Clinical guidelines for the management of neutropenic patients with unexplained fever in Japan: validation by the Japan Febrile Neutropenia Study Group

Abstract

The Japan Febrile Neutropenia Study Group (JFNSG) Trial was a multicenter, open, randomized study designed to validate the first Japanese guidelines for the management of neutropenic cancer patients with unexplained fever issued in 1998. The trial compared cefepime monotherapy with cefepime plus amikacin combination therapy in febrile neutropenic patients with hematological disorders. The JFNSG found that monotherapy with cefepime was, in general, as effective as combination therapy. In terms of subset analyses, defervescence appeared to occur more frequently in leukemic patients and in those with profound neutropenia treated with the dual combination. The conclusion of the trial was that the 1998 guidelines were applicable to the Japanese febrile neutropenic patient population. The JFNSG met again in 2003 to revise these guidelines. An important addition to the guidelines was a distinction between low- and high-risk patients. Low-risk febrile neutropenic patients can receive oral ciprofloxacin or levofloxacin, with or without amoxicillin/clavulanic acid, on an outpatient basis, or intravenous (i.v.) monotherapy with cefepime, ceftazidime or a carbapenem. High-risk patients can receive i.v. cefepime, ceftazidime or a carbapenem, or an i.v. dual combination with cefepime, ceftazidime or a carbapenem plus an aminoglycoside. Those patients with a documented infection with methicillin-resistant Staphylococcus aureus should also receive a glycopeptide. It remains to be determined whether existing assessment scoring systems apply to Japanese patients; whether a broad-spectrum cephalosporin plus an aminoglycoside combination is required as the initial management of patients with acute leukemia and/or profound neutropenia; which antibacterial drugs should be used when first- and second-line agents fail; what are the appropriate oral agents and dosing regimens for low-risk patients; whether serology or the polymerase chain reaction should be the preferred marker for initiating preemptive antifungal therapy; and whether the azoles or the candins should be the preferred antifungal agents.