Abstract
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≥38.5°C on one occasion or ≥38.0°C twice within 24 hours and granulocytopenia ≤500/μL 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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Hughes WT, Armstrong D, Bodey GP, et al. 2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer.Clin Infect Dis. 2002;34:730–751.
Link H, Böhme A, Cornely OA, et al. Antimicrobial therapy of unexplained fever in neutropenic patients.Ann Hematol. 2003;82(suppl 2):105–117.
Kern WV. Risk assessment and risk-based therapeutic strategies in febrile neutropenia.Curr Opin Infect Dis. 2001;14:415–422.
Cornely OA, Bethe U, Salzberger B, et al. Randomized controlled monocentric comparison of once daily ceftriaxone with tobramycin and cefotaxime three times daily with tobramycin in neutropenic fever.Ann Hematol. 2001;80:103–108.
Cornely OA, Bethe U, Seifert H, et al. A randomized monocentric trial in febrile neutropenic patients: ceftriaxone and gentamicin vs cefepime and gentamicin.Ann Hematol. 2002;81:37–43.
Karthaus M, Wolf HH, Kampfe D, et al. Ceftriaxone monotherapy in the treatment of low-risk febrile neutropenia.Chemotherapy. 1998;44:343–354.
Freifeld A, Marchigiani D, Walsh T, et al. A double-blind comparison of empirical oral and intravenous antibiotic therapy for low- risk febrile patients with neutropenia during cancer chemotherapy.N Engl J Med. 1999;341:305–311.
Hidalgo M, Hornedo J, Lumbreras C, et al. Outpatient therapy with oral ofloxacin for patients with low risk neutropenia and fever: a prospective, randomized clinical trial.Cancer. 1999;85:213–219.
Kern WV, Cometta A, De Bock R, Langenaeken J, Paesmans M, Gaya H. Oral versus intravenous empirical antimicrobial therapy for fever in patients with granulocytopenia who are receiving cancer chemotherapy. International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer.N Engl J Med. 1999;341:312–318.
Pizzo PA, Armstrong D, Bodey G, et al. From the Immunocompromised Host Society: the design, analysis, and reporting of clinical trials on the empirical antibiotic management of the neutropenic patient: report of a consensus panel.J Infect Dis. 1990;161:397–401.
Koh A, Pizzo PA. Empirical oral antibiotic therapy for low risk febrile cancer patients with neutropenia.Cancer Invest. 2002;20:420–433.
Hooper DC. New uses for new and old quinolones and the challenge of resistance.Clin Infect Dis. 2000;30:243–254.
Lipsky BA, Baker CA. Fluoroquinolone toxicity profiles: a review focusing on newer agents.Clin Infect Dis. 1999;28:352–364.
Del Favero A, Menichetti F, Martino P, et al. A multicenter, doubleblind, placebo-controlled trial comparing piperacillin-tazobactam with and without amikacin as empiric therapy for febrile neutropenia.Clin Infect Dis. 2001;33:1295–1301.
Tuohy M, Washington JA. Antimicrobial susceptibility of viridans group streptococci.Diagn Microbiol Infect Dis. 1997;29:277–280.
Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group.Am J Clin Oncol. 1982;5:649–655.
Deutsches Institut für Normung. DIN 58940-3. Berlin, Germany: BeuthVerlag;1996.
Malik IA, Khan WA, Aziz Z, Karim M. Self-administered antibiotic therapy for chemotherapy-induced, low-risk febrile neutropenia in patients with nonhematologic neoplasms.Clin Infect Dis. 1994;19:522–527.
Klastersky J, Paesmans M, Rubenstein EB, et al. The Multinational Association for Supportive Care in Cancer risk index: a multinational scoring system for identifying low-risk febrile neutropenic cancer patients.J Clin Oncol. 2000;18:3038–3051.
Blijlevens NM, Donnelly JP, de Pauw BE. Empirical therapy of febrile neutropenic patients with mucositis: challenge of risk-based therapy.Clin Microbiol Infect. 2001;7(suppl 4):47–52.
Bauernfeind A. Comparison of the antibacterial activities of the quinolones Bay 12-8039, gatifloxacin (AM 1155), trovafloxacin, clinafloxacin, levofloxacin and ciprofloxacin.J Antimicrob Chemother. 1997;40:639–651.
Gordon KA, Beach ML, Biedenbach DJ, Jones RN, Rhomberg PR, Mutnick AH. Antimicrobial susceptibility patterns of betahemolytic and viridans group streptococci: report from the SENTRY Antimicrobial Surveillance Program (1997-2000).Diagn Microbiol Infect Dis. 2002;43:157–162.
Di Bonaventura G, D'Antonio D, Catamo G, D'Ercole S, Piccolomini R. Comparative in vitro activity of levofloxacin and ciprofloxacin against bacterial isolates from neutropenic patients.Chemotherapy. 2002;48:134–137.
Graham DR, Talan DA, Nichols RL, et al. Once-daily, high-dose levofloxacin versus ticarcillin-clavulanate alone or followed by amoxicillin-clavulanate for complicated skin and skin-structure infections: a randomized, open-label trial.Clin Infect Dis. 2002;35:381–389.
Figuera AA, Rivero N, Pajuelo F, et al. Initial empiric therapy of febrile neutropenia with antibiotic monotherapy: piperacillin/ tazobactam versus imipenem/cilastatin.Med Clin (Barc). 2001;116:610–611.
Malik IA, Abbas Z, Karim M. Randomised comparison of oral ofloxacin alone with combination of parenteral antibiotics in neutropenic febrile patients [published erratum appears inLancet. 1992;340:128].Lancet. 1992;339:1092–1096.
Malik IA, Khan WA, Karim M, Aziz Z, Khan MA. Feasibility of outpatient management of fever in cancer patients with low-risk neutropenia: results of a prospective randomized trial.Am J Med. 1995;98:224–231.
Paganini H, Gomez S, Ruvinsky S, et al. Outpatient, sequential, parenteral-oral antibiotic therapy for lower risk febrile neutropenia in children with malignant disease.Cancer. 2003;97:1775–1780.
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Cornely, O.A., Wicke, T., Seifert, H. et al. Once-Daily Oral Levofloxacin Monotherapy versus Piperacillin/Tazobactam Three Times a Day: A Randomized Controlled Multicenter Trial in Patients with Febrile Neutropenia. Int J Hematol 79, 74–78 (2004). https://doi.org/10.1007/BF02983537
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF02983537