Tazobactam/Piperacillin (TAZ/PIPC) is a newly developed intravenous antibiotics, in which TAZ, a new potent inhibitor of β-lactamases, is combined with PIPC, a well-established beta-lactam antibiotics, at the ratio of 1: 4. In this study, we clinically evaluated efficacy of the drug in 14 pediatric patients with vaious infections, and pharmacokinetic study was applied to 3 patients. Range of age was from 1-month to 15 1/4-year. Patients consisted of 9 cases of pneumonia, 3 urinary tract infection, 1 acute otitis media, and 1 left sacroiliitis with sepsis. Standard dose of TAZ/PIPC was 50 mg/kg/dose and administered 2-4 times per day with intravenous injection or drip infusion. Two cases of pneumonia were excluded because of non-bacterial infection. Nine causative pathogens including 3 Gram-positive cocci and 6 Gram-negative bacilli were detected in 7 patients, of which 5 Gramnegative strains produced bete-lactamase. All of cases showed 100% of efficacy rate and bacteriological eradication rate. It was noted that β-lactamase-producing E. coli and B. catarrhalis were eradicated efficiently by TAZ/ PIPC, which should be resistant to PIPC alone according to MIC data. Non-serious diarrhea and discomfort of back with nausea were observed in one each patients as side effects. Both of side effects were transient, and improved with anti-diarrheic agent or cessation of the drug, respectively. As abnormal laboratory test results, moderate increases of the eosinophils and platelets counts as well as moderate elevation of the transaminases were observed in 2 separate patients. Pharmacokinetics study showed that C_max, T_1/2, and AUC were similar to the data reported in adult patients. Urinary recovery rate in the first 6 hours also resemble the data from adult patients.
Based on above results, TAZ/PIPC is a useful agents pediatric infections by β-lactamase producing strains also.

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Tazobactam/piperacillin (TAZ/PIPC) was given intravenously to 15 children with acute bacterial infections including 1 with purulent tonsillitis, 11 with pneumonia, 3 with acute pyelonephritis (2 cases are omitted from evaluation because of Mycoplasma pneumonia and intramuscular injection of gammaglobulin).
Daily dosages per kg bodyweight ranging from 132 to 156 mg were given in 3 devided doses per day for 4 to 7 days.
Clinical responses were excellent in 7 (54%), good in 6 (46%), fair and poor in 0, with an overall efficacy rate of 100%.
Good bacterial responses were obtained in all of the 8 cases from which pathogens were identified.
Any side effect was not observed.
The above results suggest that TAZ/PIPC is a useful new antibiotic for the treatment of bacterial infections in children.

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Pharmacokinetic and clinical evaluation was conducted on the combination drug, tazobactam/piperacillin (TAZ/PIPC, YP-14), of newly developed β-lactamase inhibitor, tazobactam (TAZ), and antibiotic agent of penicillin group for injections, piperacillin (PIPC), and the following results were obtained.
1. Absorption and excretion
Both serum levels of TAZ and PIPC after the intravenous drip infusion for 30 minutes at the dose of 25 mg/kg or 50 mg/kg of TAZ/PIPC showed peaks at the end of the intravenous drip infusion (in 30 minutes after the commencement of the administration) with the levels of 11.93 or 26.05μg/ml for TAZ and 49.80 or 107.50μg/ml for PIPC. The halflife times were 0.51 or 0.67 hours for TAZ and 0.51 or 0.54 hours for PIPC. The serum level of desethyl-piperacillin (DEt-PIPC), an active metabolite of PIPC, showed a peak one hour after the end of the intravenous drip infusion (in 90 minutes after the commencement of the administration) with the level of 0.79 or 1.47μg/ml.
On the other hand, cumulative recovery ratios into urine were 41.3% or 40.4% for TAZ and 38.7% or 37.8% for PIPC. The recovery ratio for DEt-PIPC, an active metabolite of PIPC, was 1.9% or 0.3%.
2. Clinical evaluation
TAZ/PIPC was administered to 47 cases (pneumonia: 25 cases, bronchitis: 16 cases, cutaneous soft tissue infection: 3 cases, urinary tract infection: 2 cases and lymphadenitis: 1 case). Clinical efficacy evaluation was conducted in 45 cases, excluding one case with bronchitis complicated by measles and other one case with left cervical cellulitis complicated by mumps. Good or more efficacy was observed in the all cases (excellent efficacy: 28 cases and good efficacy: 17 cases).
The eradication rate in 31 cases where the pathogenic bacteria were identified and bacteriological efficacy was revealed was 93.5% (29/31 cases). Out of them, bacterial replacement was observed in 5 cases. Decrease in bacteria (including partial eradication) was observed in the remaining 2 cases.
Adverse reactions were not reported in any cases. Abnormal values of clinical laboratory examination were reported in 5 cases (increase in platelet count: 2 cases, decrease in leukocyte count: 2 cases and increase in eosinophil count: 1 case). However, there was no case requiring any treatment.

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Pharmacokinetic, bacteriological and clinical studies were performed in pediatrics on tazobactam/ piperacillin (TAZ/PIPC), a combined drug of a new β-lactamase inhibitor tazobactam and piperacillin at a ratio of 1: 4.
1. Serum levels and urinary excreations of TAZ, PIPC and desethyl piperacillin (DEt-PIPC), a metabolite of PIPC, after one shot intravenous administration of 50 mg/kg of TAZ/PIPC to two children (6-7 years old) were investigated.
The serum TAZ level at 0.08 hour was 50.8-51.0 μg/ml after administration. Then TAZ concentrations gradually decreased with half-lives of 0.38-0.45 hour, and reached 1.0-1.4 μg/ml after 2 hours and was not detected after 3 hours and 6 hours.
Serum PIPC levels at 0.08 hour was 167.0-231.0 μg/ml after administration. Then PIPC concentrations gradually decreased with half-lives of 0.41-0.55 hour, and reached 1.2-2.4 μg/ml after 3 hours and was not detected after 6 hours. DEt-PIPC was detected slightly in serum. A ratio of TAZ to PIPC was about 1 to 4 in serum at each time.
Urinary recovery rates of TAZ in the first 6 hours after administration of TAZ/PIPC were 33.5-90.1% and those of PIPC were 41.9-77.8% and those of DEt-PIPC were 1.5-2.8%.
2. TAZ/PIPC was administered to 27 pediatric patients (their ages ranged between 2 months and 11 years old) with various infections, and clinical and bacteriological effects and adverse reactions were investigated. Single doses were 26.2-55.6 mg/kg, frequencies of administration were 3-4 times a day, and durations of administration were 3 1/3-71/3 days, and total dosages were 4.5-33.75g. Clinical effects were evaluable in 26 cases.
Responses were rated as “good” in acute purulent tonsillitis 1 case and acute purulent otitis media 1 case, as “excellent” in acute sinusitis 1 case, as “excellent” in 2 and “good” in 1 out of 3 cases of acute bronchitis, as “excellent” in 13 and “good” 2 out of 15 cases of acute pneumonia, as “excellent” in acute urinary tract infection 2 cases and as “excellent” in acute enteritis in 1 case, acute appendicitis in 1 case and lymphadentis in 1 case. In all cases, the results were rated as “good” or “excellent”.
Antimicrobial effects against a total of 10 strains identified or assumed to be pathogenic bacteria were evaluated. The 10 strains of bacteria included 4 strains of Streptococcus pneumoniae, 3 strains of Haemophilus influenzae (2 strains β-lactamase producing), 2 strains of β-lactamase producing Moraxella catarrhalis, 1 strain of β-lactamase producing Morganella morganii. All the bacteria listed here were judged to have been eradicated. Adverse reaction was observed in 1 case with mild diarrhea. As abnormal changes in laboratory data, leucocytopenia in 1 case, elevation of GOT·GPT in 2 cases and eosinophilia in 1 case were observed.
On the basis of the findings, TAZ/PIPC was considered to be effective and safe in the treatment of pediatric infections.

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