Once-daily oral levofloxacin monotherapy versus piperacillin/tazobactam three times a day: a randomized controlled multicenter trial in patients with febrile neutropenia.
A prospective, randomized, controlled multicenter trial was performed to evaluate the efficacy and safety of once-daily oral monotherapy with 500 mg levofloxacin in comparison with 4.5 g piperacillin/tazobactam 3 times a day in patients with low-risk febrile neutropenia. Low risk was defined by oral temperature > or = 38.5 degrees C on one occasion or > or = 38.0 degrees C twice within 24 hours and granulocytopenia < or = 500/microL for less than 10 days. The primary end point was defined as defervescence after 72 hours followed by at least 7 afebrile days. Secondary end points were overall response, time to defervescence, survival on day 30, and toxicity. Thirty-four episodes were included. Fever of unknown origin accounted for 26 (76.5%) of the episodes, microbiologically defined infection for 5 (14.7%) of the episodes, and clinically defined infection for 3 (8.8%) of the episodes. On an intent-to-treat basis, all episodes were evaluable for the primary end point. Levofloxacin and piperacillin/tazobactam were successful after 72 hours of treatment in 76.5% and 88.3% of the episodes. Overall response was achieved in 94.1% and 100% of the episodes, respectively. One inpatient in the oral treatment group died of septic shock without identification of a causative pathogen. A larger phase III trial is warranted to further evaluate the lack of inferiority of the oral monotherapy regimen versus standard intravenous therapy.
Department of Internal Medicine I, Klinikum der Universität zu Köln, Köln, Germany. oliver.cornely@uni-koeln.de
Oliver A
OA
Cornely
Thomas
T
Wicke
Harald
H
Seifert
Ullrich
U
Bethe
Martin
M
Schwonzen
Dietmar
D
Reichert
Andrew J
AJ
Ullmann
Meinolf
M
Karthaus
Kai
K
Breuer
Bernd
B
Salzberger
Volker
V
Diehl
Gerd
G
Fätkenheuer
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects; D001424:Bacterial Infections / Q000188:drug therapy* / Q000209:etiology; D004198:Disease Susceptibility; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D005334:Fever / Q000209:etiology* / Q000628:therapy; D005335:Fever of Unknown Origin / Q000209:etiology / Q000628:therapy; D006801:Humans; D016867:Immunocompromised Host; D064704:Levofloxacin; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy; D009503:Neutropenia / Q000139:chemically induced / Q000150:complications*; D015242:Ofloxacin / Q000008:administration & dosage* / Q000627:therapeutic use; D010397:Penicillanic Acid / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010878:Piperacillin / Q000008:administration & dosage* / Q000627:therapeutic use; D011446:Prospective Studies; D012449:Safety; D000078142:Tazobactam; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D064704:Levofloxacin; D010397:Penicillanic Acid; D015242:Ofloxacin; D000078142:Tazobactam; D010878:Piperacillin