Cefozopran, meropenem, or imipenem-cilastatin compared with cefepime as empirical therapy in febrile neutropenic adult patients: A multicenter prospective randomized trial

作者：Nakane Takahiko^*; Tamura Kazuo; Hino Masayuki; Tamaki Toshiharu; Yoshida Isao; Fukushima Toshihiro; Tatsumi Youichi; Nakagawa Yasuaki; Hatanaka Kazuo; Takahashi Tsutomu; Akiyama Nobu; Tanimoto Mitsune; Ohyashiki Kazuma; Urabe Akio; Masaoka Toru; Kanamaru Akihisa

来源：Journal of Infection and Chemotherapy, 2015, 21(1-2): 16-22.

DOI：10.1016/j.jiac.2014.08.026

• Febrile neutropenia
• Randomized trial
• Cefepime
• Cefozopran
• Meropenem and imipenem-cilastatin

We conducted an open-label, randomized study to evaluate the clinical efficacy of cefozopran, meropenem or imipenem cilastatin using cefepime as a control in febrile neutropenia (FN) patients. Three hundred and seventy-six patients received cefepime, cefozopran, meropenem or imipenem-cilastatinas initial therapy for FN. The primary endpoint was the non-inferiority of response rates including modification at day 7 in cefozopran, meropenem or imipenem cilastatin patients compared with cefepime in the per-protocol population (delta = 10%). The response rates for cefozopran, meropenem and imipenem cilastatin were not significantly different compared with cefepime (cefozopran: 54/90 (60%), meropenem: 60/92 (65%), and IPM/CS: 63/88 (72%) versus cefepime: 56/85 (66%) (p = 0.44, 1.0 and 0.51, respectively)), and the differences in treatment success for cefozopran, meropenem and imipenem cilastatin compared with cefepime were -5.9% (95% confidence interval (Cl): -20.1 -8.4), -0.7% (95% Cl: -14.6-13.3), and 5.7% (95% CI: -8.1-19.4), respectively. The same tendency was seen in the modified intention-to-treat population. Based on the evaluation of initial drug efficacy performed on days 3-5, there was no significant difference between the four drugs. In the subgroup with an absolute neutrophil count <= 100 x 10(6)/L for longer than seven days, there was significantly better efficacy in the carbapenem arm compared to 4th generation beta-lactams (52% versus 27% at days 3-5, p = 0.006, and 76% versus 48% at day 7, p = 0.002). Our results suggest that the effects of these four drugs as empiric therapy were virtually the same for adult FN patients, although non-inferiority was shown only in imipenem cilastatin compared with cefepime (clinical trial number: UMIN000000462).

• 出版日期2015-2