Background: Empiric intravenous antimicrobial therapy is the current standard of management for patients with febrile neutropenia. The use of oral antibiotic regimens for low-risk febrile neutropenia is a potentially cost-effective alternative if proven to be equally effective as the standard intravenous regimens Objectives: To determine if oral antibiotic regimens are equally effective as the standard intravenous therapy in the empiric management of low-risk chemotherapy-induced febrile neutropenia. Search strategy: The Cochrane Controlled Trials Register and Medline 1966-99 were searched. Citations of clinical trials, clinical practice guidelines and reviews were also examined. Selection criteria: Randomized controlled trials comparing an oral antibiotic regimen with the standard intravenous antibiotic therapy in low-risk chemotherapy-induced febrile neutropenia with clinical failure rate as the main outcome measure were included in the review.

Data collection & analysis: Inclusion criteria, trial quality assessment and data abstraction were done in duplicate. A priori subgroup analysis according to degree and duration of neutropenia and type of fever episode was planned. To assess the feasibility of out-patient management, pre-specified subgroup analysis of RCTs conducted on an out-patient basis was done.

Main results: Seven out of 19 studies (n=978) were included. Overall analysis showed no significant difference in clinical failure rates between oral antibiotic regimens and the standard intravenous antibiotic therapy [RR= 0.99, 95% CI 0.79, 1.24]. Trials were homogenous [p=0.74]. Sensitivity analysis of five good quality studies yielded similar clinical failure rates between oral and intravenous regimens [RR=1.05; 95% CI 0.79, 1.39]. A priori subgroup analysis according to type of fever episode showed no significant differences in clinical failure rates for fever of unknown origin [RR = 1.48; 95% CI 0.92, 2.37] and fever due to documented infections [RR = 0.90; 95% CI 0.72, 1.11]. Subgroup analysis of three RCTs done in an out-patient setting, likewise revealed equal effectiveness of the two modes of therapy [RR=1.43; 95% CI 0.74, 2.75]. There was no significant difference in mortality between the two regimens in six trials [RR=0.78; 95% CI 0.40, 1.52].

Reviewers' conclusions: Empiric oral antibiotic regimens are equally effective as the standard intravenous antibiotic therapy in the management of patients with low-risk chemotherapy-induced febrile neutropenia in terms of clinical failure rates. However evidence is still inconclusive with regards to mortality and out-patient effectiveness. Close monitoring for signs of treatment failure is emphasized and resistance patterns of prevalent organisms should be considered in the choice of an oral antibiotic regimen. A consensus on the definition of low-risk and a statistical model that would best stratify the risk of febrile neutropenia still remains to be developed.