, 63 received SD and 88 received HD tigecycline treatment. Patients in the two groups had similar with regard to baseline clinical conditions. The 30-day survival was affected by the source of the primary infection. Survival was significantly better in patients with non-pulmonary-infection-related BSI than in patients with pulmonary-infection-related BSI. Multivariate Cox regression confirmed that HD had a protective effect only observed in patients with non-pneumonia-related BSI.Conclusion: A tigecycline dose that is twice its standard dose is better for the treatment of XDR-AB infection only in BSI associated with non-pulmonary infection.Keywords: Acinetobacter baumannii, bloodstream infection, extensively drug-resistant, tigecycline, high-dose