Wenhui Chen1, Lingxiao Sun2, Lijuan Guo1, Bin Cao2,3,4, Yingmei Liu3, Li Zhao1, Binghuai Lu3, Binbin Li3, Jingyu Chen1, Chen Wang1,4,5,6,7,8. 1. Department of Lung Transplantation, Centre for Lung Transplantation, Centre for Respiratory Diseases, China-Japan Friendship Hospital, Beijing 100029, China. 2. China-Japan Friendship Hospital, National Clinical Research Center for Respiratory Diseases, Capital Medical University, Beijing 100029, China. 3. Laboratory of Clinical Microbiology and Infectious Diseases, Department of Pulmonary and Critical Care Medicine, Centre for Respiratory Diseases, China-Japan Friendship Hospital, Beijing 100029, China. 4. Department of Pulmonary and Critical Care Medicine, Centre for Respiratory Diseases, China-Japan Friendship Hospital, Beijing 100029, China. 5. National Clinical Research Center for Respiratory Diseases, Beijing 100730, China. 6. Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China. 7. Department of Respiratory Medicine, Capital Medical University, Beijing 100069, China. 8. WHO Collaborating Center for Tobacco Cessation and Respiratory Diseases Prevention, Beijing 100029, China.
Abstract
BACKGROUND: Infections produced by extensively drug-resistant (XDR) gram-negative bacilli (GNB) in solid organ transplant (SOT) are an important cause of morbidity and mortality. Ceftazidime/avibactam (CAZ-AVI) is a novel β-lactam/β-lactamase combination antibiotic with anti-GNB activity, but experience in real clinical practice with CAZ-AVI in lung transplant (LT) recipients is limited. METHODS: We conducted a retrospective study of patients with XDR-GNB infection who received at least 3 days of CAZ-AVI in the Department of Lung Transplantation Between December 2017 and December 2018 at China-Japan friendship hospital (CJFH). The general information, clinical manifestations, laboratory examinations, treatment course, and outcomes were summarized. RESULTS: A total of 10 patients who underwent LT at our center were included. They were all males with a mean age 51 years. Infections after LT included pneumonia and/or tracheobronchitis [n=9; 90% (9/10)], cholecystitis and blood stream infection (BSI) (n=1, patient 8). In these 10 LT recipients, the incidence of various airway complications was 70% (7/10). Carbapenem-resistant Klebsialla pneumoniae (CRKP) was the predominant pathogen, being detected in 9 patients. Multilocus sequence typing (MLST) analysis showed that all 9 CRKP isolates belonged to ST11. Six patients (6/10, 60%) started CAZ-AVI as salvage therapy after a first-line treatment with other antimicrobials. CAZ-AVI was administered as monotherapy or in combination regimens in 20% (2/10) and 80% (8/10) of patients respectively. There were no difference in temperature before and after CAZ-AVI treatment (P>0.05). White blood cell (WBC) at 7 days, and procalcitonin (PCT) at 7 days and 14 days significantly dropped (P<0.05). After 7-14 days of CAZ-AVI treatment, the PaO2/FiO2ratio (P/F ratio) significantly improved (P<0.05). Nine patients (9/10, 90%) obtained negative microbiologic culture of CRKP/CRPA, with a median time to was 6.7 days (range, 1-15 days). However, 5 patients (5/10, 50%) had relapse of CRKP/CRPA infections in the respiratory tract regardless of whether negative microbiologic culture was obtained or not. The 30-day survival rate was 100%, and the 90-day survival rate was 90% (1/10). No severe adverse events related to CAZ-AVI occurred. CONCLUSIONS: CAZ-AVI treatment of CRKP/ CRPA infection in LT recipients was associated with high rates of clinical success, survival, and safety, but recurrent CRKP/CRPA infections in the respiratory tract did occur. 2020 Annals of Translational Medicine. All rights reserved.
BACKGROUND: Infections produced by extensively drug-resistant (XDR) gram-negative bacilli (GNB) in solid organ transplant (SOT) are an important cause of morbidity and mortality. Ceftazidime/avibactam (CAZ-AVI) is a novel β-lactam/β-lactamase combination antibiotic with anti-GNB activity, but experience in real clinical practice with CAZ-AVI in lung transplant (LT) recipients is limited. METHODS: We conducted a retrospective study of patients with XDR-GNB infection who received at least 3 days of CAZ-AVI in the Department of Lung Transplantation Between December 2017 and December 2018 at China-Japan friendship hospital (CJFH). The general information, clinical manifestations, laboratory examinations, treatment course, and outcomes were summarized. RESULTS: A total of 10 patients who underwent LT at our center were included. They were all males with a mean age 51 years. Infections after LT included pneumonia and/or tracheobronchitis [n=9; 90% (9/10)], cholecystitis and blood stream infection (BSI) (n=1, patient 8). In these 10 LT recipients, the incidence of various airway complications was 70% (7/10). Carbapenem-resistant Klebsialla pneumoniae (CRKP) was the predominant pathogen, being detected in 9 patients. Multilocus sequence typing (MLST) analysis showed that all 9 CRKP isolates belonged to ST11. Six patients (6/10, 60%) started CAZ-AVI as salvage therapy after a first-line treatment with other antimicrobials. CAZ-AVI was administered as monotherapy or in combination regimens in 20% (2/10) and 80% (8/10) of patients respectively. There were no difference in temperature before and after CAZ-AVI treatment (P>0.05). White blood cell (WBC) at 7 days, and procalcitonin (PCT) at 7 days and 14 days significantly dropped (P<0.05). After 7-14 days of CAZ-AVI treatment, the PaO2/FiO2ratio (P/F ratio) significantly improved (P<0.05). Nine patients (9/10, 90%) obtained negative microbiologic culture of CRKP/CRPA, with a median time to was 6.7 days (range, 1-15 days). However, 5 patients (5/10, 50%) had relapse of CRKP/CRPA infections in the respiratory tract regardless of whether negative microbiologic culture was obtained or not. The 30-day survival rate was 100%, and the 90-day survival rate was 90% (1/10). No severe adverse events related to CAZ-AVI occurred. CONCLUSIONS: CAZ-AVI treatment of CRKP/ CRPA infection in LT recipients was associated with high rates of clinical success, survival, and safety, but recurrent CRKP/CRPA infections in the respiratory tract did occur. 2020 Annals of Translational Medicine. All rights reserved.
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