In vitro and in vivo antibacterial activity of AM-715, a new nalidixic acid (NA)-analog synthesized in the laboratory of Kyorin Pharmaceutical Co. Ltd., were examined using various species of clinical isolates.
The results are summarized as follows.
1) AM-715 showed a broad spectrum of antibacterial activity against gram-negative and gram-positive bacteria.
2) AM-715 was more active than NA, pipemidic acid (PPA) and miloxacin (MLX) against gram-negative bacteria, and especially, this compound was 4 times more active than gentamicin against Pseudomonas aeruginosa.
3) Most NA-resistant strains of bacteria were susceptible to AM-715, and cross-resistance between AM-715and NA was incomplete.
4) AM-715 displayed bactericidal action at its minimal inhibitory concentrations against various species of bacteria. Minimal bactericidal concentrations were found to be near the MICs.
5) The in vivo effectiveness of AM-715 by the oral route was greater than that of NA, PPA and MLX against systemic infections in mice with gram-negative and gram-positive bacteria.

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Experimental evaluation on AM-715, a new oral quinolinecarboxylic adid was made in vitro and in vivo. The results obtained were as follows.
1. AM-715 showed a broad antibacterial spectrum against gram-positive cocci and negative bacteria, and was confirmed having higher antimicrobial activities against species of S. aureus, S. epidermidis, S. pyogenes, E. coli, K. pneumoniae, E. cloacae, P. mirabilis, P. vulgaris, P. rettgeri, P. morganli, S. marcescens, P. aeruginosand H. influenzate.
2. Bactericidal effect of AM-715 against P. aeruginosa was stronger than those of miloxacin, pipemidic acid and nalidixic acid.
3. In vivo protecting effect of AM-715 against P. aeruginosa infection in mice was same or superior to that of miloxacin and was superior to that of pipemidic acid.

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AM-715 was evaluated microbiologically in comparison with nalidixic acid (NA), pipemidic acid (PPA) and miloxacin (MLX) and the following results were obtained.
1. AM-715 had a broad spectrum of antibacterial activity against gram-positive and gram-negative bacteria and the activity of AM-715 was higher than those of NA, PPA and MLX.
2. Distribution of susceptibility of clinically isolated strains to AM-715 was mostly superior to those of MLX, PPA and NA except for Acinetobacter cakoaceticus. The activity for Acinetobacter calcoaceticus was mostly higher in MLX and in this order of AM-715, NA, PPA.
3. Antibacterial activity for Escherichia coli, Klebsiella pneumonlae or Pseudomonas aeruginosa was not influenced by pH of culture medium, inoculum size or addition of horse serum.
4. Bactericidal effect of AM-715 was observed in the experiments using organisms such as E. coli, K. pneumoniae and P. aeruginosa.
5. Therapeutic effect on experimental infection was studied in mice. The effect of AM-715 was equal to that of MLX on infection caused by P. aeruginosa and was superior to those of MLX, PPA and NA on infections caused by E. coli, K. pneumoniae and Serratla marcescens.

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The antibacterial activity of AM-715, a new synthetic antibacterial agent, was compared with that of nalidixic acid and pipemidic acid.
The following results were obtained;
1) Against anaerobic bacteria, the antibacterial activity of AM-715 was superior to that of nalidixic acid and pipemidic acid.
AM-715 had higher antibacterial activity against anaerobic cocci, non-sporeforming gram-positive bacteria and Clostridia than pipemidic acid and nalidixic acid. While most of non-sporeforming gram-negative bacteria was resistant to AM-715.
2) AM-715 showed higher antibacterial activity in alkaline-environment than in acid-environment.

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Fifty percent growth inhibitory doses (ID₅₀) of AM-715 against bacteria were compared with its cytopathic effect on cultured Chinese hamster ovary CHO-KI, human uterus carcinoma HeLa, and mouse neuroblastoma 18 cells, to clarify the selective toxicity of the drug.
The ID₅₀s of AM-715 on Escherichia coli NIHJ JC-2 and Staphylococcus aureus NIHJ JC-1 (209P) were 0.06 and 0.25 μg/ ml, respectively. Whereas, the drug manifested less than 50% growth inhibition on the CHO-KI and HeLa cells even with 100 μg/ ml. This fact suggests that AM-715 possesses a high selective toxicity between the bacteria and the mammalian epitherial and connective tissues.
AM-715, however, showed rather high cytotoxicity against the mouse neuroblastoma 18 cell, i.e. the ID₅₀ was 5μg/ml, and 100, μg/ml, of the drug killed the cells completely. Since AM-715 does not pass through the brain-blood barrier, it may be safely used as a therapeutic agent for infectious diseases caused by either gram-positive or gramnegative bacteria unless otherwise administered per orally.

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Fundamental study on AM-715, a new chemotherapeutic agent, was carried out and following results were obtained.
1) Antibacterial activities:
The MICs of AM-715 against clinical isolated E. coli, K. pneumoniae, P.mirabilis, S. marcescens, P.aeruginosa, P.cepacia and S. aureus were examined. Range of MIC (10⁶ cells/ ml) was 0.10-3.13 μg/ ml against E. coli, 0.20-3.13μg/ ml against K. pneumoniae, 0.10-3.13 μg/ ml against P.aeruginosa, 12.5 μg/ ml against P. cepacia and 0.78-3.13 μg/ ml against S. aureus. The antibacterial activity of AM-715 was much stronger than those of nalidixic acid and pipemidic acid against E. coli, K. pneumoniae, P.mirabilis, S. marcescens, P.aeruginosa and S. aureus, and it was much stronger against nalidixic acid resistant strains and pipemidic acid resistant strains of them.
2) Plasma levels and urinary recovery rate:
AM-715 was orally given to 5 healthy male adults at a time of fasting and non-fasting in a single dose of 200 mg. At a time of fasting, the plasma levels peaked at 0.46 μg/ ml and urinary levels reached a peak of 320 μg/ ml. The urinary recovery rate during the first 8 hrs. averaged 28.3%.
At a time of non-fasting, the plasma levels peaked at 0.32 μg/ ml and urinary levels reached a peak of 206 μg/ ml. The urinary recovery rate during the first 8 hrs. averaged 19.9%.

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AM-715, 1-ethyl-6-fluoro-1, 4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid, is a new nalidixic acid analog. AM-715 has a broader spectrum and more potent antibacterial activity than other drugs of the nalidixic acid type. AM-715 had higher antibacterial activity against gram-negative bacteria including Pseudomonas aeruginosa than gentamicin (GM)
The antibacterial activity of AM-715 was little influenced by change of inoculum size or medium and the presence of metal ion, serum or sodium cholate. The activity of AM-715 was greater in alkaline medium than in acid medium. The in vitro resistance of Escherichia coli NIHJ JC-2 and P. aeruginosa IFO12689 to AM-715 was developed slower than that to nalidixic acid (NA) and pipemidic acid (PPA).
AM-715 was shown to have additive effect with GM, carbenicillin and ampicillin
The activity of AM-715 was clearly greater than that of NA, PPA, and miloxacin in systemic infection with P. aeruginosa IID1210 and ascending kidney infection with E. coli NIHJ JC-2 in mice.
When E. coli NIHJ JC-2 and P. aeruginosa V-1 were treated with AM-715, the filamcntiation and lysis of cells were observed with electron microscope and scanning electron microscope.

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Changes in fecal microflora and cecal weight were studied in mice after the oral administration of AM-715.
1. The number of aerobic and anaerobic bacteria except Enterobacteriaceae of fecal microflora, and species in Enterobacteriaceae were not changed by the daily administration of AM-715 at 50, 100 and 200mg/kg/day, twice dosing a day of 50 and 100mg/kg, thrice dosing a day of 50mg/kg for 10 days, and the recovery to normal microflora was observed within 11-20 days after cessation of administration. No appearance of resistant strains, decrease of body weight or diarrhoea in mice were observed by the oral administration of AM-715.
2. Administration of AM-715 in combination with EM, GM, CEX or CBPC showed additive effect on the fecal microflora, however the fecal microflora pattern was not affected.
3. No increase of cecal weight were observed by the oral administration of AM-715 at 100mg/kg/day for 10 days.

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Studies on the bioassay method of AM-715 in body fluid were performed and following results were obtained.
It was conceivable that the thin layer cup method, using E. coil NIHJ JC-2 as an assay organism and modified MÜLLER-HINTON Medium, was the best way for determination of AM-715 levels in body fluids. Detectable sensitivitylimit of this method for AM-715 was 0.05μg/ml.
It seemed that metabolites of AM-715 did not affect practically the bioassay of AM-715. AM-715 was stable in human serum at-40°C and in human urine at 4°C and -40°C, at least, for 15 days.

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Absorption, distribution and excretion of AM-715, a new synthetic antimicrobial agent, were examined in mice, rats, rabbits and dogs after oral administration.
1. The peak of serum levels of AM-715 appeared 0.5 to 1 hour after oral administration. The peak serum levels were 0.5 to 0.9μg/ ml in no fasted mice, rats and rabbits at a dose of 50 mg/kg, and 4.9μg/ ml in dogs at a dovse of 30mg/kg. While, the peak serum levels in fasted mice and rats were 1μg/ ml and 3μg/ ml corresponding 2 to 3 times higher than those in no fasted, respectively.
2. The urinary levels of AM-715 were more than 20μg/ ml in 6-24 hour urine in no fasted mice, rat and rabbits at a dose of 50 mg/ kg, while in dogs these were 23μg/ ml at a dose of 30 mg/ kg in 48-72 hour urine. 3.5 to 6.1 % of the dose were excreted in urine in no fasted mice, rats and rabbits, and 13.6 % in dogs for 24 hours.
3. The peak of biliary levels of AM-715 in no fasted rats at a dose of 50 mg/ kg was detected within 3 hours after oral administration, and its levels reached at 31.0μg/ ml. 2.43% of the dose were excreted in bile for 24 hours.
4. AM-715 was distributed in such tissues as lung, liver, kidney, prostate, tonsilla and sinus membrane at the same or higher than serum levels. These tissue levels in fasted mice and rats were 1.7 to 10 times and 1.4 to 4.6 times higher, respectively, than those in no fasted.

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Absorption, distribution and excretion of 1-ethyl-6-fluoro-1, 4-dihydro-4-oxo-7-(1-piperaz1ny1)-3-quinolinecarboxylic acid (AM-715) were studied in rats, mice, a dog and monkeys after oral or intravenous administration of ¹⁴C-labelled AM-715.
1. When ¹⁴C-AM-715 was administered orally to the rats, it was mainly absorbed from the duodenum, jejunum and ileum, but not from the stomach.
2. After a single oral administration of the labelled AM-715, the maximum blood levels were found in mice and rats (50 mg/kg) at 30 min, in the dog and monkeys (25 mg/kg) at 1 hr. The levels were about 1 μg/ml in mice, rats and monkeys, and about 3 μg/ml in the dog. The half-lives of blood level in mice, rats, dog and monkeys were 4.4, 3.0, 2.3 and 2.9hr, respectively.
3. In rats, the maximum levels of AM-715 in blood, urinary bladder, submaxillary gland, thymus, heart, lung, liver, pancreas, spleen, kidney and lymph nodes were higher than 1.5μg/ml or 1.5μg/g.
4. Urinary excretion in mice, rats, dog and monkeys were 6.1, 8.4, 16.6 and 17.0% of the oral dose during 4 days after a single oral administration, respectively. Biliary excretion in rats was 5.9% during 24 hr after oral adminis. tration.
5. The mean blood level in rats was 0.66μg/ml at 30 min after daily administration of ¹⁴C-AM-715 at 50 mg/kg for 21 consecutive days. The tissue levels at 24 hr after the final dose were a little higher than those after a single dose. but the level in the carcass (bone, muscle, fat and skin) was not higher than that after a single dose.

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The metabolism of l-ethyl-6-fluoro-1, 4-dihydro-4-oxo-7-(1-piperaziny1)-3-quinolinecarboxylic acid (AM-715) was studied in rats, a dog and monkeys following an oral administration of ¹⁴C-AM-715, respectively. The radioactive metabolites in the 0-24 hr urine and feces, and in the 0-8 hr bile (rats only) were analyzed by TLC, UV, mass spectrometry and HPLC.
1. Most of AM-715 orally administered was excreted in the urine and feces without receiving drug-metabolism. The portion of unchanged AM-715 was 74-85% of the excreted compounds in the urine and 83-91 % of those in the feces, irrespective of the animal species.
2. Seven metabolites were identified in the present study: 1-ethyl-6-fluoro-1, 4-dihydro-4-oxo-7-(3-oxo-1-piperazinyl)-3-quinolinecarboxylic acid (M-1); 7-(2-aminoethylamino)-1-ethyl-6-fluoro-1, 4-dihydro-4-oxo-3-quinolinecarboxylic acid (M-2); 7-(4-acetyl-1-piperaziny1)-1-ethyl-6-fluoro-1, 4-dihydro-4-oxo-3-quinolinecarboxylic acid (M-4 (1)); 1-ethyl-6-fluoro-7-(4-formy1-1-piperazinyl)-1, 4-dihydro-4-oxo-3-quinolinecarboxylic acid (M-4 (2)); 7-amino-1-ethyl-6-fluoro-1, 4-dihydro-4-oxo-3-quinolinecarboxylic acid (M-5); methyl 1-ethyl-6-fluoro-1, 4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylate (M-6); and the conjugate of AM-715.
3. AM-715 was metabolized mostly at the piperazine ring. The following metabolites were common to all of the animals: M-1, M-2, M-4 (1), M-4 (2), M-5 and the conjugate of AM-715. A metabolite unique to the rats was M-6.
4. The dog's urine and all of the animals' feces contained none of the metabolites in large quantities. The main metabolite in the rats' urine and monkeys' urine was M-1, which accounted for 12.4 % and 9.7 % of the excreted compounds in these urine, respectively.
5. The primary metabolite in the rats' bile was the methyl ester conjugate of carboxylic acid (M-6), which accounted for 57.0% of the label detected. M-6 was also found to account for 3.5% of the label in the urine of rats. This conjugation represents a novel metabolic pathway.

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The metabolism of 1-ethyl-6-fluoro-1, 4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid (AM-715), a new antimicrobial agent, was studied in man. Intact AM-715 and its metabolites in serum, urine and bile were assayed by high-performance liquid chromatography.
The serum was collected from four healthy adults dosed orally with 1, 600 mg of AM-715. In the serum, the peak level of intact AM-715 was observed about 2 hrs after administration, and its mean level was 11 μg/ml. The various metabolites found in urine were not detected even in the serum with the highest level of intact AM-715.
The urine was collected from four healthy adults dosed orally with 1, 600 mg and three healthy adults with 200 mg. In the urine, the mean peak concentration of intact AM-715 was 130 and 450 μg/ml at doses of 200 and 1, 600 mg, respectively. Almost the same pattern of metabolites was observed at doses of 200 and 1, 600 mg. About 80% of urinary excretion was intact AM-715. Urinary excretion of the main metabolite-M-1 was 1/5 of that of intact AM-715, that of M-2 was 1/5 of M-1, and those of the other metabolites M-3, M-4 and M-5 were less than 1/3 of M-2. The total recovery rate within 24 hours was about 30% of the dose at two doses. AM-715 and its metabolites found in the urine were unconjugated form.
In the bile collected from a patient administered orally with 200 mg of AM-715, the metabolite distribution was similar to one in the urine.

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AM-715, a new quinolinecarboxylic acid derivative, was administered orally to totally twenty five healthy adult male volunteers to study the safety, absorption and excretion of AM-715.
1. In single administration studies, AM-715 of 100 (5 men), 200 (5 men), 400 (5 men), 800 (3 men) and 1, 600 mg (4 men) were administered at 3 hours after breakfast.
In multiple administration studies, 3 men received 200 mg of AM-715 at every 8 hours in all 22 times for a week.
No side effects and remarkable adverse reactions could be observed and nor also abnormal laboratory data were noted during period of administration.
2. In single administration studies, serum levels of AM-715 attained to the maximum within 2 hours after oral administration.
The mean values of C_max and AUC (area under the curve) showed the dose response curve from 100 to 800 mg dose group, but in 1, 600 mg dose group, these values were higher rather than those estimated from the above relationship.
A half-life of AM-715 was 4-5 hours, not depending on the dose from 100 to 800 mg, but the mean half-life was 6 hours in 1, 600 mg dose group.
The urinary excretion ratio were 33-48% for 24 hours and did not depend on the dose from 100 to 1, 600 mg.
3. In the case of multiple administration studies, there were no significant changes in the serum concentration at 2 hours following the first, the second, 10th and the last administration.
Any significant changes between the half-life after the first and the last administration were not observed. Therefore, the trend of accumulation of AM-715 was not pharmacokinetically demonstrated.

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Experimental and clinical evaluations on AM-715, a new quinolinecarboxylic acid derivative, were carried out, and the followig results were obtained.
1. Antibacterial acitivities (MICs) of AM-715 and MLX were determined by the standard method of the Japanese Society for Chemotherapy against each 30 strains of E. coli, Klebsiella and indole postitive Proteus and 45 strains of P. aeruginosa isolated from clinical materials. MICs of AM-715 were 2-4 folds superior to those of MLX with both inoculum size of 10⁶ and 10⁸ cells/ml. Especially, MIC of AM-715 against P. aeruginosa was lower than 1/10 of that of MLX. No cross resistance between AM-715 and MLX was observed.
2. Serum concentration and urinary recovery of AM-715 were evaluated following an oral administration of 200mg to 4 patients at fasting. Bioassay of the concentration was performed by the disc method using E. coli NIHJJC-2 as the test orgnism. Peak of serum concentration was obtained at 2 hours after administration, although a little variation was observed. In one case, serum concentration was less that the assay limit. Mean urinary recovery within 8 hours was 15.4% of the dose.
3. Clinical efficacy of AM-715 in 41 cases of infectious diseases was evaluated. AM-715 was effective in 7 of 12 cases of respiratory tract infections, in 23 of 27 cases of urinary tract infections and in 2 of 2 cases of intestinal infections. As a whole, AM-715 was effective in 32 of 41 cases (78.1%). Eradication of bacteria was noted in 25 of 31 cases (80.7%). Especially, AM-715 was clinically and bacteriologically effective in all of 19 cases of actue cystitis.
4. Two cases complained of gastrointestinal disturbance, which disappeared after withdrawal of administration. No abnormal results were obtained in laboratory findings.
High efficacy rate of AM-715 in urinary tract infections was noticed.

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The clinical efficacy of a new synthetic antimicrobial agent, AM-715, was studied in the field of internal medicine, and the following results were obtained.
1) Clinical effect
In the treatment of 20 cases with respiratory tract infections, the clinical responses were excellent in 4 cases, good in 12 cases, fair in 2 cases and poor in 2 cases. The clinical effectiveness rate was 80%.
In the treatment of 41 cases with urinary tract infections (UTI), the responses were excellent in 23 cases, good in 16 cases and poor in 2 cases. The clinical effectiveness rate for the UTI cases was 95%.
In the treatment of one case with biliary tract infection and of one case with liver abscess, the response was goodin both cases.
2) Bacteriological effect
As the causative bacteria of the present cases with UTI, E. coli was most frequently isolated (23 strains). Five strains of P. mirabilis, 4 strains of K. pneumoniae, and a few strains of causative bacteria were also isolated. These were completely eliminated in 39 cases, decreased in one case and unchanged in one case, respectively, after the treatment with AM-715.
3) Side effect
The incidence of side effect was low. Dizziness was occurred in one case, and slight elevation of BUN was observed in 2 cases.
AM-715 was considered to be a useful antimicrobial agent for the treatment of mild infections in the field of internal medicine.

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Antimicrobial activity of AM-715, which is a new quinoline derivative structually related to nalidixic acid, against clinical isolates of Staphylococcus aureus was examined and compared with that of β-lactam antibiotics. Against these isolates of Staphylococci, CER was shown to be most effective among antimicrobial agents tested, followed by MCIPC and AM-715. AM-715 inhibited all the strains tested at a narrow range of the concentrations ranging from 0.2 to 6.25 μg/ ml, while β-lactam antibiotics need higher concentrations, 25 μg/ ml or more, for the inhibition of all of these strains.
Eight patients with acute bronchitis, mild or moderate in severity, were treated with oral administration of 600mg a day of AM-715. Of these patients, seven were associated with underlying diseases; one with healed pulmonary tuberculosis, one with chronic pulmonary emphysema, one with bronchiectasis, one with cerebral vascular disorder and three with lung cancer. For these patients AM-715 was given for five to ten days. An excellent and a good clinical response was obtained in three and five patients respectively. No adverse symptom and sign was noted during adminstration of AM-715.

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Laboratory and clinical investigation of AM-715 were performed and results obtained were as follows.
1) Susceptibility of clinically isolated strains to AM-715 was tested by the agar plate dilution method and compared with susceptibility to several antibiotics. The MIC₇₅ values of AM-715 for H. influenzae, P. aeruginosa, Klebsiella, E. coli, Serratia, and Enterobacter were between 0.025 to 0.05, 3.13 to 6.25, 0.05 to 0.1, 0.05 to 0.1, 0.78 to 1.56, and 0.05 to 0.1 μg/ml, respectively.
2) AM-715 was applied to 3 patients with respiratory tract infection and 7 patients with urinary tract infection. Good responses were obtained in 1 patient with respiratory tract infection and 5 patients with urinary tract infection. Especially, AM-715 was clearly effective to urinary tract infection due to Proteus group. As side effect, nausea and dizziness were noted in one case, but no abnormality in laboratory findings was noted.

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Clinical investigations were performed on AM-715, a new nalidixic acid derivative.
AM-715 was administered to total of 24 cases with respiratory tract infections consisting of 6 cases of pneumonia and 18 cases of acute bronchitis, at daily doses of 600mg for 7 days by oral route.
Clinical response of AM-715 was excellent in 13 cases, good in 6 cases, fair in 2 cases, poor in 2 cases and unknown in one case.
Side effects with AM-715 were observed in 3 cases consisting of each one of exanthema, dizziness and loose passage.

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AM-715 is a new oral antibacterial agent of quinolinecarboxylic acid derivative possessing a chemical structure that resembles to pipemidic acid.
AM-715 was orally administrated to seven attacks of six patients with urinary tract infection and five attacks of four patients with lower respiratory tract infection. These patients received the drug for 3 to 112days in doses of 200 to 300mg per day. Nine attacks of these ten patients responded well in the therapy. None of these patients recognized the side effect for AM-715.

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AM-715 was administered to 15 cases consisting of 2 cases with asymptomatic bacteriuria, 8 cases with cystitis, 2 cases with chronic urinary tract infection and 3 cases with pyelonephritis. Efficacy was evaluated to be good in 12 cases, poor in 2 cases and undetermined in 1 case. AM-715 was effective in 12 out of 14 cases in total for a rate of effectiveness of 85.7%.
No distinct side effect was observed.

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Clinical efficacy and safety of AM-715, a new oral synthetic agent, were evaluated in 10 patients with urinary tract infections.
1. AM-715 was administered in a daily dose level of 600mg t.i.d. for a duration of 5 to 43 days. Clinical efficacy was excellent in 3 cases with acute pyelonephritis, good in one case with chronic pyelonephritis. In 6 cases with chronic cystitis, clinical efficacy was excellent in 2 cases, good in 3 cases and poor in one case, respectively.
2. Bacteriological responses against isolated organisms from 7 cases were determined. Excepting Enterobacter from one case, all of the clinical isolates including P. aeruginosa from 3 cases, E. coli from 2 cases and S. marcescens from one case were eradicated.
3. No side effect was observed in subjective symptoms. Slight elevations of GOT, GPT and Al-P in one case and slight elevation of GPT in one case were respectively observed after the medication.

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Studies on AM-715, a new quinolinecarboxylic acid derivative, were carried out with respect to its antibacterial activity, absorption, excretion and clinical efficacy, and the following results were obtained.
1. AM-715 was more potent than PPA and MLX in antibacterial activity against E. coil, K. pneumoniae, P. aeruginosa, P. mirabilis and Iindole positive
Proteus, except S. marcescens.
2. Peak serum concentration of AM-715 in healthy adult volunteer was 1.14 μg/ml at 1 hour after a single oral dose of 200mg. The half life of AM-715 in serum was found to be 2.74 hours.
Peak urinary concentration of AM-715 in above examination was 348 μg/ml at 0-2 hours after administration and was still over 100μg/ml at hours. Urinary recovery rate was 42.6% within 8 hours.
3. Serum concentration of AM-715 in aged volunteer reached the peak of 1.29μg/ml at 2 hours after a single oral dose of 200mg and maintained longer than that in healthy adult volunteer. Urinary concentration of AM-715 in above examination reached the peak of 148.6μg/ml at 2-4 hours. Uninary recovery rate was 16.4% within 8 hours.
4. Clinical efficacy rate in 15 cases with urinary tract infection was 84.6%, but it was 0% in 3 cases with respiratory tract infections.
5. As to the untoward reactions of AM-715, nausea was observed in one case, but no abnormality in laboratory findings was observed.

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AM-715, a newly developed oral antibacterial agent, was evaluated experimentally and clinically for 30 patients with various infectious diseases, and results were as follows.
1. Antibacterial activities of AM-715 against clinically isolated strains of Staphylococcus aureus, Streptococcus pneumonlae, Haemophllus influenzae, Escherlchta colt, Klebsiella pneumonia., Serratla marcescens, Proteus mirabilis and Proteus vulgaris were higher than those of miloxacin. Antibacterial activity of AM-715 against Pseutlomonai aeruginosa was superior to that of gentamicin.
2. Mean serum concentrations of AM-715 reached to the peak levels of 1.1μg/ml and 1.9μg/ml at one hour after an oral administration of 200mg and 400mg at fasting to respective three healthy males. They decreased to 0.6μg/ml and 0.9μg/ml at 4 hours after and to 0.4μg/ml and 0.5μg/ml at 8 hours after the administration, respectively. Urinary recovery rate was 14.0% within 8 hours after the administration in both dose groups.
3. Transfer of AM-715 into sputum was tested in 4 cases with chronic respiratory tract infection after an oral administration of 200mg. Excepting one case, AM-715 could not be detected in sputum.
4. AM-715 was administered to 21 cases with respiratory tract infection (R.T.I.), 7 cases with urinary tract infection (U. T. I.) and 2 cases with intestinal tract infection (I. T. I). Daily dose of AM-715 was 600mg in most of the cases. AM-715 was effective in 12 cases out of 13 cases with acute R. T. I., and the causative organisms identified in 7 cases were eradicated in 4 cases. In 8 cases with chronic R. T. I., AM-715 was effective in one case, fairly effective in 3 cases and ineffective in 4 cases. Eradication of bacteria was observed in 2 cases. AM-715 was effective for all of 7 cases with U.T.I., and eradication was observed in 6 cases. AM-715 was also effective for 2 cases with I. T. I.
5. Side effect was observed in 2 cases who complained of anorexia. In the clinical laboratory tests, elevations of GPT and Al-P were observed in one case.
It was considered from above results that AM-715 was useful as an oral antibacterial agent.

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2 patients with acute bronchitis, I with chronic cholangitis, 15 with UTI were treated with AM-715, ranging from 300mg to 600mg in daily doses for 5 to 15 days.
Clinical response was excellent in 7, good in 6, fair in 1 and poor in 4 patients. Bacterial effect was eradicated in 10, supressed in 2, persisted in 3. One patient complained of a transient dizziness. No significant adverse effect was noted in laboratory examination.

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A clinical study on AM-715, a new antibacterial agent, was carried out and the following results were obtained. Four cases of bronchiectasis, 2 cases of pneumonia with lung cancer and each one case of acute tonsillitis, middle lobe Twenty-five cases of various respiratory tract infections (including 8 cases of acute pneumoia, 8 cases of bronchitis, syndrome and diffuse panbronchiolitis) were treated orally with the daily doses of 0.3-0.8g of AM-715 dividing 3-4 times, for a duration of 5-25 days.
The clinical response to patients was excellent in one case with acute bronchitis, good in fifteen cases with acute pneumonia (6), acute bronchitis (2), chronic bronchitis (4), bronchiectasis (2) and acute tonsillitis (1), fair in two cases with bronchiectasis (1) and middle lobe syndrome (1) and poor in seven cases. No side effects were noted. According to these results, AM-715 was evaluated to be a useful antibacterial agent on various respiratory tract infections.

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AM-715, a new synthetic antibacterial agent, was orally administered to 31 cases with chronic recrudescent bronchitis in a dose of 600mg tid. for a duration of 7-14days, and following results were obtained.
1) The clinical efficacy was excellent in 2 cases, good in 21 cases and poor in 8 cases, the efficacy rate was 74%.
2) It was noted that AM-715 was effective in 11 cases (68%) of 16 cases who did not respond previously to various antibiotics.
3) Bacteriologically, causative organisms in sputum were detected in 10 of 31 cases. In these cases, each 2 strains of S. aureus, H. influenzae and E. coil and one strain of P. aeruginosa were eradicated, one strain of Serratia was decreased, and K. pneumoniae, E. cloacae were remained unchanged after the administration of AM-715, thus the rate of eradication was 70%.
4) As side effects, 2 cases of gastric discomfort and each one case of anorexia and rash were observed. In one case, a slight elevation of GPT from 24 to 48 was observed on clinical examination.

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AM-715, a new derivative of quinolinecarboxylic acid, was used for the treatment of 7 aged patients with chronic urinary tract infections. The infections were complicated by indwelling catheters, underlying B. P. H. and neurogenic bladder. AM-715 was given orally in a dose of 200mg two times a day for 6 patients and of 100mg four times a day for 1 patient for 5 to 12 days. Excellent response was observed in 2 cases, good in 3 cases, fair in 1 case and poor in 1 case. It is remarkable that Enterococcal infection and γ-Streptococcal infection were eradicated by the AM-715 treatment.
No adverse reaction was noted.

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Basic and clinical studies were made on a new quinolinecarboxylic acid derivative, AM-715, which has higher antimicrobial activity aginst GNR including P. aeruginosa than those of NA and PPA. The results obtained were as follows.
1) Antimicrobial activities of AM-715 against clinical isolates such as S. aureus, S. epidermidis, S. faecalis, Citrobacter freundii, Klebsiella pneumoniae, Enterobacter cloacae, Proteus spp., Haemophilus parainfluenzae and P. aeruginosa were higher than those of TO-133, NA, PPA and MLX.
2) AM-715 was administered to the total of 107 patients including 21 cases with UTI underlying various basic diseases, 32 cases with pyelonephritis or cystitis, 27 cases with intestinal infections or cholecystitis and 27 cases with respiratory tract infections. The overall clinical efficacy was excellent in 8 cases, good in 78 cases, fair in 6 cases and poor in 15 cases, the efficacy rate being 80.4%.
3) As side effects, epigastralgia in 2, eosinophilia in 4, elevation of GOT and GPT in 4 and elevation of BUN and serum creatinine in 1 case were noted.

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Antibacterial activity and clinical effect of AM-715 were evaluated and the following results were obtained.
1) The MICs of AM-715 against species of E. coil, Klebsiella pneumoniae, Proteus mirabilis, Serratia marcescens, Pseudomonas aeruginosa were superior to those of MLX, PPA, PA and NA. The MIC of AM-715 against Pseudomonas cepacia was only inferior to that of MLX.
2) AM-715 was administered to 24 patients with several underlying diseases in the field of internal medicine. As the results, clinical response to AM-715 was excellent in 11, good in 7, fair in 3 and poor in 3 cases, and the total efficacy rate was 75.0%.
3) Side effects were observed in 2 cases: eruption in one case and gastrointestinal disorder in one case as the subjective symptoms. As the results of laboratory findings, elevation of GOT and OPT in one case and elevation of BUN and creatinine values in one case were found. Increase of eosinophile was found in one case hematologically.

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A new antibacterial drug, AM-715, was administered for 5-11 days at daily doses of 400-800mg to 22 patients, including 11 cases of acute cystitis, 6 of acute pyelonephritis, 3 of chronic pyelonephritis and 2 of acute bronchitis.
The results obtained were effective in 8 cases and ineffective in 3 cases of acute cystitis, effective in all cases of pyelonephritis, effective in 1 case and ineffective in 2 cases of chronic pyelonephritis and effective in all cases acute bronchitis.
Side effects observed were elevation of S- GOT and S- GPT in 1 case, decrease in WBC counts in 1 case and skin eruption in 1 case of 22 cases.

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The studies on antibacterial activity, absorption, excretion and clinical efficacy of AM-715 were perfomed, and following results were obtained.
1) Antibacterial activity: AM-715 showed an excellent antibacterial activity against gram-negative bacilli. About 80% of clinically isolated strains of E. coil, K. pneumonicte and P. mirabilis were completely inhibited in growth by 0.5-0.1μg/ml of AM-715, while the MIC of AM-715 against clinically isolated P. aeruginosa ranged from 0.39μg/ml to 3.13μg/ml.
2) Serum levels and urinary excretion: AM-715 was orally administered in a dose of 200mg to three healthy males at fasting. The peak of serum levels was attained at 1 hr-2 hrs after administration, and mean of the peak levels was 0.96μg/ml. Serum half life of AM-715 was about 2 hrs, but 0.16μg/ml of serum level was still noted 6 hrs after administration. The mean urinary recovery was 30.5% in 6 hrs after administration.
3) Clinical results: Clinical study on AM-715 was performed in two groups of patients mostly with acute simple cystitis. Daily dose of AM-715 was 100mg once before sleep in one group and 150mg t.i.d. in the other group, respectively. Of 10 cases in the former group, clinical efficacy was excellent in 5 cases, good in 3 cases and poor in 2 cases. Of 13 cases in the latter group, it was excellent in 5 cases, good in 6 cases and poor in 2 cases. No significant difference was observed between both groups in the clinical results. This might be due to excellent MIC (0.05 to 0.39μg/ml) of AM-715 against causative organisms and high ratio (200 to 960) of urine levels/MIC. No adverse reactions were observed, and no abnormality in laboratory findings was observed.

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AM-715 was administered to 18 patients who consist of ten cases with respiratory tract infection, one with biliary tract infection and seven with urinary tract infection. The following results were obtained:
1. Clinical response to AM-715 was excellent in 4 cases, good in 7, fair in 4, poor in 2 and unknown in 1. The clinical efficacy rate was 64.7% in 17 cases excluding 1 case with mycoplasma pneumonia (“unknown”).
2. Clinical efficacy in groups at daily doses of 300mg and 600mg was “excellent” or “good” in 5 out of 8 cases (62.5%) and in 6 out of 9 cases (66.7%), respectively. No significant difference in efficacy was observed between the two groups.
3. No subjective side effect was observed. In 3 cases, there were changes in laboratory findings such as reduced eosinoplails, anemia and transient elevation of transaminase. It could not be determined whether these were due to the administration of AM-715 because of the concomitant treatment with other drugs.

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The authors report the results of clinical investigations of AM-715, a new compound of quinolinecarboxylic acid.
The antibacterial activity of AM-715 was compared with those of nalidixic acid (NA) and pipemidic acid (PPA) in a total of 178 clinically isolated strains of S. aureus, S. faecalis, E. coli, Citrobacter, K. pneumoniae, Enterobacter, S. marcescens, Proteus and P. aeruginosa.
AM-715 exhibited far greater antibacterial activity against all of above strains, than did NA or PPA.
AM-715 was then administered to a total of 23 patients, among whom there were 16 cases of respiratory tract infections (RTI), 7 cases of urinary tract infections (UTI).
The results obtained were good in 10 (62.5%) out of 16 RTI cases, and excellent and good in 6 (85.7%) out of 7 UTI cases.
As a side effect, one patient complained of nausea and anorexia, then it was necessary to discontinue the AM-715 administration, no additional adverse reaction was noted.

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AM-715, a newly synthesized quinolinecarboxylic acid derivative, was examined on its antibacterial activity against clinical isolates and on its absorption in human. Some clinical trials were also carried out.
1) AM-715 showed the highest activity against clinical isolates including E. coil, Klebsiella, Proteus, Serratia, Eneterodacter, Citrobacter and Pseudomonas aeruginosa among the tested drugs, i. e. nalidixic acid, piromidic acid and pipemidic acid.
2) The peak blood level of AM-715, 0.25-0.46μg/ml, was observed at 1-2 hours after its oral administration of 200mg to four) healthy volunteers. The urinary recovery rate was 41.2% on average in 6 hours.
3) Nineteen patients of respiratory, urinary or biliary tract infection were treated with AM-715 for 4-5 days (100-200 mg p.o. after meal, 3 or 4 times/ day). Favourable results were obtained in fifteen of those patients.
Neither side effects nor abnormal laboratory findings were observed in the patients treated with AM-715, except for one who complained of nausea after three-day administration.

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Fundamental and clinical studies of AM-715, a new quinolinecarboxylic acid derivative, were carried out and the results obtained were as follows.
1) Sensitivities of clinically isolated strains to AM-715 were tested by agar plate dilution method and cornpared with that of nalidixic acid (NA) and miloxacin (MLX). The MICs of AM-715 against Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and Pseudomonas aeruginosa were superior to those of NA and MLX. The antibacterial activity of AM-715 against Pseudomonas aeruginosa was almost equal to gentamicin. The MICs of AM-715 against Serratta marcescens, Acinetobacter and Pseudomonas cepacia were inferior to those of MLX
2) The serum levels of AM-715 at 1 or 2 hours after 100 and 200 mg of oral administration prior to breakfast reached the peak and ranged from 0.53 to 0.70 (mean 0.61)μg/ml and 0.33 to 1.56 (mean 0.83) μg/ml respectively. And the urinary excretion rate up to 7 hours after administration ranged from 3.1 to 14.4%.
3) Eleven patients with respiratory infections and 1 patient with cystitis were given 200mg of AM-715 three times a day at a duration of 7-15 days. The efficacy of the drug was evaluated in 11 patients. It was good in 5 cases, fairly good in 5 cases and poor in 1 case. No side effects or abnormalities in laboratory findings were observed in any cases.
The results obtained suggest that AM-715 is a useful antibacterial agent.

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The MIC of AM-715 was determined against 61 strains of clincially isolated S. typhi, and then compared with those of chloramphenicol, ampicillin, nalidixic acid, piromidic acid, pipemidic acid and miloxacin in inoculum size of 10⁶ cells/ ml. The antimicrobial potency of AM-715 was much greater than those of other antibacterial agents tested.
AM-715 was administered to 7 cases of typhoid fever, 4 cases of asymptomatic fecal excretor of S. typhi, one case of asymptomatic fecal excretor of S. paratyphi B with gall stones and 6 cases of salmonellosis other than typhoid fever.
Daily dosis of AM-715 to the typhoid fever were 800 mg to 2 cases, 1, 200 mg to 2 cases and 1, 600 mg to remaining 3 cases respectively. The cases which were treated with the daily dosis of 1, 600 mg were completely cured after the 14 days medication. In the cases of the daily dosis of 800 mg, clinical effect was not observed. In the cases of the daily dosis of 1, 200 mg, clinical response was observed good in one case, and poor in another case.
To the asymptomatic fecal excretor of S. typhi and S. paratyphi B, daily dosis of 1, 200 mg of AM-715 were administered for over two weeks. But the boy of 12 years old was medicated with the daily dosis of 800 mg of the drug. The eradication of the bacilli was succeeded in all cases.
To the salmonellosis other than typhoid fever, AM-715 was administered with the daily dosis of 1, 200mg for a week. All cases were cured and the bacilli in their feces were disappeared.
No adverse reaction was observed with the exception of a slight elevation of the serum bilirubin value in one case.

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Clinical effectiveness of AM-715, a new quinolinecarboxylic acid derivative, was studied in 20 cases of adult infections. These infections consisted of 14 cases of acute urinary tract infection and 6 cases of acute or chronic respi. ratory tract infection. AM-715 was given to the patients 200-400mg/ day orally (mostly 300-400mg/day). Clinical effectiveness was evaluated after the administration for about 7 days. The cumulative efficacy including clinical effect and bacteriological effect was evaluated in 10 out of 12 cases (83%). Excellent result was obtained in 5, good in 5, and poor in 2 cases. Side effects such as epigastralgia and soft stool were noted in 2 cases. However, there was no serious adverse reaction in our study. It is concluded that AM-715 might be effective in rather mild cases of respiratory or urinary tract infections.

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Laboratory and clinical studies on AM-715, a new antimicrobial agent, were carried out and the results were as follows:
1) Antibacterial activity:
Minimum inhibitory concentrations (MICs) of AM-715 against a total of 564 strains isolated from various specimens (Escherichia coli 54, Citrobacter freundii 54, Klebsiella aerogenes 54, Enterobacter cloacae 52, Enterobacter aerogenes 54, Serratia marcescens 54, Proteus vulgaris 54, Proteus mirabilis 54, Proteus rettgeri 27, Proteus inconstans 27, Morganella morganii 26, Pseudomonas aeruginosa 54) were compared with those of nalidixic acid (NA). MICs of AM-715 against clinical isolates were 4-7 times lower than those of NA in general.
MICs of AM-715 against Mycoplasma pneumoniae (2 standard strains, FH and MaC, 5 strains of clinical isoltaes) were 5-10μg/ml.
2) Serum and sputum levels in chronic respiratory infections:
Two patients with chronic bronchitis were given 200 mg of AM-715 orally after breakfast. The peak serum levels were 1.27μg/ml 4 hours and 1.40μg/ml 2 hours after administration, and the peak sputum levels were 0.56μg/ml 4-5 hours and 0.97μg/ml 3-4 hours after administration, respectively.
3) Clinical result:
Clinical cases with respiratory infections (Acute bronchitis 1, Pneumonia 5, Bronchiectasis 4, Chronic bronchitis 6, Others 2) were given 600mg of AM-715 daily for 5-21 days. Over all efficacy rate was 43.8% (7/16)(excellent 0, good 7, fair 8, poor 1, not evaluable 2).
Hematological biological data and renal and hepatic functions were checked up before and after administration of AM-715. Raised GOT and GPT was observed in one patient, but the value of GOT and GPT became normal immediately after discontinuation of the drug. One patient complained of dizziness 9 days after administration, and this symptom subsided two weeks after discontinuation of the drug.

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Laboratory and clinical studies on AM-715, a new nalidixic acid analogue, were performed and the following results were obtained.
1. Antibacterial activity of AM-715 against respiratory pathogenic isolates from sputum was assayed. The peak values of MIC were as follows: 0.1μg/ml against Haemphilus influenzae, 0.05μg/ml against E. coli, 0.1μg/ml against Klebsiella pneumoniae, 0.39μg/ml against Pseudomonas aeruginosa and 0.1μg/ml against Enterobacter sp. These MIC values were superior to those of PA, PPA and MLX. Especially antibacterial activity of AM-715 against H. influenzae was higher than that of ampicillin.
2. As the results of the administration to a patient with doses of 200mg and 100mg, the peak levels of AM-715 in serum were 0.28μg/ml and 0.22μg/ml, respectively. The urinary recovery rate was 14.6% within 6 hours in these patients.
3. As the results of experimental administration to one patient with CPE and another one with chronic bronchiolitis at the dose of 200mg of AM-715, peak levels of AM-715 in sputum were 0.37μg/ml and 0.32μg/ml, respectively.
4. Above 2 cases were treated with daily dose of AM-715 of 600mg for 6-9 days, and the concentrations of AM-715 in sputum excreted in whole periods were assayed. The frequency of higher levels than 0.1μg/ml was 81% in the patients with CPE and 40% in the patients with chronic bronchiolitis, respectively.
5. Eleven cases of respiratory tract infections (RTI) and 10 cases of urinary tract infections (UTI) were treated at daily doses of AM-715 of 300-800mg tid. Clinical efficacy rate was 57% in RTI caused by H. influenzae and 80% in chronic brochitis. Total efficacy rate was 45 % for RTI and 100% for UTI.
6. Slight elevation of GOT and GPT was observed in 2 cases out of 21 cases.
It was concluded that AM-715 was an useful synthetic oral antibacterial agent for the treatment not only of UTI but also of RTI.

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Laboratory and clinical studies on AM-715, a new antibacterial agent, were carried out and the following results were obtained.
1) Antibacterial activity
In vitro antibacterial activities of AM-715 against 54 strains of S. aureus, 52 strains of E. coli, 47 strains of K. pneumoniae, 51 strains of P. aeruginosa, 54 strains of S. marcescens, 50 strains of E. cloacae, 26 strains of P. mirabilis and 27 strains of P. morganii were much stronger than those of nalidixic acid.
2) Serum levels:
AM-715 was orally given to 5 healthy male volunteers at a time of fasting in a single dose of 200mg. The peak of mean serum level of AM-715 was 1.56μg/ml at 1-2 hours after the oral administration.
3) Clinical results:
AM-715 was administered to 15 cases of respiratory tract infections and 1 case of cystitis at daily doses of 300-600mg t.i.d. for 4-41 days. The clinical response for the cases of respiratory tract infections was excellent in 2 cases, good in 7 cases, fair in 3 cases and poor in 3 cases. Good response was observed in one case of cystitis.
4) Side effect:
Side effect was observed in only one case as slight dull feeling of stomach.

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Laboratory and clinical studies were performed on AM-715, a new quinolinecarboxylic acid derivative, and results were as follows.
1) Antimicrobial activities
MICs of AM-715 against various clinical isolates were determined. With the inoculum size of 10⁸ cells/ml percentages of strains susceptible to 12.5 μg/ml or less were S. aureus 96%, S. epidermidis 100%, S. faecalis 77 %, E. coli 97%, Klebsiella sp. and Enterobacter sp. 100%, S. marcescens 91 %, Proteus sp., Citrobacter sp., Salmonella sp. and Shigella sp. 100%, P. aeruginosa 94%. With the inoculum size of 10⁶ cells/ml, all strains were susceptible to 6.25 μg/mi or less, expect 1 strain of S. marcescens and 2 strains of P. aeruginosa.
1) Clinical efficacy
12 patients with acute cystitis, 3 with chronic cystitis, 2 with acute pyelonephritis, and 1 with chronic pyelonephritis were treated with AM-715 in daily doses of 300-800 mg for 3-39 days. Clinical response was excellent in 8, good in 7, fair in 3 patients. Bacterial effects were very good in 12, fair in 1, unknown in 5 patients. Superinfections with S. faecalis or Candida were seen in 2 cases. No side effect was noticed and there was no change in laboratory findings.

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AM-715. an antibacterial agent of quinolinccarboxylic acid derivative, was studied experimentally and clinically. The results were as follows:
1) In vitro antibacterial activities.
The MICs of AM-715 against clinically isolated strains of gram negative bacteria were determined. About 60% of the strains of E. coil were inhibited by 0.39μg/ml or less concentration of AM-715. All of the strains of K. pneumoniae were inhibited by 0.39μg/ml-6.25μg/ml. The MIC distribution against Proteus spp. showed two peaks (inoeulum size: 10⁸cells/ml) and three peaks (10⁶cells/ml), respectively, within 0.39μg/ml-12.5μg/ml. Although about 60%-of the stains of Enterobacter spp. were inhibited by 1.56μg/ml or less concentration of AM-715, the MIC for 16%-20% of the strains were located at 50μg/ml and 100μg/ml. The MIC of AM-715 was more than 100μg/ml in 32%-36% of the strains of S. marcescens. All of the strains of P. aeruginosa were inhibited by 12.5μg/ml or less, and 40%-44% of the strains were inhibited by 3.13μg/ml of AM-715. Thus, AM-715 showed excellent antibacterial activities against clinically isolated strains of E. coli, K. pneumoniae, Proteus spp. and P. aeruginosa. In particular, the antibacterial activity against P. aeruginosa was remarkable as seen from its low MIC. The antibacterial activities against Enterobacter spp. and S. marcescens, however, were somewhat inferior to those against the other bacteria.
2) Clinical studies.
Nine patients with acute simple cystitis (ASC) and 10 patients with chronic complicated cystitis (CCC) orally treated with AM-715, 300mg daily for ASC cases and 300mg-600mg daily for CCC cases, respectively. All of 9 cases of ASC showed the excellent clinical response after the treatment with AM-715 for 3 days (effectiveness rate 100%). Clinical efficacy was evaluated in 7 cases with CCC according to the criteria for clinical evaluation in complicated U. T. I., and the response was excellent in 2 cases and good in 4 cases (effectiveness rate 85.7%).
As side effects, 3 patients had diarrhea elicited by AM-715. They became well however, with the usual therapy without discontinuation of oral administration of AM-715.

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AM-715 was orally given to 18 patients with urinary tract infections at daily dosage of 300-600 mg divided 3 times a day for a duration of 3-5 days.
1. Clinical efficacy of AM-715 in acute cystitis and pyelonephritis was excellent in 1 case and moderate in 3 cases, and the effectiveness rate was 100%.
2. Clinical efficacy of AM-715 in complicated urinary tract infections was excellent in 4 cases, moderate in 9 cases and poor in 1 case, the effectiveness rate was 92.8%.
3. Bacteriological response for 18 strains isolated was observed eliminated in 11 strains, decreased in 4 strains, unchanged in 1 strain and replaced in 2 strains.
4. No side effect was observed.

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AM-715, a new quinoline derivative, was administered to 24 cases with complicated urinary tract infections at daily dosis of 600 mg and 900 mg, and the following results were obtained.
1) Clinical efficacy for the group of 13 cases treated with a dosage of 600 mg was excellent in 2 cases, good in 3 cases and poor in 8 cases, and the efficacy rate was 38.5%.
2) Clinical efficacy for the group of 11 cases treated with the dosage of 900 mg was good in 3 cases and poor in 8 cases, and the efficacy rate was 27.3%.
3) No side effect or abnormality in the clinical laboratory findings were observed.

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A new synthetic antibacterial agent, AM-715 was studied with respect to in vitro antibacterial activity and clinical effects in the urological field, and the following results were obtained.
1) Concerning MICs for clinically isolated 28 E. coli and 98 S. marcescens, AM-715 was more effective than NA.
2) All of 77 patients withacute simple cystitis and two patients with acute simple pyelonephritis showed excellent or good response to AM-715 treatment.
3) Effectiveness rate for 33 patients with chronic complicated UTI was 73%.
4) Side effects were seen in 2 cases, one with stomatitis and the other with cheilitis. The case with cheilitis required cessation of administration of AM-715.

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AM-715, a new oral antibacterial agent having similar chemical structure to nalidixic acid, was evaluated clinically for the patients with urethritis, and the following conclusions were obtained.
Six cases with gonococcal urethritis and 10 cases with non-gonococcal urethritis were administered at daily doses of 600 mg.
Overall clinical efficacy rate was 100% in the patients with gonococcal urethritis and 60% in the patients with non-gonococcal urethritis.
No adverse reaction was observed.

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AM-715, a new quinolinecarboxylic acid derivative, was administered to 57 cases (acute simple cystitis 26 cases, complicated urinary tract infections 7 cases, gonococcal urethritis 9 cases and non gonococcal urethritis 15 cases) by oral administration of daily dosage 300-1, 000mg. Effectiveness rate was 80.7%.
Side effect was only observed in one case complained of slight nausea, and no abnormal laboratory finding was noted in any cases.

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Antibacterial activity against Serratia marcescens was examined as a fundamental study on AM-715, a newly synthesized chemotherapeutics, and clinical effect in 17 patients with genito-urinary tract infections was also evaluated.
1) Antibacterial activity
The in vitro activity of AM-715 against clinical isolates of Serratia marcescens was more potent than those of nalidixic acid (NA) and pipemidic acid (PPA) used in this study for comparison.
2) Clinical results
AM-715 was administered at daily doses of 300 or 600mg for 3-5 days to 17 patients with genito-urinary tract infections (5 with simple urinary tract infections, 10 with complicated urinary tract infections, 2 with genital infections). The rate of effectiveness was 100% in simple cystitis, complicated pyelonephritis and chronic prostatitis and 71% in complicated cystitis. In 15 of these cases, which could be judged by The Criteria of UTI Committee, rate of effectiveness was 100% in simple cystitis and 80% in complicated urinary tract infections with total rate of effectiveness of 88.2% according to the criteria.
3) Side effects
No particular side effects were observed in this trial.

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Experimental and clinical studies on AM-715, a new antimicrobial agent developed as a quinolinecarboxylic acid derivative, were carried out. The results were as follows.
1. Serum concentration and urinary excretion:
The same dose (500 mg) of AM-715 and pipemidic acid were respectively administered to 4 healthy male volunteers as a single dose at different days. The peak of mean serum level of pipemidic acid was higher about 3 times than that of AM-715, and the recovery rate in urine (0-8 hrs) of pipemidic acid was too higher than that of AM-715.
2. Very high dose (2, 000 mg) of AM-715 was administered to 5 healthy volunteers to examine whether crystal formation in urine occurred, but no crystal formation was observed and no subjective symptoms were observed.
3. 34 patients with urinary tract infection were treated with AM-715, and evaluated by the criteria of UTI (Part II). The clinical response for 19 cases with acute simple cystitis was excellent in 13 cases, moderate in 5 cases and the clinical efficacy rate was 95%. The clinical response for 10 cases with complicated UTI was excellent in 6 cases, moderate in 2 cases and the efficacy rate was 80%.
4. Bacteriological response were evaluated in above 29 cases. Eradication of bacteria was observed in 19 strains out of 20 strains (95%) in acute cystitis and in 13 strains of 19 strains (68%) in complicated UTI.
5. A slight eruption was observed in one case as side effect.

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