Outpatient single dose ceftriaxone and amikacin vs. imipenem/cilastatin monotherapy in the empiric treatment of pediatric patients with high risk fever aneutropenia. A randomized, prospective clinical trial

Abstract

8520 Background: The empiric usage of once daily ceftriaxone plus amikacin (C+A) for febrile neutropenia allows outpatient treatment for selected patients. We hypothesized that patients initially at high risk for sepsis can be candidates for outpatient therapy if at 48 hours satisfy strict “Selection Criteria”. Being a well established monotherapy agent, Imipenem was used as control. We compared the efficacy, treatment modification, toxicity, duration of hospitalization and cost between both groups. In addition we assessed risks of early discharge and rate of readmission. Design/Methods: A prospective, randomized crossover clinical trial involving 120 pediatric cancer patients with high-risk fever and neutropenia. Febrile patients at 72 hours were crossed-over together with adding vancomycin. Patients on C+A were assessed using Early Discharge Criteria, and if eligible continued treatment as outpatients. Intention-to-treat analysis was used. Results: We found a statistically significant difference between duration of hospitalization between the C+A [median 4.5 days] and control [9.5 days] (p<0.001), per episode antibiotic cost (p< 0.001) & total episode cost [study median $873 vs. control $1655, p<0.001]. Similar results were obtained using average admission costs in a corresponding North American institution. There was no statistically significant difference in the response to treatment at 72 hours, after crossover or at the end of episode. Cultures grew more Gram-positive bacteria (59%). Overall success rate was 95.8%. Conclusions: Pediatric febrile-neutropenic patients initially at high-risk for sepsis can be risk-assessed at some point in treatment for outpatient therapy. The convenience, less adverse effects and cost benefit of the once daily regimen of ceftriaxone plus amikacin will be particularly useful to reduce the overall treatment costs, and duration of hospitalization. Further studies are needed to clarify the role of risk categorization and outpatient therapy in the context of high-risk febrile neutropenia. No significant financial relationships to disclose.