Laboratory and clinical study was carried out on miconazole (MCZ), a new synthetic imidazole.
The antifungal activity of MCZ was studied and expressed as MICs for clinical isolates.The drug proved to have the highest activity against Cryptococcus neoformans, with MICs of no more than 0.16 μg/ml for all isolates of this species. MICs of Torulopsis glabrata were 0.08-5 μg/ml for all isolates and those of Candida albicans and Candida tropicalis were 5-20 μg/ml for more than 90% of the isolates. Most of other strains were less than 10 μg/ml.
When 3 healthy adult men were administered each with 200 mg of MCZ by intravenous drip infusion for 1.25 hours, the mean serum MCZ concentration was 1.39 μg/ml at the end of the infusion, then decreased rapidly to 0.49 μg/ml in following 30 minutes, and then decreased gradually to 0.17 μg/ml 6 hours later. The mean cumulative urinary excretion rate of the drug was as low as 3.0% at this stage.
A total of 25 patients with ages of 30-78 years, comprising 17 men and 8 women, were treated with 200-1,800 mg of MCZ daily for 3-93 days. The clinical effectiveness was ascertained in 19 cases among the patients; 9 cases with candidiasis, 3 with cryptococcosis and 7 with aspergillosis. Clinical responses were excellent in 2, good in 9 and poor in 8 cases, and its efficacy rates was 58%. The efficacy rate of the combination therapy with other antifungal agents was 60% in comparison with 57% of MCZ alone. Adverse reactions to the drug such as nausea, vomiting and anorexia were observed in 3 cases (12%). Abnormal changes in laboratory parameters were also observed: 3 patients with elevations of GOT and GPT, and another with eosinophilia.

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We studied 973 cases of childhood bacterial meningitis from 1979 through 1984 by means of questionnaire.
Monotherapy was carried out in 47.9% of patients with case mortality of 10.3%, whereas those treated with 2 and 3 antibiotics revealed higher rates of 15.8% and 13.5%, respectively.
Penicillins (PCs) were the most frequently used for monotherapy, and ampicillin (ABPC) accounted for 48.7%, then followed by cephalosporins (CEPs) group V including latamoxef (LMOX) for 26.8%, with fatality rates of 11.0% for the former and 9.6% for the latter.
Chloramphenicol (CP) was used in 19 cases, 4 cases were treated with antibiotics other than PCs, CEPs, CP and aminoglycosides (AGs), and no death resulted.
Among 418 cases treated with 2 different antibiotics, 241 cases with aminoglycosides (AGs) revealed a case mortality of 22.4%, and remaining 177 cases where AGs was not used showed a rate of 6.8% (P <0.05).
One hundred and thirty-one cases treated with ABPC with gentamicin gave 29 deaths showing a significantly high mortality of 22.1%. Similar results were obtained for those treated with ABPC with other AGs.
Combination of one PCs with another PCs and PCs with CEPs resulted in lower mortalities of 12.5% and 6.1%, respectively and the combination of β-lactam with non-AGs antibiotics revealed only 4 deaths out of 74 cases, i.e., a case mortality of 5.4%.
A gradual decrease of single or combined use of ABPC, mainly with AGs was observed during the survey period and a rapid increase of CEPs V and LMOX therapy occurred after 1982.

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Cefmenoxime (CMX) at a dose of 1 g was administered intravenously to each of 10 patients undergoing thoracotomy, and concentrations of CMX in the serum and pleural fluid were measured. Serum concentration of CMX reached its peak of 43.71 μg/ml at 1 hour and decreased to 4.15 μg/ml at 3 hours after the administration. The concentration of CMX in the pleural fluid eached its peak of 7.61 μg/ml at 3 hours and decreased slowly 5.26 μg/ml at 7 hours after the administration.
A clinical study with 21 patients was performed to evaluate the effect of CMX as a prophylactic antimicrobial agent in thoracotomy. Patients received intravenous administration of 4 g/day of CMX for 7-10 days following operations. Each patient was evaluated daily for fever, sign of allergic reaction, and wound infection and other symptoms.
No apparent infection occured in those clinical patients except 1 patient with a suspected infection, and 1 case of allergic reaction as exanthema was observed during this study. Prophylactic effect of CMX against postoperative infection after thoracotomy was good.

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Combination therapy of antibiotics and human intravenous gamma immunoglobulin (IgG) prepared for intravenous use is widely applied to control severe infectious diseases.
To evaluate the antimicrobial activity of astromicin (ASTM, Fortimicin®), the combination effect of ASTM with IgG was investigated ^{in vitro} and in mice with experimental infection (i.p.) with Pseudomonas aeruginosa BMH No.1. Sulfonated IgG (Venilon®, VL), and plasmin-treated IgG (Venoglobulin®, VG) were administered (i.v., 42mg/kg) 90 minutes before the infection, and ASTM was administered (s.c.) 60 minutes after the infection. Polyethyleneglycol-treated IgG (Venoglobulin-I®, VG-I) was administered (i.v., 42 mg/kg) 90 minutes before or 60 minutes after the infection.
ED₅₀ of ASTM alone and that of combination with VL were 31.0 mg/kg and 24.2 mg/kg, respectively. ED₅₀ of ASTM alone and that of combination with VG were 38.9 mg/kg and 15.5 mg/kg, respectively (P<0.05). When VG-I was administered prophylactically, ED₅₀ of ASTM alone and that of combination were 51.5 mg/kg and 13.6 mg/kg, respectively (P<0.05). When VG-I was administered simultaneously with ASTM at 60 minutes after the infection, ED. of ASTM alone and that of combination were 28.5 mg/kg and 15.5 mg/kg, respectively (P<0.05). Prophylactic effect of VG-I in immunosuppressed mice treated with cyclophosphamide (2₅₀mg/kg, i.p., 4 days before infection) was also examined. ED. of ASTM alone and that of combination were 126.1 mg/kg and 46.1 mg/kg, respectively (P<0.05).VG-I also enhanced ^{in vitro} synergistic bactericidal activity of ASTM and fresh mouse serum.
Rabbit antiserum was prepared by immunization using toluenized P. aeruginosa BMH No.1.
The prophylactic use of the diluted antiserum (1/128) was synergistic with ASTM giving ED₅₀ of ASTM of 74.1 mg/kg alone and that of combination of 35.4 mg/kg.
In addition, the combination therapy of ASTM with VG-I appeared to be effective against experimental infections with E. coli GN2411-5 in mice.
We concluded that combination therapy of ASTM and IgG in experimental infection in mice showed that it should be effective in normal and immunosuppressed host.

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Pharmacokinetic and clinical studies on cefotaxime (CTX) in plastic and reconstructive surgery field were carried out.
The results obtained are summarized as follows.
1. Two grams of CTX was administered intravenously by single bolus injection to each of 4 patients with burn blisters and mean levels of CTX concentration in blister exudates were investigated.
Thirty minutes after administration, the mean level of CTX in the exudates was 3.90μg/ml and it reached a peak of 9.81μg/ml in 2 hours.
2. The clinical efficacy rate for 30 patients with burn infections and postoperative infections was 73.3%, and the efficacy rate for 29 patients in prophylactic use was 72.4%.
3. A side effect (eruption) and abnormal laboratory findings were observed in each one case out of 59.
From the above results, CTX may be considered to be useful in plastic and reconstructive surgical treatments.

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Serum and sputum levels of ofloxacin (OFLX) were measured in 5 patients with chronic respiratory tract infections and were compared with antibacterial activity in vitro.
1. Sputum OFLX levels higher than the MIC's against H. influenzae and K. pneumoniae were maintained during the period when daily oral administrations were continued.
2. The MIC₇₀ of OFLX against S. aureus was under 0.78μg/ml and the MIC₇₀ of OFLX against P. aeruginosa was 1.56μg/ml. The maximum OFLX levels in sputum were higher than these MIC's during the period when 200-300 mg×2 times/day oral administrations were maintained.
From these results, OFLX was considered to be effective and useful for the treatment of patients with chronic respiratory tract infections.

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In vitro activities of ceftizoxime (CZX) against 328 clinical isolates were determined using the agar dilution method at an inoculum level of 10⁸ cfu/ml. CZX was highly active against Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Proteus vulgaris with MIC values below 0.20 μg/ml. It was also active against Serratia marcescens and Enterobacter aerogenes with MIC ₈₅of 3.13 μg/ml. CZX was less active against Staphylococcus aureus and Staphylococcus epidermidis, showing inhibitory activities against only 47 and 78% of these clinical isolates, respectively, at a dose level of 12.5 μg/ml. CZX was not active against Pseudomonas aeruginosa and Enterococcus faecalis.
The reliability of CZX disc diffusion susceptibility tests for quantitative estimation of anti-microbial activities was also investigated using 8 mm diameter discs (Showa) and 6 mm diameter discs (Eiken), both of which contained 30 μg/disc of CZX. These disc susceptibility test results were well correlated with MICs, hence the CZX disc susceptibility test should be useful for the estimation of proper dose levels of CZX, except against P. aeruginosa and E. faecalis.
For the interpretation of CZX disc tests, a 3 category system has been used in USA and Europe, but a 4 category system is generally used in Japan. The 3 category system uses break points to classify bacteria into 3 categories of susceptibility according to MIC values as follows: resistant (R) MIC >32 μg/ml, moderately susceptible (MS) MIC 16-32 μg/ml, and susceptible (S) MIC ≤8 μg/ml. The 4 category system uses break points as follows (+++) MIC ≤3 μg/ml,(++) 3μg/ml ≤ MIC≤15 μg/ml,(+) 15 μg/ml ≤ MIC ≤60 μg/ml,(-) MIC ≥60 μg/ml.
Based on CZX pharmacokinetic data and the recommended modest dosage schedule (2-4g/day), MIC break points of 3 μg/ml and 15 μg/ml, appear to be more useful than & mak points of 8 μg/ml and 32 μg/ml for evaluating a proper dose level.

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Cefuroxime (CXM), with its relatively broad antibacterial spectrum, good stability to betalactamases and high safety, has an established place in antibacterial therapy. However, like many other cephalosporins, its clinical application is rather limited due to the need for parenteral delivery. Recent work has led to the development of cefuroxime axetil (CXM-AX, SN407) which is the 1-acetoxyethyl ester of CXM is well absorbed from the gastrointestinal tract and promptly cleaved to cefuroxime thereafter. CXM-AX, in a dose of 500 mg, was given after meal by oral administration 3 times daily for 5-8 days to 10 lactating outpatients with acute mastitis. Ages of the patients ranged from 26 to 44 years, and body weights rangedfrom 48.0 to 59.0 kg. Clinical response was assessed as excellent in 2 cases, good in 8 cases and fair or poor in none. No adverse effects were observed.
Seven strains of organisms were isolated from 7 cases. They included 5 strains of Staphylococcus aureus and 2 strains of Staphylococcus epidermidis. The MICs of CXM were under 3.13 μg/ml with inoculume size of 10⁸ and 10⁶ cells/ml.
In 1 case, CXM concentrations in puruloid milk and in healthy milk were measured by bioassay with Bacillus subtilis ATCC 6633 as the test organism. The CXM concentrations in healthy milk ranged from 0.09 to 0.59, ag/ml (mean: 0.32±0.25 μg/ml) at 30 to 90 minutes after oral administration of 500 mg CXM-AX. The CXM concentrations in puruloid milk ranged from 0.57 to 1.05 μg/ml (mean: 0.74±0.27 μg/ml). CXM concentrations were higher in puruloid milk than in the healthy milk.
In conclusion, CXM-AX is considered to be a very useful drug when used for chemotherapy in acute mastitis.

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The in vitro and in vivo antibacterial activities of a new aminoglycoside antibiotic, arbekacin (HBK), against methicillin-cephem-resistant Staphylococcus aureus (MRSA) were compared with those of gentamicin (GM), netilmicin (NTL) and amikacin (AMK). The results obtained were summarized as follows:
1. Compared to other aminoglycoside antibiotics, HBK had the highest antibacterial activities against clinically isolated MRSA (46 strains).
2. Therapeutic effects of HBK against experimental systemic infections with MRSA in mice, were superior to those of GM, NTL and AMK. The ED₅₀'s of GM, NTL and AMK were more than 2 mg/mouse.
3. Therapeutic effects of HBK against experimental subcutaneous infections with MRSA in mice were also superior to those of GM, NTL and AMK.

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Absorption, distribution, and excretion of arbekacin (HBK) were studied in rats after intravenous or intramuscular administration of HBK at a dose of 10 mg/kg or 20 mg/kg.
1. Elimination half-lives of HBK were 0.69 hour for bolus intravenous administration, 0.55 hour for constant rate intravenous infusion, and 0.57 hour for intramuscular administration.
2. Cumulative urinary excretions within 24 hours after administration were 74.7% of the dose for bolus intravenous administration, and 79.1% of the dose for intramuscular administration. No significant difference was observed in the cumulative urinary excretions between the 2 administration routes.
3. Cumulative biliary excretions within 24 hours after administration were around 0.1% of doses regardless administration routes, bolus intravenous or intramuscular administration.
4. The tissue or organ distribution of HBK after bolus intravenous administration was similar to that after intramuscular administration. The drug was distributed most abundantly into the kidney followed by plasma and the lung. The distribution of the drug into the liver was the least among the 6 tissues or organs examined in this study.
5. The protein binding of HBK was studied by an equilibrium dialysis method at three different concentrations of HBK, 5, 10, and 20 μg/ml. Binding ratios of HBK to human serum, human serum albumin, and rat serum were less than 15%.

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A new aminoglycoside antibiotic, arbekacin (HBK) was intramuscularly and intravenously administered to dogs in order to study its pharmacokinetics in comparison to amikacin (AMK). The results obtained are summarized as follows.
1. Serum concentrations of HBK were well correlated with dose levels. The dose-serum concentration relationship with HBK was similar to other aminoglycoside antibiotics.
2. Biological half-lives of HBK and AMK were both about 1 hour in dogs. This was also similar to other aminoglycoside antibiotics.
3. There was no significant difference in peak serum concentrations between 1 hourintravenous infusion and intramuscular injection of HBK at 2 mg/kg in dogs.
4. Repetitive administration of HBK to dogs at 2 mg/kg twice a day for 14 days did not affect its serum concentration and biological half-life.
5. Urinary excretion of HBK in dogs in 24 hours after administration accounted for about 80-90%.

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A new aminoglycoside antibiotic, arbekacin (HBK) was intramusculary and intravenously administered to Beagle dogs at a dose of 10 mg/kg to study its distribution into various tissues. The results obtained are summarized as follows.
1. Biological half-lives of HBK in serum after intramuscular and intravenous injection were 1.15 hours and 1.00 hour after administration, respectively. These half-lives were similar to the results obtained in previous studies.
2. Maximum concentrations of HBK in tissues and biological fluids after intramuscular injection were the highest in kidney followed by vagina, serum, urinary bladder, uterus, ovarium, lung, parotid gland, trachea, tonsil, gall bladder, pericardiac fluid, thymus, muscle, heart, liver, mandibular gland, bile, aqueous humor, pancreas, cerebrospinal fluid and brain, in this order. Maximum concentrations were found at 4 hours in trachea, aqueous humor and cerebrospinal fluid, and at 2 hours in pericardiac fluid. In other tissues and biological fluids, they were obtained at 0.5-1 hour.
Maximum concentrations in tissues and biological fluids after 1 hour intravenous injection were the highest in kidney followed by serum, ovarium, vagina, lung, parotid gland, urinary bladder, uterus, spleen, thymus, pericardiac fluid, gall bladder, trachea, tonsil, heart, liver, pancreas, muscle, mandibular gland, bile, aqueous humor, cerebrospinal fluid and brain in this order. Maximum concentrations were found at 4 hours in trachea, cerebrospinal fluid and bile, and at 2 hours in pericardiac fluid. In other tissues and biological fluids, they were obtained at the end of the infusion.
Maximum concentrations in these biological fluids after both intramuscular and intravenous injection were similar to serum concentrations except kidney, trachea, and other biological fluids. These results suggest that HBK hardly remains for prolonged periods in tissues and biological fluids except kidney.
3. Areas under the tissue concentration-time curves (AUC) were large for kidney, urinary bladder, lung, trachea, tonsil, uterus and vagina. Also, concentrations in other tissues and biological fluids were higher than MIC levels against both Gram-positive and Gram-negative bacteria. These results suggest that HBK will be useful for such infections in these tissues.

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Fundamental and clinical studies on cefuzonam (CZON, L-105) were carried out and the results obtained are summarized below:
1. MICs against 451 clinical isolates of Staphylococcus aureus were determined. Antibacterial activity of CZON on S. aureus was similar to that of cefazolin, inferior to that of cloxacillin, and superior to those of benzylpenicillin and cefotaxime.
2. With one-shot intravenous injection of CZON, peak serum concentrations were 40.0μg/ml and 97.5-145μg/ml with a dose of 10mg/kg and 20mg/kg, respectively.Half-lives of the drug in serum were 34.2-47.9 minutes. Urinary excretion rates were 46.8-67.3% in 4 hours after injection.
3. In all of 13 cases of pediatric infections tested, the clinical efficacy was excellent or good.
4. Side effects observed were diarrhea in 4 patients, and elevated GOT and thrombocytosis in 1 patient each.
From the above results, we have concluded that CZON is useful and safe antibiotic for treating various bacterial infectinnc in chikiren.

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Cefuzonam (L-105, CZON), a new parenteral cephalosporin, was evaluated for its efficacy and safety in 22 children with bacterial infections (Table1).The results obtained are summarized below.
1. MICs of CZON to 26 strains of isolated organisms are shown in Table 2. MICS to all 14 strains of Haemophilus influenzae and 6 strains of Streptococcus pneumoniae were less than 0.05 μg/ml.The MIC to 2 strains of Staplococcus aureus was 0.39μg/ml and that to another was 0.78μg/ml.Two strains of Escherichia coli showed MICS of less than O.05and 0.10μg/ml, respectively. The MIC to 1 strain of Enterococcus faecalis was 6.25μg/ml.
2. The CZON was administered in 3 or 4 divided doses at a daily dosage ranging from 58.5 to 85.7mg/kg by 30-minute drip infusion or intravenous injection to 22 patients (9 cases of pneumonia, 9 cases of tonsillitis, 2 cases of bronchitis, 1 case each of suppurative parotitis and acute pyelonephritis) and the following clinical results were obtained; excellent: 12 cases; good: 7 cases;fair: 3 cases. The overall efficacy rate was 86% (Table 4).
3. Diarrhea was observed in four patients, and was resolved with or without discontinuation of the medication within a week. Anemia was noted in 2 cases. Leucopenia and neutropenia was observed in 1 case. There were a moderate rises in S-GOT and S-GPT activities in 1 patient (Table 4), and they necessitated the cessation of the CZON therapy. The S-GOT and S-GPT activities became normal after the drug treatment was stopped.
4. These data suggest that CZON is a useful new antibiotic in the treatment of children with susceptible bacterial infection and can be used as a first choice antibiotic for the treatment of respiratory or urinary tract infections in children.

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Fundamental and clinical studies on cefuzonam (L-105, CZON), a newly semisynthesized cephem antibiotic, were carried out in the field of pediatrics and the following results were obtained.
1. Antibacterial activities of CZON against clinically isolated strains of Staphylococcus aureus, S. epidermidis, Streptococcus pneumoniae, S. pyogenes, Escherichia coli, Klebsiella pneumoniae, Haemophilus parainfluenzae and H. influenzae were compared with those of cefmenoxime (CMX), latamoxef (LMOX), cefoperazone (CPZ), cefmetazole (CMZ), cefotiam (CTM) and cefazolin (CEZ). CZON was nearly as active as CEZ against S. aureus and S. epidermidis and superior to other antibiotics against other Gram-positive cocci. Against Gram-negative rods, CZON was as active as CMX and superior to other 5 antibiotics compared.
2. Serum concentrations and urinary excretion rates after intravenous bolus injection of CZON at doses of 10 mg/kg, 20 mg/kg and 40 mg/kg for 5 minutes in 1, 5 and 4 cases, respectively, were determined. Mean serum concentrations of CZON at these dose levels were 11.0, 43.8 and 111.5 μg/ml at 15 minutes, 2.4, 10.3 and 30.3 μg/ml at 1 hour and 0.17, 0.72 and 1.28 μg / ml at 4 hours, with serum half-lives of 1.79, 0.88 and 1.19 hours, respectively. Mean cumulative urinary excretion rates within 6 hours after administration were 47.9, 56.3 and 40.3%, respectively.
3. Thirty-four pediatric patients with various bacterial infections (tonsillitis 2, acute bronchitis 1, pneumonia 14, pyothorax 1, sepsis 1, suppurative lymphadenitis 1, UTI 13 and enteritis 1) were treated with CZON at a daily dose of 40-94 mg/kg t.i.d. or q.i.d. The overall clinical efficacy rate was 94.1%.
4.No adverse reactions were observed except 2 cases with mild diarrhea.Abnormallaboratory findings were also mild;slight elevation of GOT and GPT in 2, eosinophilia in 1 and thrombocytosis in 1.
These results clearly indicate the usefulness of CZON in the treatment of bacterial infections in children.

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1. Analysis on serum concentrations of cefuzonam (CZON, L-105) in 7 children who received different doses of CZON revealed a dose-response relationship. The half-life of the drug in blood was 0.90 hour.
2. CZON was administered to 17 pediatric patients with bacterial infections. The clinical efficacy rate was 88% (15/17), and the eradication rate of pathogens was 80% (4/5).
3. Only one case of mild diarrhea (1/17) was observed as a side effect associated with CZON.

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We have carried out laboratory and clinical studies of cefuzonam. The results were summarized as follows:
The effectiveness of cefuzonam was estimated by a plate dilution method on 26 strains each of S. aureus, E. coli, K. pneumoniae, Salmonella spp. and P. aeruginosa and 27 strains of S.marcescens isolated from patients. The distribution of MIC's of cefuzonam against S. aureus was 0.39-1.56 μg/ml and the peak of the distribution was 0.39 μg/ml. Strains of 96.2% of E. coli and Salmonella spp. were inhibited at cefuzonam concentrations less than 0.39 μg/ml. Strains of 92.3% of K. pneumoniae were inhibited at drug concentrations less than 0.20 μg/ml. The distribution of MIC's of cefuzonam against S. marcescens was ≤0.025-12.5 μg/ml and the peak of the distribution was 0.2 μg/ml and 1.56 μg/ml. MIC's against P. aeruginosa was 12.5->100 μg/ml. Cefuzonam was given by 5-minute intravenous administration to 4 children and 1-hour drip infusion to 1 child at a single dose of 20 mg/kg. After the intravenous administration, mean serum levels of cefuzonam were 30.8±4.55 μg/ml at 30 minutes, 13.8± 1.83 μg/ml at 1 hour, 0.4±0.159 μg/ml at 6 hours.
The half-life was 1.12±0.198 hours. After the drip infusion, the serum levels of the drug were 38.7 μg/ml at 1 hour, 5.25 μg/ml at 2 hours and 0.087 μg/ml at 7 hours. The half-life was 0.93 hour.
The mean urinary excretion rate was 58.1% and 33.4% up to 6 hours after the intravenous administration and the drip infusion, respectively.
Cefuzonam was effective in 4 out of 5 cases with bacterial infections.
No side effect due to the drug was observed in any case.

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Cefuzonam (L-105, CZON), a new injectable cephalosporin, was used in 12 pediatric patients with infections. The following is a summary of the results:
1. The 12 cases included 3 cases of tonsillitis (pathogen: Haemophilus parainfluenzae in 1 case, Haemophilus influenzae in 2 cases), 4 cases of pneumonia (Staphylococcus aureus in 1 case, pathogen unknown in 3 cases), 2 cases of nephropyelitis (Escherichia colt in 2 cases), 1 case of purulent lymphadenitis (pathogen unknown), 1 case of purulent thyroiditis (mixed infection of Streptococcus milleri, Haemophilus aphrophilus and anaerobes), and 1 case of vulvar abscess (E. coli). Dose levels of CZON were 42.9-93.3 mg/kg/day divided into 3 or 4 times and the drug was intravenously injected for 6 to 12 days. Clinical efficacies were excellent in 4 cases, good in 5 cases, and poor in 3 cases, with the efficacy rate of 75.0%. The 3 cases with poor efficacy consisted of 1 case each of pneumonia complicated with chronic granulomatosis, purulent thyroiditis associated with piriform recess fistula, and purulent lymphadenitis of armpit developed after surgical operation of congenital heart disease. In the first 2 cases satisfactory efficacy was not obtained by chemotherapy alone, and complete cure was seen after surgical operation.
2. Side effects were not observed clinically. One case each of slight prolongation of prothrombin time and transient elevations of GOT and GPT values were noted but no severe abnormalities were found in laboratory tests.
3. The above results are reasonable from a point of view of the broad spectrum, potent antibacterial activity, and pharmacokinetics of this compound; thus, CZON appears to be a useful new antibiotic for the pediatric field. The recommended dosage for general pediatric infections is about 20 mg/kg at a time, 3 or 4 times of administration, by which expected efficacy may be obtainable.

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Clinical studies were performed on cefuzonam (L-105, CZON), a new cephem antibiotic, as follows.
1. Cerebrospinal fluid (CSF) and serum concentrations.
CSF and serum concentrations of CZON were measured in 1 case of septic arthritis without meningitis. One hour after 50 mg/kg intravenous bolus injection, the CSF and serum concentrations were 0.10 and 18.1 μg/ml, respectively, and CSF to serum concentration ratio was 0.55%.
2. Clinical efficacy
CZON was administrated to 15 patients in doses ranging 54.5-212.4 mg/kg/day (94.1 mg/kg/day on average) t.i.d. or q.i.d. for 4-12 days (6.5 days on average). Of those patients, 9 were with pneumonia, one each was with bronchitis, with tonsillitis, with septic arthritis, with septicemia, with purulent meningitis and with urinary tract infection.
The overall efficacy rate was 100%, i.e., efficacy was excellent in 12, good in 3.
Bacteriological efficacy was excellent, i.e., 8 of 8 strains were eradicated.
Side effects were observed in 2 cases, i.e., one case with loose stool and another with eruption. Laboratory abnormalities to the drug were not observed during the treatment.
The above results suggested that CZON would be a useful antibiotic for treating pediatric bacterial infections.

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For the evaluation of efficacy of cefuzonam (CZON) on biliary infection, the drug was administered to 12 cases of hepatic, biliary, and pancreatic diseases with postoperative/postpercutaneous transhepatic biliary drainage (PTBD) infections. The results were summarized as follows:
1. The bacterial eradication rate was 33.3% (9/27 strains). Nine strains of bacteria appeared during the administration of CZON.
2. MIC's of CZON against 14 strains including 4 of K. oxytoca out of 53 strains tested were below 1.56 μg/ml, whereas MIC's against 39 strains including 22 Pseudomonas spp. were higher than 12.5 μg/ml.
3. Leukocyte counts in bile decreased in 6 cases, increased in 2 cases, and not detected in 1 case, showing no correlation with changes in bacteriology or clinical symptoms.
4. Improvements of clinical symptoms such as reduced pain and decreased fever were noted in all cases.
5. No case of adverse reaction was observed.
The results indicated that CZON would be an antibiotic with a high efficacy and safety on biliary infections.

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