Abstract
Piperacillin/tazobactam was compared with ceftazidime for the empirical treatment of febrile neutropenia in patients with acute leukemia or following autologous peripheral blood stem cell transplantation. Owing to inclusion criteria, it was possible for the same patient to be randomized several times. A total of 219 individual patients were admitted to a prospective randomized clinical study: 24 patients were included twice. Patients (23.5%) remained afebrile. Patients who developed febrile neutropenia were randomized to receive intravenous ceftazidime (n=74 patients, group I) or piperacillin/tazobactam (n=87 patients, group II). Response to first-line antibiotic treatment was seen in 55% (group I) and 53% (group II). After the addition of vancomycin, a further 19% (group I) and 24% (group II) of the patients became afebrile. Causes of fever were: microbiologically documented infection in 36 and 34 patients of group I and II; Clostridium difficile in eight and 12 patients of group I and II, and fever of unknown origin in 30 and 41 patients of group I and II. One patient died in each group. Single-agent therapy with piperacillin/tazobactam is as effective as ceftazidime in the treatment of neutropenic fever and is well tolerated. Direct and indirect costs of both treatment regimes are equivalent.
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References
Schimpff S, Satterlee W, Young VM, Serpick A . Empiric therapy with carbenicillin and gentamycin for febrile patients with cancer granulocytopenia. New Engl J Med 1971; 284: 1061–1065.
Schimpff SC . Overview of empirical antibiotic therapy for the febrile neutropenic patients. Rev Infect Dis 1985; 7 (Suppl 4): 734–740.
Leyland MJ, Bayston KF, Cohen J, Warren R, Newland AC, Bint AJ et al. A comparative study of imipenem versus piperacillin plus gentamycin in the initial management of febrile neutropenic patients with hematological malignancies. J Antimicrob Ag Chemother 1992; 30: 843–854.
Sanders JW, Powe NR, Moore RD . Ceftazidime monotherapy for empiric treatment of febrile neutropenic patients: a meta-analysis. J Infect Dis 1991; 164: 907–916.
De Pauw B, Williams K, De Neeff J, Bothof T, de Witte T, Holdrinet RS et al. Randomized prospective study of ceftazidime versus ceftazidime plus flucloxacillin in the empirical treatment of febrile episodes in severely neutropenic patients. Antimicrob Ag Chemother 1985; 28: 824–828.
Egerer G, Goldschmidt H, Streich N, Ehrhard I, Sonntag HG, Haas R et al. Ceftazidime in combination with glycopeptide antibiotic is an effective first-line therapy for patients undergoing high-dose therapy with autologous peripheral blood stem cell support. Support Care Cancer 1999; 7: 336–342.
EORTC International Antimicrobial Therapy Cooperative Group. In vitro activity of piperacillin/tazobactam against 365 aerobic bacteria isolated from blood in granulocytopenic cancer patients. 18th International Conference of Chemotherapy, Program and Abstract 380, 1993.
Cometta A, Zinner S, De Bock R, Calandra T, Gaya H, Klastersky J, et al., for the International Antimicrobial Therapy Cooperative Group of the European Organisation for Research and Treatment of Cancer. Piperacillin/tazobactam plus amikacin versus ceftazidime plus amikacin as an empiric therapy for fever in granulocytopenic patients with cancer. Antimicrob Agents Chemother 1995; 39: 445–552.
Kelsey SM, Weinhardt B, Procock CE, Shaw E, Newland AC . Piperacillin/Tazobactam plus gentamycin as empirical therapy for febrile neutropenic patients with haematological malignancies. J Chemotherapy 1992; 4: 281–285.
Pizzo PA, Armstrong D, Bodey GP, DePauw BE, Feld R, Glauser M, et al., Immune-compromized Host Society Panel. The design, analysis, and reporting of clinical trials on the empirical antibiotic management of the neutropenic patient: report of a consensus panel for the Immunocompromised Host Society. J Infect Dis 1990; 161: 397–401.
Chan I . Exact tests of equivalence and efficacy with a non-zero lower bound for comparative studies. Statist Med 1998; 17: 1403–1413.
Curtin JA, Marshall BD . Use of Antibiotics in cancer und leukemia. J Chronic Disease 1962; 15: 713–718.
Pizzo P, Hathorn JW, Hiemenz J, Browne M, Commers J, Cotton D et al. A randomized trial comparing ceftazidime alone with combination antibiotic therapy in cancer patients with fever and neutropenia. New Engl J Med 1986; 315: 552–558.
Cometta A, Calandra T, Gaya H, Zinner SH, de Bock R, Del Favero A, et al., for the International Antimicrobial Therapy Cooperative Group of the European Organisation for Research and Treatment of Cancer and the Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto Infection Program. Monotherapy with meropenem versus combination therapy with ceftazidime plus amikacin as empiric therapy for fever in granulocytopenic patients with cancer. Antimicrobial Agents Chemother 1996; 40: 1108–1115.
Freifeld A, Walsh T, Marshall D, Gress J, Steinberg S, Hathorn J et al. Monotherapy for fever and neutropenia in cancer patients: a randomized comparison of ceftazidime versus imipenem. J Clin Oncol 1995; 13: 165–176.
Hess U, Böhme C, Rey K, Senn HJ . Monotherapie mit Piperacillin/Tazobactam im Vergleich zur Kombinationstherapie mit Ceftazidim plus Amikacin als empirische Therapie bei febrilen neutropenischen Krebspatienten. Supportive Care Cancer 1998; 6: 402–409.
De Pauw BE, Deresinski SC, Feld R, Lane-Allman EF, Donnelly JP . Ceftazidime compared with piperacillin and tobramycin for the empiric treatment of fever in neutropenic patients with cancer. A multicenter randomized trial. The Intercontinental Antimicrobial Study Group. Ann Intern Med 1994; 120: 834–844.
Reich G, Cornely OA, Sandherr M, Kubin T, Krause S, Einsele H et al. Empirical antimicrobial monotherapy in patients after high-dose chemotherapy and autologous stem cell transplantation: a randomised, multicentre trial. Br J Haematol 2005; 130: 265–270.
Egerer G, Goldschmidt H, Salwender H, Hegenbart U, Ehrhard I, Haas R et al. Efficacy of continuous infusion of ceftazidime for patients with neutropenic fever after high-dose chemotherapy and peripheral blood stem cell translantation. Int J Antimicrobial Agents 2000; 15: 119–123.
Egerer G, Goldschmidt H, Hensel M, Harter C, Schneeweiß A, Ehrhard J et al. Continuous infusion of ceftazidime for patients with breast cancer and multiple myeloma receiving high-dose chemotherapy and peripheral blood stem cell transplantation. Bone Marrow Transplant 2002; 30: 427–431.
Klastersky J . Febrile neutropenia: empiric antibiotic therapy from 1975–1997. Rev Med Brux 1997; 18: 323–327.
Rossi C, Klastersky J . Initial empiric antibiotic therapy for neutropenic fever: analysis of the causes of death. Supportive Care in Cancer 1996; 4: 207–212.
Sculier JP, Weerts D, Klazersky J . Causes of Death in febrile granulocytopenic cancer patients receiving empiric antibiotic therapy. Eur J Cancer Clin Oncol 1984; 20: 55–60.
EORTC International Antimicrobial Therapy Cooperative Group. Efficacy and toxicity of single daily doses of amikacin and ceftriaxone versus multiple daily doses of amikacin and ceftazidime for infections in patients with cancer and granulocytopenia. Ann Intern Med 1993; 119: 584–593.
Anand A, Bashey B, Mir T, Glatt AE . Epidemiology, clinical manifestations, and outcome of Clostridium difficile-associated diarrhea. Am J Gastroenterol 1994; 89: 519–523.
Rolston KV . Challenges in the treatment of infections caused by gram-positive and gram-negative bacteria in patients with cancer and neutropenia. Clin Infect Dis 2005; 40: 246–252.
Sipsas NV, Bodey GP, Kontoyiannis DP . Perspectives for the management of febrile neutropenic patients with cancer in the 21st century. Cancer 2005; 103: 1103–1113.
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This study was supported by Wyeth Pharma GmbH, Muenster. The authors thank Ms Ulla Scheidler for her expert secretarial help.
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Harter, C., Schulze, B., Goldschmidt, H. et al. Piperacillin/tazobactam vs ceftazidime in the treatment of neutropenic fever in patients with acute leukemia or following autologous peripheral blood stem cell transplantation: a prospective randomized trial. Bone Marrow Transplant 37, 373–379 (2006). https://doi.org/10.1038/sj.bmt.1705256
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DOI: https://doi.org/10.1038/sj.bmt.1705256
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