Combination of Four Drugs for Bloodstream Infection Caused By Carbapenem-Resistant Enterobacteriaceae in Severe Agranulocytosis Patients after Hematopoietic Stem Cell Transplantation

Bloodstream infection (BSI) caused by multidrug‐resistant bacteria (MDRB) or extensively drug-resistant bacteria (XDRB) in immunocompromised and neutropenic patients after hematopoietic stem cell transplantation (HSCT) is a global threaten. However, effective treatment regimen is still controversial and inadequate due to the rapid deterioration, the horrific evolution of bacteria and high mortality that the mortality related to BSI caused by carbapenem-resistant Enterobacteriaceae (CRE) is 51% in adult neutropenic patients[1]. Here, we presented four cases that CRE was detected in blood of severe agranulocytosis patients undergoing HSCT.

All patients ranged from 2 to 50 years old were diagnosed as hematologic disease. CREs were detected within 1 month from the date of engraftment. In case 1, a 6-year-old boy with high-risk B-cell acute lymphocyte leukaemia received halpo-HSCT after chimeric antigen receptor T-cell therapy and the 20th chemotherapy, ultimately, he died from acute graft versus host disease and BSI that tienam and tigecycline showed little effect though the MIC value of tigecycline was less than 0.5ug/ml. The second patient is a 25-year-old female who was diagnosed as hemophagocytic syndrome with recurrent fever and a salvage haploidentical transplantation combining with a unit of umbilical cord blood stem cells was performed. Finally, she died from BSI caused by CRE although a combination therapy using polymyxin B, tigecycline and doubled-dose Tienam was given, which subsequently was changed to another therapeutic regimen using a higher dose tigecycline and fosfomycin and polymyxin B in light of the resistance of tienam. Patients in case 3 and case 4 received a combination therapy with tigecycline, polymyxin B, fosfomycin, and Tienam intravenously. For the 29-month-old boy diagnosed as acute monocytic leukemia with high expression of WT1 and abnormal karyotype and treated with cord blood stem cell transplantation in case 3, the tigecycline was given with a dose of 2.4mg/kg at the first time, followed by doses of 1.2mg per dose every 12 hours, and a dose of 2.0mg/kg at the first time, followed by doses of 1.25mg/kg per dose every 12 hours of polymyxin B, 0.15g/kg per every 12 hours of fosfomycin, as well as 30mg/kg per dose every 6 hours of imipenem were administrated. For the 50-year-old woman with multiple myeloma receiving an autologous hematopoietic stem cell transplantation (auto-HSCT) in case 4, the dose of tigecycline was 100mg at the first time, followed by doses of 1.2mg per dose every 12 hours. Fosfomycin with the dose of 8.0g was used every 12 hours, and the dose of imipenem was1.0g per dose every 6 hours, also, polymyxin B was administrated with a dose of 2.0mg/kg at the first time, followed by doses of 1.25mg/kg per dose every 12 hours. Consequently, patients in case 3 and case 4 were survival.

Therefore, a strong combination therapy, as well as the emergency of new drugs might be considered in immunocompromised and neutropenic ill patients with BSI caused by MDRB or XDRB.