T-3262 is an antibacterial drug which belongs to the group of pyridonecarboxylic acids. In this study, we investigated cytotoxicity of T-3262 for inhibition of cell growth and effects on viability of, and morphological changes in cultured Chinese hamster cells (V79 cells).
The following results were obtained.
1. The 50% inhibition dose of T-3262 for cell growth (ID₅₀, cultured for 48 hours) was 12μg/ml, showing that the inhibitory effect of T-3262 on the cell growth was stronger than that of enoxacin (ENX: ID₅₀ 44μg/ml), norfloxacin (NFLX: ID₅₀ 105μg/ml) or ofloxacin (OFLX: ID₅₀ 145μg/ml).
2. The number of cells increased and dead cells were scarcely seen at the highest concentration tested in culture medium (40μg/ml of T-3262 for 48 hours). At this concentration, degeneration of cytoplasm (atrophy and round shape) and decrease of mitotic cells were observed. These morphological changes were similar to those of the cells treated 400μg/ml of NFLX or OFLX for 48 hours.
3. After the removal of T-3262 from culture medium, the cells began to grow actively and recovered from the morphological changes. The similar phenomenon was observed with ENX treated cells but not with fluorouracil or mitomycin C treated cells.

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T-3262 is a new antibacterial drug which has been developed for oral administration in clinical use. It is known that T-3262 has cytotoxicity in cultured mammalian cells. Therefore, it is necessary to determine the cytotoxicity-related effects of T-3262 (if it is absorbed in a large quantity in animal). In this study, the toxicity of T-3262 was investigated in Sprague-Dawley rats upon intravenous injection of T-3262 at 50mg/kg/day for 14 days, and the results were compared to those obtained with ofloxacin (OFLX) and mitomycin C (MMC).
The results are summarized as follows.
1. In the T-3262-treated group, no animal died and no abnormal changes occurred regarding general symptoms during the treatment. There were no significant abnormalities in hematological, blood biochemical, ophthalmological and anatomical examinations nor changes in nucleate cells of bone marrow and myelogram. Crystal sediment (test material-like) was observed in urine of 8 of 10 rats examined. The weights of heart and prostate (including seminal vesicle) decreased and the weight of cecum increased. In histological examinations, dilatation of renal tubuli was observed in kidneys of 2 of 7 rats examined.
2. In the OFLX-treated group, no treatment-related changes were found. In histological examinations, the dilatation of renal tubuli was not observed.
3. In the MMC-treated group, the following changes were observed: decrease in body weight gain, in white blood cell (WBC) counts and number of nucleate cell in bone marrow, increase in myeloid vs. erythroid ratio. Hypoplasia of bone marrow was also observed.
From the above results, no significant abnormalities occurred in rats treated intravenously with 50mg/kg/day of T-3262 for 14 days. The cytotoxicity of T-3262 observed in cultured mammalian cells was not reflected in animals in this study.

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The present study was carried out to examine the effect of orally administered T-3262, a new synthetic antibacterial agent, on the kidney of male rats with experimental nephropathy. These rats had been treated with single intramuscular injection of mercuric chloride (HgCl₂, 3mg/kg) or daily subcutaneous administration of puromycin-aminonucleoside (PAN, 15mg/kg) for 11 days. T-3262 was administered orally to these pretreated rats at a dose of 1,000mg/kg/day for 2 or 6 days.
Twenty-four hours after the second or the sixth day of T-3262 administration, the kidneys of these rats disclosed similar biochemical and pathological findings as observed in the kidneys of the rats treated with HgC12 alone. Thus, no T-3262-related alterations were demonstrated in renal functional test, kidney weight or histopathological examinations at a dose of 1,000mg/kg of T-3262. The HgCl₂-induced nephropathy was not enhanced by the oral administration of T-3262.
Twenty-four hours after the second or the sixth day of T-3262 administration, the kidneys of the PAN-pretreated rats disclosed the biochemical and pathological findings largely similar to those with PAN-induced nephropathy. Enhancement of PAN-induced nephropathy by the oral administration of T-3262 was hardly evident.

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General pharmacological activities of (±)-7-(3-amino-1-pyrrolidinyL)-6-fluoro-1-(2, 4-difluorophenyL)-1, 4-dihydro-4-oxo-1, 8-naphthyridine-3-carboxylic acid p-toluenesulfonate hydrate (T-3262), which is a new pyridonecarboxylic acid, were examined with the following results.
1. Central nervous system: T-3262 did not show any significant pharmacological effects at oral doses of 100-1,000mg/kg but caused slow waves in spontaneous EEG in cats at intravenous doses of 10-30mg/kg.
2. Respiratory and cardiovascular system:
T-3262 produced little effect in normotensive rats and anesthetized rabbits at oral doses of 100-1,000mg/kg and intravenous doses of 3-30mg/kg, respectively. But T-3262 caused, dosedependently, an increase of respiratory rate, hypotension, decrease of heart rate and changes in ECG patterns (elevation of T waves, slow amplitudes of QRS complexes and prolongation of RR interval, etc.) in anesthetized dogs at intravenous doses of 3-10mg/kg.
3. Renal functions: T-3262 increased electrolyte excretions at oral doses of 300-1,000mg/kg but did not affect PSP excretion in rats.
4. Autonomic nervous system and smooth muscle organs:
T-3262 exerted slight inhibition of gastric output in rats and slight miosis in mice at an oral dose of 1,000mg/kg. But T-3262 did not affect the contraction of nictitating membrane in anesthetized cats at intravenous doses of 1-30mg/kg. T-3262 increased spontaneous motilities of isolated stomach, ileum and uterus, but decreased that of isolated colon at concentrations of 10^-5-10^-4g/ml.
5. Hematological examinations: T-3262 did not show any significant effects on bleeding time, blood coagulation, platelet aggregation and blood glucose level in rats at oral doses of 100-1,000mg/kg.
6. Miscellaneous effects: T-3262 exerted slight inhibitions of gastric secretion and of carrageenin-induced hind paw edema in rats at a dose of 1,000mg/kg administered intraduodenally and orally, respectively. T-3262 did not affect neuromuscular junction and bile secretion in rats at intravenous doses of 3-30mg/kg and oral doses of 100-1,000mg/kg, respectively.
From these results, it can be assumed that T-3262 has a wide safety margin as an oral antibacterial agent.

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Absorption, distribution and excretion of T-3262 were studied in rats and mice after oral administration of ¹⁴C-T-3262. The obtained results are summarized as follows.
1. ¹⁴C-T-3262 was absorbed from the upper small intestine such as duodenum in rats.
2. Serum levels of radioactivity in rats reached the highest concentration at 1 hour after an oral administration, then gradually diminished.
3. Urinary excretion was 35% and 42% of the dosed radioactivity in rats and mice, respectively, and fecal excretion was about 65% and 56% of the dosed radioactivity in rats and mice, respectively.
4. Biliary excretion in rats was about 27% of the dosed radioactivity after an oral adminisratior of ¹⁴C-T-3262, and a half amount of excreted radioactivity was reabsorbed from the intestine.
5. Radioactivity was distributed the most into the kidney and the liver among all organs other the stomach and the intestine. Radioactivity was widely distributed into other organs such as spleen, adrenal, pancreas, lung, heart and thymus. But the distribution of radioactivity into the brain was little.
6. The distribution of ¹⁴C-T-3262 was also studied with whole body autoradiography in normal male mice and pregnant mice. The radioactivity was distributed widely to whole tissues except brain, spinal cord and eye ball. In pregnant mice, radioactivity levels in the fetuses were the same as the blood level of the mother mice.
7. The binding rate of ¹⁴C-T-3262 to rats and mice serum proteins was 63-66%.
8. Urinary and fecal excretion patterns of radioactivity in mice after multiple oral administration of ¹⁴C-T-3262 for 10 days were similar to those after a single administration. This result suggests that T-3262 did not accumulate in body.
9. After oral administration of 14C-T-3262 to nursing rats, the secreted radioactivity level in the milk was higher than the blood level.

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Metabolism of (±)-7-(3-amino-1-pyrrolidinyl)-6-fluoro-1-(2, 4-difluorophenyl)-1, 4-dihydro-4-oxo-1, 8-naphthyridine-3-carboxylic acid ρ-toluenesulfonate hydrate (T-3262) was studied.
Metabolites were isolated from urine of mouse, rat, rabbit, dog and monkey following oral administration of T-3262, and identified using high performance liquid chromatography and mass spectrometry. Two metabolites, other than unchanged (±)-7-(3-amino-1-pyrrolidinyl)-6-fluoro-1-(2, 4-difluorophenyl)-1, 4-dihydro-4-oxo-1, 8-naphthyridine-3-carboxylic acid (T-3262 base), in which 3-aminopyrrolidinyl ring of T-3262 was metabolized, were identified as: (±)-7-(3-acetyl-amino-1-pyrrolidinyl)-1-(2, 4-difluoropheny1)-6-fluoro-1, 4-dihydro-4-oxo-1, 8-naphthyridine-3-car-boxylic acid (T-3262A) in all animals: (±)-1-(2, 4-difluorophenyl)-6-fluoro-7-(3-hydroxy-1-pyr-rolidinyl)-1, 4-dihydro-4-oxo-1, 8-naphthyridine-3-carboxylic acid (T-3262B) in monkey. The glucuronide of T-3262 was detected in mouse, dog and monkey, the glucuronides of T-3262A and T-3262B were detected in monkey. M-I, unidentified metabolite, was detected only in mouse.

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The fate of (±)-7-(3-amino-1-pyrrolidinyl)-6-fluoro-1-(2, 4-difluorophenyl)-1, 4-dihyro-4-oxo-1, 8-naphthyridine-3-carboxylic acid ρ-toluenesulfonate hydrate (T-3262) was studied using T-3262 and ¹⁴C-T-3262 in various animals.
1. Metabolites in serum and urine were assayed for mouse, rat, rabbit, dog and monkey following oral administration of T-3262. In serum, besides unchanged T-3262 base, T-3262A (N-acetylated) was detected in rat, rabbit and monkey; T-3262B (deamino-hydroxylated) was detected in monkey.
In urine, unchanged T-3262 base was excreted mainly. But a few of metabolites (T-3262A, T-3262B, T-3262 glucuronide, T-3262A glucuronide, T-3262B glucuronide, and unknown compound M-I) were detected, and species difference existed in types of metabolites.
2. Metabolites in bile and feces were assayed for mouse and rat following oral administration of T-3262 and 14C-T-3262. Metabolites in bile were similar to the urine, but the volume of T-3262A and T-3262A glucuronide was larger than in urine.
In feces, the excreted compounds mainly consisted of unchanged T-3262 base.
3. ρ-Toluenesulfonic acid, which is the counter acid for T-3262 base, was absorbed following the oral administration of T-3262, and excreted in urine in the unchanged form.

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Experimental peritonitis was produced in mice with Escherichia coli TPRL 10760 derived from the intestinal flora of mouse and used to evaluate the chemotherapeutic effects of semisynthetic penicillins, aspoxicillin (ASPC) and piperacillin (PIPC).
The peritonitis was induced by inserting a gelatin capsule containing the bacterial cells, sterilized cecal contents and BaSO₄ into the pelvic cavity of art anesthetized mouse. Infection with more than 10⁶ colony forming units (CFU) of the bacteria/mouse resulted in an acute peritonitis associated with 100% mortality, whereas an inoculum size of 10² CFU/mouse produced a chronic peritonitis.
In the mice with acute peritonitis, administration of 100 mg/kg×5 times of ASPC reduced the mortality to 0% but administration of 100 mg/kg×5 times of PIPC did not reduce the mortality.
In the mice with chronic peritonitis, ASPC was more effective than PIPC in decreasing the number of viable bacterial cells in the peritoneal fluid. The superiority of ASPC over PIPC was attributable to its higher bactericidal activity as well as its high drug level and more persistency in the peritoneal fluid as compared to PIPC.

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Sulbactam/Cefoperazone (SBT/CPZ) have been used in clinical infusion at ratios of 1:1 and 1:2 in Japan and U.S.A., respectively. After an administration of these drugs as a 1:1 parenteral formulation, the ratio of levels of CPZ and SBT in blood was 1:1/4 to 1:1/5 for 1 to 2 hours, whereas the ratio of free, unbound drug levels was 1:1.4 to 1:1.5. In urine these drugs were excreted at a ratio between 1:1 and 1:4 during 6 hours after the infusion. Antimicrobial interaction studies using various combinations of CPZ and SBT were performed to obtain information with respect to the effect of SBT on the antimicrobial activity of CPZ in vivo and the most appropriate ratio of these drugs for the in vitro test system.
Antimicrobial activities were determined using the agar dilution method and the disk diffusion susceptibility test. SBT increased the activity of CPZ against various clinical isolates tested except Enterococcus faecalis. CPZ-SBT at a fixed ratio of 1:1/5 significantly increased the antimicrobial activity of CPZ, resulting in decreases in MIC values and increases in disk inhibitory zone diameters. These drugs at ratios 1:1 to 1:3 maximized the synergistic enhancement of the activity. Therefore, a fixed ratio between 1:1/5 and 1:1 would be appropriate for the in vitro antimicrobial test system using either the agar dilution method or the disk susceptibility test.
Based on pharmacokinetic data for CPZ and SBT, results of the present study on antimicrobial activity would support that the parenteral formulation of CPZ-SBT at the fixed ratios of 1:1 and 2:1 for the intravenous infusion used in Japan and U.S.A., respectively, are appropriate.
The effect of SBT on the activity of CPZ was more marked against clinical isolates with greater production abilities of β-lactamase than against those with less production abilities. SBT/CPZ, however, exerted a synergistic effect against methicillin-resistant Staphylococcus aureus without β-lactamase production.
The MIC₈₀ of SBT/CPZ (1:1) against various clinical isolates with 10⁶ CFU/ml inoculum size were as follows: S. aureus 12.5 μg/ml, Staphylococcus epidermidis 3.13 μg/ml, and E. faecalis 50 μg/ml. Those of Gram-negative bacilli were: Escherichia coli 0.20 μg/ml, Klebsiella pneumoniae 0.20 μg/ml, Proteus mirabilis 0.78 μg/ml, Proteus vulgaris 0.78 μg/ml, Pseudomonas aeruginosa 12.5 μg/ml, Serratia marcescens 25 μg/ml, Enterobacter spp. 3.13 μg/ml, Citrobacter spp. 12.5 μg/ml and Acinetobacter spp. 0.78 μg/ml.

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Sulbactam/cefoperazone (SBT/CPZ), a new antibacterial drug, was administered to 14 cases with respiratory infections for a duration of 5-13 days at a daily dose of 4g. Diagnoses of these patients were 7 respiratory tract infections, and 7 bronchopneumonias.
The underlying diseases were chronic pulmonary emphysema in 6 cases, bronchial asthma in 2 cases, and one each of bronchiectasis, diffuse panbronchiolitis and lung cancer with bronchoesophageal fistula.
All patients had underlying respiratory diseases and/or were more than 70 years old. The rate of clinical efficacy was 78.6%. The incidence of penicillinase production by isolated bacteria was 18.2% and that of cephalosporinase was 63.6%. SBT/CPZ was expected to be more effective than CPZ alone in 3 cases judging from the susceptibility of the bacterial strains concerned, to antibiotics. No side effects were observed. We conclude that SBT/CPZ is useful in the treatment of respiratory infections of patients of advanced age and/or with underlying respiratory diseases.

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Ceftriaxone (CTRX), a new cephalosporin, was investigated by once daily administration for its clinical efficacy and safety on respiratory tract infections. The results obtained are summarized as follows:
1. Clinical responses to CTRX of a total of 39 cases with respiratory tract infections were excellent in 12 cases, good in 23, fair in 3, poor in 1 with an efficacy rate of 89.7%. Against acute bronchitis, lung abscess, bronchiectasis, chronic bronchitis and obstructive pneumonia, efficacy rates were 100%.
2. Serum levels and urinary excretion rates of CTRX were investigated in 2 cases after intravenous drip infusion of the drug at doses of 1g and 2g, respectively. Although urinary excretion rate tended to decrease with the deterioration of renal functions, prolongation of serum half-life was slight in those patients with normal liver function. In 1 case, it remained at 1.9μg/ml at 12 hours and in another at 0.9μg/ml at 22 hours in sputum.
According to the results, it appears that once daily administration of CTRX is effective and well tolerated in patients with acute respiratory infections.

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For seventy episodes of infection in hematologic disorders mostly during the phase of severe granulocytopenia, a trial was designed to evaluate the efficacy of a new third-generation cephalosporin, ceftriaxone (CTRX). The regimen consisted mainly of drip infusion of CTRX 2g every 12 hours. The overall response rate achived was 54.3 percent. Two episodes of an outpatient with malignant lymphoma were effectively treated by CTRX at a dose of 2-4g once a day, reflecting its long biological half-life. Gastrointestinal symptoms, hypersensitivity reactions and elevation of hepatic enzyme levels occurred rarely (6.4 and 5.1 percent of the patients, respectively), and these abnormalities were mild and reversible.
Thus, CTRX may be recommended as an effective monotherapy in the treatment of infections in immunocompromised patients with hematologic disorders.

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Ceftriaxone (CTRX), a new long acting antibiotic in the 3rd generation cephem group, was administered intravenously once or twice a day in daily doses of 1-6g for at least 3 days to 86 patients with severe infections complicating hematopoietic disorders. Underlying diseases were acute leukemia in 41 cases, chronic leukemia in 3 cases, malignant lymphoma in 19 cases, myeloma in 7 cases and others. Most patients (55 cases) suffered from sepsis or suspected sepsis. As for efficacy rates classified by underlying diseases, the treatment was effective in 61.0% of patients with acute leukemia. As for efficacy rates classified by infections, the treatment was effective in 60.0% of patients with sepsis.
No side effects were noted except rash in 2 patients. Abnormal hepatic functions were recognized in 3 patients but were not attributed to the agent in any case. The results indicate that CTRX is a safe and useful antibiotic for the treatment of severe infections accompanied by hematopoietic disorders.

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Antibacterial activities of human cervical mucus obtained from non-pregnant and pregnant women were tested using standard blood agar plates. The combined effect of cervical mucus with cefmetazole (CMZ) was also investigated. Obtained results are summarized as follows.
1. Cervical mucus spe0cimens obtained from 6 subjects at 9 to 36 weeks of pregnancy showed antibacterial activity to only one strain of Bacillus subtilis among organisms tested. The cervical mucus enhanced the activity of CMZ against 1 strain of Streptococcus pyogenes and 2 strains of Micrococcus luteus, but no effect was observed against other organisms tested.
2. Cervical mucus specimens obtained from non-pregnant women showed antibacterial activities to 8 of 11 strains (72.7%) of B. subtilis tested. The cervical mucus enhanced the activities of CMZ against 1 strain of S. pyogenes and 3 strains of B. subtilis. The tested organisms included Staphylococcus aureus, Escherichia coli, Bacteroides fragilis, S. pyogenes, B. subtilis, M. luteus, Streptococcus agalactiae, Enterococcus faecalis, and Candida albicans, but, as described above, cervical mucus samples showed antimicrobial activities only against B. subtilis (9/17, 52.9%), and specimens obtained only from non-pregnant women or pregnant women with less than 11 weeks of pregnancy showed any antimicrobial activities.

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Pharmacokinetics and clinical studies of imipenem/cilastatin sodium (IPM/CS), a combined preparation of a new carbapenem antibiotic and a dehydropeptidase-I inhibitor, respectively, were carried out in neonates and premature infants in a joint study by a co-research group.
1. Peak blood levels of IPM/CS when administered at 10mg/10mg/kg or 20mg/20 mg/kg by 30-or 60-minute intravenous drip infusion were achieved at the end of infusion. A dose response was clearly observed between the doses and the peak levels achieved.
2. The areas under the blood concentration time curve (AUC) of CS were greater than those of IPM in most patients. Blood half-lives of IPM and CS tended to be longer in younger neonates and premature infants than in older subjects. The blood half-life of CS tended to be longer than that of IPM.
3. Cumulative urinary recovery rates of CS were greater than those of IPM, cumulative urinary recovery rates tended to be greater in older neonates and premature infants than younger subjects.
4. One hundred and thirteen patients were treated for bacterial infections with IPM/CS and 32 patients were treated prophylactically. Daily doses of IPM/CS ranged from 9mg/9mg/kg to 150mg/150mg/kg.
5. Clinical efficacies of IPM/CS were evaluated in a total of 56 patients with identified etiologic pathogens. The efficacy rate was 98.2% with 33 patients rated as excellent, 22 patients as good and 1 patient as fairly good.(Diagnoses were sepsis in 10 patients and meningitis in 2 patients, etc.) Fifty-seven patients with no identified etiologic pathogens were rated as excellent for 22 patients, good for 34 patients and fairly good for 1. The efficacy rate in these patients was 98.2%. Thirty-two patients were treated prophylactically and the results obtained were satisfactory.
6. Bacteriologically, the eradication rate was 94.5% in 56 patients; i.e., 52 were eradicated, 2 were decreased, 1 persisted and 1 was unknown.
7. Adverse effects were observed in 7 (4.4%) of 160 patients, i.e., 2 patients had diarrhea and 2 patients had rash, etc. Abnormal laboratory data considered related to the therapy occurred in 28 (17.6%) of 159 patients, with 10 patients with eosinophilia (6.3%) and elevation of GOT and/or GPT, etc. All these were non serious, and all values returned to normal after discontinuance of therapy. An abnormal prothrombin (PIVKA II) was observed in 1 of 10 patients tested.
Accordingly, the dosage recommendation for IPM/CS in neonates and premature infants is as follows:
Age (days old) IPM dose (mg/kg/dose) Daily dosage 0-3 10-20 b.i.d. 4-7 10-20 b.i.d.-t.i.d. 8-31 10-20 b.i.d.-q.i.d.

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Clarithromycin (TE-031, A-56268), a new macrolide antibiotic, was administered to rats, and the distribution of the drug in the submandibular gland was studied using microautoradiography. The study revealed good accumulation of 14C-TE-031 in both the acini and the excretory ducts.
TE-031 was administered to each of 3 healthy male volunteers in a single dose of 300mg, and its concentrations in the serum and saliva was detected. Mean values of various pharmacokinetic parameters were as follows for the serum and saliva, respectively. C_max.1.49μg/ml and 1.93μg/ml; T_max 2.91 hours and 2.66 hours; T 1/2 6.31 hours and 4.15 hours; AUC 18.58μg·hr/ml and 17.70μg·hr/ml. Regarding the salivary bacterial flora, the total bacterial count decreased as the salivary TE-031 concentration increased, but it recovered to the initial level in 12 hours after administration. During the 24-hour period following an administration of TE-031, the salivary bacteria did not acquire resistance to the drug.
Therefore, TE-031 is an antibiotic which exerts little effect on the normal salivary bacterial flora in short-term administration.
Although the results differed among the individuals, the penetration of TE-031 to saliva was superior to that to the serum. Thus, TDM of TE-031 using salivary samples is possible.

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In order to objectively evaluate the usefulness of clarithromycin (TE-031, A-56268), a new oral macrolide antibiotic, in the treatment of acute dental infections, a double-blind comparative clinical trail was conducted using josamycin (JM) as the control drug. TE-031 was administered at a daily dosage of 400 mg in 2 divided doses, and JM was given at a daily dosage of 1,200 mg in 3 divided doses. The administration period was, as a rule, 7 days.
A total of 302 patients were administered with the test substances (TE-031 and JM), and the clinical efficacy was evaluated by investigators for 284 patients and by a committee using a score method for 273 patients. Efficacy rates as evaluated by the investigators were 77.2% (105/136) in the TE-031 group and 69.6% (103/148) in the JM group. Efficacy rates as evaluated by the committee by the score method were 86.0% (111/129) in the TE-031 group and 80.6% (116/144) in the JM group. The differences between the 2 drug groups were not statistically significant. The investigators' evaluation of the clinical efficacy in the treatment of osteitis of the jaw gave an efficacy rate of 83.0% (44/53) in the TE-031 group and 64.7% (33/51) in the JM group. The efficacy rate in the TE-031 group was statistically higher than that in the JM group.
Side effects were recorded in 7 patients (4.8%) in the TE-031 group and 3 patients (2.0%) in the JM group, while abnormal laboratory test values were detected in 3 cases each in the TE-031 and JM groups. None of these differences were statistically significant.
The usefulness rates (“satisfactory” plus “very satisfactory” cases) were 73.9% in the TE-031 group and 70.3% in the JM group and were thus almost the same for the 2 drug groups.
On the basis of the above results, TE-031 was concluded to be a useful drug in the treatment of acute dental infections and is expected to be able to achieve almost identical clinical efficacy as JM at only one-third of the usual dosage of JM.

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1. Supposing the hernia sac to be peritoneum, intraperitoneal transition of cefotiam (CTM) was examined on 57 cases of infantile inguinal hernia subdivided into 7 groups.
2. After one shot intravenous injection, CTM showed rapid transition into the blood and the peritoneal tissue and even at a dose of 40 mg/kg and 120 minutes later. CTM exhibited an excellent antibacterial activity considering of MIC₈₀ against clinically isolated bacterial strains.
3. Healing by first intention of operative wounds was obtained in all of the cases given CTM without any case suggestive of postoperative infection. No clinical side effect was observed in any one of the cases.

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Lomefloxacin (NY-198), a new antimicrobial quinolone, was examined for its antimicrobial activities against clinical isolates and clinical efficacies to biliary tract infections. The following results were obtained.
1. The MICs of NY-198 against Escherichia coli (20 strains) and Klebsiella pneumoniae (20 strains) were good and similar to those of ofloxacin (OFLX) or norfloxacin (NFLX). The MICs of NY-198 against Pseudomonas aeruginosa (20 strains) were inferior by 1 dilution factor to OFLX or NFLX, and against Enterococcus faecalis (10 strains), they were similar to NFLX and slightly inferior to OFLX.
2. NY-198 was administered to 8 patients with biliary tract infections (acute cholecystitis 7 cases, chronic cholangitis 1 case). The results were good in 7 and unevaluable in 1 case because the duration of the therapy was too short.
3. As for side effects, mild urticaria was observed in 1 case and epigastralgia with nausea in another. As for abnormal laboratory test values slight elevations of GOT and GPT were recognized in 1 case.
4. In conclusion, we consider NY-198 is a useful oral drug for the treatment of biliary tract infections.

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To objectively evaluate the efficacy, safety and utility of lomefloxacin (NY-198), a new quinolone antibacterial agent, in the treatment of acute uncomplicated cystitis, a comparative double blind trial was performed using norfloxacin (NFLX) as the control drug. In both groups, the drug was orally administered after meals for 3 days in a dose of 100 mg t. i. d. and clinical efficacies were assessed on the 3rd day (the 1st assessment) according to the criteria by the UTI Committee in Japan. Subsequently, either the active drug (NY-198 or NFLX) or placebo was administered for 4 days and the 2nd assessment was performed on the 7th day. Further, in patients who showed excellent responses at the 2nd assessment, recurrence was examined on the 14th day (the 3rd assessment) and on around the 21st day (the 4th assessment) following a subsequent 7-day placebo treatment.
1. A total of 258 patients was treated, and among them clinical efficacies were evaluable in 207 patients (NY-198: 106, NFLX: 101) at the 1st assessment, and in 176 patients (NY-198-NY-198 which was the combination of the 1st and 2nd administrations: 47, NY-198-placebo: 43, NFLX-NFLX: 44, NFLX-placebo: 42).
2. In the evaluation of overall clinical efficacy by the committee at the 1st assessment, the overall efficacy rates in the NY-198 group and the NFLX group were 76.4% and 64.4% (excellent), respectively, or 100% and 99.0% (excellent and good), respectively. There was no statistically significant defference between the 2 groups. In the 1st assessment on effects of drugs on pain at micturition, pyuria and bacteriuria and on bacteriological response, no significant differences were observed between the 2 groups.
3. In the 2nd assessment by the committee, there were statistically significant differences among the 4 groups in the overall clinical efficacies and the effects on bacteriuria (P<0.05). No difference was observed between NY-198 group and NFLX group, but the groups administered with active drug for 7 days, i.e. NY-198-NY-198 group and NFLX-NFLX group were significantly superior to the groups administered with active drug for 3 days and placebo for subsequent 4 days, i.e. NY-198-placebo group and NFLX-placebo group (P<0.05). There were no differences in the effects on pain at micturition and pyuria among the 4 groups.
4. In the 1st assessment on clinical efficacy by doctors, the efficacy rates (excellent and good) in NY-198 group and NFLX group were 98.1% and 97.0%, respectively, showing no significant difference between the 2 groups. In the 2nd assessment, similarly, no differences were observed among the 4 groups.
5. Recurrence was examined in 89 cases at the 3rd assessment, and in 25 cases at the 4th assessment. In either of the assessments, there were no significant differences in recurrence rates among the 4 groups.
6. Side effects were observed in 6 of 127 cases (4.7%) in NY-198 group and in 3 of 123 cases (2.4%) in NFLX group. Abnormal laboratory test values were noted in 2 of 61 cases (3.3%) in NY-198 group. The difference between the 2 groups was not statistically significant.
7. In the utility evaluated by doctors at 1st and 2nd assessments, no significant differences were observed among the 2 and 4 groups, respectively.
From these results, it was considered that NY-198 was a useful antibacterial agent in the treatment of acute uncomplicated cystitis.

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