FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 341:312-318 July 29, 1999 Number 5 Next

	Full Text PDF Editorial by Finberg, R. W. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background Intravenously administered antimicrobial agents have been the standard choice for the empirical management of fever in patients with cancer and granulocytopenia. If orally administered empirical therapy is as effective as intravenous therapy, it would offer advantages such as improved quality of life and lower cost.

Methods In a prospective, open-label, multicenter trial, we randomly assigned febrile patients with cancer who had granulocytopenia that was expected to resolve within 10 days to receive empirical therapy with either oral ciprofloxacin (750 mg twice daily) plus amoxicillin–clavulanate (625 mg three times daily) or standard daily doses of intravenous ceftriaxone plus amikacin. All patients were hospitalized until their fever resolved. The primary objective of the study was to determine whether there was equivalence between the regimens, defined as an absolute difference in the rates of success of 10 percent or less.

Results Equivalence was demonstrated at the second interim analysis, and the trial was terminated after the enrollment of 353 patients. In the analysis of the 312 patients who were treated according to the protocol and who could be evaluated, treatment was successful in 86 percent of the patients in the oral-therapy group (95 percent confidence interval, 80 to 91 percent) and 84 percent of those in the intravenous-therapy group (95 percent confidence interval, 78 to 90 percent; P=0.02). The results were similar in the intention-to-treat analysis (80 percent and 77 percent, respectively; P=0.03), as were the duration of fever, the time to a change in the regimen, the reasons for such a change, the duration of therapy, and survival. The types of adverse events differed slightly between the groups but were similar in frequency.

Conclusions In low-risk patients with cancer who have fever and granulocytopenia, oral therapy with ciprofloxacin plus amoxicillin–clavulanate is as effective as intravenous therapy.

Source Information

From the Sektion Infektiologie und Klinische Immunologie, Medizinische Universitätsklinik und Poliklinik, Ulm, Germany (W.V.K.); the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland (A.C.); the Allgemeen Ziekenhuis Middelheim, Antwerp, Belgium (R.B.); the Institut Jules Bordet, Brussels, Belgium (J.L., M.P.); and the Royal Brompton Hospital, London (H.G.). Other authors were Giorgio Zanetti, M.D., Thierry Calandra, M.D., and Michel P. Glauser, M.D. (Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland), Françoise Crokaert, M.D., and Jean Klastersky, M.D. (Institut Jules Bordet, Brussels, Belgium), Athanasios Skoutelis, M.D., and Harry Bassaris, M.D. (Patras University Hospital, Patras, Greece), Stephen H. Zinner, M.D. (Brown University, Providence, R.I.), Claudio Viscoli, M.D. (National Institute for Cancer Research, Genoa, Italy), Dan Engelhard, M.D. (Hadassah University Hospital, Jerusalem, Israel), and Andrew Padmos, M.D. (Kingston Regional Cancer Center, Kingston, Ont., Canada).

Address reprint requests to Dr. Kern at the Medizinische Universitätsklinik und Poliklinik, Sektion Infektiologie und Klinische Immunologie, D-89070 Ulm, Germany, or at winfried.kern{at}medizin.uni-ulm.de.

Full Text of this Article

Related Letters:

Oral Antibiotics for Febrile Patients with Neutropenia Due to Cancer Chemotherapy
Blot E., Héron F., Lishner M., Rubenstein E. B., Rolston K. V.I., Kim Y. J., Sezer O., Freifeld A. G., Steinberg S. M., Pizzo P. A., Kern W. V., Cometta A., Finberg R. W., Talcott J. A.
Extract | Full Text  
N Engl J Med 2000; 342:55-58, Jan 6, 2000. Correspondence

This article has been cited by other articles:

• Moores, K. G. (2007). Safe and effective outpatient treatment of adults with chemotherapy-induced neutropenic fever. Am J Health Syst Pharm 64: 717-722 [Abstract] [Full Text]  
• Klastersky, J., Paesmans, M., Georgala, A., Muanza, F., Plehiers, B., Dubreucq, L., Lalami, Y., Aoun, M., Barette, M. (2006). Outpatient Oral Antibiotics for Febrile Neutropenic Cancer Patients Using a Score Predictive for Complications. JCO 24: 4129-4134 [Abstract] [Full Text]  
• Nijhuis, C. O., Kamps, W. A., Daenen, S. M.G., Gietema, J. A., van der Graaf, W. T.A., Groen, H. J.M., Vellenga, E., ten Vergert, E. M., Vermeulen, K. M., de Vries-Hospers, H. G., de Bont, E. S.J.M. (2005). Feasibility of Withholding Antibiotics in Selected Febrile Neutropenic Cancer Patients. JCO 23: 7437-7444 [Abstract] [Full Text]  
• Bucaneve, G., Micozzi, A., Menichetti, F., Martino, P., Dionisi, M. S., Martinelli, G., Allione, B., D'Antonio, D., Buelli, M., Nosari, A. M., Cilloni, D., Zuffa, E., Cantaffa, R., Specchia, G., Amadori, S., Fabbiano, F., Deliliers, G. L., Lauria, F., Foa, R., Del Favero, A., the Gruppo Italiano Malattie Ematologiche dell'Adu, (2005). Levofloxacin to Prevent Bacterial Infection in Patients with Cancer and Neutropenia. NEJM 353: 977-987 [Abstract] [Full Text]  
• Cullen, M., Steven, N., Billingham, L., Gaunt, C., Hastings, M., Simmonds, P., Stuart, N., Rea, D., Bower, M., Fernando, I., Huddart, R., Gollins, S., Stanley, A., the Simple Investigation in Neutropenic Individual, (2005). Antibacterial Prophylaxis after Chemotherapy for Solid Tumors and Lymphomas. NEJM 353: 988-998 [Abstract] [Full Text]  
• Baden, L. R. (2005). Prophylactic Antimicrobial Agents and the Importance of Fitness. NEJM 353: 1052-1054 [Full Text]  
• Straka, C., Oduncu, F., Hinke, A., Einsele, H., Drexler, E., Schnabel, B., Arseniev, L., Walther, J., Konig, A., Emmerich, B. (2004). Responsiveness to G-CSF before leukopenia predicts defense to infection in high-dose chemotherapy recipients. Blood 104: 1989-1994 [Abstract] [Full Text]  
• Santolaya, M. E., Alvarez, A. M., Aviles, C. L., Becker, A., Cofre, J., Cumsille, M. A., O'Ryan, M. L., Paya, E., Salgado, C., Silva, P., Tordecilla, J., Varas, M., Villarroel, M., Viviani, T., Zubieta, M. (2004). Early Hospital Discharge Followed by Outpatient Management Versus Continued Hospitalization of Children With Cancer, Fever, and Neutropenia at Low Risk for Invasive Bacterial Infection. JCO 22: 3784-3789 [Abstract] [Full Text]  
• Vidal, L., Paul, M., Ben dor, I., Soares-Weiser, K., Leibovici, L. (2004). Oral versus intravenous antibiotic treatment for febrile neutropenia in cancer patients: a systematic review and meta-analysis of randomized trials. J Antimicrob Chemother 54: 29-37 [Abstract] [Full Text]  
• Niho, S., Ohe, Y., Goto, K., Ohmatsu, H., Matsumoto, T., Kubota, K., Kakinuma, R., Nishiwaki, Y. (2004). Randomized Trial of Oral Versus Intravenous Antibiotics in Low-risk Febrile Neutropenic Patients with Lung Cancer. Jpn J Clin Oncol 34: 69-73 [Abstract] [Full Text]  
• Waitt, C, Waitt, P, Pirmohamed, M (2004). Intravenous therapy. Postgrad. Med. J. 80: 1-6 [Abstract] [Full Text]  
• Peacock, J. E. Jr., Herrington, D. A., Wade, J. C., Lazarus, H. M., Reed, M. D., Sinclair, J. W., Haverstock, D. C., Kowalsky, S. F., Hurd, D. D., Cushing, D. A., Harman, C. P., Donowitz, G. R. (2002). Ciprofloxacin plus Piperacillin Compared with Tobramycin plus Piperacillin as Empirical Therapy in Febrile Neutropenic Patients: A Randomized, Double-Blind Trial. ANN INTERN MED 137: 77-87 [Abstract] [Full Text]  
• Santolaya, M. E., Alvarez, A. M., Becker, A., Cofre, J., Enriquez, N., O'Ryan, M., Paya, E., Pilorget, J., Salgado, C., Tordecilla, J., Varas, M., Villarroel, M., Viviani, T., Zubieta, M. (2001). Prospective, Multicenter Evaluation of Risk Factors Associated With Invasive Bacterial Infection in Children With Cancer, Neutropenia, and Fever. JCO 19: 3415-3421 [Abstract] [Full Text]  
• Garcia-Carbonero, R., Mayordomo, J. I., Tornamira, M. V., Lopez-Brea, M., Rueda, A., Guillem, V., Arcediano, A., Yubero, A., Ribera, F., Gomez, C., Tres, A., Perez-Gracia, J. L., Lumbreras, C., Hornedo, J., Cortes-Funes, H., Paz-Ares, L. (2001). Granulocyte Colony-Stimulating Factor in the Treatment of High-Risk Febrile Neutropenia: a Multicenter Randomized Trial. JNCI J Natl Cancer Inst 93: 31-38 [Abstract] [Full Text]  
• Donowitz, G. R., Maki, D. G., Crnich, C. J., Pappas, P. G., Rolston, K. V.I. (2001). Infections in the Neutropenic Patient-- New Views of an Old Problem. ASH Education Book 2001: 113-139 [Abstract] [Full Text]  
• Giamarellou, H., Bassaris, H. P., Petrikkos, G., Busch, W., Voulgarelis, M., Antoniadou, A., Grouzi, E., Zoumbos, N. (2000). Monotherapy with Intravenous Followed by Oral High-Dose Ciprofloxacin versus Combination Therapy with Ceftazidime plus Amikacin as Initial Empiric Therapy for Granulocytopenic Patients with Fever. Antimicrob. Agents Chemother. 44: 3264-3271 [Abstract] [Full Text]  
• Elting, L. S., Rubenstein, E. B., Rolston, K., Cantor, S. B., Martin, C. G., Kurtin, D., Rodriguez, S., Lam, T., Kanesan, K., Bodey, G. (2000). Time to Clinical Response: An Outcome of Antibiotic Therapy of Febrile Neutropenia With Implications for Quality and Cost of Care. JCO 18: 3699-3706 [Abstract] [Full Text]  
• Klastersky, J., Paesmans, M., Rubenstein, E. B., Boyer, M., Elting, L., Feld, R., Gallagher, J., Herrstedt, J., Rapoport, B., Rolston, K., Talcott, J. (2000). The Multinational Association for Supportive Care in Cancer Risk Index: A Multinational Scoring System for Identifying Low-Risk Febrile Neutropenic Cancer Patients. JCO 18: 3038-3051 [Abstract] [Full Text]  
• Mayaud, C., Cadranel, J. (2000). A persistent challenge: the diagnosis of respiratory disease in the non-AIDS immunocompromised host. Thorax 55: 511-517 [Full Text]  
• (2000). ADDITIONAL ARTICLES ABSTRACTED IN ACP JOURNAL CLUB. Evid. Based Med. 5: 35-35 [Full Text]  
• Blot, E., Heron, F., Lishner, M., Rubenstein, E. B., Rolston, K. V.I., Kim, Y. J., Sezer, O., Freifeld, A. G., Steinberg, S. M., Pizzo, P. A., Kern, W. V., Cometta, A., Finberg, R. W., Talcott, J. A. (2000). Oral Antibiotics for Febrile Patients with Neutropenia Due to Cancer Chemotherapy. NEJM 342: 55-58 [Full Text]  
• (1999). Oral Antibiotic Therapy for Fever and Neutropenia. JWatch Infect. Diseases 1999: 2-2 [Full Text]  
• (1999). Oral Antibiotics for Neutropenia and Fever. JWatch General 1999: 2-2 [Full Text]  
• Finberg, R. W., Talcott, J. A. (1999). Fever and Neutropenia -- How to Use a New Treatment Strategy. NEJM 341: 362-363 [Full Text]