A randomized comparison of empiric or pre-emptive antibiotic therapy after hematopoietic stem cell transplantation

We performed a randomized comparison of pre-emptive and empiric antibiotic therapy for adult patients undergoing allogeneic or autologous stem cell transplantation. One hundred and fifty-three patients were randomized to receive cefepime either pre-emptively on the day that neutropenia (ANC<1.0 x 10(9) cells/l) developed irrespective of the presence of fever, or at onset of fever and neutropenia (empiric). Although there was no difference between the two arms in the proportion of patients developing fever or in the median number of days of fever, the time to onset of fever was a mean of 1 day longer in each patient on the pre-emptive arm (log rank P<0.001). The number of patients with bloodstream infections was significantly reduced in those receiving pre-emptive therapy (16/75) compared to the empiric arm (31/76) (P<0.01) but this did not translate into an appreciable clinical benefit as measured by days of hospitalization, time to engraftment, use of additional antimicrobial agents or mortality at 30 days. This study does not support the use of pre-emptive intravenous antibiotic therapy in adult stem cell transplant recipients.