Eleutherakis-Papaiakovou, E., Kostis, E., Migkou, M., Christoulas, D., Terpos, E., Gavriatopoulou, M., . . . Papadimitriou, C.A. (2010). Prophylactic antibiotics for the prevention of neutropenic fever in patients undergoing autologous stem-cell transplantation: results of a single institution, randomized phase 2 trial. American Journal of Hematology, 85, 863–867.

To demonstrate the use of prophylactic antibiotics to prevent fever in autologous stem cell transplantation recipients.

Researchers used antibiotics prophylactically (ciprofloxacin and vancomycin) to prevent ElE infections during the neutropenic stage of transplantation.  Patients were randomly assigned to receive 500 mg of ciprofloxacin orally twice a day and 1000 mg of vancomycin intravenously (IV) daily or no prophylactic antibiotic use.  Antibiotics were given on day 0 and continued until neutropenia resolution or the occurrence of a febrile event.  Antibiotics were given to any patient who experienced a febrile event.  All patients received lenogastrim three days after cyclophosphamide and until harvesting and also from posttransplant day 1 until the white blood cell (WBC) count was >10x10³ µg/dL.

• One hundred fifty-seven patients were included.
• Patients were older than 18 years.
• The numbers and percentages of males and females were not specified.
• Key disease characteristics were multiple myeloma, hematological malignancies, and solid tumors.
• Most patients received high-dose mephalan.
   

• Single site  
• Inpatient  
• Greece
   

• Patients were undergoing the active treatment phase of care.
• The study has clinical applicability for late effects and survivorship. 
   

This was a randomized, controlled study.

• Incidence of febrile episodes with an axillary temperature of 38ºC over 12 hours on two or more occasions or a temperature of 38.5°C with neutropenia
• European Organization for Research and Treatment of Cancer(EORTC)/Invasive Fungal Infections Cooperative Group definitions

Between cell reinfusion and bone marrow reconstitution, 71.3% of patients receiving prophylactic antibiotics developed neutropenic fever, compared with 91.2% of those receiving only supportive care (p < 0.001). Patients receiving the combination of ciprofloxacin and IV vancomycin had a significantly lower rate of bacteremias (5.6%) than those with no prophylaxis (35%) (p = 0.005).  The cumulative hazard ratio (HR) of fever for randomized patients demonstrated a statistical benefit in favor of prophylactic antibiotics (HR = 2.43; 95% confidence interval [1.60, 3.49]; p < 0.001). There were no infection-related deaths in the sample.  There were no differences between groups in duration of hospitalization. Median duration of treatment was six days.  Patients were followed for one month in the study.  Five patients developed severe skin rash attributed to antibiotics and discontinued treatment.  There were no clear differences between groups in adverse effects, and no other effects were severe enough to warrant discontinuation of antibiotics.

This article showed that the prophylactic antibiotics oral ciprofloxacin and IV vancomycin help to prevent neutropenic fever after transplant but that their usage is not helpful in either decreasing the overall length of stay in the hospital or decreasing the risk of complication-related deaths.

• No blinding was performed, which had a related risk of bias.
• Limited sample demographic and disease-related information was provided, so it is unclear how much the findings can be generalized. 
• Cost-effectiveness of antibiotic prophylaxis was unclear.

Findings support the use of prophylactic antibiotic therapy for reducing the prevalence of febrile neutropenia in this group of patients.