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

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

Research output: Contribution to journalArticle

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Abstract

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 (CI): -20.1-8.4), -0.7% (95% CI: -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 × 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).

Original languageEnglish
Pages (from-to)16-22
Number of pages7
JournalJournal of Infection and Chemotherapy
Volume21
Issue number1
DOIs
Publication statusPublished - Jan 1 2015

Fingerprint

meropenem
Fever
Febrile Neutropenia
Confidence Intervals
Therapeutics
Drug Evaluation
Carbapenems
Imipenem
beta-Lactams
cefozopran
imipenem drug combination cilastatin
cefepime
Pharmaceutical Preparations
Population
Neutrophils

Keywords

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

ASJC Scopus subject areas

  • Medicine(all)

Cite this

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

In: Journal of Infection and Chemotherapy, Vol. 21, No. 1, 01.01.2015, p. 16-22.

Research output: Contribution to journalArticle

Nakane, T, Tamura, K, Hino, M, Tamaki, T, Yoshida, I, Fukushima, T, Tatsumi, Y, Nakagawa, Y, Hatanaka, K, Takahashi, T, Akiyama, N, Tanimoto, M, Ohyashiki, K, Urabe, A, Masaoka, T & Kanamaru, A 2015, 'Cefozopran, meropenem, or imipenem-cilastatin compared with cefepime as empirical therapy in febrile neutropenic adult patients: A multicenter prospective randomized trial', Journal of Infection and Chemotherapy, vol. 21, no. 1, pp. 16-22. https://doi.org/10.1016/j.jiac.2014.08.026
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. / Cefozopran, meropenem, or imipenem-cilastatin compared with cefepime as empirical therapy in febrile neutropenic adult patients : A multicenter prospective randomized trial. In: Journal of Infection and Chemotherapy. 2015 ; Vol. 21, No. 1. pp. 16-22.
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AU - Tamura, Kazuo

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AU - Tamaki, Toshiharu

AU - Yoshida, Isao

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AU - Tatsumi, Youichi

AU - Nakagawa, Yasuaki

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AU - Takahashi, Tsutomu

AU - Akiyama, Nobu

AU - Tanimoto, Mitsune

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AU - Urabe, Akio

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AU - Kanamaru, Akihisa

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N2 - 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 (CI): -20.1-8.4), -0.7% (95% CI: -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 × 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).

AB - 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 (CI): -20.1-8.4), -0.7% (95% CI: -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 × 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).

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KW - Meropenem and imipenem–cilastatin

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