Historical Cohort Study of the Efficacy and Safety of Piperacillin/Tazobactam Versus Fourth-Generation Cephalosporins for Empirical Treatment of Febrile Neutropenia in Patients with Hematological Malignancies

Takashi Saito, Tatsuo Ichinohe, Junya Kanda, Miki Nagao, Shunji Takakura, Yutaka Ito, Yoshitsugu Iinuma, Kouhei Yamashita, Tadakazu Kondo, Takayuki Ishikawa, Takashi Uchiyama, Satoshi Ichiyama

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DOI: 10.4236/ijcm.2011.21005                

Abstract

We retrospectively evaluated the efficacy and safety of the combination drug piperacillin/tazobactam (PIPC/TAZ) in comparison with those of fourth-generation cephalosporins (4th Cephs) as initial empirical treatment in hematological malignancies patients with febrile neutropenia (FN). Among 200 patients assessed in this study, 49 had received PIPC/TAZ and 151 4th Cephs. Patient background characteristics were comparable between the two treatment groups. The overall efficacy rate in those receiving 4th Cephs and PIPC/TAZ was 57.0% (86/151 patients) and 59.2% (29/49 patients), respectively, with no significant difference detected between the two treatment regimens (P = 0.78). Treat-ment did not need to be discontinued or interrupted due to development of adverse drug reactions in any of the patients. Therefore in this study the efficacy and safety of PIPC/TAZ as initial antimicrobial treatment for FN in patients with hematological malignancies were not inferior to those of 4th Cephs. Based on the preliminary data obtained in this study, we propose to conduct a multicenter, prospective, controlled study to compare PIPC/TAZ versus CFPM given as empirical antimicrobial treatment against FN in patients with hematological malignancies.

Keywords

Febrile Neutropenia, Piperacillin/Tazobactam, Fourth-Generation Cephalosporins, Safety, Efficacy

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	W. T. Hughes, D. Armstrong, G. P. Bodey, E. J. Bow, A. E. Brown, T. Calandra, et al., “Guidelines for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer”, Clinical Infectious Diseases, Vol. 34, No. 6, 2002, pp. 730-751. doi:10.1086/339215
[2]	NCCN Clinical Practice Guideline in OncologyTM 2007, “Prevention and Treatment of Cancer-Related Infections VI 2007 Initial Therapy for Fever and Neutropenia FEV1”. http://www.nccn.org/professionals/physician_gls/PDF/fever.pdf .
[3]	T. Masaoka, “Evidence-Based Recommendations for Antimicrobial Use in Febrile Neutropenia in Japan: Executive Summary”, Clinical Infectious Diseases, Vol. 39, Suppl 1, 2004, pp. S49-52. doi:10.1086/383054
[4]	A. Glasmacher and M. von Lilienfeld-Toal, “An Evidence Based Review of the Available Antibiotic Treatment Options For Neutropenic Patients And A Recommendation for Treatment Guidelines”, International Journal of Infectious Diseases, Vol. 10, Suppl 2, 2006, pp. S9-16. doi:10.1016/S1201-9712(06)60003-9
[5]	M. Yoshida and R. Ohno, “Current Antimicrobial Usage for the Management of Infections in Leukemic Patients in Japan: Results of a Survey”, Clinical Infectious Diseases, Vol. 39, Suppl 1, 1995, pp. S11-4. doi:10.1086/383044
[6]	D. R. Burwen, S. N. Banerjee, and R. P. Gaynes, “Ceftazidime Resistance among Selected Nosocomial Gram-Negative Bacilli in the United States,” Journal of Infectious Diseases, Vol. 170, No. 6, 1994, pp. 1622-1625.
[7]	A. C. Basustaoglu, H. Gun, M. A. Sara?li, M. Baysallar, T. Haznedaroglu, “Development of Resistance to Imipenem among Nosocomial Isolates of Pseudomonas Aeruginosa” European Journal of Clinical Microbiology and Infectious Diseases, Vol. 14, No. 5, 1995, pp. 469-470. doi:10.1007/BF02114909
[8]	N. Troillet, M. H. Samore and Y. Carmeli, “Imipenem- Resistant pseudomonas aeruginosa: Risk Factors and Antibiotic Susceptibility Patterns”, Clinical Infectious Diseases, Vol. 25, No. 5, 1995, pp. 1094-1098. doi:10.1086/516092
[9]	National Nosocomial Infections Surveillance System, “National Nosocomial Infections Surveillance System Report, data summary from January 1992 to June 2002, issued August 2002”, American Journal of Infection Control, Vol. 30, No. 8, 2002, pp. 458-475. doi:10.1067/mic.2002.130032
[10]	D'Agata EM, “Rapidly Rising Prevalence of Nosocomial Multidrug-Resistant, Gram-Negative Bacilli: A 9-Year Surveillance Study”, Infection Control and Hospital Epidemiology, Vol. 25, No. 10, 2004, pp. 842-846.
[11]	N. Ohmagari, H. Hanna, L. Graviss, B. Hackett, C. Perego and V. Gonzalez, et al., “Risk Factors for Infections with Multidrug-Resistant Pseudomonas Aeruginosa in Patients with Cancer”, Cancer, Vol. 104, No. 1, 2005, pp. 205-212. doi:10.1002/cncr.21115
[12]	A. Bohme, P. M. Shah, W. Stille and D. Hoelzer, “Piperacillin/Tazobactam Versus Cefepime as Initial Empirical Antimicrobial Therapy in Febrile Neutropenic Patients: A Prospective Randomized Pilot Study”, European journal of medical research, Vol. 3, No. 7, 1998, pp. 324-330.
[13]	F. Bauduer, T. Cousin, O. Boulat, F. Rigal-Huguet, L. Molina and N. Fegueux, et al., “A Randomized Prospective Multicentre Trial of Cefpirome Versus Piperacillin-Tazobactam in Febrile Neutropenia”, Leukemia Lymphoma, Vol. 42, No. 3, 2001, pp. 379-386. doi:10.3109/10428190109064594
[14]	M. A. Sanz, J. López, J. J. Lahuerta, M. Rovira, M. Batlle and C. Pérez, et al., “Cefepime Plus Amikacin Versus Piperacillin-Tazobactam Plus Amikacin for Initial Antibiotic Therapy in Haematology Patients with Febrile Neutropenia: Results of an Open, Randomized, Multicentre Trial”, Journal of antimicrobial chemotherapy, Vol. 50, No. 1, 2002, pp. 79-88. doi:10.1093/jac/dkf087
[15]	E. J. Bow, C. Rotstein, G. A. Noskin, M. Laverdiere, A. P. Schwarer and B. H. Segal, et al., “A Randomized, Open-Label, Multicenter Comparative Study of the Efficacy and Safety of Piperacillin-Tazobactam and Cefepime for the Empirical Treatment of Febrile Neutropenic Episodes in Patients with Hematologic Malignancies”, Clinical Infectious Diseases, Vol. 43, Suppl 1, 2006, pp. 447-459.doi:10.1086/505393
[16]	K. Tamura, K. Imajo, N. Akiyama, K. Suzuki, A. Urabe and K. Ohyashiki, et al., “Randomized Trial of Cefepime Monotherapy or Cefepime in Combination with Amikacin as Empirical Therapy for Febrile Neutropenia”, Clinical Infectious Diseases, Vol. 39, Suppl 1, 2004, pp. S15-24.doi:10.1086/383046
[17]	K. Tamura, H. Matsuoka, J. Tsukada, M. Masuda, S. Ikeda and E. Matsuishi, et al., “Cefepime or Carbapenem Treatment for Febrile Neutropenia as a Single Agent Is as Effective as a Combination of 4th-Generation Cephalosporin + Aminoglycosides: Comparative Study”, American Journal of Hematology, Vol. 71, No. 4, 2002, pp. 248-255. doi:10.1002/ajh.10236