The therapeutic effect on syphilis of Vistamycin (abbr. VSM), a new aminoglycoside antibiotic, was compared with that of penicillin G.
The result of the experiments was as follows :
In a rabbit group infected with syphilis intracutaneously in the back, VSM revealed the therapeutic effect similar to penicillin G.
In a rabbit group infected with syphilis intratesticularly, the therapeutic effect was similar macroscopically with either drug, though the same effect of VSM was slightly inferior histo-pathologically to that of penicillin G. The administration method and dose of VSM should be pursued further on the present theme.

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Vistamycin is a new antibiotic developed at Central Research Laboratories of Meiji Seika Kaisha, Ltd. in 1967.
In vitro and in vivo studies on the antimicrobial action of vistamycin have been carried out, and the following results were obtained :
1) Vistamycin was broadly effective against both Gram-positive and-negative bacteria. The antibacterial spectrum of Vistamycin was the same as that of kanamycin.
2) As for the antibacterial activity against the Susceptible strains, the minimum inhibitory concentration of Vistamycin was the same or a little less in comparison with that of kanamycin.
3) It was confirmed that there may be the distinct cross-resistance between Vistamycin and kanamycin.
4) The antimicrobial activity of Vistamycin tended to increase when the pH of culture increases at alkaline side.
5) In the studies with mice experimentally infected with Staphyolcoccus aureus, Diplococcus pneumoniae or Escherichia coli, Vistamycin showed the curative effects which were parallel with its minimum inhibitory concentration values, its ED₅₀ being no more or less than that of kanamycin.

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The pharmacological actions of Vistamycin (O-β-D-ribofuranosyl- (1→5) -O- [α-2, 6-diamino-2, 6-dideoxy-D-glucopyranosy1-1 (1→4)] -2-deoxy-streptamine), a new aminoglycoside antibiotic, were investigated.
Vistamycin given intravenously at a dose of 80 mg/kg caused tempararily a fall of blood pressure in the urethane anesthetised rabbit without any change in the respiration. The effects of adrenaline and acetylcholine on the blood pressure of the rabbit were not modified by the pretreatment with Vistamycin. Vistamycin, 100 mg/kg injected intravenously, showed no effect on ECG (lead-II) of the rabbit, whereas the spontaneous contractile force of the isolated guinea-pig atrium and frog heart was decreased with Vistamycin at concentrations of 10^-3 g/ml and 10^-4 g/ml respectively. The perfusion experiment with Vistamycin using the isolated rabbit ear caused an increase in the perfusion flow at a concentration of 10^-2 g/ml. An increase in capillary permeability was observed with 0.1 ml of Vistamycin injected intracutaneously to the rabbit at a concentration of 10^-4 g/ml.
The spontaneous movement of the isolated rabbit intestine was inhibited with Vistamycin at a concentration of 5 × 10^-4 g/ml, while no effect was found on the isolated guinea-pig intestine even at a greater concentration as 10^-2 g/ml. The action of acetylcholine, histamine or barium on the isolated rabbit intestine was inhibited, and that of barium on the isolated guinea-pig intestine was antagonized by Vistamycin at the concentrations from 2 × 10^-4 to 2.10^-3 g/ml.
It is concluded that Vistamycin produces the pharmacological actions similar to those of other aminoglycoside antibiotics, and yet the effects of Vistamycin are noticed with much higher dose than that of the therapeutic one.

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The antimicrobial activities of Vistamycin (VSM), newly developed at the Central Research Laboratories of Meiji Seika Kaisha, Ltd., were studied in in vitro and in vivo. The results obtained are summarized as follows.
1. The antimicrobial activities of VSM were maintained at pH 6.0 to 8.0, but they were reduced at pH 5.5 and 8.5.
2. The antimicrobial activities of VSM were not affected by the addition of human, bovine or horse serum at the concentration of 10%.
3. The antibacterial effects of VSM against 18 strains of stock culture were equal or somewhat weaker than thoes of KM.
4. The minimum inhibitory concentrations (MIC) of VSM were ranged from 3.12 to 6.25 mcg/ml against all strains of Staphylococci, Streptoccoci, Diplococci, Shigella and Klebsiella isolated from patients, and more than 50 mcg/ml against all strains of Micrococci, Escherichia, Pseudomonas and Proteus.
5. The numbers of survived bacilli were counted din nutrient agar containing different concentrations of the drug. As the results, the antimicrobial effect of VSM was about a half of that of KM against Staphylococcus, while equal to that of KM against Escherichia.
6. The effects of VSM treatment on experimentally infected mice were examined. In comparison with the effect of VSM and that of KM in the treatment of bacillary infections, both drugs are equally effective against Klebsiella. The VSM treatment was also effective against Diplococci, Staphylococci and Proteus infections, whereas insignificantly effective against Streptococci and Pseudomonas infections.

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The laboratory and clinical investigations have been performed on Vistamycin (abbr. VSM), an antibiotic produced by Streptomyces ribosidificus, and the following results were obtained.
1) As for the M.I.C. (minimum inhibitory concentration) of VSM on 58 strains of Staphylococcus aureus, about 90% was distributed below 12.5 mcg/ml. Strain 209P was inhibited the growth by 6.3 mcg/ml of VSM.
2) The cup method would be recommended to measure VSM in body fluid. Mycin assay agar is employed there at pH 7.2 using Bacillus subtilis ATCC 6633 as a test organism.
3) To examine the VSM excretion in bile, the antibiotic was administered intravenously to dogs, and only a quite small quantity was excreted in the fluid.
4) To examine then the VSM concentration in tissue, the antibiotic was administered intramuscularly to rats and dogs, and the concentration was high in kidney, while it was low in liver, lung, spleen and muscle.
5) The bound ratio of VSM to serum protein was about 10% by the ultrafiltration method.
6) To examine the effect of VSM on tissue, the antibiotic was administered intraperitoneally to rats for 2 weeks at a daily dose of 200 mg, and yet no change was observed in the tissue of liver, while the influence similar to the case of kanamycin (KM) was recognized in the tissue of kidney.
7) VSM was administered to 18 cases of respiratory organ infection and urinary tract infection, and the effective result was obtained in 14 cases. A patient complained of a headache, so that the administration was interrupted.

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The clinical study has been performed with a new antibiotic Vistamycin, and the results were obtained as follows :
1) Vistamycin was administered intramuscularly at the daily dose of 500-2, 000 mg to 9 cases of bacterial infection consisting of 3 cases of renal and urinary tract infection, 2 cases of respiratory organ infection, 1 case of urinary tract infection complicated with respiratory organ infection, 1 case of urinary tract infection complicated with skin infection, 1 case of oral cavity infection and 1 case of bacterial endocarditis. The results were effective in 3 cases, slightly effective in 3 cases and ineffective in 3 cases.
2) No side effect was recognized with Vistamycin. A tinnitus was complained in a case who received Vistamycin at the daily dose of 2 g for 53 days, though it was impossible to decide the tinnitus as a side effect of the antibiotic.

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On a new antibiotic Vistamycin (abbreviated as VSM), several laboratory and clinical studies were performed, and the following results were obtained.
1. The susceptibilities of various clinical isolates to VSM were measured in comparison with kanamycin (KM) and streptomycin (SM), and those of VSM were almost equal to those of KM. There seemed to exist a cross resistance between VSM and KM in many instances, however, SM-resistant strains were mostly sensitive to VSM.
2. The mode of action of VSM was considered to be principally bactericidal.
3. In the inhibitory effect against abscess formation following a subcutaneous infection of Staphylococcus aureus in mice, VSM seemed to be next to KM, exceeding SM.
4. The standard curve of VSM for bioassay was represented by the vertical method using Bacillus subtilis PCI 219 as the test organism.
5. No adsorption to red blood corpuscle was observed with VSM. The serum protein binding rate using cellophane bag dialysis was at a moderate grade of 60%.
6. The peak level following, an intramuscular injection of VSM at the dose of 20 mg/kg to rabbits reached 50 mcg/ml after 30 minutes.
7. The bile level in the same experiment was about one-fifth of that of serum peak, the urine level being as much as 20 times or more than serum level.
8. The organ level was determined following an intramuscular injection to mice at the dose of 40 mg/kg, and the peak was recorded in the lung 30 minutes after the infection and in the kidney 1 hour and thereafter, whereas any level was not detected in the liver, spleen and brain.
9. By mixing organ homogenates of mice with VSM solution of known concentration, the activity of VSM was markedly reduced, especially in the cases of liver and spleen, showing an unmeasurable low value.

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The minimum inhibitory concentration (MIC) of Vistamycin (VSM) against Staphylococcus aureus was 0.8-6.25 mcg/ml in 50 strains, 25 mcg/ml in 1 strain, and 100 mcg/ml or higher in the remaining 16 strains. The MIC against E. coli was 3.2-12.5 mcg/ml in 8 strains, and 100 mcg/ml or higher in 2 strains. The MIC against Klebsiella was 6.25 mcg/ml in 8 strains, and 100 mcg/ml or higher in the remaining 2 strains. When the MIC of VSM was compared with that of kanamycin (KM), the former was generally equal or slightly higher than the latter.
The protein binding rate of VSM was determined using the equilibrium dialysis method, and it was found that 29.5% of VSM was bound to horse serum.
The blood concentration following an intramuscular injection of 1 g of VSM was determined in 3 adults. The maximum concentration of 23.0 mcg/ml was obtained 1 hour after the injection. The concentration of VSM was lower than that of KM, of which the determination was made in the same persons.
Two cases of pyelonephritis due to Escherichia coli, 1 case of pneumonia and 1 case of bronchiectasis were treated with VSM at the dose of 1 g per day. As the result, VSM was effective in 3 cases, but 1 case of pyelonephirits did not respond to the treatment. No side effect was observed throughout the therapy.

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Vistamycin has been applied clinically, and the following results were obtained.
Vistamycin was administered intramuscularly for 7-18 days at a daily dose of 500 mg × 2 to 7 cases of respiratory organ infection, 1 case of septicemia and 1 case of pyelitis. As the result, the effectiveness was obtained in 8 cases except a case of septicemia. There observed no side effect which would have been caused by Vistamycin.

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The laboratory and clinical investigations have been performed on Vistamycin (VSM), and the results were obtained as follows :
(1) The antibacterial activity of VSM was slightly weaker than that of kanamycin (KM) against both Gram-negative bacilli and Gram-positive cocci. MIC was> 100 mcg/ml against Pseudomonas.
(2) After an intramuscular injection of 500 mg of VSM, the one reached a peak of blood concentration in 30 minutes, while the other in 1 hour. The highest value was 27 mcg/ml on an average after 30 minutes, and the value was 8 mcg/ml after 6 hours.
(3) VSM was administered to 3 cases of bacterial pneumonia and 9 cases of urinary tract infection. The effectiveness was obtained in 10 cases out of 12 cases (83.3%).
(4) No remarkable side effect was observed.

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The laboratory and clinical investigations have been carried out on a new antibiotic Vistamycin (abbr. VSM), and the results were obtained as follows :
(1) The M.I.C. (minimum inhibitory concentration) of VSM was 1.56-6.25 mcg/ml against 32 strains of Shigella, 1 strain of pathogenic Escherichia coli, 3 strains of Salmonella typhosa, 1 strain of Salmonella paratyphi A and 1 strain of Salmonella paratyphi B which were all isolated recently from patients, while it was 6.25-100 mcg/ml against 16 strains of another Salmonella, and 12.5-25 mcg/ml against 7 strains of Vibrio cholerae or El Tor Vibrio.
(2) VSM was administered orally for 5 days at a daily dose of 2 g for adults and 1 g for children to 4 cases of bacillary dysentery, 1 case of Escherichia coli infection, 2 cases of Salmonellosis other than typhoid or paratyphoid, 4 cases of Vibrio parahemolyticus infection and 10 cases of acute enteritis from which no pathogenic germ was detected.
As for the clinical effect, it proved remarkably effective in 14 cases, effective in 3 cases, in other 4 cases, its effectiveness was undecided, whereas as for the bacteriological effect, the effectiveness was obtained in 2 cases of bacillary dysentery, 1 case of E. coli infection and 4 cases of enteritis due to Vibrio parahemolytica.

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Fundamental and clinical tests of Vistamycin were performed in this study.
1. Minimal inhibitory concentrations of Vistamycin were the same or twice as those of kanamycin against various pathogenic organisms.
2. After a single intramuscular injection of 500 mg of Vistamycin in two patients with normal renal function, the peak serum levels were 19.5-25 mcg/ml, the half life being in 1.1-4.8 hours. After the injection, the urinary concentrations of Vistamycin were higher than 100 mcg/ml for 6 hours, and the urinary recovery rates were 51-82% within 9 hours.
3. In the patients with severely impaired renal function, the peak serum levels of Vistamycin were two to three times higher, and the half life was more than ten times longer than in patients with normal renal function. In the same patients, a single 500 mg intramuscular injection of Vistamycin resulted the urinary concentrations higher than 50 mcg/ml for 48 hours, and the recovery rates were 57?'93%.
4. A dosage schedule of Vistamycin was modified according to the degree of impaired renal function.
5. Nephrotoxicity of Vistamycin with or without a combination of 0.4% solution of Na alginate in rabbits was more slight than that of kanamycin, while slightly higher than that of streptomycin.
6. The clinical use of Vistamycin in five patients resulted excellent or good in three, fair in one, and indeterminate in one.
No side effects appeared in renal or auricular function, besides no allergic reaction occurred even when Vistamycin was used at a large dose or for a long term, in combination with another aminoglycoside antibiotic, or in elderly patients.

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The laboratory and clinical studies on a new antibiotic Vistamycin (VSM) have been carried out, and the following results were obtained.
(1) Staphylococcus, Escherichia coli and Klebsiella pneumoniae demonstrated mostly the sensitivity to VSM. The antibacterial activity of VSM is equal to kanamycin (KM) against Escherichia coli and Klebsiella pneumoniae, while it is slightly inferior to KM against Staphylococcus.
(2) The serum concentration of VSM reached its peak 30 minutes after an intramuscular injection of 500 mg of the antibiotic, revealing about 21 mcg/ml, and it lowered to about 2 mcg/ml after 8 hours. The recovery rate of VSM in urine was about 60% within 8 hours after the administration.
(3) VSM was administered to 4 patients with respiratory infection and 4 patients with urinary infection. The results obtained were remarkably effective in 5 patients, effective in 1 patient, and ineffective in 2 patients. No side effect was observed throughout the cases treated.

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We have treated with Vistamycin seven cases (3 cases of pyelonephritis, 1 case of cystitis and pharyngitis with drug intoxication, 1 case of chronic bronchitis, 1 case of bronchopneumonia, and 1 case of osteomyelitis with diabetes mellitus). Vistamycin was effective in four cases, and no side-effect was observed.

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The effect of oral administration of Vistamycin (VSM) has been investigated on 16 patients of enterobacterial infection, and the antibacterial activity of VSM, kanamycin (KM) and aminodeoxykanamycin (AKM) has been examined respectively on 60 strains of dysentery bacilli isolated.
1) Dysentery bacilli were inhibited the growth mostly by 3.12-12.5 mcg/ml of VSM.
2) The antibacterial activity of VSM to dysentery bacilli isolated was a step lower than that of KM, while it was slightly higher than that of AKM.
3) VSM was administered orally to the carriers of dysentery bacilli and the patients of vibrio enteritis and acute enteritis. The antibiotic was effective both clinically and bacteriologically.
4) No bacterial effect was obtained by VSM in salmonellosis.

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The laboratory and clinical studies have been carried out with Vistamycin (abbr. VSM), a new antibiotic produced by Streptomyces ribosidificus, and the following results were obtained.
(1) The in vitro antibacterial activity of VSM was almost the same as that of kanamycin (abbr. KM) against Staphylococcus aureus, Escherichia coli and other Gram-negative bacilli. VSM inhibited the growth. of streptomycin (abbr. SM) resistant strains similarly in the case of SM sensitive strains. A cross resistance was exhibited between VSM and KM.
(2) As for the VSM blood concentration, a peak was 15.6 mcg/ml and 22.0 mcg/ml respectively in 2 adults 1 hour after they received intramuscularly 500 mg of VSM. The above values are slightly lower than those of the same amount of KM. The antibacterial activity of VSM in serum against Staphylococcuswas slightly weaker than that of KM.
(3) VSM was administered intramuscularly for 10-21 days at a daily dose of 500 mg ×2 to 3 cases of mixed infection in pulmonary tuberculosis or tumor. As the result, the clinical effect was obtained by VSM without any side effect.

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Vistamycin was administered intramuscularly for 4-21 days at the daily dose of 1-2 g to 11 patients consisting of suppurative tonsillitis, bronchitis, pyothorax, nephropyelitis and cystitis. The results obtained were remarkabley effective in 3, effective in 4, slightly effecitve in 2 and ineffective in 2.
No side effect was observed except an ache of the injected site in 1 case.

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The results of the studies on Vistamycin were summarized as follows :
1. A total of 683 strains of recently isolated from clinical materials and 21 standard strains were tested for their in vitro susceptibility to Vistamycin (VSM), kanamycin (KM) and aminodeoxykanamycin (AKM) by the plate dilution method.
The antibacterial spectrum of VSM was the same as that of KM or AKM. The antibacterial activity of VSM was not higher than that of KM and lower than that of AKM against most strains except α, β-Streptococci.
It was confirmed that there may be the cross-resistance among VSM, KM and AKM.
2. Minimum inhibitory concentration of VSM, KM or AKM was affected by pH of the medium for Staphylococcus aureus 209 P and Escherichia coli NIHJ. Antibacterial activities of these three drugs were more effective in alkaline medium.
3. Tissue concentration of VSM in rats after intramuscular injection (20 mg/kg) was measured by means of cup plate method using Bacillus subtilis ATCC-6633 as test organism, and it was almost equal to that of KM or AKM. The kidney showed the highest concentration, and the other organs exhibited the concentrations as follows in order of blood, lung and liver, among which the latter's concentration was especially poor.
The serum peak levels (21.9 mcg/ml) in 5 healthy humans (500 mg, I.M.) was attained on an average 1 hour after the administration, then dropped to 3.5 mcg/ml after 6 hours, indicating yet thus the higher values.
The urinary recovery rate of VSM, KM or AKM was more than 70% on an average within 6 hours.

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A series of investigations has been performed on Vistamycin (abbr. VSM), a new Japanese antibiotic, in the field of pediatrics, and the results were obtained as follows :
1) The M.I.C. (minimum inhibitory concentration) of VSM was 0.19-0.39 mcg/ml against Pneumococcus, 1.56-3.12 mcg/ml against coagulase-positive Staphylococcus, 3.12-6.25 mcg/ml against pathogenic Escherichia coli, and 6.5-25.0 mcg/ml against Shigella dysenteriae. It was scarcely possible to find the resistant strains among the above species.
2) As to the VSM blood concentration after its intramuscular injection, the very high peak was obtained after 30 minutes of the administration, and the concentration maintained to be measurable unit 7 hours later.
3) As for the VSM excretion after its injection, 50-83% of the administered amount was excreted at an active state in urine within 7 hours.
4) As to the clinical effect of VSM, the effective ratio obtained was 88.1% for 59 cases including 12 kinds of infantile infection. A daily dose of 20.0 mg/kg VSM for acute tonsillitis, lacunar tonsillitis and acute urinary tract infection, and that of 40.0-50.0 mg/kg VSM for pneumonia and pyothorax exhibited a similar result to the usual dose of KM for acute infections of children.
5) There included several cases which proved the usual antibiotics resistant strains of Staphylococcus and Escherichia coli among 59 cases. The cases of the kind responded well to the intramuscular injection of VSM.
6) No noticeable side effect of VSM was encountered, as the tests were made on blood, urine, hepatic function and auditory acuity throughout all the cases treated.

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Vistamycin (abbr. VSM) was administered intramuscularly for 5-11 days at a daily dose of 40-50 mg per kg of body weight to 12 cases of bacterial pneumonia, 2 cases of cystitis, and each 1 case of pyothorax, bronchitis, purulent meningitis and peritonsillar abscess in the field of pediatrics, and the clinical effects were investigated.
The results obtained were remarkably effective in 2 cases, effective in 12 cases and ineffective in 4 cases.
Neither hepatic nor renal function revealed any damage by VSM administration.

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Vistamycin was administered intramuscularly for 4-14 days at a daily dose of 0.5-1.5 g to 23 cases of surgical infection as pulmonary pyosis, cholecystitis, abscess and panaritium. The results obtained were effective in 13 cases, slightly effective in 6 cases and ineffective in 4 cases.
Neither damage of hepatic or renal function nor other side effect was encountered, except that a case complained of numbness.

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1) The antibacterial activity of that of Vistamycin is almost the same degree as that of kanamycin (KM) against Escherichia coli, while it is a grade inferior to kanendomycin (KDM). There encountered many resistant strains in Proteus and Pseudomonas.
2) The antibacterial activity of Vistamycin is stronger as the pH of both medium and diluent is higher, and it is better as the inoculum size is smaller. Only a slight difference was observed among the actionties of various media.
3) The test of resistance aquisition of Escherichia coli B resulted that M.I.C. was more than 100 mcg/ml after 4 transfers with Vistamycin. The value is similar to that of KM, and earlier than that of KDM.
4) The blood concentration of Vistamycin reached the peak after 30 minutes, and then decreased gradually. The antibiotic was excreted mostly in urine within 4 hours, and the recovery ratio was high within 6 hours.
5) As for the Vistamycin concentration in organs, it was distinctly higher in kidney, next in lung where as it was small in other organs.
6) Vistamycin was applied therapeutically for the surgical Infections and prophylactically for the postoperative infections. From the results obtained, the effective ratio with Vistamycin was 69.2%.

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Laboratory and clinical evaluations of Vistamycin, a new antibiotic, were studied in the surgical infections.
Among 56 strains of Staphylococcus aureus isolated from the surgical infections, MIC of 50 strains distributed in the range from 6.25 mcg/ml to 0.09 mcg/ml.
The average peak blood level of Vistamycin in 3 healthy adults was 19.3 and 28.5 mcg/ml respectively 1 hour after the drug was administered intramuscularly at the dose of 500 mg and 1, 000 mg, and the values of 3.5 and 5.0 mcg/ml were detected even after 6 hours.
The average urinary excretion rate in the above 3 adults was 80.1% and 67.3% respectively within 6 hours.
Vistamycin was given to 22 cases of surgical infections, including furuncle, phlegmon, abscess, infectious sebaceous cyst, lymphadenitis, peritonitis and panaritium, and the antibiotic was found to be effective

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Vistamycin (VSM), a new broad spectrum antibiotic, was examined on blood level, urinary recovery, antibacterial activity, clinical effectiveness and side effects.
1) Blood level : Following a single intramuscular injection of 500 mg of VSM in 3 normal adults, the mean blood level showed a peak of 24.1 mcg/ml 1 hour after the administration.
2) Urinary recovery : In the same cases, the urinary recovery of VSM was 271.3 mg (54.26%) within 3 hours, and 459.1 mg (91.8%) within 24 hours.
3) Sensitivity of organisms isolated from surgical foci : The sensitivity to VSM, kanamycin (KM), and aminodeoxykanamycin (AKM) was examined in 25 strains of Staphylococcus aureus, 18 of Escherichia coli, 7 of Proteus vulgaris, 11 of Klebsiella, and 12 of Pseudomonas aeruginosa. In comparison with KM and KDM, VSM was almost equally effective to Gram negative bacilli, whilst it was slightly less effective to Staph. aureus.
4) VSM was used in 30 cases of surgical infections, including cellulitis, abscess, lymphadenitis and perforative peritonitis, and the effective rate obtained was 85.7%.
5) No noticeable side effects were observed with VSM.

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The present studies were undertaken to investigate the nephrotoxicity of Vistamycin (VSM).
Materials and Methods :
Sixty male rats (100 ± 20 g) of Donryu strain were divided into 6 groups consisting of each 10 rats. VSM was given intramuscularly to the rats for 21 days at the different doses as follows : 50, 100, 200, 400, and 800 mg/kg. Meanwhile, KM (200 mg/kg) was administered intramuscularly to rats for 21 days.
All the experimental animals were examined for proteinuria, glycosuria, urinary keton, urinary occult blood, BUN, and serum creatinine, and the kidney was examined histopathologically with hematoxylin-eosin, PAS, and Toluidine blue. At the same time, the comparative studies of histochemical changes of kidney in rats administered VSM or KM were performed with Acid-phosphatase, β-glucuronidase, LAP, and Alkaline-phosphatase stain.
Results :
1) No evidence of nephrotoxicity was noted histopathologically in Donryu-rats received intramuscularly VSM 200 mg/kg for 21 days.
2) When VSM 400 mg/kg were administered intramuscularly for 21 days, the nephrotoxicity seemed to be similar histopathologically to that of the group received intramuscularly KM 200 mg/kg for 21 days.

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Vistamycin was administered intramuscularly for 5-13 days at a daily dose of 500-1, 000 mg therapautically to 6 cases of surgical infection and prophylactically to 30 cases of possible postoperative infection.
The results obtained were effective in 3 cases and slightly effective in 3 cases for surgical infection, and effective in 29 cases and slightly effective in 1 case for prophylaxis of postoperative infection.
No side effect was observed.

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Vistamycin was administered intramuscularly for 1-10 days at a daily dose of 500 mg therapeutically to 20 cases of trauma and 14 cases of suppurative infection and prophylactically to 6 cases of possible postoperative infection. The results obtained were effective in 19 cases, 12 cases and 6 cases respectively.
No side effect was observed.

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The present author has examined the Vistamycin concentrations in the blood and bone marrow, and discussed its distribution. In this experiment, the normal male albino rabbits were given intramuscularly a dose of 10 mg of vistamycin per kg of body weight. After Vistamycin was administered the blood was aspirated from the ear vessel, and the greater trochanter was punctured to obtain the marrow tissue. Both the specimens of blood and marrow were assayed to determine the Vistamycin concentrations by means of OKUBO's band culture method.
The concentrations distribution of Vistamycin was compared with those of kanamycin and aminodeoxykanamycin in the blood and bone marrow in the experimints under the same conditions. The concentrations of Vistamycin in the blood and marrow were both lower than those of aminodeoxykanamycin, while they were higher than the concentrations of kanamycin, although those of Vistamycin in the marrow were maintained for the longest period of time among three antibiotics.

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The present author has assayed the distribution of Vistamycin concentrations in the circulating blood and the fracture hematoma using normal male albino rabbits.
Vistamycin was administered at the dose of 10 mg per kg, while the femoral shaft was fractured by KONDO's osteocrasting forceps before or after the administration.
The blood level of Vistamycin and its concentration in the fracture hematoma were assayed by means of OKUBO'S band culture method modified by KONDO.
The distribution of Vistamycin in the hematoma was higher, when it had been given before the fracture than when it was injected after the fracture.
The results of the experiment are the same as those of kanamycin and aminodeoxykanamycin.
The blood level and the concentration of Vistamycin in the hematoma were also compared with the concentrations of kanamycin and aminodeoxykanamycin in the experiments under the same conditions, and the results revealed that the distribution of these antibiotic concentrations was the highest with aminodeoxykanamycin and then Vistamycin, and the concentrations of kanamycin were lower than those of Vistamycin.

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Local administration of antibiotics after surgical operations is a unique means to prevent postoperative infections, and this is made as a routine procedure in Japan. Though the excellent results are obtained by this technique, antibiotic concentrations remained at the operation wound have not been studied and no report has been published on this matter.
The author has made an experimental fracture at the femoral shaft of albino rabbit with KONDO'S osteocrasting forceps, and administered Vistamycin into the fracture hematoma. The blood level of Vistamycin was assayed 45 minutes, 90 minutes, 3 hours, 6 hours, 12 hours and 24 hours after the administration. The hematoma was punctured directly to aspirate the hematoma 24 hours after the administration, and the remained concentration of Vistamycin was assayed. The assay was done by means of modified OKUBO's band culture method.
Even 24 hours after the administration, the remained concentrations in the hematoma were higher than M. I. C. for many suppurative infectious organisms, and the results proved that this treatment technique is an excellent method to avoid postoperative infections.
The above experiment results were compared with those under the same conditions using kanamycin and aminodeoxykanamycin, and some discussions were made among three antibiotics.

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Vistamycin (abbr. VSM) was administered for 5-12 days at a daily dose of 1-2 g to 57 suppurative lesions of bone and joint in 34 patients. The results obtained were remarkably effective in 24 lesions, effective in 24 lesions, slightly effective in 6 lesions and ineffective in 3 lesions.
The above results would be related largely to the VSM concentrations in each lesion following the different administration methods, as well as to the drug sensitivity of each causative organism.
No side effect was observed with VSM treatment.
To support these results, VSM was administered intramuscularly to rabbits and the blood level, the concentrations in the bone marrow, and in the fracture hematoma were assayed, meanwhile VSM was directly injected into the fracture hematoma of the rabbits and the blood level after the administration was also assayed.
The results of these experiments were coincidental to the clinical experiences above mentioned.

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Vistamycin has been applied to the purulent infections in the field of orthopaedic surgery, and the results were obtained as follows :
(1) Vistamycin was used to 29 cases of purulent infections in the field of orthopaedic surgery. The cases consisted of 14 cases of purulent osteomyelitis, 3 cases of spinal caries complicated with infectious fistula, 3 cases of postopertive infection, 3 cases of spinal infection complicated with cystoureteral infection, 3 cases of infectious decubitus, 2 cases of purulent myositis and 1 case of open fracture of forearm.
(2) Vistamycin was administered intramuscularly every day at a daily dose of 1, 000 mg. The dosing period varied between 7 days for the shortest and 30 days for the longest.
(3) The comparison was made before and after the treatment on clinical finding, fever type, causative organisms number, sedimentation value and leucocyte number. The judgement was done under the criteria of treatment results consisting of 4 steps as +++, ++, +and-.
(4) Among 29 cases, +++ was obtained in 3 cases (10.3%), ++ in 7 cases (24.1%), + in 16 cases (55.3%), the effective ratio being thus 89.7%. It would be noted that among 14 cases of acute or chronic purulent osteomyelitis, +++ was obtained in 2 cases (15.3%), ++ in 1 case (7.8%), + in 11 cases (76.9%). An operation may be necessary in the above infection if the case demands it.
(5) As to the causative organisms, Staphylococcus aureus was the most frequent as 12 cases, in which 50% was effective with Vistamycin. There detected Staphylococcus epidermidis, Enterococcus, Cloaca and Pseudomonas, and some cases due to one of these organisms obtained an effectiveness.
(6) No side effect was observed throughout all the cases, as a result of the comparison before and after the Vistamycin administration on blood test and biochemical test mainly composed of auditory acuity, hepatic and renal functions.
(7) Because the side effect is very scarce with Vistamycin, the antibiotic may be administered at a daily dose of 2, 000 mg or more. As the result, the antibacterial potency of Vistamycin will be equal to that of kanamycin or aminodeoxykanamycin, and the highr effect will be awaited with Vistamycin for the purulent infections in the field of orthopaedic surgery.

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1. Vistamycin was well transferred into cord blood and amniotic fluid in comparison with the usual antibiotics, when 500 mg of the drug were administered intramuscularly in mother's body.
2. The transfer of Vistamycin into milk was low similarly in the case of the usual antibiotics.
3. Vistamycin was obviously transferred into fetus even at the primary period of the pregnancy, when the drug was injected intramuscularly in mother's body.
4. When Vistamycin was injected intramuscularly in mother's body at the middle period of pregnancy, the transfer of the drug into the kidney of fetus was high, that is, higher than blood concentration in cord blood. This fact suggests that there may be a tendency of Vistamycin accumulation in the fetus' kidney and the further investigation should be pursued on this problem.
5. Vistamycin was applied to 31 cases of the infections in the field of obstetrics and gynecology. The results obtained were effective in 24 cases, the effective ratio being thus 77.4%.

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With the intention of clarifying the therapeutic evaluation of Vistamycin (abbr.VSM), a new leading antibiotic of aminoglucoside system discovered in our country, the present authors have investigated the antibacterial action, transfer in body, and clinical resutlt with VSM.
VSM showed an antibacterial spectrum against a wide range of both Gram-positive and-negative bacteria except Streptococcus and anaerobe, 65% of Stapyhloccoccus aureus indicating 1.56-6.25 mcg/ml and 83% of Escherichia coli 3.12-25 mcg/ml. The sensitivity distribution for Staphylococcus and Escherichia coli ranged AMK, KM, VSM and SM in order. There observed a sensitivity relationship between KM and VSM.
VSM demonstrated a peak level 5 hours after its intramuscular injection, and the blood concentration was maintained for 6-8 hours. The excretion ratio of VSM in urine was 56.2% within 8 hours, while the transfer value of VSM into foetus was about 1/3 of the antibiotic blood concentration in mother.
VSM was administered therapeutically for 2-12 days at a daily dose of 2-4 g to 24 cases of various infections in the field of obstetrics and gynecology, and the effective ratio obtained was 66.7%. There experienced no side effect which would have been due directly to the antibiotic.
In conclusion, Vistamycin is considered to be a useful antibiotic which will be applied in clinical practice.

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Vistamycin (abbr. VSM), an antibiotic recently isolated and identified as a member of aminoglucoside drug, was evaluated experimentally and clinically in urinary tract infections.
Antimicrobial activity of VSM was similar to that of kanamycin (abbr. KM), but MIC values on the isolates from urinary tract infections were slightly higher than those of KM especially for Pseudomonas strains. Serum level and urinary excretion of VSM administered intramuscularly were also similar to those of KM.
Clinical and bacteriological responses obtained by medication with VSM were not satisfactory yet. In acute lower urinary tract infections, a daily dose of 1 g of VSM seemed reasonable to obtain a satisfactory response. In acute upper urinary tract infections, 1.5 g of VSM given for a longer period was effecitve only temporarily. The optimum dose against gonorrhea was 2 g daily. In complicated chronic infections, daily dose of 1 g was unsatisfactory probably due to higher MIC values. Therefore, the maximum tolerant dose of VSM should be investigated to know the optimum dose for upper and/or complicated chronic urinary tract infections.

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The laboratory and clinical studies have been carried out on a new antibiotic Vistamycin (abbr. VSM), and the following results were obtained.
1) Blood concentration
When 0.5 g of VSM was administered once intramuscularly, the blood concentration reached its peak after 1 hour, then it decreased suddenly, and yet the effective blood concentration was observed until 6 hours later.
2) Excretion ratio in urine
When 0.5 g of VSM was administered once intramuscularly, the excretion ratio in urine was 84.6%, and 90.3% within 12 hours.
3) Antibacterial activity
The antibacterial activity of VSM was fairly good against Staphylococcus and Escherichia coli.
4) Clinical result
VSM was applied to 15 cases of urinary tract infection, and the results obtained were remarkably effective in 6 cases, effective in 5 cases, ineffective in 4 cases, the effective ratio being 73.3%.
5) Side effect
No noticeable side effect was observed.

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1. Minimal inhibitory concentration of Vistamycin was determined on 139 strains isolated from urinary tract infections by the plate dilution method. Most strains of Staphyloccoci, Escherichia coli, Proteus mirabilis and Klebsiella were inhibited at the concentrations below 6.25 mcg/ml, while almost all of Proteus vulgaris and Pseudomonas tested were resistant to the antibiotic.
2. With an intramuscular injection of Vistamycin 500 mg, the blood level reached the maximum level (21.0-35.0 mcg/ml) 30 minutes after the administration, decreasing rapidly thereafter.
3. The urinary recovery rate was 79.4-97.7% within 24 hours after the injection in normal 2 subjects.
4. Twelve cases with urinary tract infections were treated with Vistamycin, and good results were obtained in 6.
5. No side effect was observed throughout the treatment, except that an ascent of BUN level was noted in one of 12 patients.

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Vistamycin (abbr. VSM) was administered intramuscularly for 5 days at a daily dose of 1 g to 31 cases of urinary tract and genital organ infections, and the following results were obtained.
(1) The clinical effect was observed clearly in 22 cases out of 31 cases of urinary tract and genital organ infections, and only 1 case remained ineffective.
(2) There observed many effecitve cases in the infections due to Escherichia coli, Enterococcus and Enterobacter, whereas the results were no good in those due to Pseudomonas aeruginosa.
(3) VSM administration gave no definite influence at all on the hepatic and renal function tests as well as on the findings of peripheral blood.

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Ninety-eight patients with various urinary tract infections were treated with Vistamycin at the Department of Urology, Kyushu University, and other 10 hospitals.
One gram of Vistamycin was administered intramuscularly twice daily to 90 patients, and once daily to 8 patients each for 5 days.
Satisfactory results were obtained in 88.8% of 18 non-specific acute urinary tract infection cases, whereas 53.0% of 49 complicated cases. Satisfactory result was obtained thus in 54% in total.
No side effect was observed except mild disorder in 2 cases.
Vistamycin is evaluated therefore as a useful antibiotic for the urinary tract infections.

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Forty cases of urinary infection were treated with Vistamycin (abbr. VSM), including 15 cases of gonorrhoea. Out of 40 urinary infections, the effectiveness was obtained in 32 patients (80.0%), revealing thus satisfactory results. VSM has yes relatively weaker antimicrobial activity against Gonococcus.
Side effects were rarely encountered with VSM.

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Vistamycin (VSM) is a new aminoglycoside antibiotic produced in Japan of which antimicrobial spectrum is expected for both gram positive and negative bacteria. We have studied on the minimum inhibition concentration, serum levels, excretion in urine and clinical evaluations with VSM. Comparaitve fundamental studies were carried out among kanamycin (KM), aminodeoxykanamycin (AKM) and VSM. The results obtained were as follows :
The antimicrobial activity against Escherichia coli, Proteus, Klebsiella and Pseudomonas isolated from patients with urinary tract infections ranged as AKM >KM≥VSM by the agar plate method. Serum levels were studied after a single intramuscular dose of 500 mg VSM to 3 healthy adults. The maximum serum concentration of VSM was found to be 29 mcg/ml on an average 1 hour after the administration, being 2.5 mcg/ml 8 hours later. The case of renal insufficiency demonstrated prominently high serum levels and prolonged half-life time of the drug. Serum half-life time of VSM was shown 72 hours after a single intramuscular 500 mg dose in a case of renal failure who was undergoing hemodialysis. The recovery ratio in the urine in 3 healthy adults who received the same administration was 68.2% within 8 hours.
In contrast to healthy adults, the recovery in the urine diminished in the cases of renal lesion according to the degree of impairment. Recovery ratio in the urine within 48 hours was 0.33% in a case who was undergoing hemodialysis, whereas 18.8% within 24 hours in a case with mild renal impairment.
VSM was administered intramuscularly to 17 cases with urinary tract infections. Excellent clinical results were obtained in 85.7% of patients of acute urinary tract infection, while 30% in chronic infections. No side effect was observed in all cases.

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Vistamycin (abbr. VSM) was administered principally intramuscularly for 2-23 days at a daily dose of 1-2 g to 13 cases of purulent skin infections. The results obtained were remarkably effective in 6 cases, effective in 4 cases, slightly effective in 2 cases and ineffective in 1 case.
In addition to the above cases, VSM was administered intramuscularly for 19 days at a daily dose of 2 g to 1 case of manifest secondary syphilis. Though no improvement was observed in the swelling of lymphatic glands and the seroreaction of syphilis, the acne disappeared in each part of body, and the judgement was done as effective.

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Vistamycin (VSM) was studied fundamentally and clinically, and the following data were obtained.
1) In vitro antimicrobial activity : The sensitivity of VSM to 32 strains of coagulase-positive Staphylococcus aureus obtained from patients with pyoderma was studied by the plate dilution method. The M.I.C.s of this drug were 6.25 mcg/ml or less against all these strains.
2) Serum level : Following an intramuscular injection of VSM 1 g, the serum level was determined. in 3 adults and the averaged maximal level of 36.0 mcg/ml was obtained 1 hour later, decreasing gradually thereafter. The clinically effective blood level was retained for 6 hours.
3) Clinical evaluations : VSM was given to 6 patients with pyoderma, and the results obtained were effective in 2 patients.

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Fundamental and clinical evaluations of a new aminoglucoside antibiotic, Vistamycin, were performed. The results obtained are as follows :
1) In vitro antibacterial activity : The minimum inhibitory concentration of Vistamycin was measured by the agar plate dilution method. Vistamycin inhibited the growth of 80 strains of coagulase positive Staphylococcus aureus at 0.78-≥100 mcg/ml. Vistamycin compound also demonstrated the antibacterial effect against Escherichia coli and Proteus vulgaris isolated from clinical specimens. Vistamycin demonstrated thus a broad spectrum of antimicrobial activity.
2) Concentration in blood : The maximal level reached 35.7 mcg/ml on the average 30 minutes after the injection of 500mg to healthy adults, and the level was still 2.8 mcg/ml 6 hours after the injection.
3) Concentration in tissues : Vistamycin activity was demonstrable at the concentration of 6.6 and 6.3 mcg/g in a human palatine tonsilla specimen 1 hour after the injection of 500 mg. The plasma levels of Vistamycin were then 30.5 and 28.3 mcg/ml.
4) Clinical evaluation : In the clinical test of Vistamycin on otorhinolaryngological infections, it was found that the results were good to excellent in as many as 27 of 33 cases (82%) by the injection or local application of 10 mg/ml solution.
5) Side effect : The comparative examination of liver, electrocyte and audiogram before and after injection showed no significant disturbance. No side effect was shown with the injection or local application of Vistamycin.

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Influence of VSM on the inner ear was studied functionally and pathohistologically using guinea pigs after intramuscular injection, and the results were compared with those of KM.
No functional changes were noted with regard to the pinna reflex by Preyers test, and no abnormalities of the inner and outer hair cells of Corti organ were observed with regard to the structure and the activity of LDH-ase in both 35-day animals which were given 400 mg and 600 mg/kg/day of VSM.
On the other hand, the loss of pinna reflex and the pathohistological abnormalities were detected in the comparative groups administered 200 mg and 400 mg/kg/day of KM.
From the above findings, VSM appeared to be less ototoxic than KM.

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From the laboratory and clinical studies of Vistamycin, a new antibiotic, the following results were obtained.
1. The MIC values of Vistamycin were lower against newly isolated Staphylococcus aureus (20 strains) than those of kanamycin.
2. The bacteriolytic action of Vistamycin was observed from the automatically recorded growth curve of Staphylococcus aureus 209P strain, using Biophotometer Jouan. The same activity against the above strain was observed in the sera of patients receiving an intramuscular dose of Vistamycin 500 or 1, 000 mg. The effective concentration in serum was demonstrated 1 to 3 hours after the injection.
3. Thirty-eight cases of the infections were treated with Visatmycin, and the results were as follows : remarkably effective 20 cases (52.6%), improved 12 cases (31.6%), ineffective 6 cases (15.8%), and effecitive ratio (84.2%).
4. No eruption nor ototoxicity was encountered as the side-effect of Vistamycin.

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From the laboratory and clinical studies on Vistamycin, the following results were obtained :
1) The minimum inhibitory concentration study was done on 18 strains clinically isolated from the lesions of oto-rhino-laryngolocical infections. The sensitivity distribution was from 0.78 to 3.13 mcg/ ml in Staphylococci, Escherichia coli, Proteus vulgaris and in a majority of Klebsiella pneumoniae strains. Pseudomonas aeruginosa was highly resistant to this antibiotic. Vistamycin was found to have a cross resistance with kanamycin or aminodeoxykanamycin in these strains.
2) Levels of Vistamycin in tonsil and mucous membrane of maxillary sinus were measured on 4 patients respectively. An average of tissue concentration was 4.9 mcg/g in tonsil and 2.3 mcg/g in mucous membrane of sinus 2 hours after the intramuscular administration of 500 mg.
3) Vistamycin was given intramuscularly at the daily dose of 500 mg and 1, 000 mg to the patients with acute infections in ear, nose and throat. The antibiotic was effective in 76.2% of the patients.
4) Ten patients with chronic otitis media were treated locally with the solution containing 25 mg of Vistamycin per ml. Excellent or good results were obtained in 4 cases, and no effects were observed in the cases caused by Pseudomonas aeruginosa.
5) No damage was revealed in the inner ear, nor other side effects were observed. It was presumed clinically that the ototoxicity of Vistamycin is low in comparison with other oligosaccharide antibiotics.

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Vistamycin (VSM) is an aminoglycosidic basic antibiotic like kanamycin with a molecular formula C₁₇H₃₄N₄O₁₀, and the ototoxicity was examined with this antibiotic.
Forty-four healthy guinea pigs with normal Preyer's reflex were used for this investigation. Twenty animals were used for intramuscular injection, 14 for intratympanic application and 10 for control.
Eight animals were alive after the intramuscular injection of VSM 400 mg/kg for 10 days. Ototoxicity of VSM was investigated with the alive 8 guinea pigs by the following methods :
1. Preyer's reflex of 500, 1, 000, 2, 000 and 4, 000 csp.
2. Electrophysiological investigation : Endocochlear potential, cochlear microphonics and summating potential were measured by 500, 1, 000, 2, 000, 4, 000 and 8, 000 cps of closed sound stimulation.
3. Morphological and histochemical investigations by Sudan black B staining and succinic dehydrogenase staining : Hair cells of the oragan of Corti were observed by surface preparation from basal turn to apex.
The results showed no ototoxicity of VSM. On the contrary, the intramuscular injection of kanamycin 400 mg/kg for 10 days showed almost 100% ototoxicity.
Intratympanic application was divided into four groups. They were VSM (6 guinea pigs), kanamycin (2), oleandomycin (4) and saline solution (2). Ototoxicity was examined electrophysiologically and histochemically after 7 days. All of VSM application showed otitis media and strong ototoxicity. Although this ototoxiciy seemed to be due to otitis media, ototoxicity of VSM in the final analysis was not denied. Two cases sof kanamycin also showed ototoxicity, whereas saline solution showed no ototoxicity. Four cases of oleandomycin were dead.
In conclusion, ototoxicity of VSM was very slight in comparison with kanamycin. The ototoxicity was not yet elucidated distinctly with VSM.

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For the purpose of preventing the post-operative infections, Vistamycin was administered intramuscularly to 20 cases at the dose of 500 mg twice per day for adults and 250 mg twice per day for children respectively. As the result, no infection occurred in all cases except 1 case in which the administration of the drug was interrupted.
No abnormality was revealed by various examinations as urinary test, hepatic function test and blood test which were performed before and after the Vistamycin administration. There observed no case in which the auditory acuity lowered by the auditory acuity examination after the drug treatment.
It may be added that the eruption occurred in 2 cases during the Vistamycin administration. One case was an allergic diathesis with the history of pyrin group and penicillin hypersensitivity, and an another case was an alcoholic.

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The author examined the ototoxicity of Vistamycin, a new antibiotic, in the cochlea of guinea pigs, and concluded that the ototoxicity of this agent is scarcely or not existent.
After the consecutive intramuscular administration of 4 weeks at the dose of 400 mg/kg, no evidence of ototoxicity was proved in the cochlea of guinea pigs by the audiological, electrophysiological and histological examinations.
On the contrary, in the cases of kanamycin administration, 70 per cent of animals showed distinctly the ototoxicity on all the audiological (disappearance of PREYER's reflex), electrophysiological (decrease of cochlear microphonics) and histological (defects of nucleus in outer hair cells) examinations.

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