Background:The use of prophylactic antibiotics in the pre-engraftment period to minimize the risk of bacteremia is debatable given concerns of Clostridioides difficile (C. diff), antibiotics resistance, and disruption of gut microbiota. Methods:We retrospectively reviewed the rate and characteristics of bacteremia and C. diff infections within the first 100 days post-HSCT in all pediatric patients who received routine antibacterial prophylaxis during HSCT from 2015 to 2018. C. diff infection was defined by the presence of three or more unformed stools in 24 h and positive stool test for C. diff or its toxins.Results: One hundred and thirty-five (100 allogeneic and 35 autologous) transplants in 123 patients were eligible for analysis. Median age at transplant was 7.1 (range 0.2-13.7), 67 (55%) were women, and diagnosis was malignant condition in 68 patients.Median time to neutrophil engraftment was 18 days (13-23). Cefepime or piperacillintazobactam prophylaxis was used in 105 (78%) and 28 (21%) of patients, respectively.Only five (3%) patients had bacteremia during the pre-engraftment period, and 13 (11%) patients developed bacteremia postengraftment. Septic shock was present in only one patient pre-engraftment and was due to gram-negative bacteria. All patients who developed bacteremia received MAC. Thirteen patients (10%) of patients fulfilled C. diff infection definition. There was no mortality related to bacterial infections among our patients. Conclusions:The use of antibiotic prophylaxis was associated with low rate of bacteremia in the pre-engraftment period and a 10% risk of C. diff infections. More studies are needed to better evaluate the efficacy of antibiotic prophylaxis in HSCT patients.