The antibacterial activity of 3', 4'-dideoxykanamycin B (abbr. DKB) was measured against 852 strains of pathogenic bacteria isolated recently from clinical materials mostly in 1972, and the obtained values were compared with those of gentamicin, kanamycin and streptomycin.
(1) DKB demonstrated a strong antibacterial activity against Staphylococcus aureus, Enterococcus, Haemophilus, Enterobacteriaceae and Pseudomonas aeruginosa, and there observed no strain which would be a resistant one. There included kanamycin-and streptomycin-resistant strains among the above bacteria, nevertheless DKB exhibited a strong antibacterial activity even against those bacteria.
(2) The antibacterial activity of DKB was weaker against Streptococcus haemolyticus, whie against Pseudomonas genus except Pseudomonas aeruginosa and other non glucose fermenting Gram-negative bacilli, the antibacterial activity of DKB was generally weaker than that against Pseudomonas aeruginosa, and there observed even some resistant strains. The antibacterial activity of the drug was weak against anaerobic bacteria.
(3) Compared the antibacterial activity of DKB with that of gentamicin, DKB was slightly stronger against Pseudomonas aeruginosa, whereas it was slightly weaker against other species.

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1. The antibacterial spectrum of 3', 4'-dideoxykanamycin B (abbr. DKB) resembles to that of gentamicin. The antibacterial activity of DKB is inferior to that of gentamicin against Gram-positive bacteria, while it is almost the same each other against Gram-negative bacteria. The activity of DKB is superior to that of gentamicin against a part of Pseudomonas aeruginosa.
2. The sensitivity of Staphlococci isolated clinically is distributed among 0.19-6.25 mcg/ml for both drugs. The sensitivity distribution of E. coli isolated clinically is 1.56-6.25 mcg/ml for DKB and 0.78-3.12mcg/ ml for gentamicin, while that of Pseudomonas aeruginosa isolated clinically among 0.19-> 100mcg /ml.
3. The cross resistance is well correlated between DKB and gentamicin against every species of Staphylococcus, E. coli and Pseudomonas aeruginosa isolated clinically.
4. As to the action on growth curve using Pseudomonas aeruginosa, DKB and gentamicin show the same action both in the beginning of growth and the halfway of logarithmic phase.
5. As for the mode of action of DKB examined using phase microscope and electron microscope, the primary action point would be situated firstly in cell wall and cellular membrane against Pseudomonas aeruginosa.

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The pharmacological actions of 3', 4'-dideoxykanamycin B (DKB), which was developed as a result of studies on mechanism of inactivation of kanamycin, were investigated.
Summary of pharmacological actions and minimal effective doses (MED) of DKB were as follows : inhibition on excised frog heart (5×10^-4g/ml), inhibition on excised guinea-pig atrium (5×10^-5g/ml), bradycardia on ECG of the rabbit (50 mg/kg), dilation on excised rabbit ear vessels (10^-2g/ml), acceleration on permeability of rabbit abdominal skin vessels (100 mcg), inhibition on excised rabbit intestine (2×10^-4g/ml), inhibition on excised tracheal muscle of the guinea-pig (2×10^-4g/ml), inhibition on excised rat uterus (10-4g/ml for nonpregnant uterus and 10^-5g/ml for pregnant uterus), and fall on blood pressure of the rabbit (5 mg/kg). No effect on excised guinea-pig intestine or on respiration of the rabbit was observed at doses up to 2×10^-3g/ml and those of 10 mg/kg, respectively.
Its actions were almost identical to those of other aminoglycoside antibiotics and MED were almost equal or larger. These MED were also much larger than minimum inhibitory concentrations and maximum blood levels in clinical uses.
Therefore, it is concluded that DKB is one of the antibiotics with much less pharmacological actions.

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Laboratory and clinical investigations were performed on a new antibiotic, 3', 4'-dideoxykanamycin B (abbr. DKB), and following results were obtained.
(1) The minimum inhibitory concentration of DKB was determined on various strains preserved in our laboratory. The values obtained were 0.78-3.13 mcg/ml to Pseudomonas aeruginosa, 0.78-6.25 mcg/ml to Klebsiella, 3.13-6.25 mcg/ml to Proteus, 1.56-6.25 mcg/ml to Escherichia coli, 0.2-0.78 mcg/ml to Staphylococcus aureus, 0.2-12.5 mcg/ml to Pneumococcus, and 25 mcg/ml to Mycobacterium tuberculosis H₃₇Rv-S.
(2) In in vitro experiments with Pseudomonas aeruginosa, Klebsiella pneumoniae and Staphylococcus aureus, DKB demonstrated a slight additive action with cephalothin or penicillin G.
(3) Under the action of DKB, Klebsiella exhibited various degenerations in cytoplasma and cell wall.
(4) DKB was administered to 17 cases of respiratory tract infection at a daily dose of 50 mg×2 for 7-20 days, and the satisfactory results were obtained.

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Fundamental and clinical tests of dideoxykanamycin B were performed in this study.
1. Incubation of mixtures containing 20 parts of carbenicillin to 1 part of dideoxykanamycin B resulted in inactivation of the dideoxykanamycin B. The half-life of dideoxykanamycin B at 37°C was about 24 hours.
2. Serum concentrations of dideoxykanamycin B were kept high level and urinary recovery rate decreased in patients with severely impaired renal function. The peak of averaged serum concentration and half-life of dideoxykanamycin B after a single intramuscular injection of 100 mg were 3. 35 mcg/ml and 1. 18 hours in two subjects with normal renal function, 4.63 mcg/ml and 15. 39 hours in three patients on chronic haemodialysis respectively. The averages of urinary recovery rate after 6 hours were 76% in the normal subjects, and 12% in the patient with severely impaired renal function whose creatine clearance was 19 ml/min.
3. Nephrotoxicity of dideoxykanamycin B with or without combination of 0. 4% solution of sodium alginate in rabbits was fundamentally the same in degree as those of aminosidine and gentamicin.
4. Daily 50 mg of dideoxykanamycin B was used in two patients with peritonitis on peritoneal-or haemodialysis because of renal insufficiency, total doses were 800 mg and 1, 100 mg respectively. Excellent results were observed, and no side effects on auditory and renal function in both patients.

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Laboratory and clinical studies have been carried out on 3', 4'-dideoxykanamycin B (DKB), and the following results were obtained.
(1) The antibacterial activity of DKB was nearly the same as gentamicin (abbr. GM) against E. coli, slightly weaker than GM against Klebsiella, and slightly stronger than GM against Pseudomonas.
(2) Ten mg/kg of DKB were injected intramuscularly to rats, and the concentration in organs was measured as well as the concentration in serum. The former was high in order as kidney, lung and liver, while the latter reached to 43.6 mcg/ml at 30 minutes after the administration.
(3) As for the recovery rate of DKB from rat organ emulsion, the values were 100% with serum, 70-80% with kidney, 50% with lung, and the lowest about 30% with liver.
(4) DKB was administered clinically at a daily dose of 100-150 mg for 7-14 days to 2 cases of acute pyelonephritis and 2 cases of pulmonary suppuration. The results obtained were effective in the former, while undecided in the latter. No side effect was noticed throughout the cases treated.

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On a new antibiotic of home product, 3', 4'-dideoxykanamycin B (abbreviated as DKB), several basic and clinical investigations were performed, and the following results were obtained.
1. The mean antibacterial activities of DKB against Pseudomonas strains compared with those of gentamicin (GM) were the same or superior to GM in one degree of two-fold dilution. In cases of Staphylococcus aureus and E. coli, those of DKB were the same or inferior to GM in the same manner.
2. The mode of action of DKB was considered to be mainly bactericidal.
3. The antibacterial activity of DKB was weakened by the addition of horse serum, or Ca, Mg, Fe or Al ion and generally recovered again by the association of EDTA with each agent.
4. The comparison of the therapeutic effect of DKB with GM against experimental subcutaneous infection of Staphylococcus and Pseudomonas to mice proved similar to each other.
5. The protein binding rate by cellophane bag dialysis using horse serum was low. The adsorption rate to red blood cells was also markedly low.
6. The ratio of biliary level to serum level after intramuscular injection into rabbit was as low as 0.14.
7. The organ level after intramuscular injection into mice ranked in order of kidneys, serum, lungs, spleen and liver, being undetectable in brain. The inactivation of DKB by organ homogenate of mice was the greatest in liver, being followed by kidney.
8. DKB was administered to 4 cases clinically, either with carbenicillin or alone. In 3 cases, causative organisms disappeared at any rate. In one case, slight elevation of BUN and increase of white blood cells in the urinary sediment were observed temporarily soon after the discontinuation of treatment.

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A new antibiotic, 3', 4'-dideoxykanamycin B (abbr. DKB) was applied clinically to 16 cases of various infections in the field of internal medicine. The results obtained were remarkably effective in 7 cases, effective in 6 cases. ineffective in 2 cases and undecided in 1 case.
The minimum growth inhibitory concentrations of DKB were measured against Gram-negative bacilli isolated from lesions, and an excellent antibacterial activity of the drug was demonstrated against kanamycin resistant E. coli, Klebsiella and Pseudomonas.

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A new antibiotic, 3', 4'-dideoxykanamycin B (DKB), was administered intramuscularly for 6-57 days at daily doses of 50-100 mg to 13 patients, including 10 cases of pyelonephritis, 2 of pneumonia and 1 of bronchitis.
The results obtained showed to be effective in 7 cases and ineffective in 6 cases, 5 of which were the cases of chronic pyelonephritis accompanied by urinary disorders.
Side-effects observed included an increase of creatinine in the blood in one of the 13 cases and the feeling of an obstructed ear passage in another, which was only transient and disappeared without discontinuation of the drug.

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A new antibiotic, 3', 4'-dideoxykanamycin B (abbr. DKB) exhibited a growth inhibitory action widely against Gram-positive cocci and Gram-negative bacilli, and a stronger antibacterial activity than gentamicin against Pseudomonas aeruginosa.
DKB was administered clinically at a daily dose of 50-100 mg for 5-24 days to 15 cases in total consisting of 7 cases of respiratory tract infection, 6 cases of urinary tract infection, and each 1 case of decubitus and osteomyelitis.
The following results were obtained : Effective in 13 cases, slightly effective and ineffective in each 1 case. The administration method was all of intramuscular injection, except an inhalation therapy was combined in 2 cases of respiratory tract infection.

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3', 4'-Dideoxykanamycin B (DKB), a newly developed Kanamycin derivative, was examined on its antibacterial activity, absorption, excretion and distribution in the body.
1) Tests on the sensitivity of clinical isolates revealed that the sensitivity of Pseudomonas aeruginosa strains to DKB mostly resembled that of gentamicin among various antibiotics. Clinically isolated E. coli, Klebsiella and Proteus strains were also examined on their sensitivity to DKB as to gentamicin and kanamycin.
2) Blood levels of DKB in human adults after intramuscular injection of 50 mg were 5. 6 mcg/ml (on average of 3 cases) at one hour.
3) DKB was mainly excreted into the urine; 54. 1% of the dose recovered in 8 hours.
4) DKB was distributed in kidneys and lungs at the highest concentration among organs.
The behaviour of DKB in the rat's body closely resembled that of SM, KM and AKM, while tissue concentrations of DKB were similar to those of AKM, which showed the highest tissue levels among the latter three antibiotics.

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Laboratory and clinical investigations were performed on 3', 4'-dideoxykanamycin B (abbr. DKB), and the results were obtained as follows.
(1) Thirteen strains among 14 of Pseudomonas aeruginosa were inhibited the growth by 1.56-3.12 mcg/ml of DKB.
(2) Fifty mg or 100 mg of DKB were injected intramuscularly once, and a peak of blood concentration was exhibited 1 hour after the administration, showing 6 or 9 mcg/ml respectively. The above serum after 1 and 2 hours, inhibited the growth of Pseudomonas aeruginosa till 4 fold dilution. The blood concentration rose scarcely by inhalation of 50 mg of DKB dissolved in 4 ml of distilled water.
(3) The concentration of DKB in sputum did not attain 1 mcg/ml both after 50 mg or 100 mg of the drug were injected intramuscularly.
(4) DKB was administered to 5 cases of respiratory tract infection due to Pseudomonas aeruginosa combined with bronchiectasis or pulmonary tuberculosis, and the bacteria disappeared in 2 cases, while the clinical symptoms improved in 4 cases including the above. No favorable effect was obtained by inhalation of DKB.
As the side effect with DKB, 1 case complained of a tinnitus.

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A new antibiotic, 3'4'-dideoxykanamycin B was given by intramuscular injection at a daily dose of 50 mg×2 for 10-21 days to 8 cases; 2 cases of urinary tract infection, 5 cases of respiratory tract infection and 1 case of septicemia complicated with pneumonia.
The remarkable effect was obtained in 2 cases of urinary tract infection and fair effect in 2 cases of respiratory tract infection. All the ineffective cases were intractable or severe ones.

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The minimum growth inhibitory concentration (MIC) of a new antibiotic, 3', 4'-dideoxykanamycin B (abbr. DKB), was mostly 0. 39-1. 56 mcg/ml against Pseudomonas aeruginosa and Shigella dysenteriae isolated recently.
The blood concentration of DKB attained a peak 30 minutes after the drug was injected intramuscularly, and the high level was measured even after 6 hours.
DKB was administered to 17 cases of various infections in pediatric field including bronchopneumonia and pertussis, and the excellent results were obtained there. No untoward effect was noticed with DKB.

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A new antibiotic, 3', 4'-dideoxykanamycin B (abbr. DKB) was administered to the intractable infections as the cases with basal disease as leukemia and anomalotrophy, or those with causative bacteria as Pseudomonas. The patients were children and newborns of pneumonia (including pyothorax), otitis media, pyelitis, meningitis and colitis. The results obtained were remarkably effective in 1 case, effective in 7 cases and ineffective in 3 cases. There experienced a case of pyothorax for which DKB was effective though the causative bacteria was kanamycin resistant Pseudomonas aeruginosa.

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A new antibiotic, 3', 4'-dideoxykanamycin B (abbr. DKB) was administered principally to respiratory tract infections of children, and the good result was obtained.
The objects were 9 cases of children (from 1 year and 2 months to 12 years), and the drug was administered intramuscularly at a dose of 1-2 mg/kg for 3-7 days.
The side effect was experienced with DKB in one cace in whom a diarrhea occurred, and in another one in whom serum GOT and GPT rose slightly.

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The DKB was used for the treatment of children with the bacterial infections or a probable mycoplasma infection. The 14 cases include the 3 cases of simple urinary tract infection, the 14 cases include the 3 cases of simple urinary tract infection, the 4 cases of the complicated urinary tract infection, the 3 of sepsis or suspected sepsis, the 3 of the respiratory tract infection and a case of primary atypical pneumonia.
The DKB was given intramuscularly once or twice divided a day, at the dosage for 1.0mg/kg/day and 2.3 mg/kg/day, which seemed to be effective for the non-complicated infection. The Pseudomonas infection was as well treated with DKB as the E. coli and the staphylococcal infection, but PAP was not.
No abnormal response was recognized locally. The elevation of serum transaminase value and BUN after the use was detected in two cases and one respectively, and the appearance of the granular casts in the urine was found during the administration in a case. No other abnormal findings were revealed on the urinalysis and the kidney and liver function test. Those abnormal findings in the laboratory data should be confirmed to be or not really the side-effect of DKB furthermore.

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The MIC of 3', 4'-dideoxykanamycin B (abbr. DKB) distributed at 6.25mcg/ml against 2 strains of E. coli isolated from surgical infections, and this level of antibacterial activity shows a dilution grade higher than that of gentamicin.
The drug was applied clinically to the infections due to Pseudomonas aeruginosa mostly occurred after the operation of digestive tract, and the results obtained were effective in 4 cases, slightly effective in 2 cases, ineffective in 2 cases and undecided in 2 cases.
Summarizing from the results of sensitivity, clinical effect and side-effect, no remarkable superiority was observed for DKB in comparison with gentamicin which is widely used for infections caused by Gram-negative bacilli. The investigation should be pursued further by storing up the cases.

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1) 3', 4'-Dideoxykanamycin B blood concentration was measured in 4 patients of cholelithiasis. A peak of 8.6-27 mcg/ml was attained 30 minutes after the administration in 3 cases, decreased gradually thereafter, and lowered to less than 5 mcg/ml after 6 hours.
2) MIC was measured upon Gram-positive cocci (Staphylococcus aureus) and Gram-negative bacilli (Pseudomonas aeruginosa, Proteus vulgaris, Escherichia coli and Klebsiella pneumoniae) isolated from both lesions, and the results were 0.2-3. 13 mcg/ml against Staphylococcus aureus, 1. 56-25 mcg/ml against Pseudomonas aeruginosa, 0.78-50 mcg/ml against Proteus vulgaris, 0.2-12.5 mcg/ml against Escherichia coli, and 0.78-6. 25 mcg/ml against Klebsiella pneumoniae.
3) 3', 4'-Dideoxykanamycin B was administered intramuscularly at a daily dose of 50-200 mg for 2-16 days to 28 cases of soft tissue infection and 5 cases of perforative peritonitis, and the effective result was obtained in 30 cases of them.
4) No side effect, subjective or objective, was observed throughout the experiment except in 1 case.

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The antibacterial activity of a new antibiotic, 3', 4'-dideoxykanamycin B (abbr. DKB), was examined against the bacteria isolated from lesions in surgical field. As the result, the activity of DKB was slightly stronger than that of gentamicin against Pseudomonas aeruginosa and Staphylococcus aureus, while similar or slightly weaker against Escherichia coli, Klebsiella pneumoniae and Proteus vulgaris.
The high blood concentration of DKB was obtained by the intramuscular injection, and DKB was excreted rapidly in urine, The drug was transferred at a fair concentration into bile and lymph of humans.
DKB was applied clinically to 14 cases of mostly postoperative severe infection, and the improvement of clinical symptoms was observed in 10 cases of them.

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A new antibiotic, 3', 4'-dideoxykanamycin B (abbr. DKB) was applied clinically to 11 cases of surgical infections due to Pseudomonas aeruginosa, Proteus vulgaris or resistant Staphylococcus. The results obtained were remarkably effective in 4 cases, effective in 3 cases, slightly effective in 2 cases, and ineffective in 2 cases. DKB was injected intramuscularly for 3-42 days at a daily dose of 100-150 mg for adults and 50mg for children. In 3 cases, a dose of DKB was 10-100 mg a time, combined with local administration of DKB 12-18 times.
As the side effect with DKB, a rash was noticed in 1 case.

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A new antibiotic, 3', 4'-dideoxykanamycin B (abbr. DKB), was applied clinically to 15 cases of postoperative infection mostly due to Pseudomonas. DKB was administered intramuscularly or locally, singly or combining two methods, at a daily dose of 100-150 mg intramuscularly, while 50-100 mg locally. The results were obtained as follows : remarkably effective in 4 cases, effective in 8 cases, and slightly effective in 3 cases.
No side effect was noticed throughout the experience, though the treatment period was rather prolonged as 29 days with intramuscular injection or 60 days with local administration.

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A new antibiotic, 3', 4'-dideoxykanamycin B (abbr. DKB), was applied clinically in the field of surgery. The patients treated consisted of 12 cases of severe infections, 5 cases of infections due to Pseudomonas aeruginosa, and 3 cases of others, totalling 20 cases. The antibiotic was administered_at a daily dose of 100-300 mg (50-100 mg once).
The results obtained were remarkably effective in 5 cases, effective in 10 cases, ineffective in 4 cases, and undecided in 1 case, effective ratio being thus 78.9%. Gram-negative cocci exhibited a fairly good susceptibility to DKB.
Total dose of DKB amounted to 600-40, 000 mg in each case, and yet any side effect was not encountered throughout the experience.

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A new amino glycoside antibiotic, 3', 4'-dideoxykanamycin B (abbr. DKB) was investigated on the antibacterial activity against various bacteria isolated from lesions, and the effect for surgical infections, and the following results were obtained.
(1) All strains were inhibited the growth by DKB at the concentrations of less than 0.78 mcg/ml in 20 strains of Staphylococcus aureus, less than 3.13 mcg/ml in 20 strains of E. coli, less than 1.56 mcg/ml in 20 strains of Klebsiella, and 0.39-4.56 mcg/ml in 60 strains of Pseudomonas aeruginosa respectively.
(2) DKB was administered clinically to 13 cases of severe or intractable infections in surgical field, and the results obtained were effective in 7 cases, slightly effective in 3 cases and ineffective in 3 cases.

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Some investigations were made on the clinical application of DKB, and the results were obtained as follows.
1. The distribution of DKB sensitivity was measured on 292 strains isolated from clinical materials, and the sharp MIC was demonstrated as an excellent broad spectrum antibiotic, especially 52 strains of Pseudomonas aeruginosa exhibiting all≤<12.5 mcg/ml. DKB may be expected to exhibit a similar antibacterial action to that of gentamicin.
2. As for the human blood concentration, the peak levels of 3.1 and 5.5 mcg/ml were obtained respectively when 50 or 100 mg of DKB were injected intramuscularly, and the excretion rate in urine was 61.5%.
The transfer of DKB to fetus was 1/6-1/3 of mother's blood in dogs, and the DKB concentration in fetus organs paralleled nearly with its blood concentration in rabbits.
3. The tolerance of DKB in human would be good, as there observed only 1 case of lip numbness after the drug was injected intramuscularly at a daily dose of 50 mg twice for 10 days.
4. DKB was administered clinically to 15 cases of infections in the field of obstetrics and gynecology, and a treatment significance was noticed at 71.4%. Three cases complained of local pain with the drug.

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Ten cases of persistent urinary tract infection were treated with a new antibiotic, 3', 4'-dideoxykanamycin B (DKB). In each case, 50 mg of DKB were injected intramuscularly twice a day for 5 days.
The results are summarized as follows : remarkably effective in 1 case, effective in 7 cases and, ineffective in 2 cases.
No side effects were observed except 2 cases in which a slight rash was noticed.

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3', 4'-Dideoxykanamycin B (DKB) is a chemical modification product of kanamycin B and a potent bacteriocidal antibiotic against Proteus species and Pseudomonas aeruginosa in addition to other Gram negative enteric bacteria. Antibacterial activity of DKB expressed on the basis of MIC has been shown to be essentially similar to that of gentamicin (Table 1).
Single intramuscular 100 mg dosis of DKB gave serum concentration of 16.±4.6, 9.3±2.8, 6.8±2.8 and 2.9±1.0 mcg/ml 1, 2, 4, and 6 hours after injection. For comparison, 80 mg dosis of gentamicin (cross over study) gave 8.0±2.0, 3.9±0.9, 2.3±1.3 and 1.3±0.7 respectively (Fig. 1).
Urinary recovery of the drugs was 40.7±14.7 % in two hours and 63.9±13.0 in six hours with DKB, and 38.8±17.1 and 66.5±17.9 % with gentamicin (Table 2).
Treatment of urinary tract infections was done in 10 cases. The patients tolerated well to 100 mg daily dosis. In three acute urinary infections, the response was satisfactory by 3 or 4 days medication with DKB. Of five cases of chronic urinary tract infection, two (one with benign prostatic hyperplasia and one in postoperative course of transurethral resection of prostate) showed prompt response to DKB administration, however in three other cases (one postoperative infection following suprapubic prostatectomy and two infections through indwelt catheter for acute retention due to hypertrophied prostate, the response was unsatisfactory (Table 3). Of three upper urinary tract infections, one infected hydronephrosis and one acute pyelonephritis with gross vesicoureteral reflux showed prompt response to DKB, however one case of acute pyelonephritis complicating obstruction of ureteropelvic junction with a fragment of stone did not respond while the obstruction was unresolved. However good response was observed when obstruction was released by ureteral catheterization (Table 3 and Fig. 2).
Considering the data described above, DKB is thought to be a potent antibiotic at least as reliable as gentamicin.

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A new antibiotic, 3', 4'-dideoxykanamycin B (abbr. DKB) was injected intramuscularly once a day at a daily dose of 100-150 mg to 43 cases of acute cystitis and 5 cases of non gonorrheal urethritis, as well as DKB was administered similarly at a daily dose of 100mg to 2 cases of gonorrhea, and the clinical results were investigated.
The results obtained were remarkably effective in 23 cases, effective in 13 cases, slightly effective in 6 cases and ineffective in 6 cases in the former, while ineffective in both 2 cases in the latter.
An excellent result was exhibited in acute cystitis due to Escherichia coli, whereas a cure would be difficult to obtain in gonorrhea at a dose of 100 mg once daily.

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A new antibiotic, 3', 4'-dideoxykanamycin B (abbr. DKB) was applied to 14 cases of acute urinary tract infections and 13 cases of chronic urinary tract infections, totalling thus 27 cases. The results obtained were remarkably effective in 15 cases, effective in 9 cases, ineffective in 2 cases, and undecided in 1 case. Nine cases out of the above patients were due to Pseudomonas aeruginosa, and yet 7 cases of them resulted in remarkably effective or effective. No side effect was observed with DKB throughout all the cases.

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Twenty-five cases with urinary tract infections and 14 cases for prophylaxis of postoperative infections were treated with 3', 4'-dideoxykanamycin B at a daily dose between 50 mg and 200 mg.
Of 9 cases with acute urinary infections (cystitis 6 cases, pyelonephritis 3 cases), excellent response was seen in 5 cases, good response in 3 cases and negative response in 1 case. Of the chronic urinary tract infections (cystitis 14 cases, pyelonephritis 2 cases), excellent response was seen in 1 case, good response in 6 cases and negative response in 9 cases. Organisms of MIC of 12.5mcg/ml or lower disappeared in urine culture after treatment.
Good results were acquired clinically in 14 cases for prophylaxis of postoperative infections. No adverse side effects were observed except the pain at the site of intramuscular injection.

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Some investigations were made on a new antibiotic, 3', 4'-dideoxykanamycin B (abbr. DKB), and the results were obtained as follows.
(1) When 50 mg of DKB were injected intramuscularly once to adult dog, the highest blood concentration of the drug was 7.9mcg/ml 1 hour after the administration, and the excretory rate in urine was 59.6% within 8 hours after the administration.
When 50 mg of DKB were injected intramuscularly once to adult humans, the highest blood concentration of the drug exhibited 4.0mcg/ml 30 minutes after the administration, and the excretory rate in urine was 39.1% within 8 hours after the administration.
(2) The antibacterial activity of DKB against Pseudomonas, E. coli, Proteus, Klebsiella, Serratia and Staph. aureus was almost the same as that of gentamicin.
(3) DKB was administered clinically to 30 cases of complicated urinary tract infection, and the results obtained 'were remarkably effective in 14 cases, effective in 6 cases, and ineffective in 10 cases.No side effect was observed with DKB throughout the experiment.

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1) Minimal inhibitory concentration of 3, 4-dideoxykanamycin B (DKB) was determined on 147 strains isolated from urinary tract infections by the plate dilution method. Most strains of Escherichia coli, Proteus sp., and Klebsiella and all of Staphylococcus aureus tested were inhibited at the concentration of 6.25 mcg/ml or less and 19 of 24 strains of Pseudomonas were inhibited at the concentration of 3.12 mcg/ml or less.
2) In two cases with normal renal function, the blood levels reached to the maximum (18.2 mcg/ml, 15.2 mcg/ml) at 30 minutes after administration of DKB 100 mg i. m. and decreased rapidly thereafter. In two cases with impaired renal function the drug was detected in blood after 24 hours.
3) The urinary recovery rates were 87.2%, 81.2% during 24 hours after injection in 2 normal subjects, while in impaired cases, its recovery rates were 58.8% and 68.8%.
4) Thirty-three cases with urinary tract infections were treated with DKB, and good results were obtained in 16 cases.
5) Side effects were observed throughout the treatment in 2 of 33 cases, 1 slight increase of BUN and 1 anorexia.

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A new aminoglycoside antibiotic, 3', 4'-dideoxykanamycin B (abbr. DKB) was administered at a daily dose of 50-100 mg for 3-7 days to 22 cases of simple urinary tract infection and 10 cases of complicated urinary tract infection. The results obtained were remarkably effective in 19 cases, effective in 7 cases, and ineffective in 6 cases. From our clinical experiments, a high therapeutic value may be expected of DKB.

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The blood level of 3', 4'-dideoxykanamycin B (DKB) in healthy adults who were given 50 mg, i. m., reached maximum of 12. 6 mcg/ml 30 minutes after administration, and the level was 3.26 mcg/ml 4 hours after dosing, showing a good evidence that the drug is smoothly distributed in blood and maintained at high concentrations for a prolonged period.
Total urinary recovery of DKB during the period of 24 hours after administration was 60.2%. Bacteriologically, DKB was effective against gram-negative bacteria, especially E. coli, Pseudomonas and Proteus vulgaris.
Patients with complicated urinary-tract infections responded to DKB treatment.
No noteworthy adverse effects were recognized.

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Laboratory experiments were carried out with a new antibiotic, dideoxykanamycin B (abbr. DKB), and this drug was applied clinically to the patients of pyoderma.
1) Blood concentration and urinary excretion were measured with DKB in 2 cases of healthy adults. A peak was recognized in 30-60 minutes for blood concentration, and in 60-90 minutes for urinary-excretion.
2) As for the correlation between minimum growth inhibitory concentration and anti-rash effect with DKB, the borderline of effect difference was observed at 3.13 mcg/ml.
3) DKB was applied clinically to 28 cases of pyoderma, and the effectiveness was obtained in 23 cases of them, effective ratio being thus 82.1%.
4) As for the side effect with DKB, rash and pyrexia were noticed in 1 case.

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The MIC of a new antibiotic, 3', 4'-dideoxykanamycin B (abbr. DKB) was measured on 16 strains of Coagulase-positive Staphylococcus. The result demonstrated that the MIC was less than 32 mcg/ml with 15 strains of them, and the remaining 1 strain (exhibiting a KM (kanamycin) resistance of 25 mcg/ml) was inhibited at a concentration of less than 0.2 mcg/ml of DKB.
The skin concentration attained a peak of about 3 mcg/ml (mean of 3 cases) 30 minutes after the intramuscular administration of DKB (2.5 mg/rat) in rats.
DKB was administered clinically to 1 case of furuncle at a dose of 50 mg twice daily, and the result was ineffective.

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As the result of laboratory and clinical investigation with a new aminoglucoside derivative, 3', 4'-dideoxykanamycin B (DKB) was performed with the results which may lead to the following conclusion.
1) In vitro antibacterial activity : The minimal inhibitory concentration of DKB was measured by an agar plate dilution method. The MIC of DKB against 80 strains of coagulase positive Staphylococcusisolated from otorrhoea was distributed over a range of ≤0.19 to 1.56 mcg/ml, with a peak being observed particularly at 0.78 mcg/ml. Furthermore, the MIC against 60 strains of Pseudomonas aeruginosa and E. coli, Klebsiella pneumoniae, Proteus mirabilis, was 0.39 to 6.25 mcg/ml.
2) Concentration in blood : The maximal level reached 16 mcg/ml on the average 30 minutes after a single intramuscular injection of 100 mg to healthy adults, and the level was still 1.7 mcg/ml 8 hours after the intramuscular injection.
3) Concentration in tissues : DKB activity was demonstrable at the concentration of 0.4 mcg/g in a human palatine tonsilla and mucous membrane of maxillary specimen one hour after the intramuscular injection of 100 mg. The serum concentration of DKB was then 11 mcg/ml.
4) Results of clinical treatment : When DKB was injected intramuscularly or applied locally at 10 mg/ml aqueous solution in 44 cases of representative infections in the field of otorhinolaryngology, it was excellent in 7 cases, good in 23 cases, fair in 8 cases, and poor in 6 cases. When the cases in which it was excellent and good were considered together, good results were obtained in 30 cases, a ratio of effectiveness being 75 per cent.
5) Side effect : The comparative examination of hepatic function, electrocyte and audiotory acuity before and after injection showed no significant disturbance. No side effect was shown with the intra-muscular injection or local application of DKB.

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Laboratory and clinical investigations were made on a new antibiotic, 3', 4'-dideoxykanamycin B (abbr. DKB), and the following results were obtained.
(1) All of 37 strains of Pseudomonas aeruginosa isolated from patients, demonstrated the DKB MIC of 0.4-1.6 mcg/ml.
(2) DKB was injected intramuscularly, dripped intravenously, instillated locally or administered by nebulizer. The results obtained were effective in 10 cases, slightly effective in 1 case and ineffective in 2 cases. There experienced 1 case of remarkably effective in which the drug was dripped intravenously for the intracranial infection due to Pseudomonas aeruginosa.
(3) No side effect was observed including there an auditory disorder, except Urea-N rose after DKB administration in a patient of progressed pharyngeal cancer.

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Some laboratory examinations were made with a new antibiotic, 3', 4'-dideoxykanamycin B (abbr. DKB), as well as the drug was applied clinically to several otorhinolaryngological infections, and the good results were obtained as follows.
(1) The MIC of DKB was less than 3. 13 mcg/ml against both Staphylococcus aureus and Pseudomonas aeruginosa isolated from lesions, that is, in 22 strains out of 25 strains for the former, and in 12 strains out of 14 strains for the latter.
(2) Observing by biophotometer, the growth of Staphylococcus aureus 209 P was inhibited well by the serum (diluted 10 fold) 30 minutes and 1 hour after 100 mg of DKB were injected intramuscularly, and the growth of Pseudomonas aeruginosa was inhibited well too by the serum (diluted 10 fold) 30 minutes and 1 hour after 200 mg of DKB were injected intramuscularly.
(3) DKB concentration in tissues one hour after intramuscular injection of 2 mg/kg dosis of DKB, the concentrations of palatine tonsilla and mucous membrane of sinuitis maxillaris were titrated.
The concentrations of blood and palatine tonsilla were 6. 5 mcg/ml and 0.6 mcg/ml respectively, the concentrations of blood and mucous membrane of sinusitis maxillaris were 7.5 mcg/ml and 1. 6 mcg/ml respectively. And the concentrations of blood and inferior turbinate were 5.7 mcg/ml and 3.3 mcg/ml respectively.
(4) DKB was administered to 25 cases of otorhinolaryngological infection, and the results obtained were remarkably effective in 12 cases, effective in 8 cases and ineffective in 5 cases. The auditory disorder and other side-effect were not encountered throughout all the cases.

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Laboratory and clinical investigations were made on a new antibiotic, 3', 4'-dideoxykanamycin B (abbr. DKB), and the results obtained are as follows.
(1) The MIC of DKB was determined on 14 strains of Pseudomonas aeruginosa isolated from lesions, and the distribution in 12 strains of them was at 0.39-0.78 mcg/ml. DKB demonstrated a strong antibacterial activity as well against other species of bacteria.
(2) DKB was injected intramuscularly once at a dose of 50 mg to 5 adults, and the concentration of the drug in maxillary sinus mucosa was 1.36 mcg/ml on an average 1 hour after the administration. DKB was injected intramuscularly once at a dose of 25 mg to 3 children, and the concentration of the drug in palatine tonsil tissue was 0.49 mcg/ml on an average 1 hour after the administration.
(3) DKB was administered intramuscularly or applied locally to 33 cases of various infections in the field of otorhinolaryngology, and an excellent clinical effect was obtained. As for the side effect of DKB, slight diarrhea and sense of fever was a encountered respectively in a case of the intramuscular injected.

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The toxic action of DKB on mice was studied with special regard to the ototoxic action. DKB was found to be more toxic than vistamycin, same toxic as kanamycin, kanendomycin, but less toxic than gentamicin with regard to toxicity/g/body weight.
Toxic reactions were observed in the cochlear and vestibular sensory epithelia with more severe reactions in the cochlear than the vestibular system.
Degeneration appeared first in the outer hair cells in the basal turn of the cochlea starting with the increasing of lysosomes, degeneration of mitochondria in the subcuticle area and resulting in the complete loss of hair cells, but stria vascularis and spiral ligament showed little change.
Severe changes were observed in the sensory epithelium of the cristae ampullares and utricular maculae. Early changes with hair swelling and fusion, degeneration of mitochondria and ballooning of the cell surface were observed leading to complete degeneration first of the type I and later of the type II hair cells.

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A new antibiotic, dideoxykanamycin B (DKB) was studied to evaluate this possible uses in ophthalmology.
1) Sensitivity of organisms isolated from human clinical materials : All staphylococci in vitro studied were sensitive to 6.25 mcg/ml or less of DKB.
DKB showed similar excellent bacteriostatic effects in vitro experiments to aminodeoxykanamycin.
2) DKB showed definitely superior penetration into the aqueous humor than aminodeoxykanamycin or kanamycin in rabbit experiments after intramuscular or subconjunctival injection.
3) DKB was administered intramuscularly at the dose of 100 mg to 7 volunteers.
The blood concentration of average value of 7 cases was 15.3 mcg/ml after 1 hour, and 3.1 mcg/ml even after 6 hours.
4) Twelve patients with extraocular infection were treated intramuscularly with daily administration of 50-100 mg of DKB.
All of these cases improved by the treatment, and no side effect was observed.

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The bacterial and clinical experiments for ophthalmic use of 3', 4'-dideoxykanamycin B (DKB) were performed.
These results were summarized as follows.
1) Minimum inhibitory concentrations of DKB for various organisms in ocular infection were 6. 25 mcg/ml for KOCH-WEEKS bacillus, 0. 09-0. 39 mcg/ml for MORAX-AXENFELD diplobacillus, 3. 13-12. 5 mcg/ml for Pneumococcus, O. 09-0. 19 mcg/ml for C. diphtheriae, 0.78 mcg/ml for Gonococcus, 6. 25-25 mcg/ml for Streptococcus, O. 05-1. 56 mcg/ml for Staphylococcus and 1. 56-3. 13 mcg/ml for Ps. aeruginosa.
2) The sensitivity for 40 strains of Staphylococcus aureus was in the range of 0. 39-25 mcg/ml of DKB, and almost of them were in 1. 56 mcg/ml.
3) Twenty-eight strains of Ps. aeruginosa were sensitive at 1. 56-12. 5 mcg/ml with the peak of distribution at 1. 56 mcg/ml.
4) The peak of blood level (8. 6 mcg/ml) after intramuscular injection of 50 mg DKB at a dose was attained in half an hour, and reduced relatively quickly in 6 hours.
5) The ocular penetration of DKB in the rabbit eye was studied following local and systemic application.
The penetration level into the outer parts of the eye was the highest after subconjunctival injection, followed by intramuscular injection and instillation.
In the inner parts of the eye, the ocular tissue concentration was higher following intramuscular injection and subconjunctival injection, instillation.
6) The treatment of experimental Pseudomonas keratitis in the rabbit eye with subconjunctival injection of DKB was revealed excellent effect in comparison with the control eye (normal saline injection).
7) Various ocular suppurative disease, such as external hordeolum, blepharitis, acute and chronic dacryocystitis, corneal ulcer and panophthalmitis were well cured by DKB treatment, intramuscular inject As a ion of 50-100 mg at a dose once or twice a day.
8) As a side effect, 4 cases out of 20 cases complained of pain at injection site, and the other serious side effects, such as allergic reaction, were not observed.

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The insufficiency of renal function was experimented using Wistar strain rats. When DKB and low molecular dextran (LMD) coincidentally administrated only once, blood urea nitrogen (BUN) levels and histological findings with light microscopic observations were investigated.
Following results were obtained.
BUN levels administrated DKB 100 mg/kg and LMD 50 ml/kg were not so higher than those of aminodeoxykanamycin (AKM) and LMD administrated at same doses. When the doses were reduced, abnormalities were detected rarely on BUN levels in either groups.
As for the histological findings of ectomized kidney, the expansion of renal tubular epithelium called osmotic nephrosis was found in some cases. Nevertheless those findings were more scarce after administration of DKB and LMD than that of AKM and LMD.

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The authors have assayed the distribution of DKB in the serum and in the oral tissues such as gingiva, tongue, pulp, submaxillary-lymphonodi, submaxillary glands and parotid glands using Wistar strain rats.
DKB was administrated at the dose of 100 mg/kg with intramuscular injection. The distribution in tissues was assayed by means of thin layer cup method.
The concentrations of DKB reached the peak before half an hour either in the serum or other tissues (with the exception in gingiva). As for the concentrations of DKB determined, the serum had the highest and other tissues were in the following order : pulp, parotid glands, gingiva, tongue, submaxillary glands and submaxillary lymphonode. The patterns of the distribution of DKB were similar to those of gentamicin.

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Dideoxykanamycin B (DKB) is a derivative of kanamycin with a molecular formula C18H37N5O8. The ototoxicity of this antibiotic was examined.
Twenty-six healthy guinea pigs with normal Preyer's reflex were used for this investigation. Ten animals were used for intraperitoneal injection of DKB 200 mg/kg/day for 10 days, 10 for intramuscular injection of DKB 100 mg/kg/day for 40 days and 6 for daily intramuscular injection of gentamicin 100 mg/kg/day until getting the loss of Preyer's reflex.
The ototoxicity was investigated by the following methods.
1. Preyer's reflex of 500, 1, 000, 2, 000, 4, 000 and 8, 000 Hz was measured.
2. Electrophysiological investigation was performed. Endocochlear potential, cochlear microphonics and summating potential were measured by 500, 1, 000, 2, 000, 4, 000 and 8, 000 Hz of closed sound stimulation.
3. Morphological and histochemical investigations were performed by succinic dehydrogenase staining. Hair cells of the organ of Corti were observed by surface preparation from the basal coil to apex.
The ototoxicity of DKB was almost equally severe as that of kanamycin, although it was about a half of that of gentamicin.

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Dideoxykanamycin B, a new aminoglycoside antibiotic showed the bactericidal effect on the gram-negative bacteria, as well as gentamicin. Short treatment of Escherichia coli B, Pseudomonas aeruginosa P 28 and P 29 with dideoxykanamycin B and gentamicin resulted in bleb-formation from the outer layer of the cell wall, and prolonged treatment caused lysis of the cells. These alterations may be interpreted that dideoxykanamycin B primarily acts to distort the molecular arrangement of the cell envelope.

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