Ceftazidime-Avibactam as Salvage Treatment for Infections Due to Carbapenem-Resistant Klebsiella pneumoniae in Liver Transplantation Recipients

Abstract

Fang Chen,1,2,* Han Zhong,1,* Tengjiao Yang,3 Chuan Shen,2 Yuxiao Deng,4 Longzhi Han,2 Xiaosong Chen,2 Haomin Zhang,5 Yongbing Qian2 1Department of Pharmacy, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 3Department of Pharmacy, The Third People’s Hospital of Henan Province, Zhengzhou, People’s Republic of China; 4Department of Critical Care Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 5Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Haomin ZhangDepartment of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China, Tel [phone]Email [email protected] QianDepartment of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China, Tel [phone]Email [email protected]: Ceftazidime-avibactam (CZA) has been approved in vitro activity against carbapenem-resistant K. pneumoniae (CRKP), but the experience for the treatment of CRKP in liver transplantation (LT) recipients was limited, and previous data on its efficacy in this setting are lacking.Methods: LT recipients with CRKP infection who received CZA treatment were reviewed retrospectively, microbiological and clinical response, adverse events were also assessed. The primary outcome was 30-day mortality after CZA administration.Results: CZA was used in 21 LT recipients (including 4 pediatric patients) with CRKP infections after failure with other antimicrobials. CZA was administered as monotherapy in 4 patients. Median time from the onset of CRKP infection until the initiation of CZA treatment was 2 days (IQR, 1– 6.5), and the median treatment duration was 12 days (IQR, 8.5– 18.5). The mortality at 14 days, 30 days and all-cause was 28.6%, 38.1% and 42.9%, respectively. In adult patients, clinical response of 14 days and 30 days was 70.6% (12/17) and 58.8% (10/17), respectively, while in pediatric patients the 14-day and 30-day clinical response were both 75%, respectively. The relapse rate during the treatment developed in 3 patients after 30 days with the cessation of CZA monotherapy. CZA resistance was not detected in any case and 3 (3/21, 14.3%) patients developed acute kidney injury related to uncontrolled infection.Conclusion: CZA shows promising results, even in monotherapy, for the treatment of patients with severe infections due to carbapenem-resistant K. pneumoniae among LT recipients. The emergence of resistance to CZA was not observed.Keywords: carbapenem-resistant Klebsiella pneumoniae, ceftazidime-avibactam, liver transplantation, intra-abdominal infection, pneumonia

Keywords

• carbapenem-resistant klebsiella pneumoniae
• ceftazidime-avibactam
• liver transplantation
• intra-abdominal infection
• pneumonia