[Bacteriological, pharmacokinetic and clinical evaluations of cefpirome sulfate in the pediatric field. Pediatric Study Group of Cefpirome].
A research 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-negative 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 0.10 and 0.20 micrograms/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 micrograms/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 1.85-24.2 micrograms/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.(ABSTRACT TRUNCATED AT 400 WORDS)
Fujii
R
R
Department of Pediatrics, School of Medicine, Teikyo University.
Abe
T
T
Meguro
H
H
Tajima
T
T
Nakazawa
S
S
Sato
H
H
Hirama
Y
Y
Narita
A
A
Matsumoto
K
K
Nakazawa
S
S
D000293:Adolescent; D000367:Age Factors; D001419:Bacteria / Q000187:drug effects* / Q000302:isolation & purification; D001424:Bacterial Infections / Q000188:drug therapy* / Q000378:metabolism; D002511:Cephalosporins / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004352:Drug Resistance, Microbial; D006801:Humans; D007223:Infant; D000097572:Cefpirome
D002511:Cephalosporins; D000097572:Cefpirome