In vitro and in vivo antibacterial activities of KW-1070 against gram-positive andgram-negative bacteria were summarized as follows.
(1) KW-1070 has a broad spectrum of antibacterial activity against gram-positive andgram-negative bacteria. The MICs of KW-1070 were similar to those of KM againstaminoglycoside-susceptible strains, slightly less than those of GM or DKB.
KW-1070 had a strong activity against S. marcescens but a weak activity against P. aeruginosa.
(2) KW-1070 was active against GM-resistant S. marcescens and GM-resistant P. aeruginosa, and showed no cross-resistance with GM.
3) MBCs of KW-1070 were found to be near MIC values and KW-1070 acted bactericidally.
(4) KW-1070 was active against many aminoglycoside-resistant bacterial strains withaminoglycoside-inactivating enzymes, particularly AAC (6'), AAC (2'), AAD (2'') and APH (3'), except AAC (3)-I.
(5) The combination of KW-1070 with PIPC, CBPC or APPC acted synergistically in vitro against P. aerugtnosa.
(6) The in vivo activities of KW-1070 in mice infected with S. aureus, E. coli, Proteus sp. and S. marcescens were more favorable than those of AMK and KM.

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The antibacterial activity of KW-1070 was compared with that of amikacin (AMK), gentamicin (GM), tobramycin (TOB) and dibekacin (DKB) against a total of 724 strains of Staphylococcus, Haemophilus, Escherichia, Klebsiella, Citrobacter, Enterobacter, Serratia, Proteus, Aeromonas, Pseudomonas and Acinetobacter, isolated from clinical materials in 1979.
KW-1070 exhibited a superial antibacterial activity against gram-positive cocci and gram-negativerods except S. faecalis and P. aeruginosa.
It was observed that there existed a relatively stronger correlation between MIC of KW-1070 and GM than between MIC of KW-1070 and AMK against Staphylococcus, H. influenzae and A. anitratus.
Against other organisms except P. aeruginosa, it was also observed that there existed a strongcorrelation between MIC of KW-1070 and AMK, while there was no correlation between MIC of KW-1070 and GM.
Antibacterial activities of KW-1070 against most organisms were almost similar or slightly inferiorto those of AMK, but slightly superior to those of AMK against Serratia, especially GM-resistant Serratia.
KW-1070 and AMK exhibited an excellent sensitivity against most of GM-resistant (TOB-resistant, DKB-resis tant) E. coli, Klebsiella, C. freundii, E. cloacae, P. morganii, P. rettgeri and P. inconstans.

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The in vitro and in vivo antibacterial activities attributed to KW-1070, a new aminoglycoside, were investigated in comparison with gentamicin, dibekacin, amikacin, netilmicin, tobramycin andsisomicin. The results were as follows.
KW-1070 showed a broad antibacterial spectrum against gram-positive and gram-negative bacteria.
It exhibited excellent antibacterial activity against gram-negative bacteria; i. e., P. inconstans and S. marcescens. Its activity against P. aeruginosa was weaker, however, than the other aminoglycosides.
In vivo antibacterial activity of KW-1070 against gentamicin-resistant C. freundii, P. inconstans and S. marcescens was stronger than gentamicin or netilmicin and similar to amikacin in experimentalinfction of mice.
The serum level of KW-1070 showed a higher peak level than gentamicin and amikacin.

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The in vitro activity of KW-1070 (fortimicin), a new aminoglycoside, against anaerobic bacteriawas compared with of gentamicin. The antimicrobial spectrum of KW-1070 was similar to that ofgentamicin. MIC values of KW-1070 to anaerobic bacteria (B. fragilis, B. thetaiotamicron, F. varium, F. nucleotum, C. difficile, P. prevotii, etc.) ranged from 6.25 to> 1, 600 μg/ml. Gram-positive bacteria (MIC: 6.25-400 μg/ml) were more sensitive to KW-1070 than gram-negative bacteria (MIC: 12.5-> 1, 600 μg/ml).

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KW-1070, a new aminoglycoside antibiotic was bacteriologically evaluated. The results are summarized as follows:
1) The antimicrobial spectrum and activity of KW-1070 were similar to those of amikacin, exceptthe activity was less active than that of amikacin against Pseudomonas aeruginosa.
2) KW-1070 was effective against bacteria capable of producing aminoglycoside-inactivating enzymesexcept for AAC (3)-I and therefore, it was active against various aminoglycoside-resistant strains.
3) In sensitivity test of clinical isolates, the antibacterial activity of KW-1070 was similar orslightly less active in comparison with amikacin. KW-1070-resistant strain was only rarely observed.
4) KW-1070 showed bactericidal activity, being superior to that of amikacin.
5) On the protective effects for experimental infections of various aminoglycoside-sensitive bacteria, KW-1070 showed similar effect to amikacin. Furthermore, KW-1070 was effective both in aivi andin vitro in experimental infections due to various aminoglycoside-resistant bacteria including amikacinresistant strain.

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General pharmacology of KW-1070, mainly its muscle-relaxant effect, was investigated.
1. When KW-1070 was injected to the rabbit in a dose of 200mg/kg respiratory arrestfollowed by cardiac arrest was observed. These effects were antagonized under artificial ventilation, or by pretreatment with CaCl₂.
2. KW-1070 in a concentration of 5×10^-4M inhibited spontaneous movement of isolated guineapig atria. This effect was antagonized by CaCl₂.
3. KW-1070 in a concentration of 5×10^-4M inhibited the contraction by indirect electrical stimuliof isolated rat phrenic nerve-muscle preparation. This effect was hardly antagonized by neostigmine. The effect of KW-1070 and d-tubocurarine or MgCl₂ was additive. The muscle-relaxant effect of KW-1070 was antagonized by CaCl₂.
4. ED₅₀'s of KW-1070 to muscle relaxant effect in mice by the methods of rotarod and of KOZUMANOFF were 413-445 mg/kg s. c. and its LD₅₀ was 572mg/kg s. c. These effects were antagonized byphysosigmine or CaCl₂. The effect of KW-1070 and MgCl₂ or d-tubocurarine was additive.
5. Chronic administration of KW-1070 (12 days) in a dose of 445mg/kg (ED₅₀) to mice did notdevelop hyperreactivity to the drug and no mouse was dead.
6. Duration of halothane anethesia was prolonged, that of ether anesthesia was shortened andthat of pentbarbital sleep was not affected in mice by pretreatment with KW-1070 in a dose of 300mg/kg s. c.
7. Possible mechanism of the effects of KW-1070 and its interactions with several drugs arediscussed, compared with those of other aminoglycoside antibiotics.

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The effects of KW-1070 on the central and peripheral nervous systems were investigated in comparison with those of kanamycin (KM) and ribostamycin (RSM). The following results were obtained.
1. Like KM and RSM, intramuscular or intravenous injection of large doses of KW-1070 in mice and rats caused behavioral changes as inhibition of somatic activities induced by relaxation of skeletal muscle and sedation.
2. KW-1070 had no effects on spontaneous motor activity in Animex method, pentobarbital anesthesia, drug and electric stimulation induced convulsions, body temperature, responses to pain stimuli, spontaneous EEG, EEG arousal responses, spinal reflexes and local anesthesia.
3. Like KM and RSM, KW-1070 slightly depressed twitch responses of the tibialis anterior muscle and diaphragm to nerve stimulation.
4. Contractile responses of nictitating membrane to preganglionic stimulation of superior cervical ganglion and to injection of adrenaline were slightly depressed by large doses of KW-1070.
From these results, it was concluded that the effects of KW-1070 on the central and peripheral nervous systems were slight and nonpecific, similar to those of KM and RSM.

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The pharmacodynamic actions of KW-1070 were studied in comparison with those of kanamycin (KM) and ribostamycin (RSM). The following results were obtained.
1. Blood pressure, respiratory rate and heart rate decreased after intraveneous administration of large doses of KW-1070, KM and RSM in anesthetized dogs, rabbits and cats.
2. Like KM and RSM, KW-1070 caused slight vasodilation in hind-leg of anesthetized dogs.
3. Contractile force and heart rate of isolated guinea-pig atria and heart were decreased by KW-1070, KM and RSM.
4. Like KM and RSM, KW-1070 reduced the muscular tonus and amplitude of spontaneous contraction in isolated rabbit intestine and rat uterus, and also suppressed the contractile responses to acetylcholine, nicotine, serotonin, Ba Cl₂ and noradrenaline in isolated guinea-pig ileum, trachea and produce vas deferens.
5. Amounts of urine and Na⁺excretion were slightly decreased by KW-1070.
6. In the guinea-pig, rat and four mice strains test, multiple injections of KW-1070 failed to the antibodies of either class of Ig G or Ig E.
From these results, it was concluded that the effects of KW-1070 on cardiovascular, smooth muscular and urinary excretory system were slight and nonspecific, similar to those of KM and RSM.

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The present experimental study was made in 84 young adult guinea pigs, 57 pregnant ones and 159 new born ones to evaluate the ototoxic effect of KW-1070 on auditory function and inner ear. Four series of experiments were performed and following results were obtained.
1) In the short-term intramuscular administration for 4 weeks with KW-1070, the ototoxic damage was confined to the outer hair calls of the organ of Corti at the basal end of the unilateral cochlea and there was no severe auditory impairment (scale out) in pinna reflex test in extensive frequency range from 20 KHz to 500 Hz at dose of 200mg/kg. In the vestibular organs scattered missing of the hair cells was found. There was no remarkable dose-depandent enhancement in the damage of the hair cells in the administration at 400mg/kg.
2) In the long-term intramuscular administration for 90 days with KW-1070 at 10mg/kg, and 100mg/kg, respectively, the ototoxic damage of the hair cells in the cochlea and vestibulum was slight or not found. There was no distinct dose-dependent enhancement in the ototoxic damage of the inner ear.
3) In the short-term intramuscular administration with KW-1070 in the early and later period of pregnancy, the ototoxic effect on the oragan of Corti and vestibular organsin the maternal and newborn guinea pigs was mild or not found at dose of 100 mg/kg and 200mg/kg.
4) In the short-term intramuscular administration at 400 mg/kg, there was no district difference between the ototoxicities of KW-1070 and RSM with the least ototoxicity among the available aminoglycoside antibiotics.
5) Combined treatment with KW-1070 (200 mg/kg i. m.) and 2 hours later with fursosemide (100mg/kg i. v.) caused an enhanced extensive ototoxic damage in the outer hair cells by KW-1070. The enhanced ototoxic damage became decreased by prolongation of the period between administration of the antibiotic and the diuretic, and by decrease in the dose of the latter. The mechamism of these events was discussed.
6) The present experimental study indicates that in intramuscular administration KW-1070 belongs to the least ototoxic aminoglycoside antibiotic group.

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Renal toxicity and recovery in rats attributed to KW-1070, a new aminoglycoside, were investigated functionally and morphologically in comparison with amikacin and gentamicin.
The rats were divided into low dose groups, given 80mg/kg/day of KW-1070 and amikacin, and 24 mg/kg/day of gentamicin; medium dose groups given 160 mg/kg/day of KW-1070 and amikacin, and 48mg/kg/day of gentamicin; and high dose groups given 320 mg/kg/day of KW-1070 and amikacin, and 96 mg/kg/day of gentamicin.
The results were as follows:
1) Among general conditions, inhibited body weight increase, decreased body weight, increased water intake and decreased food intake were observed. However, these changes were the smallest for KW-1070. No deaths occurred in any of the KW-1070 dose groups, whereas there were deaths in the amikacin and gentamicin high dose groups.
2) In the renal function test, changes attributed to the administration of each drug were observed. Urinary volume, urinary proteins, urinary lysozyme and appearance of occult blood increased, while urinary osmolality decreased. But again, the changes were the smallest for KW-1070. Although decreased total serum protein and increased BUN and serum creatinine were found in the amikacin and gentamicin dose groups, none of these changes were detected in the KW-1070 dose groups.
3) As to drug concentrations in the serum, there were no significant difierences among the three drugs. In concentrations in the kidney, KW-1070 showed lower concentrations than amikacin. After drug administration was stopped, KW-1070 disappeared from the kidney faster than did amikacin and gentamicin.
4) There were dose-related increases in absolute and relative kidney weights in all dose groups, but these changes were smallest in the KW-1070 dose groups.
5) In histopathological examinations, there were dose-related changes, mainly degeneration and necrosis, in the renal tubular epithelium in all dose groups. But the degree of disorder was the mildest in the KW-1070 groups.
As indicated above, the renal toxicity of KW-1070 was clearly milder than that of other aminoglycoside antibiotics.

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A study was made on the effects and recovery in kidney of rats between KW-1070 and amikacin. Single doses of KW-1070 and amikacin (160 and 320 mg/kg/day) were given to two groups each, and combined doses of the same amount of KW-1070 and amikacin together with diuretic furosemide (30mg/kg/day) were given to two other groups each. Functional and morphological comparisons were made and the results are given below.
Renal toxicity for both the KW-1070 and amikacin groups was higher for the combined doses with furosemide than with the single doses. The changes in the KW-1070 groups, however, were milder than those in the amikacin groups.
Recovery from kidney disorders was faster in the KW-1070 dose groups than in the amikacin dose groups.
The serum level for both the KW-1070 and amikacin groups was higher for the combined doses with furosemide than with the single doses, while no difference was observed in kidney concentration between single doses and combined doses.

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KW-1070 is a new aminoglycoside antibiotic produced from Micromonospora olivoasterospora which was isolated from a soil in Hiroshima City, Hiroshima Prefecture, Japan. KW-1070 exhibited potent and unique broad-spectrum antibacterial activity against gram-negative bacteria (Serratia, Proteus inconstans, etc.). Toxicolological studies of KW-1070 were carried out for safety evaluation as follows:
1) Studies on acute toxicity were carried out by intravenous, intramuscular, intraperitoneal, subcutaneous and oral administration to ICR strain mice and Wistar strain rats and by intramuscular and intravenous administration to Beagle strain dogs, comparing with kanamycin.
2) Studies on subacute toxicity were carried out by intramuscular administration (25, 50, 100, 400 and 600 mg/kg) to Wistar strain rats for 30 days, comparing with kanamycin (100 and 400 mg/kg).
3) Studies on chronic toxicity were carried out by intramuscular administration (6, 12. 5, 25, 50, 100 and 200 mg/kg) to Wistar strain rats for 180 days.
The results of the studies are summarized as follows:
1) Acutoxicity varied with species used, being higher in mice>dogs>rats.
2) In subacute toxicity studies, some animals were observed dead at the dose of KW-1070 600mg/kg and kanamycin 400mg/kg respeectively. Main changes observed in subacute toxicity studies were renal tubular disorder, anemia and bad general conditions which were due to renal tubular disorder. These chenges were observed mainly at the dose of KW-1070 50-100 mg/kg or more.
3) The changes in chronic toxicity studies were almost similar to those observed in subacute toxicity studies, and they were observed mainly at the dose of KW-1070 12.5-25mg/kg or moe. The toxicological effects observed with KW-1070 were qualitatively similar to those observed with kanamycin and other aminoglycoside antibiotics, and were quantitatively judged to be less toxic than kanamycin at the dose of 400 mg/kg.

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Toxicological studies of KW-1070 were carried out in dogs for safety evaluation as follows:
1) Studies on subacute toxicity: Beagle strain dogs given intramuscularly KW-1070 at dose levels of 12.5, 25, 100, 200 and 400 mg/kg and kanamycin (positive control) at dose levels of 100 and 400mg/kg for 30 days, respectively.
2) Studies on chronic toxicity: Beagle strain dogs were intramuscularly given KW-1070 at dose levels of 3, 6, 12.5 and 100 mg/kg for 180 days.
The results of the studies are summarized as follows:
1) In subacute toxicity studies, animals were observed dead only at the dose level of kanamycin 400mg/kg (4/4) within one month. Main changes observed in subacute toxicity studies were renal tubular disorder, which showed a close similarity to subacute toxicity studies in rats. It was observed histologically at the dose level of KW-1070 25-100 mg/kg or more. Kanamycin produced more toxic effects than KW-1070 at the dose level of 400 mg/kg. The results were same as those of subacute toxicity studies in rats.
2) The changes observed in chronic toxicity studies were almost similar to those observed in subacute toxicity studies. An animal was observed dead only at the dose level of KW-1070 100mg/kg (1/6). Renal tubular disorder was observed at the dose level of KW-1070 12.5-50mg/kg or more.

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1) Tetarological studies (rats)
KW-1070 was administered intramuscularly at doses of 25, 110 and 500 mg/kg to pregnant Wistar strain rats from day 7 through 17 of pregnancy.
2) Teratological studies (rabbits)
KW-1070 was administered intramuscularly at doses of 25, 90 and 300 mg/kg to pregnant rabbits from day 6 through 18 of pregnancy.
3) Fertility studies (rats)
KW-1070 was intramuscularly administered daily for 60 days to male rats starting at 5 weeks of age at doses of 25, 110 and 235 mg/kg. The compound was also administered to mature female rats for 22-30 days at the same dose levels. After administrations, male and female rats of the same dosage group were randomly cohabitated for mating. Administration of the compound was continued during this period and further until day 7 of pregnancy in mated female rats.
4) Peri-and postnatal studies (rats)
KW-1070 was intramuscularly administered daily from day 17 of pregnancy until day 21 of lactation at the same doses as in fertility studies.
The main changes observed in the above studies were renal damages and bad general conditions of parent animals which were treated at high doses of KW-1070. No significant and dose-related changes were observed in mating and pregnant abilities of parent animals, in malformation in fetuses, and in growth, mobilities and reproductive functions of newborn animals.

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Absorption, tissue distribution and excretion of KW-1070 were studied in rats and dogs in comparison with Amikacin (AMK), and the following results were obtained.
1) KW-1070 was extremely well absorbed after intramuscular administration of 20 mg/kg to rats and dogs. The peak of plasma level of KW-1070 was obtained earlier than that of AMK.
2) KW-1070 was rapidly distributed into various organs and the concentration in the kidney was higher and persisted longer than in other tissues after intramuscular administration of 20 mg/kg to rats. These results were similar to AMK, which the kidney concentration of KW-1070 was higher than that of AMK.
3) Remarkable accumulation of KW-1070 and AMK was observed in the kidney after multiple administrations of 4 and 6 mg/kg to rats. The kidney concentration of AMK was higher than that of KW-1070.
4) KW-1070 was mostly excreted through the urinary tract. Approximately 65 to 94% of KW-1070 administered was excreted within 24 hours in the urine of rats and dogs. Biliary excretion was very small in rats.
5) The binding of KW-1070 to human serum protein was as low as that of AMK.
6) No metabolite was found in the urine of rat, dog and human volunteer after administration of KW-1070.

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Biosynthesized ¹⁴C-KW-1070, a new aminoglycoside antibiotics, was administered intramuscularly in rats (20mg/kg), and absorption, distribution and excretion have heen studied.
¹⁴C-KW-1070 was rapidly absorbed from the administmtion site to show the highest plasma level of 30μg/ml at 15 min., and was eliminated with a biologlcal half life of 30 minutes.
The drug was highly distributed in cartilageous tissues and was mostly eliminated in 4hours.The mdioactivitywas localized at the kidney cortex for longperiod with a biological half life of approximately 5.4 days, ¹⁴C-KW-1070 was exclusively excreted into urine and biliary excretion was very sman.
No metabolite nor degradation product was found in the ruine collected for 6 hours.
Transfer of KW-1070 into the perilymph in guinea pigs has been also investigated. ¹⁴C-KW-1070 showed the higbest level (22.0μg/ml) in the perilymph of guinea pigs at 4 hours after administration (100mg/kg, im) and wase liminated with a biological half life of 6.8 hours, which was much longer than plasma elimination half life of 50 minutes, estimated simultaneously.

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The placental transfer and transition into milk of KW-1070, a new aminoglycoside antibiotic, have been studied with ¹⁴C-KW-1070 administered intramuscularly in the pregnant snd lactating rats, respectively.
The level of ¹⁴C-KW-1070 in the umbilical cord blood was 5.4% of the peak maternal blood level and the radioactivity was eliminated slowly. At the peak fetus level (1 hour after administration), the radio activity transferred into the fetuses was found to be 0.6% of the dose.
¹⁴C-KW-1070 was distributed into the uterus, ovary and censistently into the fetal membrane.
¹⁴C-KW-1070 was excreted into milk, but the concentrations of radioactivity in milk did not exceed the maternal peak blood level.

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KW-1070, a new aminoglycoside antibiotic, was administered intramuscularly to seven healthy adult volunteers to study its safety and pharmacokinetics.
In single dose studies, volunteers were administered 4mg/kg or 8mg/kg of KW-1070. In multiple dose studies, volunteers received 4mg/kg of KW-1070 every 12 hours for 5 days.
No side effect or abnormal laboratory findings were found in either the single or multiple dose studies.
The serum level of KW-1070 peaked at 10.08μg/ml after one hour in the 4mg/kg dose group, and at 15.90μg/ml after 30 minutes in the 8mg/kg dose group. The serum level decreased gradually, and the concentration after 8 hours was 1.07μg/ml for the 4mg/kg dose group and 2.34μg/ml for the 8mg/kg dose group.
The serum half-life of KW-1070 was 1.95 hours for the 4mg/kg dose group, and 2.35 hours for the 8mg/kg dose group, which indicates that dose response is dependent on the dose level. The urinary recovery rate 12 hours after administration was 53.0% for the 4mg/kg dose group and 62.5% for the 8mg/kg dose group. No significant differences were observed in absorption or excretion rates between single and multiple administrations of KW-1070 to healthy adult volunteers.

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Pharmacokinetics were studied on KW-1070, a new aminoglycoside, to compare with amikacin. Thirty minutes after single intramuscular administration of KW-1070 (200mg and 300mg) and amikacin (200mg), mean peak blood levels were 13.8, 18.7 and 13.1μg/ml, mean serum half-lives were 1.8, 1.9 and 1.6 hours and urinary excretion rates within 8 hours were 64.7%, 67.6% and 55.5%, respectively. AUCs, one of pharmacokinetic parameters, were 47.7, 64.8 and 35.3μg·h·ml^-1, respectively. Dose response of blood levels was observed between 200mg and 300mg of KW-1070.

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Clinical pharmacology was evaluated with KW-1070, before and after intramuscular administration of 100mg or 300mg 9 times twice daily in 6 aged patients.
Pharmacokinetic parameter was found at the 1 at and the 9 th administration as increasing of distribution volume, prolongation of T 1/2 in 4 cases, shortening of T 1/2 in 1 case, and prolongation grade was dominant in those with declined renal function.
Slight cumulative tendency was found, as, comparing with first administration, maximum serum levels increased as well as area under serum the curve.
These changes with multiple administreation for longer period may cause adverse reaction, so that a deep caution showed be given about multiple administration in aged or declined renal function patients.

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KW-1070 was investigated in terms of antibacterial activity and clinical effect.
1) Antibacterial activity
Antibacterial activity of KW-1070 was slightly weaker than other aminoglycosides (gentamicin, dibekacin, tobramycin, amikacin, sisomicin) against clinical isolated E. coli, indole positive Proteus, K. pneumoniae and E. cloacae. However, its MIC was lower than 12.5 μ g/ml against each of the above strains.
From the fact that no strains strongly resistant to KW-1070 were observed, KW-1070 seemed to be superior to the other aminoglycosides. While its activity against P. aeruginosa was weaker by 2 to 3 ranks than the other aminoglycosides, against S. marcescens it was stronger by 2 to 3 ranks than the other aminoglycosides and no resistant strains were observed.
2) Clinical effect
KW-1070 was used in 14 cases of infection, including Septicemia and urinary tract infection. The clinical efficacy was good in 10 cases, fair in 1 case, and poor in 3 cases. No side effect was observed.

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Susceptibility to clinical isolates and clinical effect were studied on KW-1070, a new aminoglycoside. MICs of KW-1070 against 54 strains of E. coli ranged from 0.4 to 6.3 μ g/ml with an inoculum size of 10⁶cells/ml. MICs were 6.3 μ g/ml and less against 50 strains of Klebsiella, mostly 0.4-4.3 μ g/ml against 45 strains of P. aeruginosa, 0.8 μ g/ml and less against 25 strains of indolepositive Proteus and 1.6 μ g/ml and less against 20 strains of indole-negative Proteus, respectively.
Twenty one patients with respiratory and urinary infections were treated intramuscularly with KW-1070 at a daily dose of 200 to 400 mg. Clinical response was excellent in 10 out of 21 patients, good in 5, fair in 1, poor in 4 and unevaluable in 1.
No side effect and abnormal laboratory findings were observed.

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A clinical trial of KW-1070, a new aminoglycoside antibiotic, was carried out on 9 patients with respiratory tract infection including 4 acute pneumonia, 3 acute bronchopneumonia and 2 exacerbation of chronic bronchitis.
KW-1070 was administered intramuscularly at a daily dose of 400 to 600mg.
1. Clinical response of KW-1070 was excellent in 3 cases and good in 6 cases.
2. Pathogens isolated before treatment from 8 cases were all eliminated.
3. No adverse reaction was observed.

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Laboratory and clinical investigations on KW-1070 were conducted, and the results were as follows:
1) The susceptibility of clinically isolated Serratia marcescens to KW-1070 was tested using the agar plate dilution method and compared to the susceptibility of the same to other aminoglycoside derivatives. The minimum inhibitory concentration of KW-1070 for 50% inhibition of Serratia marcescens was less than 1.56 μ g/ml. No cross-resistance was observed among KW-1070, AMK, and GM.
2) Five patients were treated with KW-1070 for respiratory and urinary tract infections and an abscess in the abdominal wall, and clinical results were good in 4 patients. No side effects were observed.

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In vitro antimicrobial activities of KW-1070, a new aminoglycoside antibiotic, against clinically isolated potential pathogens were examined with Dynatech MIC 2000. Following 206 strains of various species were included in this study; 19 of Stapylococcus aureus, 40 of Pseudomonas aeruginosa, 45 of Klebsiella pneumoniae, 41 of Escherichia coli, 16 of Serratia marcescens and 45 of Enterobacterspp.
Minimum inhibitory concentrations against these strains were determined immediately on the day of the isolation of the microorganisms from clinical specimens. The three-month period of investigation lasted from December 1980 to February 1981.
The results of determination of MICs of KW-1070 were compared with those of gentamicin, dibekacin, tobramycin and amikacin. It was found that KW-1070 showed more potent antimicrobial activities than other aminoglycosides with an exception of gentamicin. The effect of gentamicin on gram-negative bacilli was almost equal to or stronger than KW-1070. However, KW-1070 was not so effective as other aminoglycosides on Pseudomonas aeruginosa.
No evident cross-sensitivity was found between KW-1070 and amikacin, especially when Serratia marcescens and Enterobacter spp. were used as test microbes.

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The clinical effectiveness and side effects of KW-1070 were studied in 12 cases of R.T.I., 14 cases of U.T.I. and 2 cases of sepsis.
The overall clinical efficacy was 85.7%(24/28) and bacteriological eradication was 87.1%(27/31). Within 3 days, Serratia marcescens showing resistance to other antibiotics was eradicated in all cases of U.T.I.(12 cases) and sepsis (2 cases).
Side effects such as renal- and oto-toxicity were not observed except for transient elevation of GOT and GPT in 1 case.

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The susceptibility of 34 strains of clinical isolates to KW-1070 was examined and the results were compared with those of amikacin, gentamicin and dibekacin. To evaluate the drug clinically, KW-1070 (200-400 mg) was given intramuscularly twice daily to 10 patients ; 3 with respiratory tract infections, 6 with urinary tract infections and one with both infections.
Antimicrobial activities of KW-1070 against gram-negative bacilli were inferior to gentamicin, while comparable to amikacin and dibekacin except P. aeruginosa.
Clinical efficacy rate of KW-1070 therapy was 50% in respiratory tract infections and 71.4% in urinary tract infections.
No adverse reactions were seen in any cases.

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The nephrotoxicity of KW-1070 was examined in rabbits, comparing with that of amikacin.
The rabbits were placed in individual cages and given only “okara” without water. Each of two aminoglycosides was administrated intramuscularly to three rabbits at a dose of 150 mg and 300 mg/kg/day for 10 days. The rabbits injected 150 mg/kg/day of KW-1070 or amikacin did not cause marked proteinuria, hematuria, increase in serum creatinine and proximal tubular damage in light microscopy. On the other hand, some of rabbits injected 300 mg/kg/day recognized marked proteinuria and hematuria. Serum creatinine increased significantly in a rabbit injected amikacin, while it did not increase in the all rabbits injected KW-1070. The proximal tubular damage was more remarkable in the amikacin-injected group than in the KW-1070-injected group.
For the clinical evaluation of KW-1070, the drug was intramuscularly administrated to 2 patients of cerebrovascular disease with pneumonia and 2 patients with acute pyelonephritis. The patients received KW-1070 in a dose of 400 mg/day for 8 to 14 days. Three patients responded well to the therapy. No side effect was observed in any patients.

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KW-1070, a new aminoglycoside antibiotic, was studied.
The antibiotic was found to demonstrate the strong antimicrobial activity against gram-negative bacilli such as E. coli, Klebsiella, Proteus, Serratia and Entsrobacter.
The disposition of the antibiotic was investigated in male Wistar rats administered 20 mg per kg of body weight intramuscularly. Its absorption and excretion was as good as other aminoglycoside antibiotics. The tissue level of the drug was highest in kidney, followed by serum, lung and spleen, but not detected in liver.
One case of chronic purulent bronchitis complicated with pulmonary fibrosis responded slightly to KW-1070 treatment without any adverse reaction.

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Nine hematological patients as acute leukemia, aplastic anemia and multiple myeloma were treated with KW-1070, a new aminoglycoside, or in combination with other antibiotics. Maximum blood concentration measured by radioimmunoassay was about 14μg/ml when 200 mg of KW-1070 was given by one-hour drip intravenous infusion as well as by intramuscular injection. Out of 9 cases consisted of 4 cases with septicemia, 4 possible septicemia and 1 urinary tract infection, 4 cases were cured by treatment with KW-1070. Septicemin caused by Klebsiella pneumoniae in a case with acute leukemia was cured by treatment with KW-1070 and cephalothin, as Klebsiella isolated from the patient was sensitive to KW-1070 while not gentamicin or dibekacin. In none of 9 cases, any side effect snch as hearing disturbance or impaired renal function was observed.

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The in vitro antimicrobial activity of fortimicin, a new aminoglycoside antibiotic, and its absorption and elimination were studied in three subjects.
The antibiotic was found to be less active against E. coli and P. aeruginosa than gentamicin. However, it demonstrated a moderate activity against gentamicin-resistant Serratia app., as MICs of gentamicin were ≥50μg/ml, while MICs of this antibiotic were 6.3-12.5μg/ml.
The serum concentrations in three healthy volunteers after intramuscular injection of 200mg fortimicin averaged 20μg/ml at 30 min. and declined with the biological half life of 1.4 hours. Mean total amount of the antibiotic eliminated in urine within 8 hours corresponded to 62.7% of the administered dose.

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MICs of KW-1070 against 25 strains clinically isolated each of E.coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, Serratia marcescens, Proteus morganii and Pseudomonas aeruginosa were compared with those of GM, AMK and netilmicin. Antibacterial activity of KW-1070 was slightly inferior to those of aminoglycoside antibiotics. KW-1070 showed a low sensitivity against Pseudomonas aeruginosa. MIC value of 50μg/ml to netilmicin was observed in 1 strain each of E.coli and Serratia marcesens and MIC values of 6.25μg/ml and 1.56μg/ml to KW-1070 were noticed in strains of E.coli and Serratia marcescens.
Serum level of KW-1070 1 hour or 6 hours after 200mg intramuscular injection to a patient had a peak of 9.5μg/ml and 1.06μg/ml, respectively. Serum level of KW-1070 1 hour after 400 mg intramuscular injection to other patient showed a peak of 11.2μg/ml, and no cumulative effect was noted even with 400mg multiple administration (twice dialy).
Clinical effect was evaluated on these bases after 200mg intramuscular injection (twice daily); exellent in 1 and good in 4 out of 5 cases of RTI, good in 1 case of fever unknown origin, exellent in 2, good in 3 and poor in 1 out of 6 cases of UTI, and poor in 1 case of BTI.
As for side effect of the antibiotic, no abnormality as deafness was observed clinically, while abnormal laboratory values were noted as in 2 cases increased GOT and GPT.

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Five with RTI, 2 with BTI and 4 with UTI were treated with KW-1070, at a daily dose from 400mg to 600g by intramuscular injection for 5 to 25 days. Clinical response was excellent in 2, good in 4, poor in 3 and undetermined in 2 cases. Isolates organisms was eradicated in 3, persisted in 4 and obsecure in 4 cases.
No adverse effect was noted.

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KW-1070 was intramuscularly administered to 23 patients with infectious recurrence of chronic bronchitis and 2 patients with pneumonia in a daily dose of 400mg (in two divided doses) or 800mg (in two divided doses).
The patients were relatively refractory cases, 13 of them being insusceptible to previous antibacterial treatment.
Of 11 patients with chronic bronchitis who received 400mg daily, one obtained excellent response and 7 had good response with a response rate of 73%, while 3 had poor benefit. The response of the remaining 11 bronchitis patients to the 800mg regimen was good in 6 but none in 5, with a response rate of 55%. The two patients with pneumonia had good response to the 800mg regimen.
Causative organisms. including H.influenzae, Klebsiella and E.coli were eradicated after treatment, while it was in only 2 of 6 patients that Ps.aeruginosa was eradicated. These two patients had been on the 800mg regimen.
One patient had fever with eruption after a day of administration and this was the only adverse reaction observed.
The above results suggest the usefulness of the daily dose of 400 to 800 mg of KW-1070 in the treatment of recurrences of chronic respiratory tract infections regarded as relatively refractory diseases. KW-1070 seems to be a drug worthy of further evaluation.

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KW-1070, a new antibiotic aminoglycoside developed in Japan, was given to 2 patients with acute cystitis, 3 with acute pyelonephritis and 1 with pneumonia.
The daily dosage was 400 mg. The duration of administration ranged from 7.5 days to 12.5 days.
The efficacy rate was 100 percent.
Thrombocytepenia was detected in 1 patient, and an elevation in both serum GOT level and serum GPT level was detected in 1 patient. However, these side effects were all reversible, and no other side effects were observed.

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The authors reported on the results of their clinical investigations of KW-1070, a new aminoglycoside antibiotic.
1. The antibacterial activity of KW-1070 was compared to that of gentamicin (GM), amikacin (AMK) and netilmicin (NTL) in a total of 178 clinically isolated strains of S.aureus, S.faecalis, E.coli, Citrobacter, Klebsiella, Enterobacter, Serratsa, Proteus and P.aeruginosa.
Antibacterial activity of KW-1070 against E.coli, Enterobacter, Serratia, P.msrabilis, P.vulgaris and P.rettgeri was almost the same as that of AMK, while MIC of KW-1070 against S.aureus and P.aeruginosa was higher than that of GM, AMK and NTL.
2. KW-1070 was administered to a total of 14 patients, consisting of 10 cases of respiratory tract infections (RTI) and 4 cases of urinary tract infections (UTI).
The results obtained were good in 6 (60.0%) out of 10 RTI and in 3 (75.0%) out of 4 UTI cases.
No adverse reaction was observed.

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KW-1070, a new member of a series of aminoglycoside antibiotics, was applied to the treatment of five patients with respiratory infections.
The drug was administered intramuscularly, at a daily dose of 400mg-800mg six to fifteen days.
The results obtained were good in four cases, and unassessable in one case due to the lack of inflammatory symptoms. No side effects were observed.

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KW-1070, a new aminoglycoside antibiotic recently developed by Kyowa Hakko Kogyo Co., Ltd. was examined on its in vitro antibacterial activity, distribution in the body, as well as on its clinical availability. The results obtained were as follows:
1) In vitro antibacterial activity against bacteria isolated from human infection foci: As to Staphylococcus aureus, E.coli, Klebsiella spp., Serratia spp., and Proteus mirabilis strains, KW-1070 was found to be active similarly to amikacin, but somewhat less than gentamicin; although the antibiotic showed least activity against Pseudomonas aeruginosa strains among the three drugs tested.
2) Blood levels and urinary excretion rates in humans (assayed by band culture method): Four healthy volunteers received a single intramuscular injection of KW-1070 200mg. Peak of the blood level, being 10.7μg/ml on the average, was obtained one hour after the administration. Urinary excretion rates within six hours were 82. 3% on the average.
3) Distribution in rat's body: The highest concentration of KW-1070 after i. m. administration of 40mg/kg was found in kidneys, followed by serum, lung, muscles, and spleen.
4) Clinical trials: Thirteen cases with various infections (pneumonia 4, chronic bronchitis 4, U. T. I. 5), mostly having some underlying diseases, were treated with KW-1070. Eight of the cases responded at least fairly to the therapy. Neither side effects nor abnormal laboratory findings attributable to the drug were observed, except a case which showed an elevation of BUN and creatinine in blood after the therapy.

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Fundamental and clinical studies of KW-1070, a new aminoglycoside, were carried out, and the results obtained were as follows.
1) Sensitivity of clinically isolated strains to KW-1070 was tested by agar plate dilution method, and compared with that of GM, DKB and AMK. The MICs of KW-1070 against clinically isolated gram-negative rods were similar to AMK, except for P.aeruginosa and S.marcescens. The antibacterial activity of KW-1070 against P.aeruginosa was inferior to that of GM, DKB and AMK, whilu against S.marcescens, KW-1070 showed superior activity even in resistant strains to GM.
2) The serum levels of 200mg of KW-1070 with single intramuscular injection reached the peak after 30 minutes of administration and ranged from 14.0 to 16.0μg/ml with mean concentration of 15.0μg/ml.
Urinary excretion rate within 6 hours after administration was 27.3-64.2%.
3) KW-1070 was given to 2 patients with chronic respiratory infection and 1 patient with cystitis at a daily dosage of 100-200 mg×2 for 4-6 days. The clinical effect of KW-1070 was good in 2 cases and fair in one. Adverse reaction and laboratory data abnormalities were not seen throughout the patients.

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Laboratory and clinical studies were made on KW-1070, a new aminoglycoside antibiotic with the following result.
The in vitro antibacterial activity of KW-1070 against 22 standard strains and 833 routine clinical isolates including gram-positive cocci, Enterobacteriaceae glucose non-fermentative gram-negative bacilli and Haemophilus species was compared with that of gentamicin. Against most of these organisms other than Serratia marcescens, Proteus rettgeri and P.inconstans KW-1070 had comparable levels of antimicrobial activity, generally slightly less than that of gentamicin. KW-1070 had relatively weak activity against Pseudomonas aeruginosa strains. KW-1070 showed good activity against gentamicin resistant organisms other than Pseudomonas.
KW-1070 was administered intramuscularly at a dose of 200mg to four patients. The peak serum levels were 16.5-26.0μg/ml at half to one hour after injection. The level ranged from 3.2-11.0μg/ml at 6 hours.
Enterobacter cloacae in the urine of a patient with cystitis began to decrease from the initial 10⁸ cells/ml to 10³-10⁴ cells/nil for the first 6 hours after intramuscular injection of 400mg, and peak urine level was 460μg/ml in this patient.
Twenty patients with respiratory infections and three with urinary infections were treated with KW-1070 by intramuscular injection. Fourteen of the 21 patients responded satisfactorily to the treatment and the effectiveness rate was 66. 7%.
Adverse reaction was noticed in only two cases with slight elevation of S-GOT and S-GPT.

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Labcratory and clinical studies on a new aminoglycoside antibiotic KW-1070 (fortimicin) were performed, comparing the results with other aminoglycoside antibiotics (GM, AMK, TOB, KM).
The antimicrobial activities of these drugs were examined against several respiratory pathogenic organisms. The peak value of KW-1070 against Serratia marcescens was about twice that of the other aminoglycoside antibiotics. However, the antimicrobial activities of KW-1070 against Klebsiella pneumoniae, E. coli, Enterobacter, Proteus, and Pseudomonas aeruginosa were almost the same as those of the other aminoglycoside antibiotics. The peak value of KW-1070 against Pseudomonas aeruginosa was only about half that of the other aminoglycoside antibiotics.
When 50mg/kg intramuscular injections of KW-1070 were administered to rats, the tissue concentration attained the peak fifteen minutes after administration. The concentration was highest in the serum (200μg/ml), followed in descending order by the kidney, lung and liver at their peak. High level concentration in the kidney remained even four hours after administration.
When 200mg of KW-1070 were given to young women with pyelonephritis, the serum peak level was reached thirty minutes after administration (16.8μg/ml). And when 200mg intramuscular injections were administered to a patient with chronic bronchitis, the highest peak level of bronchial secretion was 10.4μg/ml two hours after administration, and the sputum peak level was 1.68μg/ml at the same time.
In the clinical study, KW-1070 was effective in 93%(13/14 cases) of the cases of respiratory infection.
Side effects of this drug were not observed in any of the cases. KW-1070 was evaluated to be very effective and safe, compared with the aminoglycoside antibiotics already in wide use.

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1) Antibacteriological activity
The antibacteriological activity of KW-1070 was slightly weaker than that of GM, but equal to that of AMK.
2) Concentrations in the serum
KW-1070 was transferred quickly in the serum. The highest consentrations were shown 30 and 60 minutes after 200 mg administration to two patients (14 and 16μg/ml, respectively).
3) Clinical results
The drug was used in 7 cases of respiratory tract infection. The efficacy was good in 6 cases and poor in 1 case.
No side effects were observed, except for a slight elevation of GOT and GPT in 1 case.

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The authors have carried out the laboratory study of KW-1070.
The results were as follows;
The sensitivity was measured by plate dilution method on 27 strains of S.aureus, 26 strains of E. coli and K. pneumoniae, 22 strains ofSerratia, 52 strains of P. aeruginosa and 8 strains of GM-resistant P. aeruginosa isolated from pediatric patients.
The distribution of sensitivity of S. aureus was 0.39-6.25μg/ml and the peak of distribution was 1.56μg/ml.
The distributions of sensitivity of E. coli and K. pneumoniae were 0.78-25μg/ml and the peaks of distribution were 3.13μg/ml and 1.56μg/ml, respectively.
The distributions of sensitivity of Serratia and P. aeruginosa were 0.39-12.5μg/ml and 6.25-100μg/ml, respectively.
The growth of 54.4% of Serratia was inhibited in concentration of less than 1.56μg/ml.
KW-1070 inhibited 5 of 8 strains of GM-resistant P. aeruginosa in concentration of 12.5 μg/ml.

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Fundamental studies were made on a new aminoglycoside antibiotic KW-1070. The MIC to this antibiotic was evaluated of 173 stains of various kinds of bacteria from clinical isolates. In the majority of organisms, it was higher by two plates than that to gentamicin. When compared with amikacin, however, an MIC was definitely lower of Serratia marcescens and almost equal of other species of bacteria. The MIC of Pseudomonas aeruginosa to KW-1070 was higher than that to amikacin.
Passage of this antibiotic into CSF was examined in experimental staphylococcal meningitis in rabbits
following a single intramuscular injection of 5 mg/kg. CSF levels were measurable in only one of six rabbits, i. e., 1.48 μg/ml (1 1/2 hr) and 1.24 μg/ml (2 hr). These findings may indicate that the passage into CSF is lower compareed with other aminoglyosides.
When the above results are taken into consideration along with the least ototoxicity compared with other aminoglycosides, KW-1070 is a new aminoglycoside antibiotic which deserves a further evaluation of clinical efficacy in children.

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A new aminoglycoside antibiotic, KW-1070 (fortimicin) was administered intramuscularly to 23 patients ; 5 with cholecystitis, 9 with acute peritonitis, 5 with infections of skin and soft tissue and 4 with acute appenditis.
Clinical response was excellent in 5 cases, good in 16 cases, fair in 1 case and poor in 1 case. Effective rate was 91.3%.
In those patients, KW-1070 in a dose of 200-300mg was given, once or twice daily for 3-13 days.
For measurement of KW-1070 concentration in various body fluids and tissues, KW-1070 at a dose of 200-300mg was administered intramuscularly before the operation to 20 patients; 3 with cholecystitis, 9 with acute peritonitis, 2 with infectious skin and soft tissue diseases and 6 with others. KW-1070 concentration was measured by bioassay method with Bacillus subtilis ATCC 6633.
In most cases, KW-1070 concentrations in infectious tissues were good, and those were higher than the MICs of KW-1070 against causative bacteria.
No adverse effect was observed.
Therefore, KW-1070 was suggested to be useful drug for the treatment of surgical infcetions.

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We have examined the antibacterial activity and the pharmacokinetics as well as the therapeutic efficacy against surgical infections of KW-1070 (fortimicin), a novel aminoglycoside antibiotic.
The antibacterial activity of KW-1070 against gram-negative bacteria was similar to that of amikacin: it was slightly more active than amikacin against S. marcescens, but less active against P. aeruginosa. KW-1070 was active against isolates of S. marcescens multiply resistant to aminoglycoside antibiotics including gentamicin.
The pharmacokinetics of KW-1070 administered intramuscularly were studied in three healthy male volunteers. Volunteers given 200mg of KW-1070 had peak serum concentration within 60 min ranging from 11.2 to 14.0μg/ml. The pharmacokinetic parameters were calculated as follows: T 1/22.08 h; Kel 0.42 h^-1; T-max 0.45 h; C-max 11.3μg/ml, Vd 14.6 1; AUC 32.1 (μg/ml) h.
The urinary excretion rate within 6h was averaged 42.3% of the dose.
Twelve out of sixteen patients with various surgical infections responded well to the treatment with mainly 200mg of KW-1070 twice a day for 7 to 14 days.
The elevation of transaminase in two cases and that of BUN in three cases were encountered during the therapy.

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Fundamental and clinical studies of KW-1070 were performed and following results were obtained.
1) Antibacterial activity
The in vitro antimicrobial activity of KW-1070 was compared with gentamicin and amikacin against 53 strains of E. coli, Klebsiella and Serratia marcescens. Against E. coli and Klebsiella KW-1070 and amikacin had comparable levels of antimicrobial activity, generally slightly less than that of gentamicin.
But against Serratia marcescens KW-1070 had the most significant activity among drugs.
2) Excretion of KW-1070 in bile
The excretion of KW-1070 in bile was examined on the patient with cholelithiasis. The peak biliary level 3.4 μg/ml was obtained by the intramuscular injection with 200mg of KW-1070. Biliary level of KW-1070 was as low as other aminoglycosides.
3) Clinical results
KW-1070 was administered to 3 patients with surgical infections and the clinical results were good in 2 cases and poor in one. No side effects could be found.

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KW-1070, a new aminoglycoside antibiotic, was given to 27 patients with various surgical infections, and the results obtained were excellent in 5 cases, good in 15, poor in 6 and unknown in 1 case. Its effectiveness rate was 76.9%. Among untoward side effects, these were included liver dysfunctions (increased GOT, GPT values) and renal dysfunction (increased BUN values). Serum and bile levels of KW-1070 and its urinary excretion were investigated in 3 healthy volunteers and 2 patients, using the thin layer cup assay method. Following a one shot intramuscular injection of either 200mg or 400mg KW-1070, the mean serum concentration showed 7.6μg/ml as peak at 30 minutes after administration of 200mg, 21.3μg/ml as peak at 30 minutes after administration of 400mg.
The mean cumulative urinary was 97.0%(200mg, i. m.) and 68.8%(400mg, i. m.). The mean biliary concentration was 4.5μg/ml as peak at 2 hours after administration of 200mg. The authors' assessment of KW-1070 is that it is an effective chemotherapeutic agent for various surgical infections.

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KW-1070 is a new aminoglycoside antibiotic showing antimicrobial activity almost equal to GM, AMK and DKB against gram positive cocci. It has a broad antimicrobial spectrum and good antimicrobial activity against gram negative bacilli similar to other aminoglycosides. It exhibits excellent activity against E. coli, Proteus, and Serratia resistant to other drugs. Another feature of KW-1070 is its low nephrotoxicity and ototoxicity compared with current aminoglycosides.
With these fundamental data as a base, KW-1070 was investigated in 7 cases of postoperative infection, and the following results were obtained.
All 7 cases showed primary diseases: 5 cases of rectal or colono cancer, 1 case of decubitus with diabetes mellitus, and 1 case of hernia of abdominal wall. Seven cases of infectious disease included 6 cases of wound infection and 1 abscess. Among 7 cases of infectious diseases, treatment was good in 5 cases, and poor in 2 cases.
KW-1070 was administered by intramuscular injections of 200mg twice a day in all cases for 5 to 23 days. The effective rate was 71.4%(5/7). In 2 cases showing no response to KW-1070, the original condition of the patient was extremely severe.
Bacteriological investigation was performed in 7 cases. Of 7 cases, 6 species including 11 strains (E. coli 3, Proteus spp. 2, Ps. aeruginosa 2, Edwardsiella tard 1, Bacteroides fragilis 2, St. e pidermidis 1) were isolated. Among 11 strains, 1 strain of Bacteroides fragilis, 1 strain of Proteus mirabilis and 1 strain of Ps. aeruginosa showed no response to KW-1070.
No adverse reactions, such as allergy, renal disturbance or hearing disturbance were observed. Considering the fact that primary diseases of 7 cases were severe, and that all cases were severe infection, KW-1070 proved its usefullness in treating postoperative infection.

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KW-1070, a new aminoglycoside antibiotic, was studied experimentally and clinically for the urinary tract infection.
The results were as follows:
1) Antibacterial activity
KW-1070 showed the excellent antibacterial activity against clinically isolated E. coli, K. pneumoniae, Proteus spp., Enterobacter spp. and S. marcescens, except that only P. aeruginosa clinically isolated, was resistant to the drug.
2) Serum concentration of KW-1070
Intramuscular injection of 200 mg and 400mg KW-1070 represented 13.2μ/ml and 23.1μg/ml at the maximum level of serum concentration respectively.
3) Clinical studies
The clinical effectiveness rate of KW-1070 for 25 patients with the chronic complicated urinary tract infection was 92.0 per cent, in which the excellent and the moderate clinical response was obtained in 12 and 11 respectively.
4) Side effects
The transient elevation of serum transaminase was noted only in 3 patients out of 25 patients, although this disappeared within a week when the intramuscular injection of KW-1070 had been over.

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