Fourteen patients suffering from female genital organ infections including mastitis and urinary tract infections were treated with cefoperazone (CPZ). CPZ was administered intravenously or by drip infusion at a dose of 2.0-4.0g/day for 3-7days. Clinical results obtained were as follows: Of 8 patients with genital organ infections, excellent responses were seen in 2 patients, good responses in 5 patients. Of 3 patients with mastitis, good responses were seen in all the patients. Of 3 patients with pyelonephritis, excellent and good responses were seen in all the patients.
No adverse effects and abnormal laboratory findings were observed.
From the above results, we considered that CPZ was an effective and safe antibiotic against infections in the field of obstetrics and gynecology.

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[in Japanese]

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The antigenicity of fosfomycin (FOM), a new antibiotic agent, was studied.
The binding of ³H-FOM with human serum protein was measured by the short term dialysis method. The binding was very weak only by 2.16% and reversible.
The rabbits were immunized subcutaneously by fosfomycin as sodium salt (FOM-Na) with FREUND'S complete adjuvant. Antigenicity of IgG was examined by means of agar gel precipitation, passive cutaneous anaphylaxis and passive hemagglutination. To study the antigenicity of IgE, the BALB/cA mice were immunized intraperitoneally by FOM-Na with aluminium hydroxide gel and, passive cutaneous anaphylaxis in the rats was used. In these experiments, FOM-Na showed no antibody formation of IgG and IgE.
Consequently, it can be concluded that FOM dose not conjugate with human serum protein to form its hapten and has no antigenicity.

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[in Japanese]

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The present paper reports the results which were obtained in a clinical trial of cefadroxil (CDX), a new oral cephalosporin, in the pediatric field.
(1) A total of 20 patients with infectious diseases including 9 urinary tract infection, 7 acute tonsillitis, 2 scarlet fever, 1 pyodermia and 1 recurrent bronchitis were treated with CDX. Of the. 20 cases, the clinical response was excellent in 15 cases (75%), good in 4 cases (20%), and fair in 1 case (5%).
(2) Efficacy classified by causative organisms was as follows; E. coli, 100%; S. pyogenes, 87, 5%.
(3) Neither adverse reactions nor abnormal laboratory results were observed.

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Fundamental and clinical studies were made on cefadroxil, a new oral cephalosporin, and the following results were obtained.
(1) Antibacterial activity of the drug against S. aureus, S. epidermidis, E. coli, Klebsiella, Salmonella and P. mirabilis was almost equal to that of cephalexin. The MIC of indole positive Proteus, Enterobacter, Citrobacter, S. marcescens and P. aeruginosa to cefadroxil was higher than 100ug/ml in almost all strains.
(2) Serum concentrations following an oral administration of 10.0 to 14.3mg/kg of cefadroxil dry syrup was highest at 2 hours in 2 cases and 1 hour in 1 case, respectively, which were 13.4 to 17.1μg/ml, and 1.8 to 6.8μg/ml at 4 hours with an T1/2 of 1.04 to 1.62 hours and apparently longer continuation of serum concentration than that of cephalexin. Urinary recovery rate was 75-96% up to 6 hours.
(3) Fourteen patients, i. e., 6 with tonsillitis and 8 with urinary tract infection, were treated with a daily oral dose of 30-50 mg/kg divided in. 4 doses except 1 case divided in 3 doses. The overall efficacy rate was 100%, i. e., excellent in 13, good in 1 and no failure. Causative organisms disappeared in all cases.
(4) Adverse reactions, such as diarrhea and skin rash, were not noted at all and 1 case presented a mild elevation of GOT and GPT.
(5) Taste and flavor of the drug was well palatable to children.
(6) Based on the above results, it was concluded cefadroxil dry syrup is a new potent cephalosporin for oral use in the treatment of acute bacterial infection in children. Daily dose of 40mg/kg in 3-4 divided doses appeared to be appropriate.

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The authors have carried out the laboratory and clinical studies of cefadroxil (CDX). The results were as follows; The sensitivity was measured by plate dilution method on 27 strains of S. aureus and E. coli, 26 strains of K. pneumoniae isolated from patients.
The distribution of sensitivity of S. aureus was 3.13-12.5 μg/ml and the peak of distribution was 3.13 μg/ml and 6.25 μg/ml, of E. coli was 6.25 μg/ml by 108 cells/ml. And the distribution of sensitivity of K. pneumoniae was 6.25-25 μg/ml and its peak was 6.25 μg/ml by 10⁸ cells/ml.
CDX were given orally at dose of 10mg/kg to 3 children. The serum levels of CDX were 10.5± 1.78 μg/ml, 15.8±3.25 μg/ml, 12.0±0.41 μg/ml and 3.9±0.9 μg/ml at 0.5, 1, 2, 4 hours after administration respectively, and was 2.3±0.48 μg/ml at 6 hours.
The urinary excretion rate was 55.6% up to 8 hours after administration.
CDX were administered to 39 cases of pediatric infectious disease (26 cases with tonsillitis, 5 cases with enterocolitis, 3 cases with UTI, 2 cases with impetigo, each one case with bronchitis, cervical lymphadenitis and epididymitis).
And CDX were given 25.0-65.2 mg/kg daily. Clinical results obtained were above good in all cases.
No side effects were observed in any cases, except for one case with diarrhea, 6 cases with the elevation of serum transaminase and 1 case with eosinophilia.

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We have been investigating novel antimycotics as well as substances indicated synergistic effects of antimicrobial activities with addition of small amount of recently-developed imidazole antimycotics shown in Fig. 1. This time, we isolated Pericillium sp. No.Y-11930 which yielded a physiologically active substance. The substance was obtained as pillar-shaped crystals and showed 30-125-fold strong synergistic effects against Candida sp. with addition of econazole 1), miconazole 2) and clotrimazole 3). The substance was hereinafter called as synergisidin in relation to this synergism. Synergisidin showed C₁₆H₂₄O₄ (MW: 280.2552), [α] ¹⁰_D+106.23° (c 0.33, MeOH) and mp. 200°C and identical with brefeldin A and ascotoxin (decumbin) from physicochemical properties and comparison with them.
This paper deals with production, extraction, purification, biological properties and physicochemical properties of synergisidin.

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Laboratory and clinical investigations were performed on cefadroxil, and the results were obtained as follows.
(1) Sensitivity distribution of cefadroxil:
In S. aureus, two peaks were observed with inoculum size of 10⁸/ml: 1.56-3.13μg/ml and 12.5-25μg/ml, while with inoculum size of 10⁶/ml, the distribution was in the range of≤0.1-25μg/ml, and the sensitivity peak was 0.78-1.56μg/ml.
In S. Pyogenes, with inoculum size of 10⁸/ml, sensitivity distribution was in the range of 0.05-1.56μg/ml, and the peak was 0.05μg/ml. On the other hand, with inoculum size of 106/ml, distribution was 0.006-1.56μg/ml, and the peak was 0.006-0.012μg/ml, thus sensitivity of cefadroxil being 2 tubes higher.
In E. coli, with inoculum size of 10⁸/ml, strains showed mostly high resistance as more than 100μg/ml, whereas with inoculum size of 106/ml sensitivity was distributed between 3.13-50μg/ml, and the peak was 12.5-25μg/ml.
(2) Absorption and excretion of cefadroxil:
A dose of cefadroxil 5 mg/kg, 10 mg/kg or 20 mg/kg was administered to 9 cases of children aged from 4 years and 6 months to 11 years and 9 months, and serum levels of the drug were measured. As the results, in the group of 5 mg/kg dosing, the value was 0.94μg/ml at 30 minutes, 3.55μg/ml at 60 minutes, 7.65μg/ml at 2 hours, 2.55μg/ml at 4 hours, and 1.09μg/ml at 6 hours. In the group of 10μg/kg dosing, value of the drug was 4.18μg/ml at 30 minutes, 10.70μg/ml at 1 hour, 12.75μg/ml at 2 hours, 8.05μg/ml at 4 hours, and 2.33μg/ml at 6 hours.
In the group of 20 mg/kg dosing, value was 9.93μg/ml at 30 minutes, 18.43μg/ml at 1 hour, 24.70μg/ml at 2. hours, 15.50μg/ml at 4 hours, and 6.45μg/ml at 6 hours. Dose response was observed thus distinctly among 3 groups. Recovery ratio of cefadroxil in urine was 76.14% within 6 hours.
(3) Clinical trial with cefadroxil:
Cefadroxil was applied clinically in 80 cases (76 patients). These included 22 cases of lacunar tonsillitis, 13 cases of pharyngitis, 24 cases of bronchitis, 6 cases of pneumonia, 8 cases of urinary tract infection, 5 cases of hemolytic streptococcal infection, 1 case of cellulitis, and 1 case of otitis media. Efficacy was obtained in 72 cases out of 80 cases ratio being thus 90%. Change oforganisms was proven in 35 cases, among which disappearance and reduction of oaganism were observed in 32 cases (91.4%).
No adverse reaction was noticed throughout all cases. No abnormal value was recognized in laboratory findings.

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Laboratory and clinical investigations were performed in the field of pediatrics with cefadroxil dry syrup, a new semi-synthetic chephalosporin antibiotic.
(1) MIC of cefadroxil was measured, to compare with that of cephalexin (CEX), on 30 strains of S. aureus, 30 strains of S. pyogenes and 26 strains of E. coli, all of which were isolated clinically in the field of pediatrics.
Two strains of S.aureus showed more than 100μg/ml with inoculum size of 10⁸cells/ml, and remaining 28 strains were distributed between 1.56-12.5μg/ml, while at inoculum size of 10⁶cells/ml, each 1 strain showed 25μg/ml and 50μg/ml, and the remaining strains were distributed between 1.56-3.13μg/ml. All 30 strains of S. pyogenes were inhibited the growth by less than 0.2μg/ml with inoculum size of both 10⁸cells/ml and 10⁸cells/ml.
Three strains of E. coli showed MIC of more than 100μg/ml with inoculum size of 10⁸cells/ml, and the remaining 23 strains were distributed between 12.5-25μg/ml, while with inoculum size of 10⁶cells/ml, 3 strains showed more than 100μg/ml, and the remaining strains were distributed between 6.25-12, 5μg/ml. In comparison with the results of CEX, cefadroxil was nearly equal to S. aureus and E. coli, whereas it was 2 grades superior to S. pyogenes.
(2) A dose of 10mg/kg of cefadroxil dry syrup was administered before 30minutes of breakfast in 3 cases of children, and serum level, urinary level and recovery rate in urine were investigated. Average serum level was 15.2±3.9μg/ml in 1/2 hour, 16.4±2.3μg/ml in 1 hour, 10.1±2.8μg/ml in 2 hours, 3.8±1.5μg/ml in 4 hours and1.0±0.4μg/ml in 6 hours, and average T1/2 was 1.24±0.22 hours. Average urinary level was 857±232μg/ml in 0-2 hours, 690±180μg/ml in 2-4 hours and 249±55μg/ml in 4-6 hours, and average recovery ratio in urine was 86.3±17.5% within 0-6 hours.
(3) Cefadroxil dry syrup was administered clinically in 20 cases of acute purulent tonsillitis, 5 cases of acute bronchitis, 14 cases of acute pharyngitis, 5 cases of acute purulent cervical lymphadenitis and 2 cases of acute urinary tract infection. Clinical efficacy, bacterioiogical effect and its side effect were investigated in total 46 cases of bacterial infection. A dose of 21.1-57.1mg/kg of cefadroxil was administered daily, divided into 3, after each meal for 1-10days, total dose being 0.5-11.0g.
Efficacy rate of cefadroxil, including excellent and effective effects, was 90.0% in acute purulent tonsillitis, 60.0% in acute bronchitis, 100.0% in acute pharyngitis, 80.0% in acute purulent cervical lymphadenitis and 100% in acute urinary tract infection, the rate being 88.9% throughout all cases.
Among presumed pathogens, 15 strains of S. pyogenes, 5 strains of S. pneumoniae and 2 strains of E. coli were all eradicated by administration of cefadroxil. Out of 5 strains of H. influenzae, 1 strain disappeared, 2 strains reduced and 2 strains persisted. One strain of β-Streptococcus (non group A) decreased.
As the side effects of the drug, diarrhea was noticed in 2 cases, though this was improved by administering antidiarrheics. One case refused the drug administration.
No abnormal value was observed in laboratory findings before and after the administration of cefadroxil.

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Serotypes and antibiotic susceptibility of Streptococcus pneumoniae from various clinical specimens from Jan. 1979 to July 1980 were examined.
(1) The serotype of the organism widely distributed, and predominant serotypes were type 6, type 15, type 19, type 3 and type 23. Strains of type 2, 12 and 25, which were used as pneumococcal vaccine, were not found.
(2) From the results of susceptibility test the most active drug was PCG among penicillins and CER among cephalosporins. There was one strain which was resistant to PCG and CER as well as CP and TC. Sixty-five % and 48% of the strains were resistant to TC and CP respectively. Almost of the strains were sensitive to macrolides and LCM. The occurrence of resistant strains to CP, TC, EM and LCM varied to the serotypes.

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[in Japanese]

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The combination effect of chromomycin A₃ and amphotericin B against HeLa cell and Bacillus subtilis ATCC 6633 by the agar plate diffusion and the serial dilution method was examined.
As a result, evident synergistic effect was observed when the HeLa cell was used as the test cell.

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