Bacterial, pharmacokinetic and clinical evaluations of cefpirome sulfate in the pediatric field

R. Fujii, T. Abe, H. Meguro, T. Tajima, S. Nakazawa, H. Sato, Y. Hirama, A. Narita, K. Matsumoto, S. Nakazawa, H. Suzuki, Y. Nakanishi, K. Nagao, K. Niino, K. Sunakawa, H. Akita, S. Iwata, Y. Sato, Y. Toyonaga

Research output: Contribution to journalArticle

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Abstract

A recearch group was organized with the purpose of making basic and clinical studies on cefpirome sulfate (HR810, CPR), a newly developed cephalosporin antibiotic, in the pediatric field. Through meetings a joint research was done involving 19 key institutions and their related facilities throughout Japan. The obtained results are summarized as follows. 1. Antibacterial Activities, Minimum inhibitory concentrations (MICs) were determined against 71 Gram-positive and 110 Gram-nagative bacteria in the present clinical trials. CPR showed antibacterial activities 2 ~ 16 times higher than those of ceftazidime (CAZ) against Staphylococcus aureus and other Gram-positive bacteria including MRSA. Against Gram-negative bacteria, CPR showed a somewhat broad range of distribution in MIC against Branhamella catarrhalis, while the antibiotic inhibited the growth of all the strains of Escherichia coli and Haemophilus influenzae at concentrations no more than 0.l0 and 0.20 μg/ml, respectively. 2. Blood Concentrations and Urinary Excretion Rates. The pharmacokinetics in pediatric patients was investigated with a dose of 20 mg/kg in most cases via one shot intravenous injection or 30- and 60-minute intravenous drip infusion. Mean blood concentrations of CPR at 15 minutes after one shot intravenous injection of 10, 20, and 40 mg/kg were 51.2, 70.5, and 123.5 μg/ml, with half-lives of 1.21, 1.39 and 1.53 hours, respectively. Urinary excretion rates in 6 hours were 63.6, 66.0 and 71.6%, respectively for the 3 dose levels. After 30- and 60-minute intravenous drip infusions at the same dose, the pharmacokinetic parameters observed were similar to those obtained with one shot injections. 3. Concentration in the Cerebrospinal Fluid. CPR penetrated well into the cerebrospinal fluid in patients with purulent meningitis and levels of l.85 ~ 24.2 μg/ml 45 ~ 60 minutes were achieved after intravenous injection at a dose of 40 ~ 80 mg/kg, the penetration rate of CPR was at an intermediate degree compared with other cephalosporin antibiotics. 4. Clinical Results. Clinical efficacies of CPR on infectious diseases were analyzed in 454 plus 3 cases which were complicated with other infectious diseases, hence totaling 457 cases out of 499 cases originally chosen for clinical evaluation. The remaining 45 cases were excluded from the clinical evaluation. As for the clinical efficacy, CPR was found to be effective (good or excellent) in 430 (94.1%) of the 457 cases. CPR was found to be effective in 243 (95.3%) of 255 cases for which causative bacteria were identified. The efficacy rate was 92.6% (187 of 202) in those cases in which causative bacteria were not identified. All these figures indicated a high efficacy of CPR. As for clinical efficacies according to different causative bacteria, CPR showed a high efficacy rate of 95.0% for infections with Gram-positive bacteria including S. aureus, and this value was as high as the efficacy rate for Gram-negative bacteria, 95.7%. The efficacy rate was also equally high (94.4%) for polymicrobial infections. As for bacteriological effects on the basis of different causative bacteria, a total number of 266 bacterial strains out of 276 strains that had been identified as causative bacteria was eliminated, thus representing an excellent eradication rate of 96.4%. As for the eradication of Gram-positive bacteria, a high eradication rate of 89.5% (34 out of 38 strains) was observed for S. aureus and for Streptococcus pneumoniae an eradication rate of 97.4% (37 out of 38 strains) was obtained. The overall eradication rate for Gram-positive bacteria was 95.1%. Among Gram-negative bacteria, an eradication rate of 96.6% (85 out of 88 strains) was obtained for H. influenzae. All of B. catarrhalis (12 out of 12 strains), E. coli (43 out of 43 strains), Klebsiella pneumoniae (5 out of 5 strains), and of Pseudomonas aeruginosa (3 out of 3 strains) were eradicated. As for the clinical efficacy of CPR in 135 cases which had not been responsive to other antibiotics, CPR showed good or excellent effects in 126 of 135 cases, representing a high efficacy rate of 93.3%. 5. Side Effects and Laboratory Test Results. The safety was evaluated in 492 of 499 cases, excluding 7 cases of non-compliance due to concomitant uses of other antibiotics, insufficient in durations of administration, etc. Twenty three symptoms of side effects, e.g., diarrhea, stools loose, eruption, etc., were observed in 20 cases. Most side effects occurred in the digestive system. As for abnormal laboratory test values, we obtained 142 abnormal findings including increased levels of GOT, GPT, total bi1irubin and creatinin, thrombocytosis, thrombocytopenia, eosinophilia, and leukopenia in 101 cases (20.5%). All the side effects and abnormal laboratory test values observed were normalized during the administration or by discontinuance of the administration, and none of them were found to be serious.

Original languageEnglish
Pages (from-to)84-109
Number of pages26
JournalJapanese Journal of Antibiotics
Volume44
Issue number1
Publication statusPublished - 1991
Externally publishedYes

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cefpirome
Cardiopulmonary Resuscitation
Pharmacokinetics
Pediatrics
Intravenous Infusions
Gram-Positive Bacteria
Bacteria
Gram-Negative Bacteria
Intravenous Injections
Staphylococcus aureus
Moraxella (Branhamella) catarrhalis
Haemophilus influenzae
Microbial Sensitivity Tests
Cephalosporins
Anti-Bacterial Agents
Communicable Diseases
Cerebrospinal Fluid

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Fujii, R., Abe, T., Meguro, H., Tajima, T., Nakazawa, S., Sato, H., ... Toyonaga, Y. (1991). Bacterial, pharmacokinetic and clinical evaluations of cefpirome sulfate in the pediatric field. Japanese Journal of Antibiotics, 44(1), 84-109.

Bacterial, pharmacokinetic and clinical evaluations of cefpirome sulfate in the pediatric field. / Fujii, R.; Abe, T.; Meguro, H.; Tajima, T.; Nakazawa, S.; Sato, H.; Hirama, Y.; Narita, A.; Matsumoto, K.; Nakazawa, S.; Suzuki, H.; Nakanishi, Y.; Nagao, K.; Niino, K.; Sunakawa, K.; Akita, H.; Iwata, S.; Sato, Y.; Toyonaga, Y.

In: Japanese Journal of Antibiotics, Vol. 44, No. 1, 1991, p. 84-109.

Research output: Contribution to journalArticle

Fujii, R, Abe, T, Meguro, H, Tajima, T, Nakazawa, S, Sato, H, Hirama, Y, Narita, A, Matsumoto, K, Nakazawa, S, Suzuki, H, Nakanishi, Y, Nagao, K, Niino, K, Sunakawa, K, Akita, H, Iwata, S, Sato, Y & Toyonaga, Y 1991, 'Bacterial, pharmacokinetic and clinical evaluations of cefpirome sulfate in the pediatric field', Japanese Journal of Antibiotics, vol. 44, no. 1, pp. 84-109.
Fujii R, Abe T, Meguro H, Tajima T, Nakazawa S, Sato H et al. Bacterial, pharmacokinetic and clinical evaluations of cefpirome sulfate in the pediatric field. Japanese Journal of Antibiotics. 1991;44(1):84-109.
Fujii, R. ; Abe, T. ; Meguro, H. ; Tajima, T. ; Nakazawa, S. ; Sato, H. ; Hirama, Y. ; Narita, A. ; Matsumoto, K. ; Nakazawa, S. ; Suzuki, H. ; Nakanishi, Y. ; Nagao, K. ; Niino, K. ; Sunakawa, K. ; Akita, H. ; Iwata, S. ; Sato, Y. ; Toyonaga, Y. / Bacterial, pharmacokinetic and clinical evaluations of cefpirome sulfate in the pediatric field. In: Japanese Journal of Antibiotics. 1991 ; Vol. 44, No. 1. pp. 84-109.
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abstract = "A recearch group was organized with the purpose of making basic and clinical studies on cefpirome sulfate (HR810, CPR), a newly developed cephalosporin antibiotic, in the pediatric field. Through meetings a joint research was done involving 19 key institutions and their related facilities throughout Japan. The obtained results are summarized as follows. 1. Antibacterial Activities, Minimum inhibitory concentrations (MICs) were determined against 71 Gram-positive and 110 Gram-nagative bacteria in the present clinical trials. CPR showed antibacterial activities 2 ~ 16 times higher than those of ceftazidime (CAZ) against Staphylococcus aureus and other Gram-positive bacteria including MRSA. Against Gram-negative bacteria, CPR showed a somewhat broad range of distribution in MIC against Branhamella catarrhalis, while the antibiotic inhibited the growth of all the strains of Escherichia coli and Haemophilus influenzae at concentrations no more than 0.l0 and 0.20 μg/ml, respectively. 2. Blood Concentrations and Urinary Excretion Rates. The pharmacokinetics in pediatric patients was investigated with a dose of 20 mg/kg in most cases via one shot intravenous injection or 30- and 60-minute intravenous drip infusion. Mean blood concentrations of CPR at 15 minutes after one shot intravenous injection of 10, 20, and 40 mg/kg were 51.2, 70.5, and 123.5 μg/ml, with half-lives of 1.21, 1.39 and 1.53 hours, respectively. Urinary excretion rates in 6 hours were 63.6, 66.0 and 71.6{\%}, respectively for the 3 dose levels. After 30- and 60-minute intravenous drip infusions at the same dose, the pharmacokinetic parameters observed were similar to those obtained with one shot injections. 3. Concentration in the Cerebrospinal Fluid. CPR penetrated well into the cerebrospinal fluid in patients with purulent meningitis and levels of l.85 ~ 24.2 μg/ml 45 ~ 60 minutes were achieved after intravenous injection at a dose of 40 ~ 80 mg/kg, the penetration rate of CPR was at an intermediate degree compared with other cephalosporin antibiotics. 4. Clinical Results. Clinical efficacies of CPR on infectious diseases were analyzed in 454 plus 3 cases which were complicated with other infectious diseases, hence totaling 457 cases out of 499 cases originally chosen for clinical evaluation. The remaining 45 cases were excluded from the clinical evaluation. As for the clinical efficacy, CPR was found to be effective (good or excellent) in 430 (94.1{\%}) of the 457 cases. CPR was found to be effective in 243 (95.3{\%}) of 255 cases for which causative bacteria were identified. The efficacy rate was 92.6{\%} (187 of 202) in those cases in which causative bacteria were not identified. All these figures indicated a high efficacy of CPR. As for clinical efficacies according to different causative bacteria, CPR showed a high efficacy rate of 95.0{\%} for infections with Gram-positive bacteria including S. aureus, and this value was as high as the efficacy rate for Gram-negative bacteria, 95.7{\%}. The efficacy rate was also equally high (94.4{\%}) for polymicrobial infections. As for bacteriological effects on the basis of different causative bacteria, a total number of 266 bacterial strains out of 276 strains that had been identified as causative bacteria was eliminated, thus representing an excellent eradication rate of 96.4{\%}. As for the eradication of Gram-positive bacteria, a high eradication rate of 89.5{\%} (34 out of 38 strains) was observed for S. aureus and for Streptococcus pneumoniae an eradication rate of 97.4{\%} (37 out of 38 strains) was obtained. The overall eradication rate for Gram-positive bacteria was 95.1{\%}. Among Gram-negative bacteria, an eradication rate of 96.6{\%} (85 out of 88 strains) was obtained for H. influenzae. All of B. catarrhalis (12 out of 12 strains), E. coli (43 out of 43 strains), Klebsiella pneumoniae (5 out of 5 strains), and of Pseudomonas aeruginosa (3 out of 3 strains) were eradicated. As for the clinical efficacy of CPR in 135 cases which had not been responsive to other antibiotics, CPR showed good or excellent effects in 126 of 135 cases, representing a high efficacy rate of 93.3{\%}. 5. Side Effects and Laboratory Test Results. The safety was evaluated in 492 of 499 cases, excluding 7 cases of non-compliance due to concomitant uses of other antibiotics, insufficient in durations of administration, etc. Twenty three symptoms of side effects, e.g., diarrhea, stools loose, eruption, etc., were observed in 20 cases. Most side effects occurred in the digestive system. As for abnormal laboratory test values, we obtained 142 abnormal findings including increased levels of GOT, GPT, total bi1irubin and creatinin, thrombocytosis, thrombocytopenia, eosinophilia, and leukopenia in 101 cases (20.5{\%}). All the side effects and abnormal laboratory test values observed were normalized during the administration or by discontinuance of the administration, and none of them were found to be serious.",
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TY - JOUR

T1 - Bacterial, pharmacokinetic and clinical evaluations of cefpirome sulfate in the pediatric field

AU - Fujii, R.

AU - Abe, T.

AU - Meguro, H.

AU - Tajima, T.

AU - Nakazawa, S.

AU - Sato, H.

AU - Hirama, Y.

AU - Narita, A.

AU - Matsumoto, K.

AU - Nakazawa, S.

AU - Suzuki, H.

AU - Nakanishi, Y.

AU - Nagao, K.

AU - Niino, K.

AU - Sunakawa, K.

AU - Akita, H.

AU - Iwata, S.

AU - Sato, Y.

AU - Toyonaga, Y.

PY - 1991

Y1 - 1991

N2 - A recearch group was organized with the purpose of making basic and clinical studies on cefpirome sulfate (HR810, CPR), a newly developed cephalosporin antibiotic, in the pediatric field. Through meetings a joint research was done involving 19 key institutions and their related facilities throughout Japan. The obtained results are summarized as follows. 1. Antibacterial Activities, Minimum inhibitory concentrations (MICs) were determined against 71 Gram-positive and 110 Gram-nagative bacteria in the present clinical trials. CPR showed antibacterial activities 2 ~ 16 times higher than those of ceftazidime (CAZ) against Staphylococcus aureus and other Gram-positive bacteria including MRSA. Against Gram-negative bacteria, CPR showed a somewhat broad range of distribution in MIC against Branhamella catarrhalis, while the antibiotic inhibited the growth of all the strains of Escherichia coli and Haemophilus influenzae at concentrations no more than 0.l0 and 0.20 μg/ml, respectively. 2. Blood Concentrations and Urinary Excretion Rates. The pharmacokinetics in pediatric patients was investigated with a dose of 20 mg/kg in most cases via one shot intravenous injection or 30- and 60-minute intravenous drip infusion. Mean blood concentrations of CPR at 15 minutes after one shot intravenous injection of 10, 20, and 40 mg/kg were 51.2, 70.5, and 123.5 μg/ml, with half-lives of 1.21, 1.39 and 1.53 hours, respectively. Urinary excretion rates in 6 hours were 63.6, 66.0 and 71.6%, respectively for the 3 dose levels. After 30- and 60-minute intravenous drip infusions at the same dose, the pharmacokinetic parameters observed were similar to those obtained with one shot injections. 3. Concentration in the Cerebrospinal Fluid. CPR penetrated well into the cerebrospinal fluid in patients with purulent meningitis and levels of l.85 ~ 24.2 μg/ml 45 ~ 60 minutes were achieved after intravenous injection at a dose of 40 ~ 80 mg/kg, the penetration rate of CPR was at an intermediate degree compared with other cephalosporin antibiotics. 4. Clinical Results. Clinical efficacies of CPR on infectious diseases were analyzed in 454 plus 3 cases which were complicated with other infectious diseases, hence totaling 457 cases out of 499 cases originally chosen for clinical evaluation. The remaining 45 cases were excluded from the clinical evaluation. As for the clinical efficacy, CPR was found to be effective (good or excellent) in 430 (94.1%) of the 457 cases. CPR was found to be effective in 243 (95.3%) of 255 cases for which causative bacteria were identified. The efficacy rate was 92.6% (187 of 202) in those cases in which causative bacteria were not identified. All these figures indicated a high efficacy of CPR. As for clinical efficacies according to different causative bacteria, CPR showed a high efficacy rate of 95.0% for infections with Gram-positive bacteria including S. aureus, and this value was as high as the efficacy rate for Gram-negative bacteria, 95.7%. The efficacy rate was also equally high (94.4%) for polymicrobial infections. As for bacteriological effects on the basis of different causative bacteria, a total number of 266 bacterial strains out of 276 strains that had been identified as causative bacteria was eliminated, thus representing an excellent eradication rate of 96.4%. As for the eradication of Gram-positive bacteria, a high eradication rate of 89.5% (34 out of 38 strains) was observed for S. aureus and for Streptococcus pneumoniae an eradication rate of 97.4% (37 out of 38 strains) was obtained. The overall eradication rate for Gram-positive bacteria was 95.1%. Among Gram-negative bacteria, an eradication rate of 96.6% (85 out of 88 strains) was obtained for H. influenzae. All of B. catarrhalis (12 out of 12 strains), E. coli (43 out of 43 strains), Klebsiella pneumoniae (5 out of 5 strains), and of Pseudomonas aeruginosa (3 out of 3 strains) were eradicated. As for the clinical efficacy of CPR in 135 cases which had not been responsive to other antibiotics, CPR showed good or excellent effects in 126 of 135 cases, representing a high efficacy rate of 93.3%. 5. Side Effects and Laboratory Test Results. The safety was evaluated in 492 of 499 cases, excluding 7 cases of non-compliance due to concomitant uses of other antibiotics, insufficient in durations of administration, etc. Twenty three symptoms of side effects, e.g., diarrhea, stools loose, eruption, etc., were observed in 20 cases. Most side effects occurred in the digestive system. As for abnormal laboratory test values, we obtained 142 abnormal findings including increased levels of GOT, GPT, total bi1irubin and creatinin, thrombocytosis, thrombocytopenia, eosinophilia, and leukopenia in 101 cases (20.5%). All the side effects and abnormal laboratory test values observed were normalized during the administration or by discontinuance of the administration, and none of them were found to be serious.

AB - A recearch group was organized with the purpose of making basic and clinical studies on cefpirome sulfate (HR810, CPR), a newly developed cephalosporin antibiotic, in the pediatric field. Through meetings a joint research was done involving 19 key institutions and their related facilities throughout Japan. The obtained results are summarized as follows. 1. Antibacterial Activities, Minimum inhibitory concentrations (MICs) were determined against 71 Gram-positive and 110 Gram-nagative bacteria in the present clinical trials. CPR showed antibacterial activities 2 ~ 16 times higher than those of ceftazidime (CAZ) against Staphylococcus aureus and other Gram-positive bacteria including MRSA. Against Gram-negative bacteria, CPR showed a somewhat broad range of distribution in MIC against Branhamella catarrhalis, while the antibiotic inhibited the growth of all the strains of Escherichia coli and Haemophilus influenzae at concentrations no more than 0.l0 and 0.20 μg/ml, respectively. 2. Blood Concentrations and Urinary Excretion Rates. The pharmacokinetics in pediatric patients was investigated with a dose of 20 mg/kg in most cases via one shot intravenous injection or 30- and 60-minute intravenous drip infusion. Mean blood concentrations of CPR at 15 minutes after one shot intravenous injection of 10, 20, and 40 mg/kg were 51.2, 70.5, and 123.5 μg/ml, with half-lives of 1.21, 1.39 and 1.53 hours, respectively. Urinary excretion rates in 6 hours were 63.6, 66.0 and 71.6%, respectively for the 3 dose levels. After 30- and 60-minute intravenous drip infusions at the same dose, the pharmacokinetic parameters observed were similar to those obtained with one shot injections. 3. Concentration in the Cerebrospinal Fluid. CPR penetrated well into the cerebrospinal fluid in patients with purulent meningitis and levels of l.85 ~ 24.2 μg/ml 45 ~ 60 minutes were achieved after intravenous injection at a dose of 40 ~ 80 mg/kg, the penetration rate of CPR was at an intermediate degree compared with other cephalosporin antibiotics. 4. Clinical Results. Clinical efficacies of CPR on infectious diseases were analyzed in 454 plus 3 cases which were complicated with other infectious diseases, hence totaling 457 cases out of 499 cases originally chosen for clinical evaluation. The remaining 45 cases were excluded from the clinical evaluation. As for the clinical efficacy, CPR was found to be effective (good or excellent) in 430 (94.1%) of the 457 cases. CPR was found to be effective in 243 (95.3%) of 255 cases for which causative bacteria were identified. The efficacy rate was 92.6% (187 of 202) in those cases in which causative bacteria were not identified. All these figures indicated a high efficacy of CPR. As for clinical efficacies according to different causative bacteria, CPR showed a high efficacy rate of 95.0% for infections with Gram-positive bacteria including S. aureus, and this value was as high as the efficacy rate for Gram-negative bacteria, 95.7%. The efficacy rate was also equally high (94.4%) for polymicrobial infections. As for bacteriological effects on the basis of different causative bacteria, a total number of 266 bacterial strains out of 276 strains that had been identified as causative bacteria was eliminated, thus representing an excellent eradication rate of 96.4%. As for the eradication of Gram-positive bacteria, a high eradication rate of 89.5% (34 out of 38 strains) was observed for S. aureus and for Streptococcus pneumoniae an eradication rate of 97.4% (37 out of 38 strains) was obtained. The overall eradication rate for Gram-positive bacteria was 95.1%. Among Gram-negative bacteria, an eradication rate of 96.6% (85 out of 88 strains) was obtained for H. influenzae. All of B. catarrhalis (12 out of 12 strains), E. coli (43 out of 43 strains), Klebsiella pneumoniae (5 out of 5 strains), and of Pseudomonas aeruginosa (3 out of 3 strains) were eradicated. As for the clinical efficacy of CPR in 135 cases which had not been responsive to other antibiotics, CPR showed good or excellent effects in 126 of 135 cases, representing a high efficacy rate of 93.3%. 5. Side Effects and Laboratory Test Results. The safety was evaluated in 492 of 499 cases, excluding 7 cases of non-compliance due to concomitant uses of other antibiotics, insufficient in durations of administration, etc. Twenty three symptoms of side effects, e.g., diarrhea, stools loose, eruption, etc., were observed in 20 cases. Most side effects occurred in the digestive system. As for abnormal laboratory test values, we obtained 142 abnormal findings including increased levels of GOT, GPT, total bi1irubin and creatinin, thrombocytosis, thrombocytopenia, eosinophilia, and leukopenia in 101 cases (20.5%). All the side effects and abnormal laboratory test values observed were normalized during the administration or by discontinuance of the administration, and none of them were found to be serious.

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