Cefprozil (CFPZ), a newly developed oral cephalosporin in a fine granular form for pediatric use, was administered to children with bacterial infections. MICs were determined for 6 drugs including CFPZ, cephalexin (CEX), cefaclor (CCL), ampicillin (ABPC), methicillin (DMPPC) and cloxacillin (MCIPC) against the following 84 strains isolated from cases to which CFPZ was administered; 55 strains of Gram-possitive cocci (GPC) including 2 strains of
Staphylococcus aureus, 49 strains of
Streptococcus pyogenes, 4 strains of
Streptococcus pneumoniae, and 29 strains of Gram-negative bacilli (GNB) including 10 strains of
Haemophilus influenzae, 18 strains of
Escherichia coli, and 1 strain of
Proteus mirabilis. MIC determination of these strains was done with an inoculum size of 10
6 CFU/ml.
In pharmacokinetic studies, serum concentrations, urinary concentrations and urinary recovery rates were investigated using bioassay and high-performance liquid chromatography (HPLC). CFPZ was orally administered 30 minutes before meals to 9 children with ages ranging from 7 years and 1 month to 12 years and 3 months. Three groups of 3 children were tested with doses of 4.0, 7.5 and 15.0 mg/kg, respectively.
In addition to the above, clinical and bacteriological studies were performed in a total of 160 cases consisting of children with ages ranging 5 months to 12 years and 5 months. A mean dose of 8.6 mg/kg in 3-4 divided doses (130 cases of t. i. d. and 30 cases of q. i. d.) was administered for an average of 7 days. The 160 cases included 34 cases of pharyngitis, 5 cases of tonsillitis, 8 cases of acute bronchitis, 8 cases of pneumonia, 52 cases of scarlet fever, 4 cases of acute purulent otitis media, 47 cases of urinary tract infection, 1 case of purulent lymphadenitis and 1 case of posthitis. Adverse reactions and abnormal clinical laboratory test results were also examined in 166 cases, including 6 cases excluded from the evaluation of clinical efficacy. The results obtained are summarized as follows:
1. With regard to GPC, MICs of CFPZ against 2 strains of
S. aureus were 0.78 or 1.56μg/ml and CFPZ showed the second highest activity to MCIPC. MICs of CFPZ against 49 strains of
S. pyogenes were all less than 0.025μg/ml. These MIC values were the same as those of ABPC and superior to those of the other 4 drugs. MICs against 4 strains of
S. pneumoniae ranged from 0.20 to 1.56μg/ml, these values were the same as or similar to those of DMPPC and MCIPC and superior to those of CEX and CCL, but inferior to those of ABPC.
Regarding GNB, all MICs against 10 strains of
H. influenzae were 1.56 or 3.13μg/ml and the MIC
90 of CFPZ was 3.13μg/ml. It was similar to those of CCL and DMPPC, lower than those of CEX and MCIPC and higher than that of ABPC. MICs against 18 strains of
E. coli ranged from 0.78 to 50μg/ml and the MIC
90 was 12.5μg/ml. These MIC values were similar to those of CEX and CCL and superior to those of ABPC, DMPPC and MCIPC. MIC against 1 strain of
P. mirabilis was 1.56μg/ml, and was similar to the MICs of CCL and ABPC and superior to the MICs of CEX, DMPPC and MCIPC.
2. CFPZ was administered to 9 cases at 4.0, 7.5 and 15.0mg/kg, respectively, for 3 cases each and serum concentration was determined by bioassay. Average peak concentrations for each dose group were 3.18, 3.88 and 8.43μg/ml, respectively. Thus a dose response was observed between the 4.0 or 7.5 mg/kg and 15.0mg/kg dose groups.
Average half-lives for the 3 groups were very similar, 1.0, 1.2 and 1.1 hours, respectively. Mean AUCs were 7.8, 9.9 and 25.2μg·hr/ml, respectively and a dose response was observed between the 4.0 or 7.5mg/kg and 15.0mg/kg dose groups. The mean pharmacokinetic parameters determined by the HPLC method showed similar results to those of bioassay.
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