Eighteen patients received 2.0 grams of piperacillin sodium (PIPC) intravenously. The concentrations of PIPC in serum, cancellous bone, and cortical bone were measured approximately 30 minutes after injection. Serum concentrations ranged from 9.10 to 167.0μg/ml (mean 95.61 ± 10.03μg/ml). Cortical bone concentrations varied between 0 and 17.5μg/g (mean 4.58 ± 1.03μg/g). The levels measured in cancellous bone ranged from 0.62-13.1μg/g (mean 8.07 ± 1.43μg/g). PIPC achieved high concentrations in bone.

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The predisposing factors of funguria and the clinical efficacy of treatment with ketoconazole, a new oral imidazole antifungal drug were studied in 10 patients with complicated urinary tract infection due to fungi.
Preceding antibiotic therapy, presence of indwelling catheter and malignant tumor were regarded as the important factors that predisposed to the fungal urinary tract infections.
Patients received 200mg of ketoconazole once a day for 5 to 14 days. Of the 9 patients in whom clinical efficacy of ketoconazole was evaluated, excellent response was obtained in 4 patients, moderate in 2 and poor in 3 patients. Of the 9 strains of fungi isolated before treatment, 6 strains or 67% were eradicated after treatment.
Neither subjective nor objective side effects were observed in any of 10 patients receiving ketoconazole, and laboratory tests showed elevated BUN and serum creatinine in 1 patient.
From the results obtained in this study, ketoconazole was regarded as useful in the treatment of complicated urinary tract infection due to fungi.

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Blood levels and urinary excretion of cefmenoxime (CMX) in children of 8 to 13 years old who received 50mg/kg of CMX by one shot intravenous injection or 1-hour drip infusion were evaluated.
1. One shot intravenous injection
(1) Blood levels
The mean blood levels in 2 cases by intravenous injection were 125.0±24.0, 56.8±10.0, 17.8±6.2, 2.2±0.7 and 0.4±0.2μg/ml, after 1/2, 1, 2, 4 and 6 hours, respectively.
The mean biological half-life was approximately 0.7 hour.
(2) Urinary excretion
The average urinary excretion rate in 2 cases were 57.8, 63.9 and 64.1% after 2, 4 and 6 hours, respectively.
2. 1-hour drip infusion
(1) Blood levels
The mean blood levels in 2 cases by drip infusion were 115.5±0.5, 29.05±0.25, 5.0±0.8 and 1.15±0.45μg/ml, immediately after the completion of infusion, after 1, 3 and 5 hours, respectively.
The mean biological half-life after drip infusion was approximately 0.8 hour.
(2) Urinary excretion
The average urinary excretion rate in 2 cases were 42.2, 55.5 and 56.5% after 2, 4 and 6 hours, respectively.
On the basis of these results, it was concluded that CMX was excreted relatively rapidly in a massive dose of 50mg/kg a time.

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Transfer of cefmenoxime (CMX) into the burn blister fluids was studied in 10 burned patients with 2 administrated doses (25, 50mg/kg). CMX concentrations in serum and burn blister fluid after 1 hour intravenous drip infusion were measured using Proteus mirabilis ATCC 21100 as the test organism grown in the DST agar medium.
In the case of CMX 25mg/kg dose, the peak serum concentration was observed 61.5μg/ml at 1 hour, while the peak burn blister fluid concentration was observed 15.2μg/ml at 2 hours. Pharmacokinetic parameters of serum concentration calculated were 1.02 hours as half-life (β) and 0.42L/kg as distribution volume, respectively.
In the case of CMX 50mg/kg dose, the peak serum concentration was observed 122.0μg/ml at 1 hour and the peak burn blister fluid concentration was observed 40.8μg/ml at 2 hours. Pharmacokinetic parameters of serum concentration calculated were 1.27 hours as half-life (β) and 0.55L/kg as distribution volume.
From this study, the dose dependency between 25mg/kg dose and 50mg/kg dose in serum and in burn blister fluid is recognized.

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The effectiveness of miconazole was evaluated in 9 documented fungal infections, 4 of which were candidal sepsis. All patients were receiving therapy for hematological malignancies. Miconazole revealed the excellent effect in 3 patients with candidal esophagitis and 1 patient with candidal sepsis and esophagitis. Twelve patients who received miconazole for presumed or documented fungal infection were evaluated for toxicity. No particular side effects, except for only 1 case of mild hepatic dysfunction, were observed. Miconazole is apparently an effective antifungal agents for treatment of systemic fungal infection in patients with hematological malignancies.

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Prophylactic antimicrobial therapy for the prevention of infection during total joint arthroplasty or spinal surgery was investigated using cefotiam (CTM) and cefmenoxime (CMX), which are cephems having broad antimicrobial spectrum.
Seven patients received 2 g of CTM, and 12 patients 2g of CMX, by intravenous drip infusion over 15 minutes.
Blood, bone marrow and osseous tissue samples were obtained at the end of the infusion, and 30, 60, 90 and 120 minutes after the beginning of the infusion. The concentrations of CTM and CMX were detected by the agar-well method.
CTM and CMX were smoothly distributed from blood to bone marrow and osseous tissue, and kept on the effective concentrations for prophylaxis against postoperative infections. The primary wound healing was obtained in all cases, and no side effects were also recognized.

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Cefaclor (CCL) is a cephem antibiotic for oral use.
Thirty cases of infection of oral regions, in the First Department of Oral and Maxillofacial Surgery, School of Dentistry, the University of Tokushima, were treated with CCL at 750mg/day.
The results were as follows:
1. The efficacy rate for all kinds of diseases was 80.0% in 3 days and 96.7% in 5 days and 86.7% as an overall assessment by the patients' doctors.
2. With regard to the degree of symptoms, the efficacy rate for cases with moderate symptoms was less than that for mild cases in 3 days and according to the assessment by the patients' doctors.
3. Some moderate cases required increased medication because no beneficial effect was observed.
4. In sensitivity tests, CCL was shown to be effective on all 27 isolated clones of bacteria tested.
5. CCL caused no detectable changes in laboratory data.
6. No side effects were observed in any case.
From these results, it is concluded that CCL is a highly effective antibiotic for use on infections of the oral regions.

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Forty-two pediatric patients were treated with ceftazidime (CAZ) in the doses ranging from 45.6 to 120mg/kg/day for 2 to 10 days, and the clinical efficacy and side effects were evaluated. Among the 37 children with bacterial infections including pneumonia, bronchitis, tonsillitis, croup, cervical lymphadenitis, abdominal abscess and urinary tract infections, the results were excellent in 22, good in 12, fair in 2, and poor in 1 patient with pneumonia. Out of the 42 patients, 5 cases showed eosinophilia, but no clinical sign such as rash, fever or diarrhea, attributable to CAZ was observed during the study.
The serum concentrations of CAZ in 4 patients ranged from 60.8 to 71.0μg/ml (mean 66.1μg/ml) at 30 minutes and from 0.5 to 1.2μg/ml (mean 0.8μg/ml) at 8 hours after 20mg/kg intravenous bolus injection of the antibiotic. The mean serum half-life was 1.42 hours (85 minutes). Patients with impairment of renal function were excluded from this study.

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Thirteen patients mainly with lower respiratory tract infections were treated with ceftazidime (CAZ). The drug was given intravenously in a dose of 11-34mg per 1kg of body weight 2-3 times per day. The clinical response to treatment was satisfactory in 10 patients (76.9%). There was no side effects. CAZ appears to be an safe and effective antibiotic for the treatment of children with bacterial infections.

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1. Clinical responses of ceftazidime (CAZ) in 13 cases of respiratory tract infections were excellent in 7 and good in 6, and those in 4 of urinary tract infections were excellent in 1 and good in 3. Clinical responses of CAZ in 3 cases of acute gastroenteritis were good in 1 and fair in 2. CAZ was considered to be effective both in respiratory and urinary tract infections; however, CAZ did not seem to be very effective clinically in gastrointestinal infections.
2. As to side effects, slight elevation of GOT was observed in 3 cases and skin rash in 1 case, but all these abnormalities were mild and transient.

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Ceftazidime (CAZ) is a newly developed cephalosporin. Clinical studies on this drug was carried out and the results were as follows.
Twenty-nine patients (acute purulent tonsillitis 2, acute bronchitis 1, pneumonia 15, acute purulent lymphadenitis 2, pyoderma 1, skin abscess 2 and urinary tract infection 6) were treated with CAZ in doses of 42-71mg/kg (mean 59mg/kg) divided 2-3 times per day for 3-10 days (mean 5.7 days) intravenously. The overall efficacy rate was 96.6%.
As to adverse reaction, drug fever was observed in 1 patient. Abnormal laboratory data were noted in 4 cases (elevation of serum GOT, GPT and BUN in 1, elevation of serum GOT and GPT in 1, elevation of BUN in 1 and leukopenia in 1).

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We have studied ceftazidime (CAZ), a cephem antibiotic of the new generation, for its antibacterial activity against H. influenzae and clinical effects.
1. Antibacterial activity: MICs of CAZ for 142 strains of H. influenzae including 11 ABPC-resistant strains which were clinically isolated, were determined, and the results were good for all the strains.
2. Clinical effects: CAZ was administered to 9 children with infections. Suspected causative organisms were H. influenzae, E. coli, P. aeruginosa, group B Streptococcus and S. pneumoniae. Eradication of these organisms was confirmed in all the strains except for one in which the antibacterial effect of CAZ was unknown. Clinical efficacy was excellent or good in all the cases. No side effect was observed except for eosinophilia noted in 1 case.

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Ceftazidime (CAZ) was evaluated for its safety and efficacy in 31 children. Of the 25 confirmed bacterial infections, 23 were cured by the CAZ therapy (efficacy rate, 92%). CAZ was assessed as effective in acute pharyngitis with vomitings (4), acute laryngitis (1), pneumonia (8), urinary tract infections (5), acute gastroenteritis (1), infection accompanying acute leukemia (septicemia suspected)(1), acute purulent meningitis (2) and abscess of the lateral cervical cyst (1). The main pathogens which responded to CAZ were H. influenzae, S. pyogenes, E. coli and P. aeruginosa.
As adverse events, mild melena with prolonged prothrombin time (1) was found to be associated with the CAZ therapy.
Half-life of the CAZ serum level was 0.97±0.10 hours, and urinary excretion was high. Penetration into the CSF in 2 cases of acute purulent meningitis was satisfactory.
The data suggest that CAZ is a safe and effective injectable antibiotic when used in children with infections of CAZ-susceptible bacteria including P. aeruginosa.

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Ceftazidime (CAZ), developed by Glaxo U. K., was used in pediatric patients with acute infections, and the following results were obtained.
1. The mean blood concentrations of CAZ in 2 children were 142. 70.3, 46.9, 35.7, 16.2, 5.82 and 2.36 μg/ml at 5, 15, 30 minutes, 1, 2, 4 and 6 hours, respectively, after start of 5 minutes' intravenous injection of 20 mg/kg, with the half-life of 1.25 hours.
2. CAZ was administered to 19 pediatric patients with acute infections. Out of them, 15 patients, i.e., 3 with acute tonsillitis, 1 with acute bronchitis. 5 with bronchopneumonia, 2 with pertussis accompanying pneumonia, 2 with Salmonella enteritis, 1 with impetigo staphylogenes and 1 with subdural abscess, were adopted for the evaluation, and the other 4 were excluded from the evaluation because of inadequate indications. The efficacy rate in these 15 cases was 93.3%. The doses used in 14 out of the evaluated 15 cases ranged from 31 to 50 mg/kg/day, the frequency of dosing was twice daily in 8 cases and 3 times daily in 7 cases. One shot intravenous injection was used in 6 cases, intravenous drip infusion in 8, and combination of these, in 1 case. The duration of treatment was 2 days in 3 cases, 3 days in 3, 4 days in 4, and 5 days in 3 cases. Patients with severe infections were generally given large doses for long-term.
No clinical adverse event was observed in any case. In laboratory examinations, slight elevation of S-GPT alone was observed in 1 case.
From the above results, CAZ was considered to be a highly useful drug in the field of pediatrics.

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Basic and clinical studies were made on ceftazidime (CAZ) in pediatric field, and the following results were obtained.
1. The antibacterial activity of CAZ against clinically isolated and maintained strains was examined. CAZ was unequivocally more active than CEZ and CMZ against Gram-negative rods, with MIC distribution similar to that of CTX, except for that for P. aeruginosa. The MIC of CAZ was lower than that of CTX for P. aeruginosa. Compared with the MICs of CEZ, CMZ and CTX, CAZ showed slightly higher MICs for Gram-positive bacteria.
2. The blood concentrations of CAZ, at 0.25, 0.5, 1, 2, 4 and 6 hours after a one shot intravenous injection of 10 mg/kg of CAZ were 64.9, 36.9, 28.3, 14.7, 4.92 and 2.42μg/ml, respectively, with the half-life of 1.27 hours. The blood concentrations of CAZ, at 0.25, 0.5, 1, 2, 4 and 6 hours after a 1-hourdrip infusion of 10 mg/kg of CAZ were 16.6, 24.5, 41.4, 17.1, 5.38 and 2.62μg/ml, respectively, with the half-life of 1.28 hours. The blood concentrations of CAZ, at 0.25, 0.5, 1, 2, 4 and 6 hours after a one shot intravenous injection of 20 mg/kg of CAZ were 73.1, 60.8, 39.3, 17.3, 8.23 and 4.45μg/ml, respectively, with the half-life of 1.42 hours. The blood concentrations of CAZ, at 0.5, 1, 2, 4 and 6 hours after a 1-hour drip infusion of 20 mg/kg of CAZ were 55.1, 69.0, 32.1, 11.4 and 4.56μg/ml, respectively, with the half-life of 1.27 hours.
3. Urinary recovery rate of CAZ during the first 6 hours after a one shot intravenous injection of 10 mg kg of CAZ was 86.7%.
4. CAZ was administered to 17 children with infections, and the clinical response was excellent or good in 94%.
5. CAZ was bacteriologically effective in 14 patients, all bacteria having been eradicated in them. The bacteria were E. coli in 10 patients, H. influenzae in 2, P. aeruginosa in 1 and S. pneumoniae in 1.
6. As for side effects, slight elevation in GOT was observed in 1 case and eosinophilia, in another case.

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Fundamental and clinical studies of ceftazidime (CAZ) were performed, and the following results were obtained.
1. MICs of CAZ for E. coli which was recently isolated from patients, were less than 1.56μg/ml and that for K. oxytoca were less than 0.39μg/ml, and that for Salmonella were less than 0.39μg/ml, and that for B. pertussis were less than 0.20μg/ml.
2. The mean serum levels after the drip infusion at the doses of 20 to 36 mg kg for 30 to 60 minutes were between 11.8 and 66.7μg/ml at 1 hour, and the mean half-lives (T 1/2) were between 58 and 105 minutes, and the excretion rates in urine up to 6 hours were between 86.3 and 96.5%.
3. CAZ was given to 35 pediatric patients (include 2 drop cases) by intravenous injection for 4 to 10 days, and the total dosage was beteen 2.4 and 14.5 g.
4. Thirty-three patients with acute respiratory tract infections, pertussis and acute urinary tract infections with ABPC-resistant E. coli were treated with CAZ by intravenous injection or drip infusion. The efficacy rate of excellent+good was 90.9% (30 cases/33 cases) and the efficacy rate of excellent+good+fair was 100%. The daily doses of CAZ were 50 to 110 mg/kg, given in 2 or 3 divided doses per day.
5. S. pyogenes, S. aureus, H. in. Iluenzae, B. pertussis and ABPC-resistant E. coli were isolated from the culture of sputum or urine in the patients, and they were all eradicated by treatment with CAZ.
6. No side effect was observed except for temporary eosinophilia in 2 cases and temporary platelets increased in 1 case.

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Fundamental and clinical studies were carried out on ceftazidime (CAZ), a newly synthesized cephalosporin C antibiotic (CEPs). The antibacterial activity of CAZ was compared with those of CER, CEZ, CMZ and CPZ against clinical isolates of S. aureus, S. pyogenes. E. coli, K. pneumoniae and P. mirabilis, and with those of GM and CFS against P. aeruginosa. Against S. aureus, the antibacterial activity of CER was highest, followed by that of CEZ. The peak MIC after inoculation of 100-fold dilution was 0.10 μg/ml with CER and 0.78 μg/ml with CEZ. But in view of the peak MIC of 6.25 μg/ml, the antibacterial activity of CAZ was inferior to that of CPZ by about 2 tubes. This was not surprising, because CAZ was one of the antibiotics in the fifth group of CEPs. The CEPs in the fifth group naturally show high antibacterial activity against S. pyogenes. CAZ, as expected, inhibited the growth of all the strains at the concentration of 0.10 μg/ml at the inoculation of 100-fold dilution. In the gut bacterial flora such as E. coli, K. pneumoniae and P. mirabilis, CAZ showed the results almost equal to those of other CEPs in the fifth group; the peak MICs of CAZ were 0.20-0.39, 0.20-0.39, 0.10 μg/ml, respectively, at the inoculation of 100-fold dilution, which was good results. In P. mirabilis with the undiluted inoculation, the result of CAZ was slightly inferior to those of the other CEPs in the fifth group previously reported; however, CAZ was prone to be affected by inoculum size, and with the inoculation of 100-fold dilution, MIC of CAZ turned to be as low as 0.10 μg/ml. Against P. aeruginosa, CAZ showed the activity comparable to that of CFS, the antibiotic considered to have the highest antibacterial activity of all CEPs used in Japan. This finding is in accordance withthe findings reported by other authors. The peak MICs of CAZ were 3.13, 12.5 μg/ml at the inoculation of undiluted solution, and from 1.56 to 3.13 μg/ml at the inoculation of 100-fold dilution, which were the results equal to, or even better than those of GM.
The change in blood levels of CAZ was studied by one shot intravenous injection and 1 hour intravenous drip infusion. After one shot intravenous injection in the doses of 10, 20, 40 and 50 mg/kg, the dose-dependent peak levels of 30.0, 68.2, 87.1 and 129.0 μg/ml, respectively, were obtained at 30 minutes, then decreased gradually, and at 6 hours, the levels were 0.9, 2.3, 3.5 and 6.8 μg/ml, respectively. The half-lives were 1.19, 1.47, 1.33 and 1.33 hours, respectively, showing no significant difference. In drip infusion, comparison was carried out in 3 dose-level groups except for 50 mg/kg group, i. e., 10, 20 and 40 mg/kg. The peak levels of CAZ were obtained on completion of the drip infusion in the doses of 10, 20 and 40 mg/kg; the levels were 34.2, 69.5 and 116.3 μg/ml, respectively, which clearly showed the dose response. After that, the levels continued to decrease gradually up to 2 hours later, and then, decreased rapidly, and at 6 hours, the levels were 1.3, 3.3 and 3.3μg/ml with the half-lives of 1.00, 1.44 and 0.97, respectively. The urinary recovery rate was determined in 26 cases. The rate higher than 100% on calculation was recorded in 3 cases, but in all other cases, the rate ranged from 44.5 to 95%.
The CSF levels were determined in 5 cases. In the patient who received CAZ in the dose of 40 mg/kg, the CSF level was 1.6-4.5μg/ml in acute period, and the ratio of CSF level vs. serum level was considered to be about 5-8%. In the 2 cases treated with the dose of 50 mg/kg, the CSF levels were 21.9, and 5.5 μg/ml, which were fairly high results, though both determined only once, and transfer into CSF was 20% or higher.

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Twenty-four pediatric patients with infections were treated with ceftazidime (CAZ) by one-shot intravenous injection in the doses of 39-149 mg/kg/day in 4 divided doses as a rule. These patients'ages ranged from 2 months to 13 years 4 months. The duration of the administration ranged from 4 to 19 days, and total doses ranged from 1.38 to 57 g.
Infections consisted of respiratory tract infections in 19 cases (acute tonsillitis in 3, acute bronchitis in 7, and pneumonia in 9), urinary tract infection in 1 case, acute peritonitis in 1 case, and suspected sepsis in 3 cases. Clinical efficacy was excellent in 18, good in 1, fair in 1, and poor in 4 cases, and the efficacy rate (excellent+good) was 79.2%.
Bacteriological response was evaluated on 14 strains of bacteria isolated from lesions, assumed as the causative organisms (7 strains of S. aureus, 3 of P. aeruginosa, 1 of H. influenzae, 1 of K. pneumoniae, 1 of E. coli, and 1 of S. marcescens). Out of these strains, 10 were eradicated, and 1 (P. aeruginosa) decreased, but 2 strains (both S. aureus) persisted.(One strain of S. aureus was not examined.)
No adverse effect suspected to be related to the drug was observed either in subjective symptom or in objective findings.

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Laboratory and clinical studies on ceftazidime (CAZ), a new cephem antibiotic, were carried out in the field of pediatrics.
The results were as follows:
1. Antibacterial activities of CAZ against clinically isolated strains of S. pneumoniae, H. influenzae, E. coli and P. aeruginosa were compared with those of cefotaxime (CTX), ceftizoxime (CZX), latamoxef (LMOX), cefoperazone (CPZ) and cefmetazole (CMZ), and also with cefsulodin (CFS) and gentamicin (GM) against P. aeruginosa. Against S. pneumoniae and H. influenzae, CAZ was almost as active as CTX, CZX and CPZ. Against E. coli, it was almost as active as CTX, CZX and LMOX. Against P. aeruginosa, it was almost as active as CFS and GM.
2. Serum concentrations and urinary excretion rates after intravenous bolus injection of CAZ at doses of 20 mg/kg and 10 mg/kg for 5 minutes in each 2 cases (4 cases in total) were determined. The mean serum concentrations of CAZ were 78.9 and 52.0 μg/ml at 15 minutes, 38.5 and 27.4 μg/ml at 1 hour, and 6.5 and 4.8 μg/ml at 4 hours, with serum half-lives (T 1/2) of 1.39 and 1.80 hours respectively. Mean cumulative urinary excretion rate within 6 hours after administration was 84.6%. In a patient with chronic renal failure, serum half-life was 3.22 hours and urinary excretion rate within 6 hours was 22.8% (after intravenous bolus injection of CAZ at a dose of 10 mg/kg).
3. CAZ was administered at a dose of 55.5 mg/kg by intravenous bolus injection to a child with purulent meningitis. The levels of CAZ in the cerebrospinal fluid (CSF) at 1 hour after administration were 2.7-38.9 μg/ml with CSF/Serum ratios of 3.2-28.8%.
4. Forty-two pediatric patients with various bacterial infections (pyelonephritis 14, tonsillitis 1, bronchopneumonia 3, pneumonia 17, purulent meningitis 1, bacteremia 2, SSSS 1, enterocolitis 3) were treated with CAZ at a daily dose of 49-222 mg/kg t. i. d. or q. i. d.(as a rule 60 mg/kg t. i. d.). The efficacy rate was 97.6% clinically and 97.8% bacteriologically.
5. No adverse reactions were observed except 1 case with mild diarrhea. Abnormal laboratory findings were also only mild; eosinophilia in 1, slight elevation of GOT in 5 and that of GOT & OPT in 3 cases.
These results indicate the usefulness of CAZ in the treatment of bacterial infections in children.

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Ceftazidime (CAZ), a new cephem antibiotic for injection, was used in the field of paediatrics, and the following results were obtained. Antibacterial activity of CAZ was high against Gram-negative rods including P. aeruginosa, but slightly low against Gram-positive cocci.
Absorption and excretion of CAZ were rapid, and 90% or more was excreted at 6 hours after administration. The clinical efficacy was excellent or good in all the 4 cases treated with CAZ, and no side effects were observed.

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Fundamental and clinical studies were carried out on ceftazidime (CAZ), a new cephalosporin, in the field of pediatrics.
1. Antimicrobial activity MICs of CAZ were determined for clinical isolates of 24 strains of S. aureus, 15 of S. pyogenes, 8 of H. influenzae, 22 of E. coli, 20 of K. pneumoniae, 18 of P. mirabilis, 3 of P. morganii, and 21 of P. aeruginosa, and compared with those of the control drugs, i. e. CEZ, CXM, CMZ, CTX, LMOX and CMX. For P. aeruginosa, CPM, CFS and GM were also employed as the control drugs. CAZ was as active as CTX, LMOX and CMX, its MICs distributing in the range not higher than 0.10μg/ml for H. influenzae, 0.78μg/ml for E. coli, 0.39μg/ml for K. pneumoniae, 0.10μg/ml for P. mirabilis, and 0.10μg/ml for P. morganii in all the strains. Against P. aeruginosa, CAZ showed MICs in the range between 0.39 and 3.13μg/ml, which showed activity higher than that of CTX, LMOX, CPM, CMX and GM, and comparable to that of CFS. Against S. pyogenes, CAZ was as active as all the control drugs except for LMOX, its MICs for all strains tested being 0.20μg/ml or below. Against S. aureus, CAZ was slightly more active than LMOX, but less active than the other control drugs, its MICs being relatively high ranging from 6.25 to 50μg/ml.
2. Pharmacokinetics
After a one-shot intravenous injection of CAZ 20mg/kg, serum levels and urinary excretion were studied in 3 children aged 6 to 9 years, and CSF levels were determined in 2 children aged 6 to 7 years with aseptic meningitis. The mean serum levels of CAZ were 85.3μg/ml at 1/4 hour, 53.3μg/ml at 1/2 hour, 32.0μg/ml at 1 hour, 16.1μg/ml at 2 hours, 5.3μg/ml at 4 hours, and 2.0μg/ml at 6 hours, with the mean half-life of 1.18 hours. The mean urinary levels were 9,700μg/ml at 0 to 2 hours, 803μg/ml at 2 to 4 hours, 540μg/ml at 4 to 6 hours, and the mean urinary recovery rate during the first 6 hours was 83.9%. The CSF levels at 1 hour after intravenous injection were 0.44μg/ml in acute stage and 0.10 to 0.22μg/ml in convalescent stage.
3. Clinical study
Thirty-one pediatric patients with bacterial infections were treated with CAZ, and the clinical efficacy, bacteriological response, and side effects were evaluated. The clinical responses in 2 cases of acute purulent tonsillitis, 2 of acute purulent lymphadenitis, 1 of acute sinusitis, 1 of chronic otitis media, 19 of acute pneumonia, 1 of chronic cystitis, and 5 of acute pyelonephritis were excellent in 27, good in 3, and poor in 1 case, and the efficacy rate (excellent and good) was 96.8%. As for the bacteriological responses against 2 strains of S. aureus, 1 of S. faecalis, 11 of H. influenzae, 4 of E. coli, 1 of K. pneumoniae, 1 of P. morganii, and 1 of P. aeruginosa, bacteria were all eliminated except for S. faecalis which persisted. No clinical side effect was observed. Abnormal laboratory findings were observed in 3 cases (elevation of GOT and GPT in 2 cases, eosinophilia in 1 case), which however, were all found to have returned to normal in the reexamination.

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The authors have carried out the laboratory and clinical studies of ceftazidime (CAZ) and obtained the following results.
The antibacterial activities of CAZ against the clinical isolates of S. aureus, E. coli, K. pneumoniae, E. cloacae, E. aerogenes, S. marcescens, C. freundii and P. aeruginosa were measured by the plate dilution method with inoculum size of 10⁶ cells/ml.
The susceptibility distribution of S. aureus to CAZ ranged from 3.13 to 100μg/ml, and the peak of distribution was 12.5μg/ml.
The peak of susceptibility distribution of E. coli, K. pneumoniae and E. cloacae was 0.2μg/ml, and the distribution of E. aerogenes ranged from 0.1 to 100μg/ml and that of S. marcescens, from 0.05 to 3.13μg/ml.
The growth of 92% of P. aeruginosa was inhibited at the concentration of 3.13μg/ml or lower.
For pharmacokinetic study, CAZ was given in a single dose of 10mg/kg by intravenous administration for 5 minutes in 1 child and by drip infusion for 30 minutes in 2 children.
After intravenous administration of CAZ, the serum level got to the peak of 41.0μg/ml at 15 minutes, and was 1.0μg/ml at 6 hours. Half-life time was 1.30 hours.
With drip infusion of CAZ, the mean peak serum level was 52.45±2.05μg/ml on completion of the infusion, and 1.05±0.05μg/ml at 6 hours. Half-life time was 1.30 hours.
CAZ was effective in 9 cases out of 11 cases with bacterial infection.
No side effect was observed except for elevation of serum GOT and GPT in 1 case and eosinophilia in 1 case.

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Ceftazidime (CAZ), a new injectable cephem antibiotic, was used for treatment of infections in children, and the following results were obtained.
1. After an intravenous injection of CAZ at a dose of 20 mg/kg, the mean blood levels in 2 patients were 41.5 μg/ml at 30 minutes, 18.1 μg/ml at 2 hours and 2.55 μg/ml at 6 hours, with the half-life (T 1/2) of 1.37 hours. In a 22-day-old baby with meningitis given CAZ intravenously at a dose of 43.5 mg/kg, the blood levels were 100 μg/ml at 30 minutes, 68 μg/ml at 2 hours and 25 μg/ml at 6 hours, with the half-life (T 1/2) of 2.96 hours.
2. After intravenous administration of CAZ in doses ranging from 35.7 to 50 mg/kg, CSF concentrations ranged from N. D. to 6. 3 μg/ml in 3 patients with purulent meningitis, although 19 μg/ml at 1 hour and 13 μg/ml at 2 hours in 1 patient after intravenous administration of 46.7 mg/kg. In patient with mumps meningitis, CSF concentrations were undetectable after intravenous administration of 35.7 mg/kg.
3. Seventeen patients (each 1 patient with lymphadenitis, tonsillitis and septicemia, each 2 patients with pneumonia, bronchiectatic bronchitis, pyothorax and purulent meningitis, each 3 patients with pyelonephritis and enteritis) were treated with CAZ intravenously, at the daily doses of 178.2 mg/kg and 200 mg/kg in 4 divided doses in patients with meningitis and 44.1 to 103.4 mg/kg in 3 divided doses in patients with other infections (two of them were given by intravenous drip infusion for 30 minutes). The clinical responses were excellent or good in all the patients except for 1 case of Salmonella enteritis (poor) and 1 case of Campylobacter enteritis (poor). The efficacy rate was 88.2%. It was noteworthy that the clinical response was excellent in 1 case of septicemia with P. aeruginosa with leukemic stage of malignant lymphoma and in 2 cases of purulent meningitis.
4. As side effects, fever, eruption, leukocytopenia, elevation in GOT and positive CRP considered to be allergic, were observed on day 16 of administration in 1 case of pyothorax. These symptoms disappeared by discontinuance of administration. In addition, there were elevation in GOT and GPT in 2 cases and elevation in GOT in 2 cases and elevation in GPT in 1 case; they were all mild or transient, and there was nothing to be worried about.
5. The above results suggest that CAZ is a useful new antibiotic for the treatment of infections in children caused by indicated organisms, with efficacy obtained by either intravenous bolus or drip infusion at unit doses of 20 mg/kg three times daily in patients with common infections and intravenous injection at unit doses of 50 mg/kg four times daily in patients with meningitis.

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Ceftazidime (CAZ), a newly-developed parenteral cephem antibiotic, was administered to 8 children; by one shot intravenous (i.v.) injection in the doses of 20 and 40 mg/kg each to 2 children, and by 30 minutes' i.v. drip infusion in the doses of 10 and 20 mg/kg each to 2 children, and the serum levels, urinary levels and recovery rates were determined. CAZ was also administered to 2 patients with purulent meningitis, one complicated with subdural abscess and the other with bacteremia, in the doses of 19.2 and 50.7 mg/kg, respectively, by one shot i.v. injection, and the CSF level of CAZ was determined. In addition, CAZ was administered to 2 children with acute bronchitis, 1 with chronic bronchitis, 37 with pneumonia, 3 with pleuropneumonia, 1 each for purulent meningitis, purulent meningitis accompanied with subdural abscess and purulent meningitis with bacteremia, 5 with urinary tract infections and 3 with purulent lymphadenitis (total 54 children), in the mean dose of 85.8 mg/ kg/day mostly in 4 divided doses by one shot i.v. injection for 9 days on the average, and clinical effectiveness and bacteriological response were evaluated in these cases, and adverse events and abnormal laboratory findings were examined in the 66 cases which included 12 drop-out cases.
1. After the administration of CAZ to 4 children; 20 and 40 mg/kg each to 2 children, by one shot i.v. injection, the mean serum levels got to the peak of 115.8 and 199.5 mcg/ml, respectively, at 5 minutes. The results were good, showing dose response. The mean half-lives were 1.48 and 1.37 hours, respectively.
After the administration of 10 and 20 mg/kg of CAZ each to 2 children by 30 minutes' i.v. drip infusion, the mean serum levels got to the peak of 58.5 and 80.0 mcg/ml, respectively, on completion of the administration, showing dose response. The mean half-lives were 1.06 hours in the former 2 cases, and 1.38 and 3.26 hours, respectively, in the latter 2 cases. The reason for the prolongation observed in 1 case was not clear.
2. In the above mentioned each 2 cases receiving one shot i.v. injection, the mean urinary levels got to the peak of 4,240 and 4,445 mcg/ml, respectively, at 0-2 hours after the administration, and the urinary recovery rates during the first 6 hours were high, 95.7% and 99.5%, respectively.
In each 2 cases receiving 30 minutes' i.v. drip infusion, the peak urinary levels were obtained at 0-2 hours after the administration, the mean peak levels being 1,425 and 5,030 mcgiml, respectively, and the mean recovery rates during the first 6 hours were 85.3 and 93.2%, which were good results like those in the cases of one shot i.v. injection.
3. In the case of purulent meningitis accompanied with subdural abscess, treated with CAZ in the dose of 19.2 mg/kg by one shot i.v. injection on the 13th day of illness, the CSF level determined at 1.5 hours was 2.77 mcg/ml. In the case of purulent meningitis with bacteremia, treated with CAZ at 50.7 mg kg by one shot i.v. injection on the 4th day of illness, the CSF level was 10.2 mcg/ml, and the serum level, 72.6 mcg/ml at 1 hour after the administration, the ratio of the CSF level versus serum level being 14.0%. The CSF and serum levels were 6.32 and 66.9 mcg/ml, respectively, on the 15th day of illness, showing satisfactory transfer into the CSF of CAZ at the ratio of 9.45% to serum level.
4. As to the clinical effectiveness in 54 cases, 46 cases w ere assessed as excellent or good, which showed high efficacy rate of 85.2%.
5. The clinical efficacy classified by isolated organism could not be evaluated because the number of the cases for each isolated organism was insufficient for evaluation.
6. As to the overall bacteriological response, 11 out of 18 strains (61.1%) were eradicated.

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