[in Japanese]

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S-6437 is a preparation of sustained release cefalexin consisting of non-enteric coated granules and enteric coated ones and it is reported that the drug shows good effectiveness with b.i.d. regimen.
Various infections in pediatrics were treated with S-6437 and the following results were obtained. Dose used was 40-100 mg/kg/day at 2 divided doses after breakfast and dinner.
1) Twenty patients (87.0%) of the 23 with respiratory tract infections and 3(60.0%) of the 5 with the other infections responded to the drug. Overall effectiveness was 82.1% (23/28 cases).
2) As for side effects, tentative diarrhea was observed in 5 patients (17.2%) of the 29 but no other severe side effects were found.
3) S-6437 is considered to be a drug which overcomes inconvenience of giving regular cefalexin four times a day.

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Oral sustained release cephalexin (S-6437) was administered to 24 pediatric patients. Daily dose used was 18-60mg/kg, which was divided into two doses and given after breakfast and dinner. The following are the results of the study.
Out of 24 patients, 6 showed very good response, 10 good response, 6 fair, 1 poor and 1 unknown, Ratio of effectiveness was 69.6%.
Two patients were reluctant to receive the drug and, therefore, they took other drugs. The other 22 patients, however, were easily given.
No remarkable side effects due to S-6437 were found.
From the above results, it was recognized that S-6437 has good effectiveness and safety, and that it is convenient to give to children because the frequency of the drug administration is only twice a day.

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Sustained release cephalexin (S-6436) was studied in 23 outpatients (20 males, 3 females) who visited surgery of our hospital. The summary of the study is as follows:
1) The drug was administered for 2-8 days and the average was 3.5 days. Clinical effectiveness was 87.0% with the following breakdown: excellent 4, good 16, and poor 3.
2) Causative organisms isolated from the patients showing excellent effectiveness were all staphylococci.
3) No side effects were observed in any patients receiving the drug.
From the above results, it is expected that S-6436 has good effectiveness and can be used as a first choice drug to outpatients with mild infections such as superficial infections who want to go to the office or school over their receiving the treatment.

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Clinical studies of S-6436 were conducted in 30 urinary tract infection patients in urology with the following conclusion. The patients received the drug twice a day after breakfast and dinner.
1. Of the 30 patients, excellent efficacy was observed in 9 patients, good efficacy in 14, fair in 5 and poor in 2. The effectiveness (excellent or good) was 76.7%.
2. Twenty-seven (27) strains were isolated from the 30 patients and 23 strains (85.2%) of the 27 disappeared with the administration of the drug.
3. Side effects were found in 3 patients (10%) of the 30. The incidence was almost similar to that of regular cephalexin. No remarkable changes in laboratory data were observed.
4. S-6436 which requires the administration of only twice a day is a preparation which is more convenient for patients than regular cephalexin which requires the administration of four times a day.

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Clinical study of sustained release cephalexin (S-6435 and S-6436) was conducted with the following results:
1) Pediatric patients with 1.5-12 years of age having acute tonsillitis and pharyngitis were orally administered 500-1,000mg/day of S-6435 or S-6436 divided into 2 doses after breakfast and dinner.
Out of 21 patients receiving the preparations, 19 patients satisfactorily responded to them and 2 fairly did.
2) In only one patient of the 21, rash was observed during the treatment. The side effect, however, disappeared 2 days after the initiation of the treatment, and was considered to be due to underlying disease of the patient. No other side effects were observed.
Since it has become our concern to conduct injectable therapy in children, oral therapy should first be recommended to them. However, oral drugs, like a regular cephalexin, requiring q. i. d. regimen are inconvenient in giving the drugs to patients because they have to take the drugs once at midnight. S-6435 and S-6436, however, have no such disadvantage and prove to have as much effectiveness and safety as regular cephalexin has.

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S-6436 or S-6437 was orally administered to 30 patients with bacterial infections including some patients with secondary infections. The following results were obtained: 21 patients had excellent effect, good 5, fair 2 and poor 2. The effectiveness was 86.7%.
One gram (potency)/day of sustained release cephalexin was given to most of the patients divided into 2 doses after breakfast and dinner. This b. i. d. regimen was popular among outpatients as well.
Staph. aureus isolated from 73.3% of the patients disappeared. Overall bacteriological effectiveness was 72.2%.
In only 2 patients, side effects were observed. One had a mild pain in stomach and the other had aggravation of itching in complication of eczema. No abnormalities in laboratory studies which were conducted in some patients were found.

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[in Japanese]

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Fosfomycin (FOM), a new antibiotic having a broad-spectrum, was isolated from Streptomyces fradiae, S. viridochromogenes and S. wedmorensis. Its action is bactericidal and involves interference with cell wall synthesis as evidence by the fact that it causes spheroplast formation by susceptible bacteria.
In this work, we studied about toxicological effects of FOM on the visual and auditory organs of Hartley strain guinea pigs, rabbits and beagle dogs.
FOM-Ca salt was suspended with 0.1% CMC and FOM-Na salt was disolved into the distilled water.
A. FOM-Ca
FOM-Ca at the doses of 200 and 400mg/kg were orally administered to rabbits for 35 days exceptevery Sunday and after the treatment effects of FOM-Ca on the electroretinogram (ERG) of the rabbits. The light stimulation of 2 joules was given at 50cm from rabbits eyes and then ERG was measured at 1, 18 and 35 days after the application of the drug. There was no remarkable difference between the treatment and control groups during the experiments.
In second experiments, effects of the drug on the optic fundus of Beagle dogs were also studied. FOM-Ca at the dose of 560mg/kg was orally administered for 35 days to examine by a camera (RC-2) made by Kowa Kogyo. There was also no remarkable difference between the treated and control groups during experiments.
In third experiments, the ototoxic effects of FOM-Ca on the inner ear of guinea pigs, were studied.
FOM-Ca at the doses of 250,500 and 750mg/kg were given by subcutaneous injections for 28 days respectively. After the last administration, we studied the ototoxic effects with following methods.
(a) Succinic dehydrogenase (SDH) activity: The organs of CORTI were soaked in intravital perfusion of 0.1% NBT solution for 15 minutes. After 24 hours of fixation with 10% neutral formalin, the surface preparation specimens were prepared under the stereomicroscope. After that, SDH activities of outer and inner hair cells of organs of CORTI were estimated by observation under the light microscope.
(b) Pathological examination of organ of CORTI: The specimen obtained from organ of CORTI were fixed with WITTMAACK solution and we prepared the serial celloidin horizontal section and stained with hematoxylin-eosin. And then, the outer hair cells and inner hair cells of organ of CORTI were observed under the light microscope.
There was no remarkable difference between the treated and control groups by these treatments.
B. FOM-Na
FOM-Na at the doses 100 and 400mg/kg were intravenously administered to rabbits and Beagle dogs was given 500mg/kg for 35 days except every Sunday. After these treatments, the ERG of rabbits and optic fundus of Beagle dogs were examined. There was no remarkable difference between the treated and control groups during the experiments.
In other experiments, the ototoxic effects of FOM-Na on the inner ear of guinea pigs were studied.
FOM-Na at the doses of 200, 400 and 800mg/kg were intramuscularly given for 28 days respectively. After the last administration, the ototoxic effects of the drug were examined by the established method.
There was no remarkable difference in all animals used in this work.

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Pivmecillinam is a new synthetic penicillin1) for oral use which was developed in 1972 by LUND, et al. The molecule is a new type of 6-aminopenicillanic acid derivative, of which the 6-position substitute is combined with an amidino structure (Fig. 1).
Pivmecillinam is converted to mecillinam at the time of absorption through the intestinal walls by the action of non-specific esterases, the pivaloyloxymethyl-ester moiety at the 3-posi-tion of the molecule being hydrolyzed to give mecillinam which is the antimicrobially active form of pivmecillinam.
As mecillinam has a potent antibacterial activity against Gram-negative bacteria, pivmecillinam has mainly been evaluated for treatment of urinary-tract infections 2-5). We have previously performed a double-blind comparative study on pivmecillinam for treatment of acute simple cystitis using amoxicillin as control 6). The results have indicated that pivmecillinam is significantly superior to amoxicillin in efficacy as well as about adverse reactions with such a small dosage [150mg (potency)/day] as one-fifth the dosage of amoxicillin.
The good results obtained with pivmecillinam in treatment of simple cystitis have prompted us to evaluate the efficacy and safety of the drug in treatment of intractable complicated urinary-tract infections using amoxicillin as reference drug.

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