T-2588 is a new oral cephalosporin ester of T-2525. T-2525 has a broad antibacterial spectrum. The in vitro and in vivo antibacterial activities of T-2588 (T-2525) against gram-positive and gramnegative bacteria were compared with those of cefaclor (CCL), cephalexin (CEX) and amoxicillin (AMPC). The results are summerized as follows.
1) T-2525 had broad antibacterial spectrum and was more active than CCL, CEX and AMPC against Serratia marcescens, Enterobacter cloacae, Citrobacter freundii and Indole-positive Proteus sp., which are insensitive to three reference drugs. Moreover, it was far more active than three reference drugs against Streptococcus pyogenes, Streptococcus pneumoniae, Haemophilus influenzae and Neisseria gonorrhoeae.
2) T-2525 showed the high bactericidal activity at low concentrations, and minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were much the same.
3) T-2525 was stable against β-lactamases.
4) T-2525 showed the high affinity to the penicilin binding protein (PBP) 3, 1Bs of Escherichia coli JE 1011, the PBP 1, 2, 3, 4 of Staphylococcus aureus FDA 209 P JC-1, and the PBP 2 of Bacteroides fragilis NCTC 9343.
5) The in vivo antibacterial activities of T-2588 against experimental infections in mice were more active than those of CCL and CEX. Especially, against β-lactamase producing strains, the activity of T-2588 was markedly potent.

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T-2588 is the pivaloyloxymethyl ester of T-2525. The in vitro and in vivo antibacterial activity of T-2588 was evaluated and compared with cefixime, cefaclor and augmentin. The following results were obtained.
The antibacterial spectrum of T-2525 was similar to cefixime. The activity of T-2525 against Escherichia coli, Proteus species, and Klebsiella-Enterobacter-Serratia of clinical isolates was superior to cefaclor and augmentin, but was similar or weak to cefixime. Against penicillinase producing Neisseria gonorrhoeae (PPNG) was more active than the other β-lactam antibiotics, respectively, although its anti-pseudomonas aeruginosa and methicillin resistant Staphylococcus aureus (MRS A) were weak.
-2525 was highly stable to various types of β-lactamase. In the experimental bacterial infection of β-lactamase producing gram negative bacilli in mice, the therapeutic activity of T-2588 was superior to the other β-lactams.

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T-2588 is a novel oral prodrug of T-2525 that is a cephem antibiotic with broad spectrum. T-2588 is converted into an active form, T-2525, after being absorbed from the intestine.
The antibacterial activity of T-2525 was compared with that of other oral β-lactam antibiotics, i. e. ampicillin, cephalexin, and cefaclor.
MIC80μg/mps of T-2525 to 22 to 59 clinical isolates of S. aureus, S. epidermidis, β-streptococci, E. coli (R⁺), K. pneumoniae, P. mirabilis, P.vulgaris, M. morganii, P. rettgeri, C. freundii, E. cloacae, S. marcescens, A. calcoaceticus, H. influenzae, and B. fragilis were 6.25, 50, 0.025, 0.39, 0.39, 0.1, 0.78, 1.56, 6.25, 3. 13, 50, 6, 25, 50, 0.05, and 6.25μg/ml, respectively.
T-2525 is stable against PCase type β-lactamases. Although the antibiotic is also stable to the type la β-lactamase, it is hydrolyzed by the type Ic β-lactamase in some extent.
T-2525 binds to PBPs of S. aureus at the same level as cefaclor. This antibiotic, however, manifests much stronger binding affinity to PBPs of E. coli, S. marcescens and A. calcoaceticus than cefaclor.
Addition of the complement and serum results in enhancement of bactericidal effect of T-2525. Filamentous cells of E. coli induced by sub MICs of T-2525 are phagocytized well and easily digested by mouse cultured macrophages.
T-2525 would be a useful antibiotic if its safety and pharmacokinetic are satisfactory.

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The in vitro and in vivo antibacterial activities of T-2588, a new oral cephalosporin, against anaerobic bacteria were evaluated and compared with those of cephalexin (CEX), cefaclor (CCL) and ampicillin (ABPC). The results were as follows:
1. The antibacterial spectrum of T-2525 against reference strains of anaerobic bacteria was somewhat broader than that of CEX and CCL, and was most equal or narrower than that of ABPC. T-2525 provided potent antibacterial activity against almost all of the strains tested except strains of the C. difficile.
2. The susceptibility distribution of T-2525 against clinical isolates reflected the results with reference strains of anaerobic bacteria; T-2525 provided a satisfactory antibacterial activity against these organisms.
3. T-2525 was more stable than CCL and CER to β-lactamase by B. fragilis.
4. The effect of T-2525 on viability suggested that the drug had a bactericidal activity against B. fragilis.
5. In experimental model with mice, T-2588 provided a therapeutic effect against polymicrobial subcutaneous infections with E. coli and β-lactamase producing B. fragilis.
6. T-2588, unlike amoxicillin (AMPC), caused no abnormal growth of C. difficile in mouse caecum contents.

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The in vitro and in vivo antibacterial activities of T-2588, a new oral cephem antibiotic, were compared with those of cephalexin (CEX) and cefaclor (CCL).
T-2525 (the active form of T-2588) had a broad antibacterial spectrum against Gram-positive and Gram-negative organisms, and was especially active against indole-positive Proteus spp., Serratia marcescens, and Enterobacter cloacae which were not susceptible to CEX or CCL. T-2525 showed the high bactericidal activity at low concentrations against Escherichia coli, Klebsiella pneumoniae, and S. marcescens used in this study. The bactericidal activity of T-2525 against Staphylococcus aureus was similar to that of CEX and CCL. The β-lactamase stability of T-2525 was superior to that of CEX and CCL.
The therapeutic effects of T-2588 against experimental intraperitoneal infections caused by Grampositive cocci, such as Streptococcus pyogenes and S. pneumoniae, and Gram-negative bacilli in mice were superior to those of CEX and CCL, but were less active against S. aureus than those of reference agents. In addition, T-2588 was active against experimental infections in mice caused by β-lactamase producing E. coli, which CEX and CCL were not effective.
The 6hr urinary recovery in mice was 32.3% for T-2588, 84.9% for CEX, and 50.8% for CCL after a single oral dosing with 50mg/kg.

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The therapeutic efficacy of T-2588, a new oral cephem antibiotic, was evaluated in models of local infections in mice and compared with that of cephalexin (CEX) and cefaclor (CCL), and following results were obtained.
In experimental pulmonary infection with Klebsiella pneumoniae in mice, T-2588 demonstrated superior efficacy to CEX and CCL and also showed strong bactericidal action and inhibitory activity of regrowth.
In experimental urinary tract infections with Escherichia coli, K. pneumoniae, and Serratia marcescens in mice, the efficacy of T-2588 was superior to that of CEX and CCL.
In experimental uterine infection with E. coli in mice, T-2588 was more potent than CEX and CCL.
These findings suggest that T-2588 is useful in various infections caused by Gram-negative organisms.

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T-2588 is a new orally absorbable prodrug of T-2525. In vitro and in vivo antibacterial activity of T-2588 and T-2525 was examined and the following results were obtained.
1) T-2525 had a broad antibacterial spectrum against gram-positive and gram-negative bacteria, including resistant ones to the other cephem antibiotics, and showed the potent antibacterial activity, especially against Streptococcus pyogenes, S. pneumoniae, Citrobacter sp., Enterobacter sp., Indole (+) Proteus sp., Serratia marcescens, Haemophilus influenzae and Bacteroides fragilis.
2) The antibacterial activity of T-2525 was hardly changed by pH of medium and the kind of medium, and the addition of human serum into culture media. However, the antibacterial activity of T-2525 against several bacterial species and strains tended to decrease slightly with the increase of inoculum size.
3) The antibacterial activity of T-2525 was bactericidal at MIC.
4) T-2525 was very stable to penicillinase and cephalosporinase.
5) The affinity of T-2525 for penicillin binding proteins of E. coli was stronger in the following order, PBP 3>1Bs>1A.
6) The therapeutic effects of T-2588 in mice infected with gram-negative bacteria were superior to those of reference compounds, while they were inferior to those of reference compounds against infection with Staphylococcus aureus.

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The therapeutic effects of T-2588 on various experimental infections in mice and in rats were studied in comparison with other oral antimicrobial agents.
1) The therapeutic effect of T-2588 was equal to that of ofloxacin and was superior, to those of pipemidic acid and fosfomycin against systemic infection in mice.
2) The therapeutic effect of T-2588 was superior to those of cephalexin (CEX), cefaclor (CCL) and cefroxadine (CXD) against systemic infection in mice treated with imrnunosupressive cyclophosphamide or azathioprine.
3) On pyelonephritis with Staphylococcus aureus and gram-negative bacteria in mice, the therapeutic effect of T-2588 was equal or superior to those of CEX, CCL and CXD.
4) On pneumonia with Klebsiella pneumoniae and Streptococcus pneumoniae in mice, the therapeutic effect of T-2588 was superior to those of CEX and CCL.
5) On intrauterine infection with Escherichia coli in rats, the therapeutic effect of T-2588 was superior to those of CEX and amoxicillin.

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1) After oral administration of T-2588 to three groups of beagle dogs (200, 400 and 800 mg/kg/day) for 79 consecutive days, simplification of the intestinal microflora was observed. The simplification occured in parallel with the increase in dosage.
2) A dose-response relationship was observed between the number of obligate anaerobes and the dosage of the drug.
3) Among the aerobes, the members of Streptococci and Enterobactsriaceae were increased.
4) C. difficile was detected in average of 10^8.9 per gram of feces in the groups administered the drug, whereas it was not detected in the feces of the control group.
5) All of the C. difficile isolates showed toxin production in vitro. The toxin was, however, not detected in any of the fecal samples. Diarrhea or abnormal stools were not observed.

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1. When T-2588 was administered orally to 4 volunteers for 14 days, the degrees of changes observed in the fecal microflora and drug concentrations were dependent on individual volunteers.
2. Degrees of alteration in the flora correlated well to the concentrations of the drug in the fecal contents. T-2525 caused reduction and elimination of the sensitive bacteria in parallel with the increase in concentrations in the fecal contents.
3. Among the members of microflora, Bacteroidaceae, lecithinase-negative Clostridia, Streptococcaceae, Pseudomonas, and Yeasts were relatively resistant to this drug, resulting in an increase in number during the period of drug administration.
4. In volunteers No.1 and No.3, there were no great changes in their fecal flora during the period of study, suggesting that the drug-resistant bacterial flora, including beta-lactamase-producing bacteria, had already been formed.
5. More than 35 days after the withdrawal of the drug were required to recover the normal fecal flora.
6. In volunteer No.2, C. difficite toxin, but not the organisms, was once detected in his feces during the period of study, although there were no abnormalities of stool character.
7. Loose stool was observed once in each of the two volunteers during the period of study.

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A microbiological assay method for quantitative determination of T-2588 in body fluids was investigated.
T-2588 concentration in the body fluids was determined as the concentration of T-2525, a parent compound of T-2588. The suitable condition for assay was paper disc method or cylinder method using Klebsiella pneumoniae ATCC 10031 as the test organism in the originally prepared medium which consisted of 10g of polypeptone, 5g of beef extract, 1.5g of glucose, 15g of agar, and 1, 000ml of distilled water and whose pH was adjusted to 6.5 to 6.6.
For the quantitative determination of T-2525 concentration in human serum, pooled human serum and consera were suitable for the use as the diluent of the standard solution of T-2525. For the quantitative determination of T-2525 in urine and bile, 1/15 M phosphate buffer (pH 6.0 or 7.0) was suitable.
The concentrations of T-2525 in the serum obtained by the bioassay method were well in agreement with those obtained by the high pressure liquid chromatography.
T-2525 in body fluids was stable at-20°C for at least 30 days.

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The extent of the binding of T-2525 to serum protein, which is the parent compound of T-2588 (a new oral cephem antibiotic), was studied by the equilibrium dialysis and the centrifugal ultrafiltration method.
The following results were obtained.
(1) T-2525 was bound reversibly to human serum albumin (HSA).
(2) The binding rates of T-2525 as well as cefaclor (CCL) and cephalexin (CEX) were influenced by the concentration of the drug and HSA. That is to say, the binding rate of T-2525 became higher as the concentration of HSA became higher, and became lower as the concentration of T-2525 became higher.
(3) From the results of SCATCHARD plot, rat and rabbit serum proteins, and HSA seemed to have 2 binding sites for T-2525.
(4) In vivo binding rates of T-2525 after oral administration of T-2588 in rats, rabbits and humans were similar to those obtained in vitro, respectively.
(5) T-2525 showed no influence on the binding of bilirubin to HSA.

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The pharmscokinetics of T-2588, the pivaloyloxymethyl ester of (+)-(6 R, 7 R)-7-[(Z)-2-(2-amino-4-thiazolyl)-2-methoxyiminoacetamido]-3-[(5-methyl-2 H-tetrazol-2-yl) methyl]-8-oxo-5-thia-1-azabicyclo [4. 2. 0] oct-2-ene-2-carboxylic acid (T-2525), were studied in experimental animals. The results were as follows:
1. T-2588 showed the favorable serum levels and the slow elimination from the serum in each species a animal except dogs.
2. T-2588 was well distributed to all tissues measured in mice and rats.
3. Urinary excretion of T-2588 was the highest in mice (33.2%), followed by rabbits (20.6%), rats (17.7%) and dogs (4.2%). Biliary excretion in rats was about 1/50 of the urinary excretion.
4. When T-2588 was administered to animals in the nonfasting state, the serum levels and urinary excretion were greater than those in the fasting state.
5. In rats, administered with 50mg/kg of T-2588 twice a day for thirteen doses, there was no significant difference in, the serum levels and urinary excretion between first and thirteen doses, showing no accumulation of T-2588.
6. The serum levels and urinary excretion of T-2588 in rats with dysfunction liver induced by CCl₄ or D-gaiactoeamine were similar to those of normal rats.
7. Tck determine the active substance, urine of animals and human orally administered with 2588 were examined by the bioautographic method. Only T-2525 was detected in all urine samples.

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T-2588, a new oral cephem antibiotic, is a prodrug of T-2525 having antimicrobial activity. Absorption and excretion of T-2588 after oral: administration were studied. Especially, the effect of various conditions (fasting state, after light meal and heavy meal) on the absorption was investigated. T-2588 was orally given to 6 healthy male volunteers at a dose of 200 mg (equimolar of T-2525).
Pharmacokinetic parameter of T-2588 was given, Cmax as T-2525 after dosing in fasting, having light meals and having heavy meals were 1.7μg/ml, 2.7μg/ml and 2.5μg/ml, respectively. The tmax were 1.6 hr, 2.1 hr and 2.5 hr, respectively. T1/2 were same among these conditions; 0.9 hr. AUC were 5.52μg·hr/ml, 9.09μg·hr/ml and 8.43μg·hr/ml, respectively.
Urinary recovery rate within 8 hrs was 18.7%, 32.8% and 28.8%, respectively. From the above results, absorption of T-2588 depended on food intake, and the absorption rate after light meal was higher than in fasting, and was almost same between light meal and heavy meal.
Pharmacokinetic parameter, of BAPC in case of administration of 250mg after light meal was given; C_max as ABPC, t_max, T1/2 and AUC were 6.0μg/ml, 1.2 hr, 1.0 hr and 12.84μg·hr/ml respectively, and urinary recovery rate was 68. 8%.
From the above results, the pharmacokinetic profile between T-2588 and BAPC was extremely different.

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The influence of food on the absorption of T-2588 was studied in 4 volunteers. A 100mg of T-2588 (capsule or tablet) was orally administered with 100 ml of water at 30 min. after meal to the following groups: fasted group I, light meal-receiving group, II, fatty meal-receiving group III, heavy mealreceiving group IV. The concentration of T-2588 was determined as T-2525, the parent compound of T-2588, using Klebsiella pneumoniae ATCC10031 as the test organism. The bioavailability of T-2588 was influenced by food intake. Urinary excretion within 8 hr. after dosing were 33. 15 to 33. 39% in nonfasted groups and 18.25% in fasted group. Although the serum levels of T-2525 were increased by food intake, the time to reach peak levels was delayed. The similar delay was also observed between group II and IV, and group HI and IV. The influence of fat on the absorption of T-2588 was not found in this study. The absorption constant (Ka) calculated by one-compartment open model did not differ significantly among each group.
These results indicate that the higher absorption of. T-2588 after meal may be explained by the long stay of the drug at upper small intestine where the drug is thought to be mainly absorbed.

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The pharmacokinetics of T-2525, an active form of a new oral cephem antibiotic T-2588, were studied in 4 healthy volunteers and 14 patients with various degrees of renal impairment after a single oral administration of 100 mg dose of T-2588. The endgeneous creatinine clearances (Ccr) of each subject were used as indicator of renal function. Pharmacokinetic parameters were obtained following the one-compartment open model with lag phase in the absorption.
The peak concentrations of T-2525 in serum were achieved 4 hours after administration without relation to the renal functions. The serum concentration of T-2525 increased in patients having the level of Ccr of 20 to 30ml/min. The mean serum half-life of T-2525 was calculated for 0. 83±0.02 hour in normal subjects and increased in patients along with increasing impairment of renal function. The excretion rate constant well correlated with Ccr (r=0.739, p<0.005).
In normal subjects, 22.2±1.9% of the drug was excreted in the urine as T-2525 within the first 8 hours, and the urinary excretion rate declined gradually in patients as a degree of renal impairment advanced.
In the patients with severely impaired renal function (Ccr of 20 to 30ml/min), the drug accumulation should be predicted by giving 100 mg oral dose of T-2588 repeated at interval of 8 hours, but not in patients who have the level of Ccr of 40 to 70ml/min.

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Metabolism of T-2588, a new esterified oral cephem, was studied using serum and urine obtained in phase I study. Following results were obtained.
1) Besides T-2525, the parent compound of T-2588, T-2525 A was detected in serum and urine.
2) Urinary recoveries of T-2525 and T-2525 A were higher in non-fasting state than those in fasting state.
3) Urinary recoveries of T-2525 and T-2525 A were not affected by multiple administration.
4) Pivalic acid, the metabolite derived from ester moiety of T-2588, was detected in serum and urine in a form of free acid or conjugate.
5) 5-Methyl-1 H-tetrazole (T-2588 F), the moiety at 3-position, was detected in urine.

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Acute toxicity study of T-2588 was carried out in mice, rats and beagle dogs, and the following results were obtained.
1) In the oral administration, LD₅₀ values were more than 6 g/kg in mice and rats, and more than 2g/kg in beagle dogs.
No hematological and serum biochemical changes were observed in beagle dogs.
2) In the subcutaneous administration, LD₅₀ values were more than 6g/kg in mice and rats. At necropsy, administered test articles were remained in the injected site of mice and rats, and granulation tissue were found in the injected area of mice and rats. Enlargement of cecum lumen was observed in rats.
3) In the intraperitoneal administration, LD₅₀ values were more than 6g/kg in male and 5.86g/kg in female mice, and 5.63g/kg in male and 5.09g/kg in female rats.
At necropsy, inflammatory adhesion of abdominal organs were observed in mice and rats.

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A newly developed antibiotic, T-2588, is metabolized in vivo to T-2525, which demonstrates antibacterial activity. Subacute toxicity test on T-2525 sodium (T-2525 Na) was carried out in Sprague-Dawley rats by intravenous injection of 250, 500, 1000 mg/kg and saline for 35 days.
One hundred and twenty rats (60 males, 60 females) were divided into three T-2525 Na-treated groups and a control group. Ten rats (5 males, 5 females) of each group were used for the recovery study after the termination of treatment.
The following results were obtained.
1) There were neither dead animal nor abnormalities in growth curves, urinalysis and hematological examinations on T-2525 Na-treated groups.
2) Soft feces and enlarged cecum lumen were observed in T-2525 Na-treated groups, however no histological changes were seen at the mucosa of cecum. In recovery study, enlargement of cecum lumen was restored.
3) In serum biochemical examinations, decreased cholinesterase activity and increased A/G ratio were observed to a small extent in T-2525 Na-treated groups, then these changes disappeared in recovery study.
4) Hyaline droplet degeneration of the renal proximal tubular epithelium was seen to a moderate extent in one of ten male rats at 1000mg/kg treated group, and the histological change disappeared in recovery study.
5) From these results, the maximum no-effect dose of T-2525 Na was estimated to be 500mg/kg in this study.

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One hundred and fifty rats (75 males, 75 females) were divided into five groups consisting of four T-2588 groups at dose levels of 1000, 500, 250 and 125mg/kg/day and control group. T-2588 was administered orally with gastric tube daily for 6 months. Ten rats (5 males, 5 females) of each group were used for the recovery study after the termination of treatment.
The following results were obtained.
1) Slight soft feces was observed in rats receiving T-2588 at 500mg/kg/day and 1000mg/kg/day.
2) Body weight gain was slightly suppressed in female rats receiving T-2588 at 1000mg/kg/day. There was no T-2588-related abnormality in urinalysis, hematological examinations and ophthalmological examination.
3) Dose-related decrease of blood glucose was observed. And, in higher dose groups, slight decrease of total protein were observed. However, these biochemical changes disappered in one month recovery.
4) Enlargement of lumen of cecum was observed in T-2588-treated male and female rats. Slight increase of liver, kidney and uterus weight were observed. However, histologically, T-2588-related abnormality was not observed.
5) Although tumors were observed in three of 150 rats, these seemed unrelated to this T-2588 toxicity test.
6) The maximum safety dose of T-2588 was estimated to be 125mg/kg/day in this experiment.

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The chronic toxicity study of T-2588 was carried out in 40 beagle dogs (20 males and 20 females) by oral administration. The dogs were devided into three groups at dose levels of 50, 150 and 400 mg/kg/day and a control group.
The following results were obtained.
1) No mortality occurred during the course of the study. Compound-like material was observed in the stools of all treated dogs. There were no significant changes in body weight gain, food intake, water intake, urinalysis, hematological examination, direct antiglobulin test and ophthalmic examinations.
2) Three of the 8 dogs at dose level of 150 mg/kg and 5 of the 12 dogs at dose level of 400 mg/kg showed transient elevation of serum transaminase levels after approximately 4-5 weeks of administration. However, these dogs showed no significant changes in other clinical chemistry measurements and elecrocardiogram. No gross anatomical changes were noted at necropsy that were considered to be related to treatment with T-2588.
3) The result of the histological examination did not distinguish treated from control dogs except that the hyaline bodies were observed in hepatocytes of some dogs at dose levels of 150 mg/kg and 400 mg/kg.
Electron microscopy of these bodies showed a swelling of the mitochondria and absent or distorted cristae.
4) Based upon the above results, the maximum no-effect dose of T-2588 was estimated to be 50 mg/kg.

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Teratological study on T-2588 was carried out in Sprague-Dawly strain rats. T-2588 was administered orally to pregnant rats from day 7 to 17 of gestation at the daily doses of 250, 500 and 1000 mg/kg as a suspension in 0. 5%CMC and 0. 1%HPC-L solution. Of 34 to 37 pregnant rats in each group, 20 pregnant rats were sacrificed on day 21 of gestation and remaining rats were allowed to deliver naturally. Dams, fetuses and offspring were examined.
Following results were obtained.
1. After administration of T-2588, in pregnant rats, soft feces and transient decrease in food intake at all doses of T-2588, increase in water intake at the doses of 500 and 1000 mg/kg and depression of body weight gain at the dose of 1000 mg/kg were observed.
3. In the postnatal examination, there were no significant differences in duration of gestation, number and body weight of newborn offspring, external development, function of sensory, reflex, learning ability and reproductive performance between the T-2588 treated groups and the control group. In 1000 mg/kg treated group, however, decrease in weaning rate and increase in number of rearing and ambulation, of female in open field test were observed.
4. From these results, the maximum non-effective dose of T-2588 on dam, fetus and offspring is estimated to be 500 mg/kg.

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Susceptibility of T-2588, a new oral cephem antibiotic, that is prodrug of T-2525 having antimicrobial agent, was tested against 162 clinical isolates of 7 species using plate dilution method with inoculum size of 10⁶ cells/ml. The MICs range of T-2525 were obtained at 0.78-3. 13 μg/ml and over 100 μg/ml, biphasic, for S. aureus, under 0.78 μg/ml for E. coli and K. pneumoniae, under 0.1 μg/ml and over 6.25 μg/ml, biphasic, for P. mirabilis and P. morganii, 0.39>200 μg/ml for S. marcescens and over 12. 5 μg/ml for P. aeruginosa. The above mentioned activity was superior to that of reference drugs which were CEX, CCL, CXD, CFT and ABPC except the activity against S. aureus.
Thirty-five patients with infections were treated with T-2588 at a daily oral dose of 100 mg b. i. d. or t. i. d., in 4-14 days. The clinical effects to the treatment was excellent in 18 cases, good in 15 cases, fair in 1 case and not evaluated in 1 case. The effective rate was 97. 1%. Eradication of bacteria was noted especially in the cases of E. coil, H. influenzae and S. pneumoniae. No adverse reaction and no abnormal laboratory findings were observed.

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T-2588, a new oral cephem drug, was administered to 8 patients with chronic respiratory tract infections, which had occasionally occurred following some pulmonary diseases. Significant causative organisms isolated from sputum in these cases were each 3 strains of H. inf fluenzae and B. catarrhalis and each one of P. aeruginosa (mucoid type) and E. coli. The drug was administered orally at a daily dose of 400 mg, distributed twice a day, for 13. 5 to 27. 5 days. As a result, 3 strains of H. influenzae were eradicated, one strain of E. coli was decreased and 3 strains of B. catarrhalis and one of P. aeruginosa were unchanged. Global evaluation including clinical efficacy, such as the relief of symptoms and the improvement of laboratory findings, revealed that 4 of 8 patients had good responses. No undesirable symptoms and signs were observed during the drug administration. Slight impairment of the liver function was discovered in two cases, but this did not seem to be serious because the laboratory data normalized after discontinuation of the drug.
Serum concentration of T-2525 (the active form of T-2588) reached the peak by 1. 5 μg/ml in average after 3 to 5 hours of a single administration of 200 mg of T-2588.
The sensitivity distribution of T-2525 against 73 strains of H. influenzae and 84 strains of B. catarrhalis, both clinically isolated between 1981 and 1984, was compared with that of ABPC or CCL. The data revealed that T-2525 was extremely sensitive to H. influenzae, but not so active against B. catarrhalis.

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T-2588, an ester derivative of T-2525, was developed in Japan as a new cephem for oral use. In vitroantimicrobial activity of T-2525 was examined by a broth dilution method using the Dynatech MIC 2000 system, and therapeutic effects of T-2588 on lower respiratory infections were evaluated.
The minimum inhibitory concentrations (MICs) of T-2525, cefixime (CFIX), cefaclor (CCL), cephalexin (CEX) and amoxicillin (AMPC) against 223 clinical isolates consisting of nine species were determined. T-2525 was more highly active against H. influenzae and E. coli than any other antibiotics. T-2525 was almost as active as cephalexin or cefaclor against S. aureus, and as active as amoxicillin against S. pneumoniae and S. pyogenes. T-2525 was as active as cefixime against E. cloacae. Against K. pneumoniae and S. marcescens, T-2525 was more active than cefaclor or amoxicillin, but somewhat less active than cefixime. T-2525 was found to be less active against all the strains tested of P. aersginosa with MICs above 100 μg/ml.
A daily dose of 200 to 600 milligrams of T-2588 was given orally to a total of 16 cases which consisted of one patient with acute bronchitis, eight patients with acute pneumonia, six patients with chronic respiratory diseases and one patient with infection associated with lung cancer. The clinical effects were excellent in four patients, good in 11, and there was no case evaluated as fair or poor. One patient with Mycoplasma pneumoniae pneumonia was excluded from clinical evaluation.
A total of eleven strains which consisted of two strains of S. pneumoniae, eight strains of H. influenzae and one strain of K. pneumoniae, were identified as causative organisms, and all of them were eradicated by the treatment with T-2588.
No any side effect was observed in all patients. An elevation of values of serum transaminase was observed in two patients. These adverse reactions disappeared after completion of the therapy with T-2588.
From the above results, it was concluded that T-2588 is one of the most useful antibiotics for oral use, for the treatment of lower respiratory infections.

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Pharmacokinetic studies of T-2588, a new oral cephem, were carried out and its therapeutic efficacy on respiratory tract infections (RTIs) was evaluated.
A cross-over estimation of plasma-and sputum concentrations was made by administration 60 minutes after breakfast of capsule or tablet, containing two hundreds mg each of T-2588, to five patients with chronic pulmonary diseases. Plasma concentrations reached 2.02 or 2.92μg/ml maximally three to four hours after taking capsule or tablet and remained at 1.18 or 0. 89 μg/ml urntill six hours after the administration.
Estimated concentrations of the drug in the sputa ranged from 0. 02 or below to 0.08 μg/ml, although time-related process of transfer into the sputum could not be succeeded to demonstrate clearly.
A capsule containing one hundred mg of T-2588 was administered orally two or three times a day to 19 patients with RTI and a tablet containing the same amount of the drug to 14 patients.
Six out of seven potential pathogens, which had been isolated from the patients before the treatment with the capsule, were eradicated with a eradication rate of 85. 7%, while nine out of ten were eradicated by the treatment with tablet with a rate of 90.0%. Thus, there was no difference in eradicated rates between the patients treated with capsule and those with tablet and a total eradication rate of 88.2% was obtained.
The clinical responses to the treatment with the capsule in a total of 19 patients were excellent in four, good in 14 patients and fair in one patient (efficacy rate: 94.7%), while those with tablet in a total 14 patients were excellent in two, good in 11 patients and poor in one patient (efficacy rate: 92.9 %).
Thus, there was no difference in efficacy rate between the treatment groups with capsule and with tablet, and a total efficacy rate was 93. 9%. No side effect was observed. A very slight degree of elevation of serum transaminases occurred in two patients.
From the results mentioned above, it is concluded that T-2588 is an effective and useful oral cephem antibiotic in treatment of RTI.

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In vitro and in vivo clinical evaluations were carried out on T-2588, a newly developed cephalosporin, and the following results were obtained:
The MICs of 123 clinical isolates of 8 species were compared with those of the other cephalosporins (CEX, CCL, CPZ, CMX) and AMPC.
Antibacterial activity of T-2588 against gram-positive bacilli was the highest among CEX, CCL, CPZ, CMX and AMPC. Against gram-negative bacilli, antibacterial activity of CMX was the highest and that of T-2588 was higher than the other antibiotics studied (CEX, CCL, CPZ, AMPC).
In this clinical study, a daily dose of 200-300 mg of T-2588 was given orally for 3-17 days to a total of 12 patients of six each with respiratory tract infections and with urinary tract infections. The clinical efficacy was excellent or good in 12 out of the 12 cases (efficacy rate: 100%). None of adverse effect was observed.

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The antibacterial activity, absorption, excretion and clinical efficacy on T-2588 were investigated and the following results were obtained.
1) Antibacterial activity
The antibacterial activities of T-2525 against the following clinically isolates of E. coli, K. pneumoniae, Klebsiella spp., P. mirabilis, Indole (+) Proteus spp., E. cloacae was superior to that of cefaclor and cephalexin. The activity against clinically isolates of S. aureus was same as that of cefaclor and cephalexin. The activity of T-2525 was superior against E. coli, K. pneumoniae and P. mirabilis, those resistant to cefazolin, to that of cefaclor and cephalexin.
2) Absorption and excretion
The peak serum levels of T-2588 in healthy adults volunteers was 1. 00 μg/ml and 1. 43 μg/ml 2 and 3 hour after oral dose of 100 mg and 200 mg with capsules at 30 minutes after meal. The peak serum levels of T-2588 tablets was 1. 69 μg/ml at 4 hour after oral dose of 200 mg at non-fasting. The mean urinary concentration after 2-4 hours were 55. 4 μg/ml, 138. 0 μg/ml, 144. 3 μg/ml andthe mean urinary recovery rate were 25.1%, 26.1%, 27. 3%, by 8 hours after administrations.
3) Clinical results
T-2588 was administered to 10 patients including 3 cases of respiratory tract infection and 7 cases of urinary tract infection. T-2588 was found to be excellent in 3 cases, good in 4 cases, fair in 2 cases and poor in 1 case.
No side effect was observed clinically, but a slight elevation of S-GPT was noted in 1 case.

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T-2588, a newly developed oral prodrug of oxime type third generation cephem, was studied for its clinical efficacy and adverse effects. T-2588 was used in the treatment of 12 cases of respiratory infectious disease comprising 6 cases of chronic bronchitis, 4 cases of bronchiectasis with infection, one case of chronic bronchiolitis and one case of pneumonia.
T-2588 was administered orally at a dose of 100 mg, 3 times daily for 7 to 14 days except one case (at a dose of 200 mg, 3 times daily for 14 days) and results obtained were excellent in one case, good in 7 cases, fair in 2 cases, poor in one case and not determined in one case, effective rate being thus 72. 7%.
Adverse reaction such as drug eruption, drug fever, nausea, vomiting, diarrhoea and abnormal laboratory findings were not obtained.
From these above clinical experiences, T-2588 would be a clinically useful antibiotic agents against respiratory infectious disease.

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Fundamental and clinical studies on T-2588, a new oral cephem antibiotic of ester type, were performed and the following results were obtained.
Serum levels and urinary excretions of T-2525 were determined in three healthy adults after fasted oral administration of T-2588 100 mg. Influence of probenecid on the serum levels and urinary recovery rate were also investigated.
The peak serum levels were obtained at 2 to 3 hours after administration, and averaged 1. 06±0.06μg/ml (1.00-1.12 μg/ml). The mean urinary recovery rate of T-2525 in 6 hours was 23.16%.
When subjects were predosed with probenecid, the peak serum levels of T-2525 were obtained at 3 hours after administration, and averaged 2. 02±0. 52 μg/ml (1.00-2.65 μg/ml). The mean urinary recovery rate of T-2525 in 6 hours was 16. 58%. This value was decreased from those without administration of probenecid.
The clinical effect of T-2588 was evaluated in 3 cases of acute bronchitis, 1 case of pneumonia and 1 case of chronic pyelonephritis using 200 to 400 mg per day, and found to be effective in all these cases.
No side effects were observed.

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The effect of T-2588 was clinically evaluated in 11 cases of respiratory tract infection (4 cases of pneumonia, 4 cases of chronic bronchitis, 2 cases of diffuse panbronchiolitis and 1 case of upper respiratory tract infection). Two hundred mg of T-2588 was orally administered 2 or 3 times a day.
Clinical responses were excellent in 2 cases and good in the 2 other cases among 4 cases of pneumonia, and good in 3 cases and fair in the 1 other case among 4 cases of chronic bronchitis, and good in 1 case and fair in the 1 other case among 2 cases of diffuse panbronchiolitis and good in 1 case of acute pharyngitis. The efficacy rate was 81. 8%.
As to the side effects, dizziness was observed in 1 case.
From the results, it was considered that T-2588 would be expected to be useful for the treatment of patients with respiratory tract infection.

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T-2588, a new oral third generation cephem, was given to 7 aged patients with urinary tract infections and 2 aged patients with biliary tract infections in a dosage of 100 mg bid. Six out of the seven patients with urinary tract infections showed satisfactory response. T-2588 eliminated all the urinary isolates of gram negative bacteria, including E. coli, K. pneumoniae, P. mirabilis, P. rettgeri, M. morganii, S. marcescens and C. diversus except each one strain of S. marcescens and Enterococcus. Superinfection with Enterococcus occurred in one patient.
Two patients with cholecystitis responded satisfactorily to T-2588.
No adverse reaction was observed.

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Fundamental and clinical studies on T-2588, a new oral ester type of cephem antibiotic, were carried out and the following results were obtained.
The antibacterial activity of T-2525 against E. coli, K. pneumoniae, E. cloacae, P. mirabilis and S. marcescens was 2 to 6-fold more potent than CCL and CXD.
After oral administration of 100, 200 and 400mg of T-2588 to healthy volunteers in the non-fasting state, the peak serum levels were 1.20, 1.97 and 3.81μg/ml after 3 to 4 hours, and declined with half-life of 1.03, 1.01 and 1.07 hours, respectively. The urinary recovery rate up to 8 hours after administration was 20-30%.
Cross over study administering 100 mg of T-2588 to healthy volunteers, fasted and non-fasted, showed: C_max, 0.86 and 1.19μg/ml, Tmax 1.75 and 3.15 hr and urinary recovery rate (0-8 hr) 19 and 28%, respectively.
T-2588 was administered 200 to 400mg per day for 6 to 15 days to total 19 cases with respiratory tract infections (15 cases) and urinary tract infections (4 cases). The overall efficacy rate was 89.5%(excellent 5, good 12, poor 2)
No side effect was observed.
As laboratory findings, slight elevation of Al-P in 2 cases, and slight elevation of GOT and eosinophilia in one case were observed.

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The clinical efficacy of T-2588, a new oral cephem antibiotic, was studied in 10 cases consisting of 9 cases with respiratory tract infections and one case with urinary tract infection. T-2588 was administered at a daily dose of 200mg, 300mg or 400mg.
The clinical efficacy was evaluated as excellent in 2 cases, good in 5 cases and fair in 3 cases. The overall efficacy rate was 70%. Bacteriological elimination was in 3 strains of S. pneumoniae, 2 strains in H. influenzae and one strain in Serratia sp.
No side effects was observed except in one case of nausea inappetence. No abnormal laboratory findings was observed.

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T-2588 was administered 100mg-200mg, 3 or 4 times a day (most patients received 100mg, 4 times a day or 200mg, 3 times a day) for 7 to 39 days, to total 12 patients with respiratory tract infections.
On the pneumonia (4 cases), acute exacerbation of chronic bronchitis (2 cases) and infected bronchiectasis (6 cases), the following clinical responses were obtained: excellent in 2 cases, good in 8 cases, fair in 1 case and poor in 1 case. No adverse reaction related to T-2588 except for 1 case of elevation of GPT was obtained.

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T-2588 is a new ester type cephem derivative with broad spectrum (Gram positive bacteria, Gram negative bacteria).
T-2588 was administered orally to 19 patients (pneumonia 3 cases, acute bronchitis 8 cases, chronic bronchitis 4 cases, acute tonsillitis 2 cases, acute pharyngitis 1 case, acute cystitis 1 case) at daily doses of 300mg. One case with mycoplasma pneumonia was non-evaluable. T-2588 was effective in 14 cases (efficacy rate 77.8%).
Abdominal distention was noted in one case and diarrhea were noted in two cases. No abnormal findings were noted in haematological, renal and hepatic function.

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Clinical effects and adverse effects of T-2588, a new cephem antibiotic, were studied in 29 patients with respiratory tract infections receiving orally 100mg to 200mg t. i. d.
Among them, 3 cases were pneumonia, 26 cases were lower respiratory tract infections (10 cases of bronchiectasis, 7 of diffuse panbronchiolitis, 4 of bronchial asthma, 2 of pulmonary emphysema and one of chronic bronchitis as underlying diseases).
Main causative organisms were H. influenzae (15 strains isolated).
The clinical effects were excellent in 3 cases, good in 19 cases, fair in 4 cases and poor in 3 cases.
The efficacy rate was 76%.
As adverse effects, diarrhea was observed in one case. Al-P, γ-GTP elevation and eosinophilia in one case and eosinophilia in one case were observed after treatment.
From these results, it was concluded that T-2588 was useful drug for the treatment of the patients with respiratory infections.

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T-2588, a newly developed cephalosporin antibiotic for oral use, was given to 16 patients with 1 case with acute pharyngitis, 3 with acute tonsillitis, 7 with acute bronchitis, 1 with acute pneumo. nia, 1 with acute cystitis, 2 with acute pyelonephritis and 1 with chronic pyelonephritis at a daily dosage from 300 mg to 600 mg. The duration of chemotherapeutic period ranged from 4 to 9 days.
One case was excluded from clinical evaluation. The clinical efficacy was “good” in 13, “poor” in 2cases. Overall clinical efficacy rate reached 86.7%.
Mild diarrhea was noted in 1 case possibly related to T-2588 therapy. The slight elevation of serum Al-pase was observed in one case during this antibiotic administration, which improved shortly after T-2588 therapy.
These data suggest T-2588 will be one of the effective cephalosporin antibiotic orally administered without significant side effects on the clinical base.

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T-2588, an oral cephem antibiotic of ester type, was administered to 12 patients with respiratory tract infection including 1 acute bronchopneumonia, 5 acute bronchitis, 4 chronic bronchitis and 2 bronchiectasis. The dosage was 600mg in divided doses taken 3 times daily for 7 to 9 days.
The clinical response was good in 10 cases, fair in 1 case and poor in 1 case. The efficacy rate was 83.3%.
Bacteriological examination was performed on all cases and the causative organisms were isolated in 7 cases: S. pneumoniae (2 cases), H. influenzae (1 case), B. catarrhalis (2 cases), E. agglomerans (1 case) and S. pneumoniae+H. influenzae (1 case). All these isolates excepting each one case of S. pneumoniae, B. catrrhalis and E. agglomerans were eradicated.
Neither side effect nor abnormal laboratory findings due to the drug were observed in any case.
It was concluded that T-2588 was a useful oral antibiotic for respiratory tract infection.

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The clinical effect of a new cephem derivative for oral use, T-2588, which had been administered to fifteen patients with respiratory tract infections at my hospital was excellent in one, effective in twelve, fair in one and inevaluable in one cases respectively.
All of causative organism that were identified at four patients disappeared.
One patient complained of discomfort of stomach and another one showed the elevation of LDH.
From these observations, T-2588 impressed to be a useful antibacterial drug in general.

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Nineteen patients with respiratory tract infections were treated with T-2588, a new cephem antimicrobial agent. The drug was administered orally at daily doses of 300-600mg divided into 3 for 3-28 days. The clinical effects were excellent in 4, good in 10, fair in 4, unknown in 1.
The efficacy rate was 77.8%. No side effects nor abnormal laboratory findings due to the drug were observed.

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T-2588, a new cephem antibiotic, was orally administrated to 10 patients with respiratory tract infection and 7 patients with urinary tract infection. Severity of these infections was mild or moderate. The patients were administrated the drug for 6 to 24 days in dose of 100-400mg/day.
Clinical effects were excellent in one case, good in 13 cases, fair in 2 cases, poor in one case, showing an efficacy rate of 82.4%.
Concerning the side effects, each one patient showed exanthema and bitter taste. Abnormal laboratory findings possibly related to this drug were not observed in any of these cases.

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We carried out basic and clinical studies on a new macrolide antibiotic, RU 28965, in respiratory infection.
The in vitro antibacterial activity of RU 28965 was evaluated and compared with erythromycin (EM), josamycin (114) and midecamycin (MDM) using 301 clinical strains of Gram-negative and-positive bacteria. The MICa of RU 28965 showed good antibiotic activity against Gram-positive bacteria (inferior only to EM), but not so active against H. influenzae as other MLs.
Serum and sputum concentrations of RU 28965 were investigated in four patients with chronic or secondary bronchitis. The results revealed the incomparably good absorption and long half-life of RU 28965 as compared with existing MLs, resulting in high blood and sputum levels over a long period. Nine cases of respiratory infection were treated with RU 28965 at 300mg or 400 mg/day and the clinical efficacy rate was 56%.
As to adverse reactions, there was 1 case of GOT elevation in the laboratory findings, but no other abnormalities were found, and no problems were noticed in terms of the drug's safety.

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A new oral cephem antibiotic T-2588 was used to treat 41 patients with respiratory tract infection, 5 with urinary tract infection and 1 with fever unknown origin, and its safety and efficacy were studied. The study was carried out from May 1984 to July 1985. The patients consisted of 15 adult males and 32 adult females in this study. The mean age of the total patients was 61. 0years (range 18 to 88). Eighteen patients were more than 70 years of age.
T-2588 was given three times a day at a dose of 100mg or 200mg in the patients with respiratory tract infection and fever unknown origin. Except one patient with CRF, 50 mg was given three times a day in the patients with urinary tract infection. In the case with CRF, it was given once a day at a dose of 50mg. The duration of therapy ranged from 3 to 22 days, and the total dose ranged 0.15-8.4 g.
The therapeutic effect was “good” in 32 patients, “fair” in 4, “poor” in 4, “undetermined” in 7, with a high effectiveness rate of 80.0%. As an adverse reaction, eruption, epigastralgia and diarrhea were observed in each one case. Laboratory tests revealed an elevation of GPT in one case and an elevation of GOT and GPT in another one. However, these findings were slight and no severe side effects caused by the drug were observed.

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The author reports on the results of clinical investigation of T-2588, a new ester bond compound of cephaloeporin antibiotic.
Clinical evaluation was carried out in 21 patients of respiratory tract infection including 2 with tonsillitis, 6 with acute bronchitis, 7 with chronic bronchitis, 2 with bronchiectasis and 4 with pneumonia. Response was good in 15 cases (71.4%) out of 21 patients.
As a side effect eosinophilia was observed in one ease, but the adverse reaction disappeared within one week following discontinuance of administration.

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T-2588 was prescribed to 6 patients with respiratory tract infections, and studied about clinical effect and adverse effect. T-2588 was administered 100 or 200mg 3 times a day for 7 days.
Clinical effects were excellent or good in 4 patients whose causative organism was Haemophilus influenzae or Streptococcus pneumoniae, and poor in 2 patients whose causative organism was Pseudomonas aeruginosa, or was not detected. No adverse effect was observed in all patients.

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T-2588, a new cephem antibiotic, was orally administered at a dose of 300mg divided three times a day during 3 days to 14 days to 5 patients, and at a dose of 400mg divided four times a day for 15 days to 1 patient of respiratory tract infection.
The clinical efficacy in 4 evaluable pts, was good in 2 and fair in 2. The effectiveness rate was 50%. Clinical pathogens were detected in 4 pts, mucoid type Pseudomonas aeruginosa (1), Streptococcus pneumoniae (1), Haemophilus influenzae (1), and S. pneumoniae and H. influenzae (1). These organisms without mucoid type P. atruginosa were eradicated. No subjective side effect was observed. No abnormal laboratory datum was recognized.

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Antibacterial activity of T-2525 and the clinical effect of T-2588 were investigated and the following results were obtained
1) Antibacterial activity: Antibacterial activity of T-2525 was investigated against 227 clinical isolates such as S. aureus, E. faecalis, E. coli, K. pneumoniae, P. mirabilis, P vulgaris M morganii, S. marcescens or P. aeruginosa comparing with that of CCL, CEX and AMPC. T-2525 was inferior to CCL, CEX and AMPC against S. aureus, but was superior against E. coli, K. pneumoniae and P. mirabilis. T-2525 had antibacterial activity against P. vulgaris, M. morganii and S. marcescenswhich were resistant to CCL, CEX and AMPC, whereas it showed resistance against E. faecalis and P. aeruginosa.
2) Clinical effect: T-2588 was administered to 13 patients consisting of 6 cases of acute bronchitis and 7 cases of pneumonia (including each 1 case of atypical pneumonia and mycoplasmal pneumonia). Clinical efficacy was judged on 11 patients, since the cases of atypical pneumonia and mycoplasmal pneumonia were not evaluable. Therapeutic response was good in 10 cases and poor in 1 case, and efficacy rate was 90.9%. Bacteriological examination revealed that 1 case which had normal flora was changed to H. influenzae. Neither side effect nor abnormal laboratory findings due to the drug were observed.

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T-2588, a new cephem antibiotic for oral use, was administered to twenty four patients with respiratory infections. The diseases included in the present study were acute bronchitis in 4 patients, pneumonia in 7, chronic bronchitis in 10, bronchiectasis in 2 and lung abscess in one patient.
The drug was administered orally 200mg to 600mg daily; total dose ranged from 1.6g to 13.2g (6 to 22 days).
Clinical efficacy was evaluated as excellent or good in 17 patients (71%), fair in 5, poor in 1 and unknown in one patient. Excellent or good results were obtained in 6 out of 7 patients with pneumonia, and 7 out of 10 patients with chronic bronchitis, mostly with H. influenzae or S. pneurnoniae infections.
One patient, 79 year-old male with pulmonary emphysema, complained nausea and dysphoria of stomach on the 5 th day of the administration for pneumonia, and the drug was discontinued on the 6 th day. Transient rise in GOT and GPT was noticed in three patients, who finished the treatment without cessation of the drug.
The results suggested that T-2588 was a safe and useful oral drug for respiratory infections.

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T-2588, a new cephem for oral use developed by Toyama Chemical Laboratory, was examined on its antibacterial activity in vitro and its kinetics in the human body (seral concentration and urinary recovery), as well as on its clinical availability. The results obtained were as follows:
1) Antibacterial activity in vitro: As T-2588 is converted into its active form T-2525 after its enteral absorption, T-2525 was used for estimation of the antibacterial activity of the drug against bacterial strains isolated from clinical infection foci, and compared with those of ampicillin (ABPC), cefaclor (CCL), and cefroxadine (CXD).
Although the activity of T-2525 against S. aureus strains was found to be similar to those of CCL and CXD, the greater part of the strains of gram negative species (E. coli, K. pneumoniae, P. mirabilis, P. reitgeri, P.vulgaris, S. marcescens, etc.) showed significantly higher sensitivity to T-2525 than to other antibiotics examined, while P. aeruginosa strains were not sensitive to T-2525 similarly to others.
2) Kinetics in the human body, with special reference to the influence of meal: Serial estimation of T-2525 concentration in serum and urine were made in two women showing normal laboratory data, one 73y. old and the other 93y. old, after ingestion of T-2588 200mg or 100mg, respectively. Cross-over tests revealed that the enteral absorption of the drug was significantly faster after meal than in fasting.
3) Clinical trials: Out of the seven patients (four of RTI and three of UTI) treated with T-2588, 100mg× 3/day for 4-8 days, four well responded to the therapy. Among the remaining three cases, two could fairly respond, but one with UTI caused by P. aeruginosa failed, corresponding to our above-mentioned data on the in vitro activity of the drug.
None of the cases showed any clinical and laboratory abnormalities attributable to the drug.
These findings obtained suggest the promising availability of T-2588 as a new antibiotic drug for oral use.

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