Antimicrobial activity of ceftazidime (CAZ) was compared with those of other cephem antibiotics against clinically isolated strains sent to us by medical institutions throughout Japan in 1989 and 1991. Those strains separated and identified from samples collected from patients with various infections were also examined, and the following results were obtained.
1. The results suggested that, compared with reports of studies conducted with clinical isolates in early 1980's, MIC₉₀ of CAZ in 1991 were markedly higher against Staphylococcus spp., Streptococcus pneumoniae, Escherichia coli, Enterobacter spp., Serratia marcescens, Proteus vulgaris, Morganella morganii, and Pseudomonas aeruginosa. Also, among other bacteria such as Providencia rettgeri, Providencia stuartii, Xanthomonas maltophilia, and Bacteroides fragilis group, strains resistant to CAZ were observed in high proportions.
However, large time-course changes were not observed in microbial activities of CAZ on Streptococcus pyogenes, Klebsiella spp, Proteus mirabilis, Pseudomonas cepacia, Acinetobacter calcoaceticus, Haemophilus influenzae and Anaerobic GPC (Gram-positive cocci).
2. Among the strains used in the study, methicillin-resistant Staphylococcus aureus (MRSA), Benzylpenicillin (PCG)-insensitive S. pneumoniae (PISP), cephamycin and oxime type cephemresistant Gram-negative bacilli of Enterobacteriaceae and new quinolone-resistant organisms wereobserved in high proportions. It appears therefore, that CAZ failed to exert sufficient antimicrobial activities to these strains because of combination of resistance in these strains.
3. Antimicrobial activities of CAZ on recent clinical isolates showed problems as mentioned above. However, it was also demonstrated that CAZ maintained effective antimicrobial activities against most of the clinical isolates which could be causative organisms of infectious diseases in the clinical practice. When it is additionally taken into account that CAZ is one of those limited drugs with activity against P. aeruginosa, and it has excellent permeability through outer membrane, it is concluded that CAZ still is one of the clinically useful cephem drugs in 1990's.

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The authors studied antimicrobial activities of cefetamet (CFMT) and other leading oral antimicrobials of β-lactam class against clinically isolated strains from urban respiratory tract infection (RTI) patients from January to March, 1992.
1. CFMT showed potent antimicrobial activities against “3 primary pathogens” of RTIs i. e., Streptococcus pyogenes, Streptococcus pneumoniae, and Haemophilus influenzae, but the drug had a slightly higher MIC than those of a few oxime-type cephems already on the market.
2. CFMT was as stable as cefixime to β-lactamase, generated by Moraxella subgenus Branhamella catarrhalis, which reduces the antimicrobial activity of cephems.
3. Blood concentrations of CFMT after administering cefetamet pivoxil (CFMT-PI), an oral form of the drug, exceeded the MIC₈₀, against the “3 primary pathogens” as well as M.(B) catarrhalis and Klebsiella pneumoniae, for a duration of approximately 9 and 11 hours, respectively, after single doses of 250 and 500mg. This suggests that CFMT could remain above the MICs for a sufficient time period with twice daily dosages of normal dose levels.
4. It is concluded that CFMT-PI will be useful for treating urban RTIs.

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Cefuzonam (CZON) was used to treat severe infections in 151 patients with hematopoietic disorders, and its efficacy and safety were assessed. The drug was given in doses of 2.0 to 6.0g a day, divided into 2 or 3, intravenously by injection or infusion.
The clinical effects were excellent in 34 cases, good in 40 cases, fair in 5 cases, and poor in 57 cases.
Therefore, the results were excellent or good in 54.4% of the patients treated. The efficacy rates were 43.8 and 35.9% for groups of patients whose neutrophil counts were 500/μl or less and 100/μl or less, respectively. It was excellent or good in 70.6% of patients in whom causative agents were identified, and in 66.7 and 80.0% of patients infected with Gram-negative and-positive bacilli, respectively. The efficacy rate for patients infected with unidentified agents was 52.1%.
The rate for patients who had received other antibiotics previously was 41.5%. The rate for patients having received only one antibiotic for the preceding treatment was 50.0%.
Six (3.9%) of the treated patients experienced adverse effects including changes in laboratory test results observed in 4.

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The Pharmacokinetics of cefprozil was studied upon oral administration of 25mg/kg to fasted infant and adult Beagle dogs.
When the pharmacokinetic parameters between infant and adult dogs were compared, the mean peak concentration (C_max) in infant dogs (21.2 μg/ml) was significantly (P<0.01) lower than that of adult dogs (27.8 μg/ml). But significant differences were not found in the areas under the concentration-time curve (AUC, in infant dogs: 121 μg·hr/ml, in adult dogs: 130 μg·hr/ml), half-lives (T 1/2, in infant dogs: 4.7 hours, in adult dogs: 4.7 hours) or urinary recovery rates (UR, in infant dogs: 36.3%, in adult dogs: 34.7%) between the 2 groups.
These results suggest the distribution volumes of infant dogs are larger than those of adult dogs, and the absorption rates of infant dogs are slower than those of adult dogs, whereas the absorption quantities are similar.

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Cefprozil (CFPZ, BMY-28100), a new oral cephalosporin antibiotic, was studied for its effect on the intestinal bacterial flora in pediatric patients.
The subjects were children admitted for infections (2 males and 2 females, 9 months to 6 years 3 months old, weighed 4.3 to 19.0kg). CFPZ granule was orally administered at a dose between 10.0 to 11.6mg/kg, 3 doses daily, over 4 to 14 days. The feces from these children were collected before, during and after administration, and bacteria were identified and counted. CFPZ concentration, β-lactamase activity were also assayed.
Bacterial flora in feces during CFPZ administration showed some variance, but no significant change was observed in main aerobes and anaerobes. And in no case, glucose nonfermentative Gram-negative bacilli or fungi were found dominant. β-Lactamase activity was positive in the feces in all cases. CFPZ concentrations were not detectalbe in feces before, during and after administration.
The above results suggest that CFPZ is a drug with little influence on the intestinal bacterial flora in children.

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The absorption and excretion were studied in the field of pediatrics, and pharmacokinetic analyses were performed.
1. Influence of food: Cefprozil (CFPZ, BMY-28100) was given to 6 school children in a before and after meal cross over design. With before meal administration, T_max. was 1.11±0.08 hours, C_max was 5.08±0.27 μg/ml, T 1/2 was 0.77±0.09 hour, and urinary recovery rate (0-8 hours) was 55.2±4.7%. With after meal administration, these values were 1.31±0.04 hours, 3.98±0.38 μg/ml, 0.72±0.03 hour and 46.3±9.0%, respectively. A shorter T_max, value was, obtained higher C_max and more or less higher urinary recovery rate when the drug was administered before meal, hence the food was considered to influence the absorption of the drug.
2. Dose effect: CFPZ was given on empty stomach to 6 school children in doses of 7.5mg/kg and 15.0mg/kg in the cross over design. With the lower dose C_max was 6.19±0.36 μg/ml and AUC was 14.90±1.02 μg·hr/ml, and with the higher dose they were 12.38±1.29 μg/ml and 28.56±1.79 μg·hr/ml. Dose effects appeared to exist for CFPZ. A higher urinary recovery rate was obtained at the dosage of 7.5mg/kg (82.1±6.4%) compared to the dosage of 15.0mg/kg (51.1±7.1%).
3. Influence of age: CFPZ was given on empty stomach to 17 school children, 19 younger children and 5 infants. T_max were 1.07±0.09, 1.06±0.07, and 1.40±0.09 hours, respectively for the 3 groups, hence significantly longer T_max was observed in infants. C_max were higher in older children and they were 5.62±0.38, 4.72±0.53 and 4.05±0.33 μg/ml, in the 3 age groups, respectively. T 1/2 were 0.73±0.04, 0.78±0.09 and 0.98±0.12 hour, respectively, it was longer in infants. The AUCs were not different among the 3 groups, but different urinary recovery rates were obtained with higher recovery in school children, with values of 64.1±4.3, 44.3±3.8 and 51.6±3.3%, respectively.

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Cefprozil (CFPZ, BMY-28100) was evaluated for its efficacy, safety and pharmacokinetics in children.
CFPZ was effective against streptococcal pharyngitis, pneumococcal lower respiratory tract infections, staphylococcal skin infections and Escherichia coli urinary tract infections, but was less effective against lower respiratory tract infections and otitis media due to Haemophilus influenzae. No adverse reactions were encountered in 46 cases treated with CFPZ. With a premeal administration of 7.5mg/kg, the C_max was approximately 3.2 μg/ml and the T 1/2β was 1.4 hours.
From the present study, CFPZ appears to be safe and effective against community-acquired childhood infections.

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Cefprozil (CFPZ, BMY-28100) granules was administered to a group of pediatric patients. The new oral cephalosporin, CFPZ, was evaluated clinically in 42 pediatric patients, and a pharmacokinetic study was performed in 6 patients.
Serum and urinary concentrations of CFPZ were determined in 6 patients who were given single dose of 7.5 or 15.0mg/kg. Serum concentrations were determined at 1, 2, 3, 4 and 6 hours after dosing. Urinary concentrations were measured for periods of 0-6 hours after dosing.
With oral administrations of 7.5mg/kg and 15.0mg/kg, peak serum concentrations were 2.13 μg/ml and 6.22 μg/ml, respectively, at 2 hours, and biological half-lives were 1.06 hours and 1.36 hours, respectively. Urinary recovery rates were 44.8% and 56.1%.
The clinical evaluation was conducted in 41 patients including 16 patients with acute tonsillitis, 8 patients with lacunar tonsillitis, 4 patients with scarlet fever, 3 patients with acute bronchitis, 1 patient each with pertussis, furuncle, impetigo and lymphadenitis, and 6 patients with urinary tract infections. The ages of the patients were 10 month to 11 years 1 month, and they were treated with CFPZ at doses ranging 9.0-45.0mg/kg daily for 3-14 days, the overall clinical efficacy rate was 92.7%.
An eradication rate of 79.2% was achieved for 28 strains of 8 species identified in the patients.
No side effects were observed. Abnormal laboratory test results obtained were eosinophilia in 2 patients.

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Fundamental and clinical effects of cefprozil (CFPZ, BMY-28100) granules, a new oral cephalosporin antibiotic, in pediatric field were investigated. The result obtained were summarized as follows.
1. CFPZ (10% granules) was given to 1 child in a single dose of 7.5mg/kg. The peak serum concentration of CFPZ was 4.51 μg/ml at 2 hours after administration. Half-life and AUC values were 0.98 hour and 20.7 μg·hr/ml. The mean peak urinary concentrations of CFPZ and 6 hours recovery rates were over 200 μg/ml at 2-6 hours and 27.6%, respectively.
2. Clinical efficacy of CFPZ was investigated in a total of 41 children, including 14 with upper respiratory tract infections, 6 with acute bronchitis and pneumonia, 2 with acute otitis media, 3 with skin and soft tissue infections and 16 with urinary tract infections. The clinical efficacy rate was 95.1%. The bacteriological eradication rate was 84.6%.
3. Two patients showed abnormal laboratory test results. One had elevations of both GOT and GPT, and another had eosinophilia which were attributed to this antibiotic as side effects.

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Clinical efficacy and safety of cefprozil (CFPZ, BMY-28100), a newly developed oral cephalosporin, were studied in our pediatric department.
Clinical effectiveness, bacteriological effectiveness and side effects were studied in 116 pediatric patients with ages ranging 4 months to 11 years. CFPZ was given 4.6-14.1mg/kg daily in 3 times for 3-10 days.
Clinical efficacies were evaluated in 112 patients, and the therapeutic effectivenesses were excellent in 1 and good in 6 for 7 patients with acute pharyngitis, excellent in 24 and good in 26 for acute purulent tonsillitis, excellent in 3, good in 8 and fair in 1 for acute bronchitis, excellent in 21, good in 7, fair in 1 and poor in 1 for acute pneumonia, excellent in 1 acute purulent parotitis, excellent in 2 and good in 7 for acute UTI, good in 1 impetigo, fair in 1 periproctal abscess and good in 1 acute enteritis. The effectiveness rate was 96.4%.
Bacteriologically, 4 strains of Staphylococcus aureus (β-lactamase producing strains), 1 strain of Staphylococcus epidermidis (β-lactamase producing strain), 2 strains of Streptococcus pneumoniae, 2 strains of Streptococcus agalactiae, 4 strains of β-Streptococcus, 1 strain of Klebsiella pneumoniae (β-lactamase producing strain) and 1 strain of Salmonella C₂ were all disappeared, and of 22 strains of Streptococcus pyogenes, 20 strains were disappeared, 1 was decreased and 1 was unknown, of 5 strains of Escherichia coli (3 β-lactamase producing strains), 4 were disappeared and 1 was decreased, of 29 strains of Haemophilus influenzae (14 β-lactamase producing strains), 14 were disappeared, 11 were decreased, 3 persisted and 1 was unknown and of 2 strains of Haemophilus parainfluenzae (1 β-lactamase producing strain), 1 was disappeared and 1 persisted. The bacteriological eradication rates for Gram-positive bacteria and Gram-negative bacteria were 97.1% and 56.8%, respectively, and the drug was especially effective against Gram-positive bacteria.
No side effects nor refusal of ingestion were observed. As abnormalities in laboratory test results, 3 cases of elevation of eosinophile counts and 1 of elevation of platelet counts were observed.
In conclusion, CFPZ was considered to be a safe and highly effective antibiotic in pediatric infections.

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Laboratory and clinical studies on cefprozil (CFPZ, BMY-28100), a new cephem antibiotic, were carried out in the field of pediatrics. The results obtained are summarized as follows:
1. Serum concentrations, urinary concentrations and urinary recovery rates of CFPZ were determined upon oral administration of CFPZ after meal at doses of 4mg/kg granules in a case, 7.5mg/kg granules in 2 cases and 15mg/kg granules in one. Peak serum levels of CFPZ were obtained at an hour in 3 cases and at 2 hours in 1 case after administration of the drug with a range of 2.7-8.6 μg/ml with half-lives of 0.69-0.95 hours. Urinary recovery rates in the first 6 hours after administration ranged from 59.4-71.3%.
2. MICs of CFPZ against 36 clinical isolates (Staphylococcus aureus 4 strains, Streptococcus pneumoniae 5, Streptococcus pyogenes 5, Escherichia coli 5, Haemophilus influenzae 12, Haemophilus parainfluenzae 4, and Branhamella catarrhalis 1) were compared with those of cefaclor (CCL) and ampicillin (ABPC). The antibacterial activity of CFPZ was superior to those of CCL against Gram-positive cocci, and to those of ABPC against E. coli, and was equal to those of CCL and inferior to those of ABPC against H. influenzae.
3. Thirty-seven pediatric patients with acute infectious diseases (pharyngitis/tonsillitis 17, bronchitis 7, pneumonia 3, skin and soft tissue infection 2, and urinary tract infection 8) were treated with CFPZ at daily doses of 10-47mg/kg t. i. d. as a rule. The efficacy rates were 100% clinically and 56% bacteriologically.
4. Side effects or abnormal laboratory test values were not observed except for an increased platelet count in 1 case and elevated GOT, GPT values in 2 cases.

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Cefprozil (CFPZ, BMY-28100), a new oral cephem antibiotic, was studied for its antibacterial activities, absorption and excretion upon administration. Its clinical efficacies were also studied in pediatric patients with infections.
A study on antibacterial activities of CFPZ against 11 clinical isolates including 6 species found that its activities against Staphylococcus aureus, α-hemolytic Streptococcus, Escherichia coli and Haemophilus influenzae were equal or superior to those of CCL.
When CFPZ was given to patients orally at 15mg/kg, maximam serum concentration was obtained between 1 to 2 hours after administration and urinary excretion rate in the first 6 hours was 33.8±17.6%.
Clinical evaluation was done in a total of 25 patients with various infections. Responses were excellent in 15 cases and good in 10 cases, hence the efficacy rate was 100%.
As side effect, soft stool was found in 1 case, and eosinophilia in 2 cases and elevation of GOT and GPT in 1 case were found as abnormal laboratory test results, but none of them was serious.
It appears that CFPZ is an effective and safe antibiotic in the field of pediatrics.

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Laboratory and clinical studies were done on cefprozil (CFPZ, BMY-28100). The results are summarized as follows. CFPZ was administered through the oral route to 2 children at a single dose of 7.5mg/kg. After administration, peak serum levels of CFPZ obtained in the 2 cases were 6.71 μg/ml at 1 hour and 6.45 μg/ml at 2 hours, respectively and half-lives were 1.28 hours and 0.92 hour, respectively. The urinary excretion rates of CFPZ were 58.9% and 59.4%, respectively. Treatment with CFPZ was made in 37 cases of pediatric bacterial infections: 1 case of pharyngitis, 16 cases of tonsillitis, 16 cases of scarlet fever, 3 cases of impetigo, 1 case of UTI. Results obtained were excellent in 24 cases, good in 13 cases. No significant side effects due to the drug were observed, except 1 case of loose stool, 3 cases of eosinophilia, and 1 case each of elevated GOT and GPT.

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Cefprozil (CFPZ, BMY-28100) granule preparation was studied for pharmacokinetic, bacteriological and clinical aspects in the pediatric infections. The results obtained are summarized as follows:
1. Serum concentrations and urinary excretion.
The pharmacokinetics of CFPZ in pediatrics was investigated by single oral administration of fine granules at doses of 4.0, 7.5 and 15.0mg/kg. Peak blood levels of CFPZ were 3.06, 4.62 and 9.65 μg/ml, respectively, at 1.00-1.30 hours after each dose and AUCs were 7.44, 12.50 and 27.01 μg·hr/ml, respectively. These data showed that C_max AUC depended on dose levels. T 1/2 (163) at these dose levels were 1.03, 0.94 and 1.01 hours, respectively. There were no differences related to dose. Urinary recovery rates in the first 6 hours after administration were 51.5-57.1%. The pharmacokinetics of CFPZ before or after meals were also investigated at a dose of 7.5mg/kg. Peak blood levels were 4.88 μg/ml at 1.17 hours after administration in the fasting state, and 4.30 μg/ml at 1.54 hours after administration in the non-fasting state. Delay of T_max and slight decrease of C_max were observed in the non-fasting state, but T 1/2 and AUC were 0.91 hour and 12.96 μg·hr/ml, respectively, in the non-fasting state, and were similar to those in the fasting state, 0.93 hour and 12.82 μg·hr/ml, respectively. Urinary recovery rates in the first 6 hours after administration were 63.8% in the fasting state and 50.7% in the non-fasting state.
2. Clinical results.
Clinical efficacies of CFPZ granules in various infectious diseases were studied in 804 cases. Twenty nine cases, mostly viral or mycoplasmal infections, were excluded from the statistical analysis.
The clinical efficacy rate in 527 cases with causative bacteria isolated was 97.2%; and in 248 cases from whom no significant isolate had been obtained was 96.0%.
The clinical efficacy rate in 475 cases with monobacterial infections (proven by culture of isolates) was 97.3%, and that in 52 case with polybacterial infections was 96.2%.
Haemophilus influenzae was isolated mostly from acute respiratory infections. In 88 cases from whom H. influenzae was isolated, clinical efficacy rate was 95.5%. In cases from whom H. influenzae was found concomitant by with Staphylococcus aureus, Streptococcus pyogenes or Streptococcus pneumoniae, the clinical efficacy rates were also high. The bacteriological eradication rate in cases with 582 strains was 83.3%; the eradication rate for Gram-positive organisms was 95.8%; and for Gram-negative organisms, it was 64.2%.
The clinical efficacy rate for cases who were non-responsive to previous antibiotic therapies given for more than 3 days was 89.1% with a bacterial eradication rate of 79.4%.
3. Side effects and clinical laboratory findings.
As for clinical adverse reactions, soft stool occured in 3, diarrhea in 3, and pale complexion and nausea in 1 patient. Laboratory tests revealed abnormal values of eosinophilia, granulocytopenia, and slight elevations of platelet, GOT and GPT. However, these side effects and abnormalities in laboratory test results were not serious and all were normalized after discontinuation of the drug or even while drug administration was continued.
4. Palatability of CFPZ.
Only 4 out of 803 cases complained of a slight bitter taste of CFPZ. But even they did not refuse CFPZ. CFPZ was considered to be one of the easiest drugs to take.
5. The optimal dose of CFPZ was 7.5mg/kg 3 times a day.

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