A phase III study of the efficacy and safety of meropenem in patients with febrile neutropenia

Kenji Imajo, Fumio Kawano, Tomohiko Kamimura, Atuko Mugitani, Naokuni Uike, Kensuke Usuki, Nobu Akiyama, Hirokazu Nagai, Mitsune Tanimoto, Yasunori Ueda, Hiroshi Sao, Yoshikazu Ito, Kenshi Suzuki, Koichi Miyamura, Yoshitaka Morimatsu, Akira Ohara, Kazutaka Takaki, Kosuke Chayama, Yoshihisa Nagatoshi, Masao UrabeKazou Tamura

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Efficacy, safety and pharmacokinetics of meropenem (MEPM) were assessed when 1 g (40mg/kg for some of the pediatric patients) t.i.d. was administered every 8 hours to 101 adult and 6 pediatric patients with febrile neutropenia (FN) as diagnosed based on the Japanese guideline for FN treatment. The efficacy rate evaluated as antifebrile effect up to Day 4 of treatment was 40.0% (40/100) in adult and 66.7% (4/6) in pediatric patients. The antifebrile effect in adult patients was analyzed after stratifying them according to their neutrophil counts up to Day 4. Treatment with MEPM produced an antifebrile effect not only in patients with higher neutrophil counts (≥500/mm 3) but also in those with lower counts (3), and the efficacy rate was comparable between the two groups: 38.2% in the 3 group and 29.4 to 55.6% in the ≥500/mm3 group. The bacteriological efficacy of MEPM evaluated as disappearance rate on Days 3 to 5 and Day 7 was both 100% (8/8 and 4/4, respectively). The time above minimal inhibitory concentration (%T>MIC) in the treatment interval was greater than 90% in 9 out of 10 patients for whom likely causative organism was isolated and identified after MEPM treatment or for whom causative organism emerging after treatment was isolated and identified. The incidence of adverse events was 93.1% in adult and 83.3% in pediatric patients. There were three deaths and one serious adverse event reported among the adult patients; however, all these cases were assessed as not related to the study medication. The incidence of adverse drug reactions was 45.5% and 66.7%, respectively. All the observed adverse drug reactions were mild or moderate in severity and none of them was severe. Adverse drug reactions which were unknown from the previous MEPM clinical studies and investigation of the results of clinical experience include 'chest discomfort', 'blood uric acid decreased', 'lymphocyte deformation', 'blood uric acid increased', 'abnormal funduscopy', 'hypesthesia' and 'hemorrhagic cystitis'. All these events were mild or moderate in severity and resolved without requiring any action or after providing symptomatic treatment. There was no unknown adverse drug reaction that resulted in treatment discontinuation. No nervous system disorders such as convulsion and impaired consciousness were reported. The results show that monotherapy of MEPM 1 g (or 40mg/kg for some of the pediatric patients) t.i.d. every 8 hours was effective, and was also safe and well tolerated in adult and pediatric patients with FN. Therefore, MEPM monotherapy is expected to be useful as the initial treatment for Japanese patients with FN.

Original languageEnglish
Pages (from-to)271-286
Number of pages16
JournalJapanese Journal of Antibiotics
Volume65
Issue number4
Publication statusPublished - Aug 2012

Fingerprint

meropenem
Febrile Neutropenia
Safety
Pediatrics
Drug-Related Side Effects and Adverse Reactions
Therapeutics
Uric Acid
Neutrophils

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Infectious Diseases
  • Microbiology (medical)

Cite this

Imajo, K., Kawano, F., Kamimura, T., Mugitani, A., Uike, N., Usuki, K., ... Tamura, K. (2012). A phase III study of the efficacy and safety of meropenem in patients with febrile neutropenia. Japanese Journal of Antibiotics, 65(4), 271-286.

A phase III study of the efficacy and safety of meropenem in patients with febrile neutropenia. / Imajo, Kenji; Kawano, Fumio; Kamimura, Tomohiko; Mugitani, Atuko; Uike, Naokuni; Usuki, Kensuke; Akiyama, Nobu; Nagai, Hirokazu; Tanimoto, Mitsune; Ueda, Yasunori; Sao, Hiroshi; Ito, Yoshikazu; Suzuki, Kenshi; Miyamura, Koichi; Morimatsu, Yoshitaka; Ohara, Akira; Takaki, Kazutaka; Chayama, Kosuke; Nagatoshi, Yoshihisa; Urabe, Masao; Tamura, Kazou.

In: Japanese Journal of Antibiotics, Vol. 65, No. 4, 08.2012, p. 271-286.

Research output: Contribution to journalArticle

Imajo, K, Kawano, F, Kamimura, T, Mugitani, A, Uike, N, Usuki, K, Akiyama, N, Nagai, H, Tanimoto, M, Ueda, Y, Sao, H, Ito, Y, Suzuki, K, Miyamura, K, Morimatsu, Y, Ohara, A, Takaki, K, Chayama, K, Nagatoshi, Y, Urabe, M & Tamura, K 2012, 'A phase III study of the efficacy and safety of meropenem in patients with febrile neutropenia', Japanese Journal of Antibiotics, vol. 65, no. 4, pp. 271-286.
Imajo K, Kawano F, Kamimura T, Mugitani A, Uike N, Usuki K et al. A phase III study of the efficacy and safety of meropenem in patients with febrile neutropenia. Japanese Journal of Antibiotics. 2012 Aug;65(4):271-286.
Imajo, Kenji ; Kawano, Fumio ; Kamimura, Tomohiko ; Mugitani, Atuko ; Uike, Naokuni ; Usuki, Kensuke ; Akiyama, Nobu ; Nagai, Hirokazu ; Tanimoto, Mitsune ; Ueda, Yasunori ; Sao, Hiroshi ; Ito, Yoshikazu ; Suzuki, Kenshi ; Miyamura, Koichi ; Morimatsu, Yoshitaka ; Ohara, Akira ; Takaki, Kazutaka ; Chayama, Kosuke ; Nagatoshi, Yoshihisa ; Urabe, Masao ; Tamura, Kazou. / A phase III study of the efficacy and safety of meropenem in patients with febrile neutropenia. In: Japanese Journal of Antibiotics. 2012 ; Vol. 65, No. 4. pp. 271-286.
@article{7a8409e48c5a4ae69dc4826fb5171efd,
title = "A phase III study of the efficacy and safety of meropenem in patients with febrile neutropenia",
abstract = "Efficacy, safety and pharmacokinetics of meropenem (MEPM) were assessed when 1 g (40mg/kg for some of the pediatric patients) t.i.d. was administered every 8 hours to 101 adult and 6 pediatric patients with febrile neutropenia (FN) as diagnosed based on the Japanese guideline for FN treatment. The efficacy rate evaluated as antifebrile effect up to Day 4 of treatment was 40.0{\%} (40/100) in adult and 66.7{\%} (4/6) in pediatric patients. The antifebrile effect in adult patients was analyzed after stratifying them according to their neutrophil counts up to Day 4. Treatment with MEPM produced an antifebrile effect not only in patients with higher neutrophil counts (≥500/mm 3) but also in those with lower counts (3), and the efficacy rate was comparable between the two groups: 38.2{\%} in the 3 group and 29.4 to 55.6{\%} in the ≥500/mm3 group. The bacteriological efficacy of MEPM evaluated as disappearance rate on Days 3 to 5 and Day 7 was both 100{\%} (8/8 and 4/4, respectively). The time above minimal inhibitory concentration ({\%}T>MIC) in the treatment interval was greater than 90{\%} in 9 out of 10 patients for whom likely causative organism was isolated and identified after MEPM treatment or for whom causative organism emerging after treatment was isolated and identified. The incidence of adverse events was 93.1{\%} in adult and 83.3{\%} in pediatric patients. There were three deaths and one serious adverse event reported among the adult patients; however, all these cases were assessed as not related to the study medication. The incidence of adverse drug reactions was 45.5{\%} and 66.7{\%}, respectively. All the observed adverse drug reactions were mild or moderate in severity and none of them was severe. Adverse drug reactions which were unknown from the previous MEPM clinical studies and investigation of the results of clinical experience include 'chest discomfort', 'blood uric acid decreased', 'lymphocyte deformation', 'blood uric acid increased', 'abnormal funduscopy', 'hypesthesia' and 'hemorrhagic cystitis'. All these events were mild or moderate in severity and resolved without requiring any action or after providing symptomatic treatment. There was no unknown adverse drug reaction that resulted in treatment discontinuation. No nervous system disorders such as convulsion and impaired consciousness were reported. The results show that monotherapy of MEPM 1 g (or 40mg/kg for some of the pediatric patients) t.i.d. every 8 hours was effective, and was also safe and well tolerated in adult and pediatric patients with FN. Therefore, MEPM monotherapy is expected to be useful as the initial treatment for Japanese patients with FN.",
author = "Kenji Imajo and Fumio Kawano and Tomohiko Kamimura and Atuko Mugitani and Naokuni Uike and Kensuke Usuki and Nobu Akiyama and Hirokazu Nagai and Mitsune Tanimoto and Yasunori Ueda and Hiroshi Sao and Yoshikazu Ito and Kenshi Suzuki and Koichi Miyamura and Yoshitaka Morimatsu and Akira Ohara and Kazutaka Takaki and Kosuke Chayama and Yoshihisa Nagatoshi and Masao Urabe and Kazou Tamura",
year = "2012",
month = "8",
language = "English",
volume = "65",
pages = "271--286",
journal = "The Journal of antibiotics. Ser. B",
issn = "0368-2781",
publisher = "Japan Antibiotics Research Association",
number = "4",

}

TY - JOUR

T1 - A phase III study of the efficacy and safety of meropenem in patients with febrile neutropenia

AU - Imajo, Kenji

AU - Kawano, Fumio

AU - Kamimura, Tomohiko

AU - Mugitani, Atuko

AU - Uike, Naokuni

AU - Usuki, Kensuke

AU - Akiyama, Nobu

AU - Nagai, Hirokazu

AU - Tanimoto, Mitsune

AU - Ueda, Yasunori

AU - Sao, Hiroshi

AU - Ito, Yoshikazu

AU - Suzuki, Kenshi

AU - Miyamura, Koichi

AU - Morimatsu, Yoshitaka

AU - Ohara, Akira

AU - Takaki, Kazutaka

AU - Chayama, Kosuke

AU - Nagatoshi, Yoshihisa

AU - Urabe, Masao

AU - Tamura, Kazou

PY - 2012/8

Y1 - 2012/8

N2 - Efficacy, safety and pharmacokinetics of meropenem (MEPM) were assessed when 1 g (40mg/kg for some of the pediatric patients) t.i.d. was administered every 8 hours to 101 adult and 6 pediatric patients with febrile neutropenia (FN) as diagnosed based on the Japanese guideline for FN treatment. The efficacy rate evaluated as antifebrile effect up to Day 4 of treatment was 40.0% (40/100) in adult and 66.7% (4/6) in pediatric patients. The antifebrile effect in adult patients was analyzed after stratifying them according to their neutrophil counts up to Day 4. Treatment with MEPM produced an antifebrile effect not only in patients with higher neutrophil counts (≥500/mm 3) but also in those with lower counts (3), and the efficacy rate was comparable between the two groups: 38.2% in the 3 group and 29.4 to 55.6% in the ≥500/mm3 group. The bacteriological efficacy of MEPM evaluated as disappearance rate on Days 3 to 5 and Day 7 was both 100% (8/8 and 4/4, respectively). The time above minimal inhibitory concentration (%T>MIC) in the treatment interval was greater than 90% in 9 out of 10 patients for whom likely causative organism was isolated and identified after MEPM treatment or for whom causative organism emerging after treatment was isolated and identified. The incidence of adverse events was 93.1% in adult and 83.3% in pediatric patients. There were three deaths and one serious adverse event reported among the adult patients; however, all these cases were assessed as not related to the study medication. The incidence of adverse drug reactions was 45.5% and 66.7%, respectively. All the observed adverse drug reactions were mild or moderate in severity and none of them was severe. Adverse drug reactions which were unknown from the previous MEPM clinical studies and investigation of the results of clinical experience include 'chest discomfort', 'blood uric acid decreased', 'lymphocyte deformation', 'blood uric acid increased', 'abnormal funduscopy', 'hypesthesia' and 'hemorrhagic cystitis'. All these events were mild or moderate in severity and resolved without requiring any action or after providing symptomatic treatment. There was no unknown adverse drug reaction that resulted in treatment discontinuation. No nervous system disorders such as convulsion and impaired consciousness were reported. The results show that monotherapy of MEPM 1 g (or 40mg/kg for some of the pediatric patients) t.i.d. every 8 hours was effective, and was also safe and well tolerated in adult and pediatric patients with FN. Therefore, MEPM monotherapy is expected to be useful as the initial treatment for Japanese patients with FN.

AB - Efficacy, safety and pharmacokinetics of meropenem (MEPM) were assessed when 1 g (40mg/kg for some of the pediatric patients) t.i.d. was administered every 8 hours to 101 adult and 6 pediatric patients with febrile neutropenia (FN) as diagnosed based on the Japanese guideline for FN treatment. The efficacy rate evaluated as antifebrile effect up to Day 4 of treatment was 40.0% (40/100) in adult and 66.7% (4/6) in pediatric patients. The antifebrile effect in adult patients was analyzed after stratifying them according to their neutrophil counts up to Day 4. Treatment with MEPM produced an antifebrile effect not only in patients with higher neutrophil counts (≥500/mm 3) but also in those with lower counts (3), and the efficacy rate was comparable between the two groups: 38.2% in the 3 group and 29.4 to 55.6% in the ≥500/mm3 group. The bacteriological efficacy of MEPM evaluated as disappearance rate on Days 3 to 5 and Day 7 was both 100% (8/8 and 4/4, respectively). The time above minimal inhibitory concentration (%T>MIC) in the treatment interval was greater than 90% in 9 out of 10 patients for whom likely causative organism was isolated and identified after MEPM treatment or for whom causative organism emerging after treatment was isolated and identified. The incidence of adverse events was 93.1% in adult and 83.3% in pediatric patients. There were three deaths and one serious adverse event reported among the adult patients; however, all these cases were assessed as not related to the study medication. The incidence of adverse drug reactions was 45.5% and 66.7%, respectively. All the observed adverse drug reactions were mild or moderate in severity and none of them was severe. Adverse drug reactions which were unknown from the previous MEPM clinical studies and investigation of the results of clinical experience include 'chest discomfort', 'blood uric acid decreased', 'lymphocyte deformation', 'blood uric acid increased', 'abnormal funduscopy', 'hypesthesia' and 'hemorrhagic cystitis'. All these events were mild or moderate in severity and resolved without requiring any action or after providing symptomatic treatment. There was no unknown adverse drug reaction that resulted in treatment discontinuation. No nervous system disorders such as convulsion and impaired consciousness were reported. The results show that monotherapy of MEPM 1 g (or 40mg/kg for some of the pediatric patients) t.i.d. every 8 hours was effective, and was also safe and well tolerated in adult and pediatric patients with FN. Therefore, MEPM monotherapy is expected to be useful as the initial treatment for Japanese patients with FN.

UR - http://www.scopus.com/inward/record.url?scp=84866372180&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84866372180&partnerID=8YFLogxK

M3 - Article

C2 - 23259257

AN - SCOPUS:84866372180

VL - 65

SP - 271

EP - 286

JO - The Journal of antibiotics. Ser. B

JF - The Journal of antibiotics. Ser. B

SN - 0368-2781

IS - 4

ER -