Bacteriological examinations were made on lividomycin (LVM), a new aminoglycosidic antibiotic developed by the Tokyo Research Laboratory of Kowa Co., Ltd.
As a result, it was found that this substance, like kanamycin (KM), has a broad antimicrobial spectrum against gram-positive and gram-negative bacteria. In vitro antimicrobial activity against standard preserved strains showed that LVM had as limited activities as KM against Streptococcus and Diplococcus pneumoniae and almost as strongly active as KM against the remaining strains studied. However, LVM often showed a better antimicrobial activity against Pseudomonas aeruginosa.
Antimicrobial activity against 50 clinically isolated Staphylococcus strains indicated that LVM and KM showed similar MIC with a peak of 6.25-12.5mcg/ml, while KM exhibited a better antimicrobial activity against 50 clinically isolated Escherichia coli strains.In contrast, LVM was superior to KM in the activity against 27 clinically isol P.aeruginosa strains; the MIC peaks ranged from 12.5 to 4% 25.0mcg/ml and from 100 to 200mcg/ml, respectively. For LVM the MIC≥100mcg/ml was found in of the strains, incontrast to 60% for KM.
The aqueous solution of each substance is stable under varying conditions and no decrease of potency was noted.
Both LVM and KM showed high activity at pH 6-8, especially at pH 8, The activity of KM decreased gradually by adding more than 10% human serum while that of LVM decreased to lesser extent.
The in vitro resistance development of LVM to Staphylococcus was found to be comparable with that of KM, while that to E.coli was more favorable for KM.There was considerable cross resistance botween the two resistant bacteria.
The antimicrobial activity progressed from bacteriostatis to sterilization depending upon the concentration. Sterilization was noticed up to 6 hours with 1-4 MIC's addition of LVM; the survived bacteria multiplied again after 8-24 hours.
In the therapeutic experiments of infected mice, there were not considerable differences between LVM and KM in the activity against strains of Staphylococcus No.50774, E.coli NIH and P.aeruginosa No.5. The effects against infections with the clinically isolated P. aeruginosa 44-1360 and No.13 strains were in good agreement with the results of the in vitro activity studies.
Thus, our present bacteriological examinations revealed that there were no considerable differences in the in vitro and in vivo antimicrobial activity against a number of bacterial species between LVM and KM except that LVM often exceeded KM in the in vitro and in vivo activities against P.aeruginosa.

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Antibacterial activity of lividomycin (LVM) was investigated and the following results were obtained.
1. Antibacterial activity of LVM was almost the same as those of kanamycin (KM) and paromomycin (PRM) against Staphylococci and gram-negative bacteria including E.coli, Klebsiella, Proteus and Aerobacter.
2. Antibacterial activity of LVM against Pseudomonas aeruginosa was stronger than those of KM and PRM, and 85% of tested Pseudomonas was inhibited with 100mcg/ml of LVM.
3. Isolation frequencies of resistant mutants were not remarkably different between LVM and KM.
4. LVM was found to be cross resistant with KM in many strains isolated clinically. But some KM-resistant and LVM-sensitive strains were isolated.
5. Antibacterial activity of LVM was highest at pH 7.0 and reduced to one-fourth at pH 9.0.

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In vitro antimicrobial activity against E.coli and Pseudomonas aeruginosa of lividomycin was tested and compared with that of kanamycin.
The inhibitory effects of lividomycin and kanamycin on the growth curves of these bacteria in the logarithmic phase were recorded automatically by a biophotometer.In the inhibition of E.coli, kanamycin was superior to lividomycin, while lividomycin was more effective against Pseudomonas aeruginosa than kanamycin.

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In the latter half of 1971, the study on antimicrobial activity of lividomycin (LVM) was conducted in our laboratory by using such pathogens isolated from various clinical specimens as Staphylococcus aureus, Haemophilus (H.influenzae, H.parainfluenzae, H.parahaemolyticus), Enterobacteriaceae including Escherichia coli and Pseudomonas aeruginosa, 357 strains in total.
1. The antimicrobial activity of LVM against S.aureus was somewhat inferior, if not equal, to that of kanamycin (KM), and those strains resistant to LVM were also more or less resistant to KM.
2. According to the result of our study, the antimicrobial activity of LVM against the strains of Haemophilus seemed to be somewhat inferior to that of KM.
3. Comparing with other common antibiotics, LVM was more effective against P.aeruginosa, though some strains were resistant to LVM.The antimicrobial activity of LVM against P.aeruginosa seemed to be inferior to that of polymyxin B (PL-B), colistin (CL) or gentamicin (GM).

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1. Assays with a series of 261 gram-positive and 514 gram-negative strains isolated from various clinical specimens revealed that gentamicin (GM) was most active against organisms susceptible to aminoglycosides.
The antibacterial activity of lividomycin (LVM) against these strains was virtually comparable to that of kanamycin (KM).Of particular note was the finding obtained with 66 strains of Pseudomonas aeruginosa, that is, LVM has proven, unlike KM and streptomycin (SM), to be capable of inhibiting the growth of P.aeruginosa with MICs from 25 to 50mcg/ml, and this characteristic of LVM is of extremely chemotherapeutic interest.
Antibiotics of the aminoglycoside series are normally rather inactive against pneumococci and betahaemolytic streptococci and LVM exhibited practically the same tendency.
2. Tissue assays for LVM were performed by the cup-plate technique, using Bacillus subtilis as reference organisms, with various organs and tissue homogenates from rats that had received 20mg of the drug per kg of body weight by intramuscular administration.
Peak concentrations in these tissue were produced 1 hour after drug administration. The highest antibiotic concentration was shown in the kidney after an intramuscular dose and serum level ranked next, while levels in the pulmonary tissues were extremely low.The antibiotic was undemonstrable at all in the liver.
The high antibacterial activity continued to be demonstrable in the kidneys up to 6 hours after drug administration.
3. Blood levels and excretions of LVM in the urine were determined in heathly adults receiving 500mg of the drug by intramuscular injection.
Peak plasma levels were accomplished half hour after administration, and the antibacterial activity continued to be demonstrable in plasma for 6 hours after drug administration.
The average urinary recovery rate was more than 70% in all instances until 6 hours after drug administration.

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1. A total of 209 strains of anaerobic bacteria isolated from clinical materials were examined for their sensitivities to lividomycin (LVM), aminodeoxykanamycin (AKM), polymyxin B (PL-B) and colistin (CL). They include 82 strains of Peptococcus, 55 of Peptostreptococcus, 3 of Veillonella, 31 of Bacteroides, 26 of Sphaerophorus, and 12 of Corynebacterium and Eubacterium. LVM has little activity against all strains of anaerobic bacteria, the MIC being higher than 100mcg/ml.
2. Antibacterial activity of LVM is weaker than PL-B and CL, and is equal to AKM.
3. A high concentration of LVM, 10,000mcg/ml, inhibited Sphaerophorus and Fusobacterium, but many strains of Bacteroides were resistant. LVM may be used for the differentiation of Sphaerophorus and Fusobacterium from Bacteroides.

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Lividomycin (LVM), a new antibiotic produced by Streptomyces lividus have been known to show highly activities against gram-positive and -negative bacteria including Mycobacterium tuberculosis. The in vitro antituberculous activity of LVM was compared with other antituberculous agents and the following results were obtained.
1) The minimum inhibitory concentrations of LVM against M.tuberculosis H₃₇Rv were 1.56mcg/ml in KIRCHNER's liquid medium, 0.39mcg/ml in Tween-albumin liquid medium and 3.13mcg/ml in KIRCHNER's agar medium.These MICs were almost similar to those of kanamycin (KM) and dihydrostreptomycin (SM) and were slightly lower than viomycin (VM) and capreomycin (CPM).
2) The antituberculous activity of LVM remarkably decreased in 1% OGAWA's medium.
3) The activity of LVM was not influenced by addition of 50% calf serum in KIRCHNER's liquid medium.
4) The MIC of LVM was varied by inoculum size, but this fluctuation was the same as that of KM and SM.
5) The resistance to LVM developed slower than KM.
6) There was strong cross-resistance between LVM and CPM, partial cross resistance between LVM and KM, but no cross resistance between LVM and SM or PAS.

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A new aminoglycoside antibiotic, lividomycin, was studied bacteriologically and clinically.
1) In a study by the agar plate dilution method on 111 strains of 18 species, Staphylococci were found to be very sensitive with the MICs of 3.12 μg/ml or less. Corynebacterium diphtheriae, Hemophilus influenzae, Neisseria gonorrhoeae, Escherichia coli, Klebsiella, Shigella and Salmonella were fairly sensitive showing the MICs of less than 12.5μg/ml. Pseudomonas aeruginosa and Proteus-Providence were mederately sensitive to the agent with the MICs of 12.5μg/ml more or less.Diplococcus pneumoniae, β-Hemolytic streptococci, α-Hemolytic streptococci and Enterococci, however, were found to be poorly sensitive to the agent, showing the MICs of more than 50μg/ml.
2) By the thin-layer cylinder-plate technique using Bacillus subtilis PCI 219 as a test organism, lividomycin was found to be assayable to the lower limit of 0.62μg/ml in serum (1: 2 in pH 7.8 phosphate buffer).
Following a single intramuscular administration of 1,000mg, peak serum levels of 20-30μg/ml were obtained at 1 or 2 hours, with persistence of more than 0, 8μg/ml over ensuing 12 hours.And the agent was recovered from urine for the most part in the microbiologically active form, showing the urinary recovery of 56-61% after 18 hours.
3) With the view of preparing grounds for application of the single-disc method to the sensitivity test in the clinical laboratory, statistical analysis of the dose-response data concerning the interrelations between MIC value and diameter of inhibition zone were conducted on each of i) conventional (overnight: approximately 16 hours) assay, ii) 4-hour rapid assay with heavy inoculum, iii) 6-hour rapid assay with heavy inoculum, iv) delayed (approximately 24 hours) assay for slowly growing bacteria.As the results, e.g.simple regression equation for conventional assay was D (diameter of inhibition zone) =26.9-9.1 log MIC.
Experimental errors of the single-disc method inherent were also obtained in comparison with the ones in the 2-fold dilution method.As the results, range of deviation of assayed MIC expressed in terms of rejection limit (α=0.05) was, e.g.3.0-0.33 for conventional method and 2.1-0.48 for dilution method, respectively.
4) Treatment with lividomycin was effective in a case of urinary tract infection caused by E.coil whose sensitivity to lividomycin was determined to be very sensitive by the above mentioned singledisc technique.

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On a new aminoglycosidic antibiotic, lividomycin (LVM), produced in Japan, several laboratory and clinical investigations were performed and the following results were obtained.
1. MIC values of LVM to strains of Pseudomonas aeruginosa were distributed from 12.5 to 50mcg/ml.That of majority of other gram-negative bacilli ranged from 3.1 to 25mcg/ml.
2. The mode of action of LVM was chiefly bactericidal.
3. Discs of various antibiotics were applied on two types of agar plates: one contained certain level of LVM and another without LVM, and each of 10 strains of Pseudomonas aeruginosa was streaked on the surface of both plates.From the change of inhibition size in diameter it was examined whether synergistic action exists between LVM and any of other antibiotics.As a result, great enlargement of zone size was found in 5 of 10 strains tested in the case of gentamicin.
4. The comparison of therapeutic effect of daily intramuscular injections of LVM and carbenicillin after Pseudomonas subcutaneous infection to mice showed that LVM was superior to carbenicillin in the same dose treatment.
5. Horse serum protein binding rate using cellophane bag dialysis was low.
6. Adsorption to sheep red blood cells was also low.
7. Serum level after intramuscular injection of LVM to rabbits reached a peak level of more than100mcg/ml.
8. Bile level after intramuscular injection of LVM proved to be about one-third of serum level, but urine level was more than 10 folds of serum in the peak value.
9. Organ level following intramuscular injection to mice ranked in order of kidney, serum and lung, being undetectable in other organs.
10. By mixing LVM with each organ homogenate of mice, marked reduction of activity of LVM was observed.
11. In one clinical case, the level of collected urine during 24 hours was determined and excretion rate was calctlated.Good excretion into urine was noticed.

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Lividomycin (LVM) is a new aminoglycoside antibiotic produced in Japan.
It is active against Pseudomonas as well as other gram-negative bacteria. In vivo effect of LVM was evaluated by using experimental pyelonephritis in rabbit, comparing with kanamycin (KM) and gentamicin (GM).
Serum and urine levels of LVM were estimated in 2 rabbits receiving intramuscular dose of 100 mg/kg/body weight.The average serum level reached to a maximum of 26.5mcg/ml one hour after administration and was 19.25mcg/ml 5 hours later.
Urine level reached to peak of 820mcg/ml and 13,000mcg/ml in 2-4 hours.
Recovery from urine in 6 hours was 3.8 and 24%.
Twenty mg/kg/body weight of LVM and KM, and 1.6mg/kg/body weight of GM were intramuscularly administered by one shot or for 1 week after inoculation of Pseudomonas into renal pelvis. Animals were sacrificed on the 8th day.
Bacteriological studies of the kidney renal pelvic urine and bladder urine as well as histopathologic studies were performed.The in vivo effect against Pseudomonas in infected kidney was in the order of LVM≥GM>KM in the one-shot group, and GM>LVM>KM in the continuously administered group.

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Twelve rabbits were divided into four groups.In group A, 150mg/kg/day of lividomycin were injected intramuscularly for 10 days.Proteinuria was found in the majority of rabbits in the late stages of the experiment.Neither haematuria, azotemia nor retention of lividomycin in the blood was present.
In group B, 300mg/kg/day of lividomycin were injected intramuscularly for the same period.In the late stages, proteinuria was found in all rabbits and haematuria in some.Azotemia and retention of lividomycin were not present on the fifth day, but both of them appeared on the tenth day.
In group C, intramuscular injection of 150mg/kg/day of lividomycin and intravenous injection of 25 ml/kg/day of 0.4% sodium alginate solution were performed for 10 days. Proteinuria and haematuria were found in the late stages in all cases. Retention of lividomycin was found on the second day and azotemia was detected on the fifth day.
In group D, 300mg/kg/day of lividomycin and 25ml/kg/day of 0.4% sodium alginate were injected for the same period. Appearance of proteinuria and haematuria was earlier than in group C, azotemia and retention of lividomycin were more marked and all rabbits died before the scheduled experiment was terminated.
By light-microscopic study, in group B marked granular necrotic alteration and localized vacuolisation were seen in the epithelium of proximal tubules.These changes of mild degree were found in group A.In groups C and D, rarely small hyalin thrombi and exsudative lesions were found in the glomeruli, extensive vacuolization including “osmotic nephrosis”and granular necrotic alteration were seen in the epithelium of proximal tubules.In some regions, the tubular lumina were filled with cellular debris, hyaline cylinder, PAS-positive granular material partially stained with hematoxylin. There were some atrophy of the epithelium and dilatation of lumina in the distal tubules.From the results of our serial experimental studies on the nephrotoxicity of aminoglycoside antibiotics with or without plasma expander in rabbits, gentamicin and aminosidine appear to be the most toxic, while the nephrotoxicity of lividomycin, aminodeoxykanamycin and kanamycin is lower than that of former two.

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Lividomycin, a newly developed aminoglycosidic antibiotic in Japan, is known to possess a comparable antimicrobial spectrum with kanamycin.
The following is the results of investigation on the effects of lividomycin as conducted by using 59 cases with various types of urinary tract infections.
The MIC of lividomycin to E.coil, which is considered to be the main causal bacteria of acute cystitis, was between 6.26 mcg/ml and 25 mcg/ml, and the dosage of 1 g per day as determined based on the studies on its blood and urinary concentrations seemed to produce favorable effects when intramuscularly administered for 2-3 days. The MIC of lividomycin to gonococcus was between 0.2 mcg/ml and 0.78 mcg/ml, which indicated to be effective on acute gonorrhea with 2g/day intramuscular injection.
Lividomycin has proven to be effective to various types of urinary tract infections showing its total effective rate of 83%.No noticeable side effects have been demonstrated so far.

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We tested the antimicrobial effects of lividomycin (LVM), and obtained following results.
1. Twenty patients with acute urinary tract infections were treated with 1,000 mg of LVM, once a day for 3 days.Good effect was observed in 17 patients but LVM was ineffective in 3 cases.
2. LVM is very effective in the treatment of acute urinary infections of E.coil, Klebsiella and Staphylococcus.
3. Six chronic cases were treated with 1,000 mg of LVM, divided in 2 portions daily for 5 days. After the treatment for 5 days, good bacteriological effect was observed in 3 patients.
4) No remarkable side effect was noted.

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Lividomycin was administered intramuscularly to twenty selected patients with acute urinary tract infections (acute cystitis) with a dose of 1,000 mg once a day for 2 days.
Excellent or good results were obtained in 18 patients (90%).The same number of patients showed bacteriological improvement.
For acute cystitis, a dosage of 1,000 mg lividomycin daily for two days is recommended and the effect will be sure by 3 days continuous administration of the same dosage.
No side effect was noted.

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Clinical effect of tividomycin (LVM) was evaluated in 130 patients with urogenital infections from 9 hospitals.
67 (83%) out of 81 cases with acute urinary infections, 20 (46%) out of 44 cases with chronic urinary infections including many complicated and intractable cases, and 4 out of 5 cases with other urological infections, seemed to show good response to LVM.These results indicated the clinical effectivtness 44 LVM.
From the bacteriological view point various analyses were made on these cases. Against all the strains which persisted in urine after LVM administration the values of MIC of LVM were more than 12.5 mcg/ml. The one-time dose of LVM must be more than 1g and in chronk infections the administration for more than 4 days seemed to be necessary.
However, the authors consider that, on actotint of its ototoxicity, the daily administration must be less than 1 week.

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In the patients with reduced renal function 0.5g of lividoinycin (LVM) was injected intramuscularly every 12 hours for 3 days, and blood and urine levels were determined many times consecutively.The correlation between the levels and the total renal function was studied in the patients with variously impaired renal function. In one case who undertook the nephrostomy the functions of both kidneys were compared in regard to the levels.
In general, the blood levels 12 hours after the intramuscular injection of 0.5g of LVM were too low to inhibit the growth of urinary pathogens, but, even after 12 hours the urine levels were sufficiently high to inhibit them in many cases (more than 100mcg/ml).
The blood levels determined every 12 hours after consecutive injections had a tendency to rise gradually. This tendency became more obvious in proportion to the reduction of renal function.Urinary recovery of LVM decreased in proportion to the degree of the impairment of the renal function.

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We report here the results of clinical application of lividomycin (LVM) for treating various urinary tract infections, as well as some fundamental investigations.
The blood level peak of LVM intramuscularly administered in a single dose of 0.5g appeared after one hour and then decreased rapidly. The effective blood level remained for 6 hours.
The antimicrobial activity of LVM against Pseudomonas and E. coli was considerably high.
LVM was effective in 53.1% of a series of 32 cases of urinary tract infections, i.e., markedly effective in 11, and moderately effective in 6 cases, and ineffective in the remaining 15 cases.
In spite of our special attention to nervous disturbances such as impaired hearing, dizziness and tinnitus, noteworthy side effects were not found.

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1) A sensitivity testing was carried out by the plate-dilution method on 18 strains of Staphylococcus aureus and 5 strains of Escherichia coli. Sixteen of the 18 strains of S.aureus were sensitive to this agent and the minimum inhibitory concentration was less than 6.25 mcg/ml, while the remaining strains were resistant (>50mcg/ml).The minimum inhibitory concentration of E.coli was less than 6.25 mcg/ml.
2) Clinical study was done on 21 patients with genitourinary tract infections.Good responses were found in 19 patients consisting of 14 with, acute pyelonephritis, 1 with chronic pyelonephritis, 2 with acute epididymitis, 1 with chronic prostatitis and 1 with prostatic abscess.No response was seen in 2 patients;1 with chronic pyelonephritis and 1 with wound infection and high fever.The drug was given intramuscularly at the dosage of 0.5-1g, 1-2 times a day for 3-19 days.
As the severe side-effect, nervous deafness resulted in two patients with extremely impaired renal function.

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1) Minimal inhibit ory concentration of lividomycin was determined by plate-dilution method on 114 strains isolated from urinary tract infections.All strains of Staphylococci, a few strains of E.coli and Proteus mirabilis tested were inhibited at concentrations below 6.25mcg/ml, and 12 of 18 strains of Pseudomonas tested were resistant to the antibiotic.
2) With an intramuscular injection of 500mg lividomycin, the blood level reached the maximum level (26.5-31.5mcg/ml) in 1 hour after administration, and decreased rapidly thereafter.
3) The urinary recovery rate was 87.5% during 24 hours after injection in 2 normal subjects.
4) Twenty one cases with urinary tract infections were treated with lividomycin, and good results were obtained in 8 cases.
4) No side effect was observed throughout the course of treatment except a decrease in P. S. P. rate in one case.

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Lividomycin, a new antibacterial agent, was used in the treatment of urinary tract infections.
The serum and urine concentrations after an intramuscular injection of 500mg lividomycin were closely similar to those reported previously.
Lividomycin was effective in 70% of 25 cases with urinary tract infections.The bacteria isolated from the effective cases were also sensitive to kanamycin.Therefore, we assumed that lividomycin has similar effects to KM.
Lividomycin was most effective against infections Escherichia coil and to some extent effective in those with Proteus and Pseudomonas aeruginosa.No obvious side effect was found.

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The following is a summary of the studies on lividomycin (LVM).
1. In susceptibility test of bacteria using the plate-dilution method, peaks of MIC of LVM against 47 strains of Staphylococcus aureus, 16 strains of Escherichia coli and 24 strains of Pseudotnonas aeruginosa appeared at 6.3mcg/ml, 25mcg/ml and 50mcg/ml, respectively.
2. In intravenous injection study with dogs, blood concentration of LVM showed an extremely high level immediately after the dose, then a gradual decline was observed from the first hour after the administration.However, 20mcg/ml of concentration level was maintained over 5 hours. The concentration in bile ran almost parall el with the changes as seen in blood.
3. Half-life hour of LVM in blood of the dogs was 1.56hours, distribution volume 0.3ml/kg, and the clearance values in blood, kidney and bile were 29.5ml/min., 30.5ml/min. and 0.07ml/min., respectively.
4. In tissue distribution study with rats following 50mg/kg intramuscular administration, its blood concentration was quite high, but that in the liver, spleen or muscles was always below the measurable level.In the lung, approximately 1mcg/ml of concentration was maintained, while a little higher concentration than blood was observed in the kidney,
5. In human subjects with healthy kidney, peaks of blood level appeared at 22mcg/ml in one hour after the administration of 0.5g of LVM;31.3mcg/ml with 1.0g in 2hours;and 76mcg/ml with 2.0g in one hour.There was no significant difference as to the half-life showing 1.8 hours in each dosage.
The level of urinary recovery was favorable showing 96-100% when 0.5g and 1.0g of LVM were admin istered.
6. The peak of blood concentration, as observed in the cases with slightly impaired renal function, appeared at the 2 nd hour and the half-life hour was between 2.2 and 3.2 hours. The rate of urinary recovery was 62% in the cases to which 1.0g of LVM was administered.
7. The protein binding ratio with bovine serum was 13.9% when tested by the cellophane bag dialysis.
8. In clinical observation of the drug, 17 cases of urinary tract infections, excellent effects were observed on acute cases, but bacteriological effects on chronic cases seemed to be inferior.In the cases with respiratory tract infections, its effects were not significant. The treatments were well tolerated by all patients.

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Clinical investigations of lividomycin, a new aminoglycosidic antibiotic, were carried out with urinary tract infections caused by Pseudomonas aeruginosa.
1. The MIC of lividomycin against P.aeruginosa was between 6.25mcg/ml and 50mcg/ml.The concentration of lividomycin in urine was significantly high as compared with in blood.When lividomycin was administered intramuscularly, the peak of urine levels reached in 1 hour after the administration, which continued for 7 hours.
2. Nine patients with urinary tract infections caused by P.aeruginosa were injected intramuscularly with 1.0-2.0g daily of lividomycin.
Good response was seen in all cases of acute or chronic cystitis, and in 2 out of 3 cases with pyelitis or pyelonephritis. Bacteriologically, remarkable response was found in all cases.No side effects were observed.

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The results of our clinical investigations on lividomycin, a new aminoglycosidic antibiotic, are summarized as follows:
The distribution of susceptibility to LVM of clinically isolated strains was examined.The MIC's for Staphylococcus ranged 3.12-25mcg/ml in 72% of the strains, and those for E.coli were below 25mcg/ml in 56% of the strains.There were strains of Pseudomonas aeruginosa for which the MIC was 25mcg/ml.
The fluctuation of bacterial colonies in the vagina after continued administration of LVM reflected the characteristics of its antimicrobial spectrum.
The blood concentrations after intramuscular injections of 500 and 1,000mg LVM reached the maximum levels of 16.6 and 25.3mcg/ml, respectively after 1 hour, and the drug could be detected even after 6 hours.The urinary excretion of the drug was 78.4%.The blood concentration in the umbilical cord which gives a measure of the migration to fetus was found to be approximately 1/4-1/8 of that in the mother's blood. The drug was detected in the amniotic fluid and the infant's urine as well.
The effect of LVM injected intramuscularly for 3-4 consecutive days with a daily dose of 2g (4g) was observed in 66.7% of 18 patients with obstetrical and gynecological infections.

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Investigations were made on clinical use of the new aminoglycosidic antibiotic lividomycin (LVM) in the field of obstetrics and gynecology.
The inhibitory concentrations of the drug for a variety of bacteria isolated from obstetrics and gynecology patients were determined and it was found that LVM has antimicrobial activities nearly identical to, or a little less than kanamycin (KM), against Staphylococcus, E. coli and Klebsiella and that the LVM excels KM to some degree in its antimicrobial activity against Pseudomonas aeruginosa.
Absorption and excretion of LVM proved effective; the maximum serum concentration about 20 mcg/ml was reached within 1 hour after the intramuscular injection of 500 mg and the urinary excretion amounted to approximately 80 within 12 hours. The drug was rated effective in cases of urinary tract infections and pelvic infections when given over about 7 consecutive days with a daily dose of 1.0 g. No side effects were recognized. LVM was judged clinically significant to obstetrical and gynecological infections from all the results described above.

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The results of bacterial and clinical experiments concerning surgical use of lividomycin were summarized as follows;
1) Antibacterial activity: The sensitivity of 32 staphylococcal strains isolated recently from infectious lesions ranged from 25.0 to 0.39 mcg/ml lividomycin.The resistant Staphylococcus aureus was found in 6.3% of all strains.The MIC to 25 strains of E.coli are distributed in from 25 to 3.13 mcg/ml. The resistant E.coli are found in 24% of all strains.The MIC of all resistant 7 strains of Pseudomonas were more than 50 mcg/ml.
2) Serum concentration: With a single intramuscular injection of 500mg, the serum concentration reached to the maximum level of 20-45 mcg/ml in 30 minutes.
3) Bile concentration: With a single intramuscular injection of 500 mg, the bile concentration reached to the maximum level in first 2 hours, but it was in low level.
4) Urine concentration: With a single intramuscular injection of 500 mg, the urine concentration reached to the maximum level as high as 680-1,100 mcg/ml in 2-3 hours.
5) Clinical evaluation: Of 39 cases of acute surgical infection treated with lividomycin 6 cases responded excellently, 15 well, 8 slightly well, 10 poorly.All 5 Pseudomonas infection treated with lividomycin responded poorly.
6) Side effect: There was no particular side effect.

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About 13% of Staphylococcus strains showed a resistance of 100 mcg/ml or more to both lividomycin (LVM) and kanamycin (KM).For LVM, the MIC peak fell on 6.3mcg/ml (47%), and no strain showed a value below 1.6mcg/ml, while for KM 27% of the strains showed a value of 1.6mcg/ml.Thus the results of KM were somewhat superior to those of LVM.
The blood concentration of LVM administered intramuscularly in a single dose of 500 mg to a healthy adult, showed its maximum level after one hour (36.67mcg/ml on average), and was measured even after 8 hours (1.81mcg/ml on average).
The urinary excretion in 24 hours was 82.5%.
The transfer of the intramuscularly administered LVM into the spinal fluid was comparatively satisfactory: for human subjects, the concentration of LVM in the fluid was 2-3 times that of KM, and for rabbits, 5-10 times that of KM.The change of blood pressure due to administration of LVM into the medullary cavity of rabbits was almost equal to the changes due to gentamicin (GM) and KM.No particular irritation was found.
LVM was administered to 18 cases of surgical infections, and effective in 15 cases (83.3%), No side effect was found except for one case of slightly impaired hearing.

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Clinical and experimental evaluation of a new aminoglycoside antibiotic, lividomycin, were performed. The results obtained are as follows:
1) In vitro antibacterial activity: The minimum inhibitory concentration of lividomycin was measured by the agar plate dilution method.Lividomycin inhibited the growth of 80 strains of coagulase-positive Staphylococcus aureus at 0.7-≥100mcg/ml.Lividomycin also demonstrated the antibacterial effect against Escherichia coli, Proteus mirabilis and Pseudomonas aeruginosa isolated from clinical specimens. Lividomycin demonstrated thus a broad spectrum of antimicrobial activity.
2) Concentration in blood: The maximum level reached 30.7 mcg/ml on the average 1 hour after the injection of 500 mg to healthy adults, and the level was still 9.8 mcg/ml 6 hours after the injection.
3) Concentration in tissues: Lividomycin activity was demonstrable in concentration of 4.5 and 2.9mcg/g on an average in 3 human palatine tonsilla and 6 maxillary sinus specimen respectively at 1 hour after an intramuscular injection of 500 mg, and serum levels of lividomycin were 30.7 and 30.2mcg/ml respectively.
4) Clinical evaluation: In the clinical tests in otorhinolaryngological infections, it was found that lividomycin showed good to excellent response in as many as 24 of the 33 patients by the intramuscular route or local application of 20 mcg/ml solution (effectiveness rate of 73 per cent).
5) Side effect: Liver function, serum electrolytes and auditory acuity were tested on subjects receiving lividomycin 1,000 mg per day for 5-`7 days, with any significant adverse findings.No side effect was observed with the injection or local application of lividomycin.

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From the laboratory and clinical studies on lividomycin, a new antibiotic of the aminoglycoside group produced by Streptomyces lividus, the following results were obtained.
1.The MIC values of lividomycin against newly isolated Staphylococcus aureus (20 strains) were lower than those of kanamycin.
2. The bacteriolytic activity of lividomycin on the growth curve of S.aureus FDA 209 P strain was observed using Biophotometer Jouan.The same activity against FDA 209 P strain was observed in the sera of the patients injected intramuscularly with 500-5,000mg lividomycin.The sera taken 30minutes, 1 hour and 3 hours after the injection of 1,000mg were active, but that taken after 6 hours was inactive.
3. Thirty cases of otorhinolaryngeal patients were treated with lividomycin.There were 16 remarkably effective cases (53.3 %), 7 improved cases (23.4%), and 7 ineffective cases (23.4%).Lividomycin was effective in 76.7 % of the patients treated.
4. As for the side effects of lividomycin, eruption or ototoxicity was not encountered.

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Sensitivity disc containing 50mcg of lividomycin (LVM) was investigated comparing with that of streptomycin using 60 strains of bacteria isolated from urinary tract.
Better results of disc sensitivity tests were obtainedfrom quantitative dilution method with preliminary diffusion than conventional method in LVM.
Reproducibility of LVM disc sensitivity tests were also higher in quantitative dilution method with preliminarydiffusion than in conventional method.
Correlations between MIC values by the streak plate method and diameters of inhibition zones by the disc method were affected by the method of measuring MIC with streak plate method.

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Lividomycin (LVM) was applied to 12 cases of post-operative urinary tract infections.Ten cases were Pseudomonas infection, and another 2 cases were Escherichia coli and Rettgerella infections.
Good responses to LVM were observed in 4 of 10 cases with Pseudomonas and an acute pyelonephritis case with E.coli, while poor response in Rettgerella infection.
No side effect was observed on renal and hepatic functions.

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Lividomycin (LVM) is a new aminoglycoside antibiotic produced in Japan.The laboratory and clinical studies have been carried out on this drug, and the following results were obtained.The antibacterial activity of LVM against Pseudomonas aeruginosa to be four times or more as great as that of kanamycin (KM).The resistant strains of which exceeded 100 mcg/ml were not found and 68% of tested strains showed MIC of 25 mcg/ml. Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris, Citrobacter and Enterobacter cloaca seem to have a certain degree of cross-resistance to KM and LVM, but KM is two to four times more effective than LVM antibacterial activities against these organisms.

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Bacteriological and clinical experiments for ophthalmic use of lividomycin (LVM) were carried out with following results.
1) Minimum inhibitory concentration of LVM was 3.13mcg/ml for KOCH-WEEKSb acillus, 0.78-3.13mcg/ml for MORAX-AXENFELD diplobacillus, 50-100mcg/ml for pneumococcus, 0.78-1.56mcg/ml for C.diphtheriae, 1.56mcg/ml for gonococcus, 50-400mcg/ml for Streptococcus, 0.78-12.5mcg/ml for Staphylococcus and 50-100mcg/ml for Ps.aeruginosa.
2) The distribution of the sensitivity for 40 strains of Staph.aureus was in the range of 0.4->100mcg/ml, and the peak existed in 3.1mcg/ml.
3) Twenty-four strains of Ps.aerugiuosa were sensitive at 50->100mcg/ml;50mcg/ml for 6 strains, 100mcg/ml for 11 and>100mcg/ml for 7.
4) Combined antibacterial effect of LVM with other antibiotics on Ps.aernginosa was studied by means of a disc method using “Showa Disc”. LVM presented a synergistic action with gentamicin and carbenicillin. No interference was observed in the combination with colistin and polymyxin B.
5) The serum level by intramuscular injection of a single dose of 500mg reached the highest (18.8 mcg/ml) after 1hour, and decreased gradually until 6 hours.
6) The penetration of LVM into rabbit eyes was examined.After the intramuscular injection of 50 mg/kg LVM, the peak of aqueous humor level was obtained in 1 hour, and the ocular tissue concentration was found in the outer and inner parts of the eye.
7) Intramuscular injection of 0.5-1.0g LVM once a day revealed good effects in all of 5 cases with external hordeolum caused by Staph.aureus, one of 2 cases with chronic dacryocystitis by Staph. aureus, 2 cases of corneal ulcer by Ps.aeruginosa, 2 cases of orbital phlegmon by Staph.aureus, and a late infection by Staph.epidertnidis and Gram-negative bacteria.
8) No side effect was noticed in all of 14 cases.

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Laboratory and clinical studies on a new antibiotic, lividomycin (LVM) were made with the results as follows:
1. Minimum inhibitory concentration of LVM against coagulase-positive Staphylococci (30 strains) isolated from ocular suppurative diseases was 0.78-25mcg/ml.
2. Aqueous humor concentration of LVM in rabbit reached maximum (26.0mcg/ml) 2 hours after an intramuscular administration of 50mg/kg, and the maximum serum concentration (240mcg/ml) was obtained 1 hour after injection.
3. Levels of LVM in serum were estimated in 7 volunteers.An average serum concentration was 37.2mcg/ml 1 hour after the intramuscular administration of 500mg.
4. Thirty-one patients with various ocular suppurative diseases were treated intramuscularly with 3ml of solution containing 500mg of LVM.All of these cases were improved by the treatment, and no side effect was observed.

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Lividomycin (LVM) was effective to acute suppurative diseases, being the effectiveness 58.4%. None of the patients had any side effect.It seems unnecessary to worry about the side effects so far as LVM is administered for less than one week and patients have no underlying diseases.
The MIC of LVM against Staphylococcus aureus isolated from lesions is about 31.3mcg/ml.LVM is almost equal to KM but inferior to GM in antimicrobial activity.LVM seems to have a cross resistance with KM and GM in S.aureus.LVM is superior to KM, but inferior to GM in its antimicrobial activity against Pseudomonas aeruginosa isolated from lesions.
LVM is not especially superior to other existing antibiotics for the treatment of pyoderma. Therefore, LVM will not be used as a drug of first choice for patients with dermatological diseases.

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A new aminoglycosidic antibiotic lividomycin was orally administered to 26 cases of infantile bacillary dysentery including 2 cases of healthy carriers. A daily dose of 1.0g (every 6 hours) was administered for 5 days, and the effect was observed for 14-21 days.
1. The minimum inhibitory concentrations of lividomycin against Shigella strains isolated from the patients were 1.56-25mcg/ml.
2. The clinical effect of lividomycin was observed in 3-`7 days. The bacilli disappeared within 2-3 days after the initiation of lividomycin therapy, but reappeared in 3 cases (11.5%).
3. No side effect was observed, and there was no Pseudomonas aeruginosa after the therapy.
The usefulness of lividomycin in the treatment of children's bacillary dysentery was confirmed.

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The authors have carried out the laboratory and clinical studies of lividomycin.The results were as follows:
The sensitivity was examined by the plate dilution method with 32 strains of coagulase-positive staphylococci, 32 strains of Pseudomonas aeruginosa, 24 strains of E.coli and 15 strains of Klebsiella isolated from patients.The growth of 87.5% of coagulase-positive staphylococci was inhibited at the concentration of less than 6.25mcg/ml. The growth of 59.4% of Pseudomonas aeruginosa and of 75.0% of E.coli were inhibited at less than 12.5mcg/ml, respectively.
Lividomycin was given by a single intramuscular injection of 25mg/kg of body weight to 2 children. The maximum blood level was reached 30minutes after injection.The blood levels 8 hours after injection were 0.6mcg/ml and 4.8mcg/ml, respectively.
The excretion rates of lividomycin in the urine after a single intramuscular injection were 30% and 42%, respectively, in 8 hours.
Lividomycin was effective in 4 of 6 cases with pneumonia.No marked side effects were encountered.

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