Prophylactic Broad Spectrum Antibiotics at the Onset of Neutropenia in HSCT Do Not Change the Number of Febrile Days or Duration of Hospitalization

There is increased interest in the use of broad spectrum antibiotics at the onset of neutropenia during hematopoietic stem cell transplant to prevent serious bacterial infections.  In 2009, our group instituted the use of cefepime starting when the ANC decreased to <  500 as one quality improvement measure to help reduce the number of serious bacterial infections.  This is a preliminary analysis on the efficacy of this intervention.

All patients undergoing a hematopoietic stem cell transplant from January 2008 to December 2011 were included in this retrospective analysis.   Assignment of patients to each group was based on intent to treat with 36 patients to have broad spectrum antibiotic initiated at the onset of neutropenia or with fevers (prophylactic antibiotic group) and 37 patients had antibiotics initiated only for febrile episodes (conventional antibiotic group).  There was no difference between the two groups in days post transplant for discharge and number of days of fever. There was a trend towards a decreased number of febrile days in allogeneic patients only although this was not statistically significant. 8 patients in the prophylactic antibiotic group and 11 patients conventional antibiotic group had positive blood culture results at some point during their immediate post-transplant courses, the majority of which were gram positive infections. There were 3 deaths prior to hospital discharge in the conventional antibiotic group, one of sepsis secondary to vancomycin resistant enterococcus and the remaining 2 died of respiratory failure due to pulmonary hemorrhage.   There was one death of pulmonary hemorrhage associated with refractory GVHD in the prophylactic antibiotic group.

Despite the fact that there was a decrease in the number of patients with bacterial infections, preliminary data from this patient population does not yet indicate an overwhelming improvement in patient outcomes following the use of prophylactic cefepime at the onset of neutropenia, perhaps due to the relative infrequency of gram negative bacterial infections.    Additional information in a larger number of patients, including patterns of antibiotic resistance and duration of antibiotics, may help to define whether prophylactic antibiotics initiated at the onset of neutropenia change outcomes. 

	Prophylactic Antibiotic	Conventional Antibiotics	P value
Total Number of Patients     Autologous     Allogeneic Cord Blood     Allogeneic Bone Marrow	36 10 10 16	37 14 9 14
Positive Blood Cultures   Gram Positive Total (#Patients)   Gram Negative Total (#Patients)	28 24  (7) 5 (1)	29 27 (10) 2 (2)
Mean Discharge Day    Autologous    Allogeneic Cord Blood    Allogeneic Bone Marrow	43.29 23.40 62.50 43.20	34.74 18.73 52.80 35	0.13 0.99 0.27 0.80
Days of Fever     Autologous     Allogeneic	8.71 7.89 9.72	11.31 6.46 14.32	0.28 0.70 0.14
PICU Admission  Need for Pressors	7 3	3 3
Clostridium difficile Diarrhea	6	4