Cefotiam hexetil (CTM-HE), an orally active ester derivative, is a new cefotiam (CMT) pro-drug. We compared the in vitro antibacterial activity and β-lactamase stability of CTM with those of cephalexin (CEX), cefatrizine (CFT), cefaclor (CCL) and cefroxadine (CXD).
CTM had stronger antibacterial activity against Gram-positive and-negative bacteria except for Pseudomonas aeruginosa than did CEX, CFT, CCL and CXD, and showed a broad antibacterial spectrum. CTM, as well as CEX, CFT, CCL and CXD, was stable to penicillinases (PCases) but was hydrolyzed by cephalosporinases (CSases) or oxyiminocephalosporinases. Against types I, II, III, and IV, PCase-producing strains of Escherichia coli and CSase-producing strains of E. coli, Providencia rettgeri, Morganella morganii, CTM had an antibacterial activity higher than did CEX, CFT, CCL and CXD.

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We determined the in vitro and in vivo antibacterial activities of cefotiam hexetil (CTM-HE)(active form; cefotiam) and compared them with those of cefaclor and cephalexin as reference drugs.
The in vitro antibacterial activity of CTM against Staphylococcus aureus, Escheri chia coli, Klebsiellapneumoniae, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Providencia rettgeri, Providencia stuartii, Enterobacter cloacae, Serratia marcescens, Haemophilus influenzae, and Bordetella pertussis was more potent than those of CCL and CEX.
In a study on mice, the therapeutic effect of oral CTM-HE against infections due to S. aureus, E. coli and K. pneumoniae was superior to that of CCL and CEX. CTM-HE was also effective against infections due to methicillin-resistant S. aureus and β-lactamase-producing bacteria against which CCL and CEX were ineffective.

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Cefotiam (CTM), which is the active moiety of a new oral pro-drug, cefotiam hexetil (CTM-HE), showed high affinity to the penicillin-binding proteins (PBPs) of Staphylococcus aureus, Streptococcuspneumoniae, Proteus vulgaris and Haemophilus influenzae.
The high binding affinity of cefotiam to the lethal target PBPs, which was superior to that of cefaclor, was consistent with its strong bactericidal activity against these pathogens.
Synergistic effect of cefotiam on phagocytosis and killing of bacteria with cultured mouse macrophages was comparable to that of other cephem antibiotics.

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We compared the in vitro antibacterial activity of cefotiam (CTM), the active moiety of cefotiam hexetil (CTM-HE) with those of cefaclor (CCL), cephalexin (CEX), cefixime (CFIX), ampicillin (ABPC) or amoxicillin (AMPC), T-2525 and chloramphenicol (CP), against 1211 clinical isolates, which were isolated in the Clinical Laboratory, of Juntendo University Hospital from January 1986 to May 1987. The results were as follows.
1. Against Staphylococcus aureus, the antibacterial activity of CTM was stronger than those of CEX, CCL, CFIX and ABPC, but CTM-resistant strains were observed in 45% of 78 strains. Against Enterococcus faecalis, CTM and other oral cephalosporins were inactive, though ABPC was active.
2. CTM showed potent antibacterial activity against Streptococcus pyogenes, Streptococcus agalactiae, Group C and G streptococci, and Streptococcus pneumoniae, but ABPC was the most potent.
3. CTM also showed potent antibacterial activity against Haemophilus influenzae, including ABPC-and/or CP-resistant strains, and was superior to that of CCL and inferior to that of CFIX.
4. Against Branhamella catarrhalis, the antibacterial activity of CTM was almost equal to CCL, and was inferior to those of CFIX and T-2525.
5. Against Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis, CTM showed potent antibacterial activity, and CTM-resistant strains were rare. Especially against E. coli, the activity of CTM was superior to that of CFIX. On the other hand, against Citrobacter freundii, Enterobacter cloacae, Serratia marcescens, Proteus vulgaris and Providencia rettgeri, the MIC distribution of CTM was divided between susceptible and resistant groups. Against C. freundii and E. cloacae, the activity of CTM was superior to that of CFIX.
6. Against Campylobacter jejuni, the activities of CTM and other drugs were rather weak.
7. Against Peptostreptococcus spp. and Veillonella spp., the activity of CTM was superior to those of CEX and CFIX, but inferior to those of ABPC and CCL.

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In this study we tested the in vitro antibacterial activity of cefotiam (CTM), the parent compound of cefotiam hexetil (CTM-HE) and the in vivo therapeutic efficacy of CTM-HE, a new orally active ester derivative of CTM, against experimental mouse infections in comparison with cefixime (CFIX), cefaclor (CCL) and amoxicillin (AMPC).
CTM had a broad antibacterial spectrum against Gram-positive and-negative organisms. Its antibacterial activity against Gram-positive organisms was between that of AMPC and CCL.
In a sensitivity test on clinically isolated Gram-negative organisms, however, the antibacterial activity of CTM was superior to those of CCL and AMPC and inferior to that of CFIX.
CTM showed dose-related bactericidal activity against all the bacteria tested.
Against intraperitoneal infections with Gram-positive organisms in mice, the therapeutic efficacy of CTM-HE was superior to that of CFIX and inferior to that of AMPC. On the other hand, the therapeutic efficacy of CTM-HE against Gram-negative organisms was slightly inferior to that of CFIX and almost equal to that of CCL.

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Cefotiam hexetil (CTM-HE) is the 1-cyclohexyloxycarbonyloxyethyl-ester of cefotiam (CTM), a widely used parenteral cephalospolin. The in vitro antibacterial activity of cefotiam and the in vivo activity of CTM-HE were evaluated and compared with those of cephalexin (CEX), cefaclor (CCL) and cefroxadine (CXD).
1. CTM (the active form of cefotiam hexetil) had a broad antibacterial spectrum against grampositive and gram-negative organisms and the antibacterial activity of CTM was superior to those of other orally active cephalosporins. Especially, CTM showed high activity against CEX-resistant Escherichia coli, Citrobacter freundii, Enterobacter cloacae, Proteus vulgaris, Morganella morganii, and Haemophilus influenzae, against which other cephalosporins were weakly active.
2. CTM was strongly bactericidal and bacteriolytic against Staphylococcus aureus and E. coli at the MIC levels. CTM was especially more active against E. coli than CEX, CCL and CXD.
3. CTM-HE protected well against lethal intraperitoneal infections in mice caused by a variety of gram-positive and negative bacteria; the activity against gram-negative bacteria was noteworthy.
4. CTM-HE was more effective than CEX and CCL against respiratory tract infection caused by Klebsiella pneumoniae DT-S and urinary tract infection caused by Proteus mirabilis IFO 3849 in mice.

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We developed assay methods for cefotiam (bioactive form of cefotiam hexetil, CTM) and related compounds in biological specimens. For determination of CTM, an agar well mathod using Proteus mirabilis ATCC 21100 as the test organism and DST agar (OXOID, pH 8.0) as the test medium was established. The sensitivity of the mothod for CTM was about 0.1μg/ml both in 0.1 M phosphate buffer (pH 7.0) and in human serum.
A method with higher sensitivity was also elaborated by using Providencia rettgeri ATCC 9250 and MacConkey agar (pH 8.0). The sensitivity of this method using agar wells and paper discs as the vehicles was about 0.03 and 0.1μg/ml respectively/
A bioautographic method using the same Probidencia strain was devised for detection of antibactetially active metabolites. By this method, CTM and two minor metabolites (SCE-1006 and SCE-1136) were shown in human plasma and urine after oral administration of cefotiam hexetil.

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Cefotiam hexetil (2HCL) is a newly developed orally active cephalosporin, whose parent drug is cefotiam. A high-performance liquid chromatographic (HPLC) method was established for the simultaneous determination of cefotiam and Δ³-cefotiam in human plasma and urine.
A sample solution was prepared after a plasma sample was deproteinized, concentrated and dissolved in a 0.1 M KH₂PO₄ solution or a urine sample was directly diluted with the 0.1 M KH₂PO₄ solution. The sample solution was loaded onto a reversed-phase ODS colum, eluted with a mixture of 0.05 M phosphate buffer (pH7.7) and acetonitrile (88: 12, V/V) and detected by UV absorbance at 254 nm. Recoveries from the spiked plasma and urine were more than 94% with coefficients of variation below 5%. The lower limits of detection in plasmaand urine were 10 ng/ml and 500 ng/ml, respectively. Concentrations of cefotiam in plasma and urine determined by the present method correlated well with those determined by microbiological assay.
For the better understanding of the absorption mechanism orbioavailability of cefotiam hexetil (2 HCL), an HPLC method was also established for the simultaneous determination of cefotiam hexetil and Δ³-cefotiam hexetil in human plasma and fecal samples. A sample solution was prepared after a plasma sample was immediately deproteinized and diluted with the mobile phase or a fecal sample was immediately extracted with 0.1 N HC1 and diluted with 0.1 M KH₂PO₄.
An ODS column, a mobile phase (0.1 M KH₂PO₄, acetonitrile and acetic acid (72: 28: 1, V/V)) and a UV detector at 254 nm were employed for HPLC. When the method was applied to clinical samples, neither cefotiam hexetil nor Δ³-cefotiam hexetil was detected in plasma and fecal samples, but cefotiam and Δ³-cefotiam were detected in the fecal samplesafter oral administration of cefotiam hexetil (2HCl) to human volunteers.

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For determining the metabolites of the ester side-chain of a newly developed oral cephalosporin, cefotiam hexetil (CTM-HE)(2 HC1), a gas chromatographic method has been established. The objective metabolites in biological materials, cyclohexanol (CH) and cyclohexanediols (CHDs), were extracted individually from biological fluids with ether oracetonitrile and then analyzed by gas chromatography using column packings coated with 10% SE-30 and 0.5% FFAP. The determination limit for CH was 0.1μg/ml in both plasma and urine, and the limits for CHDs were 0.025μg/ml in plasma and 1.0μg/ml in urine. This method was applied to the determination of CH and CHDs in clinical trials of CTM-HE (2HCl) and has proved useful for pharmacokinetic studies.

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We studied the pharmacokinetic properties of cefotiam hexetil in mice, rats and dogs.
1. The plasma and tissue levels of cefotiam after oral administration of 20 mg (cefotiam equiv.)/kg of cefotiam hexetil reached a peak at 5-10 min in mice and at 15-30 min in rats. The tissue levels of cefotiam in mice and rats were higher in liver and kidney than in plasma.
In dogs, cefotiam concentrations in plasma after oral administration of 20 mg (cefotiam equiv.)/kg of cefotiam hexetil peaked at 1 h and remained at higher levels than in other animals.
2. The 24-h urinary recovery of cefotiam after oral administration of cefotiam hexetil in mice and rats was 23.2% and 8.3%, and the 6-h urinary excretion of cefotiam in dogs was 4.7% of the dose.
The biliary excretion of cefotiam in rats after the same administration regimen was 8.4% of the dose within 24 h.
3. In rats cefotiam hexetil was absorbed mainly in the duodenum and upper parts of the jejunum; absorption in the rest of the jejunum and in the ileum was low.
4. Cefotiam was the main active metabolite detected in the urine specimens of mice and rats given cefotiam hexetil orally. Small amounts of SCE-1006 and SCE-1136 in mice, and of SCE-1006 in rats, were also detected.
5. The bioavailability of cefotiam hexetil in mice was 47.7% calculated from the AUC and 47.3% from the urinary recovery.

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We studied the metabolic fate of cefotiam hexetil (CTM-HE), the cyclohexyloxycarbonyloxyethyl ester of cefotiam, in rats, mice, and dogs.
1) Disposition of cephalosporin compounds
¹⁴C-CTM-HE administered orally was absorbed largely as cefotiam by the portal route; the extent of absorption was 17, 43, and 8% in rats, mice, and dogs, respectively. In rats given ¹⁴C-CTM-HE orally, the level of cefotiam in plasma peaked 15 min after dosing and then declined with an apparent half-life of 0.9 h. Oral administration of ¹⁴C-CTM-HE to mice gave a peak cefotiam level in plasma at 5 min and an apparent half-life of 0.5 h. In dogs, the level of cefotiam in plasma reached a maximum 30 min after oral administration of ¹⁴C-CTM-HE, this was followed by a decline with an apparent half-life of 1 h. The plasma of these animals also contained a small amount of Δ³-cefotiam. Rats, mice, and dogs excreted cefotiam and Δ³-cefotiam in both urine and feces. No detectable amounts of CTM-HE and Δ³-CTM-HE were present in the plasma and excreta of these animals.
In vitro studies using plasma and homogenates of tissues showed that in rats and mice CTM-HE was converted to cefotiam by carboxyesterase (B-esterase), mainly in the intestinal mucosa, whereas in dogs the antibiotic was hydrolyzed in the liver.
2) Disposition of the cyclohexyloxycarbonyloxyethyl side chain.
After oral administration of ¹⁴C-CTM-HE to rats, mice, and dogs, ¹⁴C derived from the side chain was well absorbed, mainly as cyclohexanol. Cyclohexanol was further metabolized in the bodies of these animals to 1, 2-cyclohexanediol, 1, 3-cyclohexanediol, 1.4-cyclohexanediol, and cyclohexanetriols.
In rats, mice, and dogs given ¹⁴C-CTM-HE orally, the ¹⁴C level in plasma reached a maximum 2, 1, and 2 h after dosing, respectively. Apparent elimination half-lives of ¹⁴C were 4.7, 2.1, and 5.1 h.
In rats and dogs, ¹⁴C was protein-bound only to a small extent (<10%). After oral administration of ¹⁴C-CTM-HE to rats, ¹⁴C was distributed widely in tissues, with relatively high concentrations in the liver and kidney. Placental transfer and lacteal secretion of ¹⁴C were observed in rats.
In rats, mice, and dogs, ¹⁴C was mostly eliminated within 48 h. These animals excreted the ingested ¹⁴C preferentially in urine (≥78%). The remainder was excreted in feces and expired air.
Once-daily oral administration of ¹⁴C-CTM-HE to rats for 14 days resulted in no accumulation of ¹⁴C-labeled materials.

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We studied the general pharmacological properties of cefotiam hexetil (2HCl) in mice, rats and cats.
Cefotiam hexetil (2HCl), at an oral dose of 1000 mg/kg, produced a slight decrease in body tone in general behavior, and a slight decrease in spontaneous locomotor activity in mice, but had no muscle-relaxant, anticonvulsant, hypnosis-potentiating, analgesic or hypothermic activity in mice or rats.
Cefotiam hexetil (2HCl) did not affect the spontaneous EEG in gallamine-immobilized cats (1000 mg/kg, p.o.), or the spinal reflex in anesthetized cats (1000 mg/kg, p.o.) Cefotiam hexetil (2HCl) had no effect on respiratory movement, blood pressure, heart rate or ECG at an intraduodenal dose of 1000 mg/kg in anesthetized cats.
In anesthetized cats, cefotiam hexetil (2HCl)(1000 mg/kg, p. o.) did not affect the bradycardic response to stimulation of the cervical vagus nerve, contraction of the nictitating membrane to preganglionic stimulation of the cervical sympathetic nerve, or changes in blood pressure in response to histamine or norepinephrine.
No significant effect on urinary volume or excretion of sodium and potassium was observed in rats (1000 mg/kg, p. o.).
Cefotiam hexetil (2HCl) slightly potentiated the intestinal transport of a charcoal meal in mice (1000mg/kg, p. o.), and produced an inhibitory effect on the gastric secretion in pylorus-ligated rats (300 and 1000 mg/kg, i. d.).
In conclusion, cefotiam hexetil (2HCl) at high doses had an inhibitory effect on the gastric secretion, but no pharmacological effect on the central, somatic or autonomic nervous system, cardiovascular system or renal function.

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We performed a phase I clinical study of cefotiam hexetil, a prodrug of cefotiam, in 114 healthy volunteers and obtained the following results.
1. Cefotiam hexetil was absorbed rapidly from the intestine as cefotiam. Cefotiam hexetil was not detected in blood and the main metabolite of the ester side chain was found to be 1, 2-cyclohexanediol.
2.α-Cyclodextrin caused a significant rise in the cefotiam plasma peak level.
3. Bioavailability for intravenous and intramuscular administration were 68.8% and 63.2%, respectively.
4. Two 50 mg tablets and one 100 mg tablet, and two 100 mg tablets and one 200 mg tablet were biologically equivalent.
5. Metabolites with the cephalosporin nucleus disappeared rapidly from the blood. While the excretion of 1, 2-cyclohexanediol was rather slow, no tendency to accumulation of 1, 2-cyclohexanediol was observed after multiple administration.
6. Although a decrease in anaerobic and some aerobic intestinal bacteria was observed after multiple administration, the follow-up examination showed recovery of the normal intestinal flora. No Clostridium difficile was detected in any case.
7. Slight abdominal pain and soft stool, observed with multiple doses of cefotiam hexetil disappeared during administration. Slight elevations of S-GPT also recovered to normal one week after administration. No other adverse reaction was observed.

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We performed basic studies on cefotiam hexetil (CTM-HE), a pro-drug of cefotiam, and obtained the following results. The antibacterial activity of cefotiam against clinically isolated Staphylococcus aureus was more potent than those of cephalexin, cephadroxil and cefaclor. Cefotiam inhibited the growth of 41 of 50 isolates (82%) of S. aureus at a concentration of 1.56μg/ml.
Six healthy volunteers were orally given a 200 mg dose of cefotiam hexetil 30 min after breakfast. The mean serum cefotiam level reached the peak level of 1.96μg/ml at 1.5 h after administration and decreased with a half-life of 0.89 h. Eight-hour urinary recovery was 33.2%. The concomitant use of probenecid produced an effect on the peak serum level of cefotiam, its AUC, the serum half-life and urinary recovery of cefotiam. these findings indicate that the renal excretory mechanism of cefotiam in humans comprises proximal tubular secretion.

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Serum and sputum concentrations of cefotiam after a single oral admimstration of 200 mg and 400 mg (cefotiam equivalent) of cefotiam hexetil (CTM-HE), anew oral pro-drug of cefotiam, to 6 patients with chronic pulmonary diseases were investigated. The maximum serum concentration reached 2.0-2.1μg/ml 2 hours after administration when 200 mg of cefotiam hexetil was administered to 2 patients, and 3.0-6.2μg/ml 1-2 hours after administration when 400 mg was administered to 4 patients. Based on the assumption of a onecompartment model, the following kinetic parameters were determined for 200 mg and 400 mg administration, respectively: Tmax is 1.58 and 1.81 h, Cmaxis 2.20 and 4.22μg/ml, T_1/2 is 0.71 and 0.83 h, and AUC 5.83 and 13.14μg·h/ml.
Transfer of the drug into sputum is somewhat slower than into blood and the maximum sputum concentration ranged from below O.06μg/g to 0.3μg/g for both 200 mg and 400 mg administration.

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Cefotiam hexetil (CTM-HE) a pro-drug of cefotiam (CTM), was studied for its transfer into rhinorrhea and otorrhea. The following results were obtained.
CTM-HE was administered to 10 patients, comprising 5 with chronic paranasal sinusitis and 5 with otitis media (1 with chronic otitis media, 2 with acute exacerbation of postoperative otitis media and 2 with cholesteatomatous otitis media) at a dose of 200 mg after meals.
1) CTM levels in rhinorrhea were rather good, being 0.2±0.3, 1.9±1.5, 2.5±4.1 and 1.1±0.6μg/g at 1, 2, 3 and 5 h, respectively.
2) CTM levels in otorrhea, on the other hand, fluctuated and were undetectable until 4 h after dosing in 2 of 5 cases. The averages were 0.4±0.6, 0.9±1.3 and 0.4±0.5μg/g at 1, 2 and 4 h, respectively, which were low compared to the transfer levels into rhinorrhea.

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We evaluated cefotiam hexetil (CTM-HE), a new antibiotic for oral administration, in the treatment of 6 cases with respiratory tract infection, bronchitis and pneumonia. CTM-HE was administered orally at a dose of 200 mg two or three time a day for 7 to 14 days.
Clinical response was excellent in 1 case, good in 2 cases, fair in 2 and unknown in 1. There were no poor cases. As to effect on the causative organisms, Haemophilus influenzae and Streptococcus, pneumoniae found in 2 cases were eradicated by treatment with CTM-HE. No side effects were observed.
We expect CTM-HE to be a safe and effective drug in the treatment of respiratory tract infections.

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We studied cefotiam hexetil (CTM-HE), an oral pro-drug of cefotiam (CTM).
CTM-HE was administered orally in a dose of 200 mg to 6 healthy male volunteers in the fasting state and after meals using the crossover method.
When CTM-HE was given in the fasting state and after meals, Tmax was 1.21 and 1.95 h, Cmax was 2.46 and 1.56μg/ml, T_1/2 was 0.63 and 0.99 h and AUC was 5.55 and 4.96μg h/ml, respectively. The 8-h urinary recovery was 34.4% and 34.1%, respectively. The absorption of CTM-HE was almost the same when the drug was given after meals and in the fasting state.
Twenty patients, 10 with respiratory and 10 with urinary tract infection were treated with CTMHE for 3-14 days. The daily dose of CTM-HE was 300-600 mg divided into 3 doses.
The clinical effect was excellent in 8 cases and good in 12. All cases showed satisfactory response. No side effects or abnormal laboratory findings were observed:
We conclude that CTM-HE is a useful drug for the treatment of internal infections.

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Cefotiam hexetil (CTM-HE), a new oral cephem antibiotic obtained by esterification of cefotiam (CTM) shows higher antibacterial activity than other oral cephalosporins.
This agent was administered at 300-1, 200 mg per day to 25 patients, 2 of whom had bronchitis, 2 pneumonia and 21 acute exacerbation of chronic bronchitis, to evaluate its efficacy and safety.
Clinical response was good in 17 patients, fair in 5 and poor in 3.
Bacteriologically, Haemophilus influenzae was eradicated in 4 cases. Staphylococcus sureus was eradicated in 2 cases, and Klebsiella pneumoniae and Streptococcus pneumoniae in one case each, but Klebsiella oxytoca was not.
Concerning side effects, diarrhea, slight elevation of GPT and eosinophilia were observed in one patient each.
From the above results, we conclude that CTM-HE is an effective and useful antimicrobial agent in the therapy of respiratory infections.

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A daily dose of 300 or 600 mg of cefotiam hexetil (CTM-HE) was administered orally to 11 patients with respiratory tract infections: 2 with acute pharyngitis, 2 with acute tonsillitis, 3 with acute bronchitis, 4 with chronic respiratory tract infections and 1 with pneumonia. Clinical response was excellent in 1, good in 7 and fair in 3 cases. No adverse reactions were observed, but slight elevation of serum transaminase in 2 and mild anemia in 1 case.

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We perfomed a clinical evaluation of cefotiam hexetil (CTM-HE) in 7 patients with respiratory tract infection.
These consisted of 5 males and 2 females aged from 34 to 80 years. Cefotiam hexetil was given orally in daily doses of 600 mg in three divided portions.
The duration of administration was 7 days in 5 cases, and 10 and 14 days in one case each.
A total of 4 strains, comprising 2 of Streptococcus pneumoniae, 1 of Staphylococcus aureus and 1 of Acinetobacter calcoaceticus, were identified from the sputum before administration. S. pneumoniae and S. aureus were eradicated but A. calcoaceticus remained, while one strain of S. aureus appered after the treatment.
The clinical efficacy rate was 100%: excellent in 2 cases and good in 5. There were no side effects, but slight elevation of GPT was observed in one case.
From the above results, we conclude that cefotiam hexetil is an effective, safe and useful new oral cephem.

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Cefotiam hexetil (CTM-HE) was administered orally to 10 patients with respiratory infection, and its clinical efficacy and safety were evaluated. Clinical response was good in 4, fair in 5, poor in 1, and the efficacy rate was 40.0%. The relatively low efficacy rate of 40%, was reasonable since 90% of the patients had chronic respiratory infections.
The antibacterial effect on Haemophilus influenzae was not good when treated with 600 mg/day of cefotiam hexetil.
No side effects or abnormal laboratory findings were observed.

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A total of 8 patients, consisting of 1 with pneumonia, 4 with acute bronchitis, 1 with bronchiectasis, and 2 with acute exacerbation of chronic bronchitis, were given 600mg daily of oral cefotiam hexetil (CTM-HE) in 3 divided doses post prandium for 5-18 days. The response to the medication was excellent in 1, good in 6 and fair in 1, with an efficacy rate of 87.5%.
No adverse reactions or any abnormal changes in laboratory tests were observed.

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Cefotiam hexetil (CTM-HE), a new oral cephalosporin, is a pro-drug of cefotiam.
The MICs of cefotiam for 260 strains of 13 species of clinical isolates were compared with those of other oral antibiotics: cefaclor (CCL), cephalexin (CEX), cefixime (CFIX), bacampicillin (BAPC), fosfomycin (FOM), and clavulanic acid/amoxicillin (CVA/AMPC). The MIC₈₀ of cefotiam (CTM), was 0.78μg/ml for Staphylococcus aureus, 12.5μg/ml for penicillinase-producing Staphylococcus aureus, 25μg/ml for methicillin-resistant Staphylococcus aureus, 0.2μg/ml for Streptococcus pneumoniae, 0.39μg/ml for Escherichia coli, 0.78μg/ml for Klebsiella pneumoniae, 25μg/ml for Enterobacter cloacae, 100μg/ml for Citrobacter freundii, 0.39μg/ml for Proteus mirabilis, 0.78μg/ml for Morganella morganii, 6.25μg/ml for Providencia rettgeri, 100μg/ml for Proteus vulgaris, and 1.56μg/ml for Haemophilus influenzae. The drug proved to have the most potent antibacterial activity of all the antibiotics used in the study against S.aureus, penicillinase-producing S.aureus, E.coli, E.cloacae and M.morganii. Seven patients, 4 with respiratory and 3 with urinary tract infection, were administered 600mg daily of CTM-HE, for 1-13 days. The clinical efficacy was evaluable in 6: excellent 1, good 4, and poor 1. Nausea and vomiting were observed as adverse reactions in 1, but no abnormal laboratory data were found.

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Cefotiam hexetil (CTM-HE), a new oral cephem and a derivative of cefotiam, was administered to 41 patients and evaluated in 39.
All 12 patients with pneumonia, all 6 patients with chronic bronchitis, 5 of 6 patients with acute bronchitis, 3 of 4 patients with other lower respiratory tract infections and 3 of 4 patients with upper respiratory tract infections, responded satisfactorily. One patient with otitis media and all 6 patients with cystitis showed good clinical, response. Adverse reactions observed were mild diarrhea in 2, skin eruption in 1, eosinophilia in 3 and slight elevation of transaminase in 1.

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We performed laboratory and clinical studies on a new oral cephalosporin antibiotic, cefotiam hexetil (CTM-HE).
In vitro antibacterial activity of CTM-HE was evaluated in comparison to cephalexin (CEX) and cefaclor (CCL), using clinically isolated strains of Gram-negative and-positive bacteria.
The antibacterial activity of CTM-HE was stronger than those of CEX and CCL against Escherichia coli and Klebsiella but only slightly effective against Staphylococcus aureus and Staphylococcus epidermidis.
This antibiotic was administered to 6 patients, 3 with acute bronchitis, 2 with acute cystitis and I with acute tonsillitis.
The clinical efficacy of CTM-HE was good in 5 cases and poor in 1.
As to side effects, nausea, vomitting and diarrhea were noted in 1 case, and transient dizziness and thrombocytopenia in 1 case each.

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We clinically evaluated cefotiam hexetil, a new oral cephem antibiotic.
A total of 8 patients, 2 with chronic bronchitis, 2 with bronchiectasis, 1 with acute bronchitis, and 3 with pneumonia, were given cefotiam hexetil in a dose of 100mg or 200mg three times a day.
Clinical response was good in 4 patients, fair in 2 and poor in 2.
No side effects were observed, except slight elevation of BUN in 1 patient.

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We evaluated the therapeutic efficacy of cefotiam hexetil (CTM-HE) in the treatment of patients with respiratory tract infections.
The subjects comprised 1 patient with acute pneumonia and 14 with various respiratory tract infections.
Clinical effect was assessed as good in 8 cases, fair in 2 and poor in 5, the efficacy rate being 57%.
Regarding adverse effects, slight transient abnormalities in liver function tests were seen in one case.
We believe cefotiam hexetil to be an effective antibiotic in the treatment of respiratory tract infections.

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Cefotiam hexetil (CTM-HE) is a new oral cephalosporin, which has been developed by Takteda Chemical Industries. It is a pro-drug of cefotiam, which has a broad antibacterial spectrum.
We report the results of our study on antibacterial activity and clinical trials.
Its antibacterial activity was studied with 25 clinically isolated strains each of Staphylococcus aureus, Streptococcus pneumoniae, Haemophllus influenzae, Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae and compared with those of cefaclor (CCL), cefadroxil (CDX), cephalexin (CEX) and amoxicillin (AMPC),
Although the antibacterial activity of cefotiam against S. aureus, E. coli, K. pneumoniae, and E. cloacae was superior to that of the other drugs, against S. pneumoniae it was slightly inferior to that of AMPC, and against H. influenzae slightly inferior to those of CCL and AMPC.
The clinical efficacy of CTM-HE was evaluated in 17 cases, 1 case of acute pharyngitis, 3 of tonsillitis, 7 of acute bronchitis, 3 of bronchiectasis, 1 of secondary infection with pulmonar) emphysema, 1 of chronic bronchitis and 3 of acute cystitis. The drug was given at a dose of 200 mg of CTM-HE three times a day for 3-15 days.
The clinical effect was good in 15 cases and fair in 1. The clinical efficacy rate was 94%. Bacteriologically, all the bacteria other than Pseudomonas aeruginosa and E. cloacae disappeared.
No side effects were noted.

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Cefotiam hexetil (CTM-HE), a new orally-absorbed pro-drug of cefotiam, was evaluated clinically in 8 patients (aged 23-67 years, mean 44.8) with respiratory tract infections. The daily dose of CTM-HE was 600 mg in three divided oral doses and the duration of treatment ranged from 4 to 10 days, The results were as follows:
1. The clinical effect of CTM-HE on respiratory tract infections was good in all 8 cases. The efficacy rate was 100%.
2. No side effect was noted.

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Cefotiam hexetil (CTM-HE) was administered clinically and the following results were obtained.
1) CTM-HE was administered to a total of 8 patients, 3 with acute and 5 with chronic respiratory tract infection, and clinical response was excellent in 1 case, good in 5, fair in 1 and poor in 1, the efficacy rate being 75%.
2) The causative organism was identified in 1 case, as Klebsiella pneumoniae and was eradicated by the administration of CTM-HE.
3) No side effects were observed.
4) Two cases of eosinophilia and one of elevation of GOT and GPT, considered to be attributable to CTM-HE, were observed.
5) We consider CTM-HE to be a useful antibiotic in respiratory tract infectio

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Cefotiam hexetil (CTM-HE) a newly developed oral cephalosporin antibiotic, was used in 18 cases of respiratory tract infection. A daily dose of 600-1, 200 mg was given in 3 divided doses after meals for 5-15 days.
The diagnosis consisted of bronchiectasis in 7 cases, chronic bronchitis in 3, bronchial asthma with infection and pneumonia in 1 case each, pulmonary abscess in 2 and acute bronchitis in 4. Clinical effect was good in 11, fair in 5, poor in 1, unknown in 1. The clinical efficacy rate was 64.7%.
As a side effect, slight diarrhea was observed in 1 patient from day 1 of administration, and disappeared 1 day after the end of 7 days' medication. In laboratory data, slight transient elevation of GOT and GPT was noted in 1 patient.

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Cefotiam hexetil (CTM-HE), a new cephem antibiotic, was administered orally to 6 patients with respiratory and 3 with urinary tract infection. The patients received the drug for 4 to 14 days in a dose of 300-600 mg/day.
Clinical effect was good in 7 cases, poor in 1, and undetermined in 1, showing an efficacy rate of 87.5%.
As for abnormal laboratory findings possibly related to this drug, there was elevation of GOT and GPT in 1 case and eosinophilia in 1.
There were, however, no side effects.

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A new oral cephem antibiotic, cefotiam hexetil (CTM-HE), was given to 10 patients with respiratory and 1 with urinary tract infection, and its efficacy and safety were studied. The study was carried out from July to November, 1986. The patients consisted of 7 adult males and 4 adult females. The mean age of the patients was 59.3 years (ranging from 27 to 90 years).
CTM-HE was given three times a day at a dose of 200 mg, 300 mg or 400 mg to the patients with respiratory tract infection, and similarly at a dose of 200 mg to the patient with urinary tract infection, The duration of therapy ranged from 4 to 11 days and the total dose from 2.4 to 12.0 g. The therapeutic effect was good in 5 patients, fair in 2, poor in 2 and undetermined in 2, with an efficacy rate of 55.6%. Laboratory tests revealed a slight decline in prothrombin activity in 1 case. No severe side effects caused by the drug were observed.

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The author reports the results of a clinical investigation of cefotiam hexetil (CTM-HE), a new ester -bond compound of cefotiam.
Clinical evaluation was carried out in 15 patients with respiratory tract infections, including 1 with tonsillitis, 10 with chronic bronchitis, 3 with bronchiectasis, and 1 with pneumonia. Response was excellent in 2 and good in 12 patients (the efficacy rate being 93.3%).
As a side effect GOT, GPT, Al-P and γ-GTP were elevated in one case and GOT and GPT were elevated in another, but the adverse reactions disappeared within one week following discontinuance of administration.

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Cefotiam hexetil (CTM-HE) is a new oral cephem antibiotic which is an ester of cefotiam. We investigated the efficacy and safety of CTM-HE in 17 elderly patients. Of the 17, 13 had urinary and 4 lower respiratory tract infection. Excluding one patient whose response was not assessable, clinical response as good in 10 cases, fair in 2, and poor in 4, giving an efficacy rate of 62.5%.
Bacteriological assessment produced the following results. Of two strains of Staphylococcus aureus, one was eradicated, while the other was replaced by Klebsiella oxytoca. One strain of Streptococcus pneumoniae was eradicated, while one strain of Enterococcus was replaced by Pseudomonas aeruginosa. Of four strains of Escherichia coli, three were eradicated and one was replaced by Enterobacter agglomerans. One strain each of Enterobacter aerogenes, Proteus mirabilis and Morganella morganii persisted. Serratia liquefaciens was replaced by Citrobacter freundii. Of three strains of P.aeruginosa, one decreased and the remaining two strains persisted.
There were no adverse reactions or abnormal laboratory findings noted throughout the test. As the subjects were elderly patients with underlying diseases, the above results suggest that CTM-HE is effective in the treatment of elderly patients.

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Cefotiam hexetil (CTM-HE), a cefotiam (CTM) pro-drug which is an ester derivative, exhibits antibacterial activity in vivo. We evaluated the activity of CTM and the clinical efficacy of CTMHE.
1) Antibacterial activity
The MICs of CTM were determined for clinically isolated organisms and the results compared with those of cefaclor (CCL).
CTM was more active than CCL against Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, Morganella morganii and Serratia.
2) Clinical evaluation
CTM-HE was administered to a total of 23 patients, i. e. 4 with pneumonia, 5 with acute bronchitis, 13 with acute exacerbation of chronic RTI, and 1 with chronic bronchitis.
We evaluated the clinical efficacy in 21 patients, and side effects and laboratory findings in 23 patients. The efficacy rate was 66.7%.
Bacteriologically, 2 strains of Streptococcus pneumoniae, 3 of Haemophilus influenzae and 1 of a Gram-negative bacterium were eradicated, but 2 strains each of H. influenzae, K. pneumoniae, Serratia marcescens and Pseudomonas aeruginosa were isolated after CTM-HE administration.
As for adverse events, heartburn was observed in one patient, and as an abnormal laboratory finding, eosinophilia was noted in 2. These symptoms were, however, mild.

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Cefotiam hexetil (CTM-HE), a pro-drug obtained by esterification of the carboxyl group of cefotiam, was given to patients with respiratory tract infection and its efficacy and safety were evaluated.
Two patients with acute exacerbation of chronic bronchitis and 3 with pneumonia were given cefotiam hexetil at an oral dose of 200 mg after meals three times a day for 7 to 14 days.
One patient was excluded from evaluation because his clinical course was unknown. Clinical response was good in the 2 patients with acute exacerbation of chronic bronchitis, and in 2 patients with pneumonia, good in 1 and poor in 1.
As for bacteriological effect, 2 strains of Streptococcus pneumoniae were eradicated and 1 of Haemophilus influenzae persisted.
No side effects or abnormal laboratory findings were observed except slight eosinophilia in 1 patient.

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Cefotiam hexetil (CTM-HE), an orally active ester pro-drug of cefotiam, was administered to 11 patients with chronic respiratory tract infection. Clinical efficacy and safety were evaluated.
1) Eleven patients with chronic respiratory tract infection (chronic bronchitis 2, asthma with infection 3, pulmonary emphysema with infection 1, bronchiectasis with infection 5) were treated with 300-600 mg daily of oral CTM-HE for 7 to 15 days. The efficacy rate was 72.7%(good in 8, fair in 2, poor in 1). In one case of chronic bronchitis, the causative organism, Haemophilus influenzae was not eradicated by a 300 mg daily dose of CTM-HE.
2) As for adverse reactions, neither objective symptoms nor abnormal laboratory findings were noted in any patients.
From the above results, we consider CTM-HE to be a useful drug for chronic respiratory tract infections at a daily dose of 600 mg or more.

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We performed laboratory and clinical studies on cefotiam hexetil (CTM-HE), a new cephalosporin antibiotic and pro-drug of cefotiam, and the results were as follows.
1) Antimicrobial activity
MICs of cefotiam against various clinical isolates were determined with an inoculum size of 10⁶cells/ml. MICs of most strains of Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniaewere less than 1.56 μg/ml, and of most Proteus mirabilis and indole (+) proteus strains were 3.13-6.25 μg/ml, while most of Serratia marcescens were less than 25 μg/ml. But resistant strains with MICs of more than 25 μ/ml were observed in the case of Enterococcus faecalis, Enterobacter spp. and Citrobacter spp. MICs for all strains of Pseudomonas aeruginosa were more than 100 μg/ml. Activity was excellent as compared with those of cefaclor, cephalexin and cefroxadine.
2) Clinical efficacy
Cefotiam hexetil at 100-600 mg/day was given to 3 patients with tonsillitis, 1 with pharyngitis, 1 with acute bronchitis, 3 with acute exacerbation of chronic bronchitis, 1 with chronic bronchitis, 6 with pneumonia, 1 with acute cystitis and 1 with acute pyelonephritis for 3-49 days. Clinical response was excellent in 5, good in 7, fair in 2 and poor in 3 patients. Lip paresthesia and diarrhea as side effects were observed in 1 and 3 patients, respectively. Altered laboratory findings were observed in 1 patient with elevation of GOT, GPT, and Al-P, 1 with elevation of GPT, and 1 with increased eosinophils.

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We examined cefotiam hexetil (CTM-HE), a new oral cephem antibitotic, for its pharmacokinetics in serum, sputum and bile, and for its clinical availability in respiratory tract infections. The results obtained were as follows.
1) Pharmacokinetic study: cefotiam hexetil was given orally at 200 or 400 mg to 4 patients with chronic respiratory tract infection, and 400 mg to 2 PTCD-operated patients with post-hepatic jaundice. The levels of cefotiam (active form of cefotiam hexetil) were assayed micro-biologically. Peak serum levels were 2.5-2.8 μg/ml and peak bile levels were 2.3-2.6μg/ml at the 400 mg dose. Peak sputum levels were 0.1 and 0.3 μg/g at doses of 200 and 400 mg, respectively.
2) Clinical study: cefotiam hexetil was administered to six patients with respiratory tract infection at doses of 600-1200 mg/day for 7-10 days. Clinical response was exellent in 1, good in 3, and fair in 2. One patient showed transient and mild elevation of BUN. Consequently, we consider cefotiam hexetil to be a useful antibiotic in respiratory tract infections.

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Cefotiam hexetil (CTM-HE), a new oral cephem antibiotic, was evaluated basically and clinically to provide the following facts:
1) Antimicrobial activity: the in vitro antimicrobial activity of CTM-HE was tested by the MIC-2000 system. The minimum inhibitory concentrations (MICs) of CTM-HE for a total of 456 strains, consisting of 29 standard strains and 427 clinical isolates, were compared with those of cephalexin (CEX), cefroxadine (CXD), cefaclor (CCL) and amoxicillin (AMPC). CTM-HE showed more potent antimicrobial activity against Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Enterobacter aerogenes and Proteus mirabilis than CEX, CXD, CCL and AMPC. Its activity against Streptococcus pneumoniae and Haemophilus influenzae was inferior to that of AMPC but superior to those of CEX, CXD and CCL.
2) Clinical ealuation and adverse events: 71 patients with respiratory infection were treated with 300-1, 200 mg daily of oral CTM-HE for 3-19 days. The efficacy rate was 76.9%(50/65)(excellent 11, good 39, fair 13, poor 2 and not assessable 6). One patient complained of wooziness, which disappeared immediately after cessation of administration.
Hemato-chemical tests were performed before and after treatment with CTM-HE. Four patients showed abnormal liver function. Eosinophilia and a positive Coombs' test were noticed in two and one Patient respectively. Those transient abnormal laboratory results became normal after cessation of the drug. Consequently, we believe CTM-HE to be a useful antibiotic in treating patients with bacterial respiratory infection.

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We performed laboratory and clinical studies on cefotiam hexetil (CTM-HE), the pro-drug of cefotiam (CTM), in order to evaluate its usefulness in respiratory tract infections.
Minimum inhibitory concentrations (MICs) of CTM against 46 strains of respiratory pathogenic Haemophilus influenzae were 0.20-3.13μg/ml, against 49 strains of Streptococcus pneumoniae 0.10-12.5μg/ml, 41 strains of Branhamella catarrhalis 0.05-6.25μg/ml, 23 of 50 strains of Staphylococcus aureus 0.39-1.56μg/ml and 20 of 21 strains of Klebsiella pneumoniae 0.2-0.78μg/ml.
Peak serum concentration of CTM after oral administration of CTM-HE at doses of 200 mg or 400 mg was 3.1μg/ml at 1 hour. Peak sputum concentration was 0.13μg/ml with a dose of 400 mg-3 times/day. The ratio of peak sputum level to peak serum level was 4.2%.
Twenty-five patients with respiratory tract infection (chronic bronchitis 20, bronchiectasis 2, chronic bronchiolitis 1, pneumonia 1, and acute bronchitis 1) were treated with CTM-HE in doses ranging from 300 mg to 1200 mg daily. Clinical efficacy was observed in 17 of 25 patients (68%). Eight of 16 causative organisms (H.influenzae 2/6, S.pneumoniae 1/4, B.catarrhalis 4/5 S.aureus 1/1) were eradicated. In one case, transient elevation of transaminase was found. CTM-HE was evaluated as an effective and safe cephem antibiotic against respiratory tract infections.

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Cefotiam hexetil (CTM-HE), an oral cefotiam, was administered to 5 patients with respiratory tract infection, of which 2 cases were bronchiectasis, 1 chronic bronchitis, and 2 acute bronchitis, to evaluate the drug's clinical efficacy. The clinical response was good in 3 cases and poor in 2. Bacteriologically, 4 strains of the causative organisms in 3 cases, of which 2 were Haemophilus influenzae, 1 Streptococcus pneumoniae and 1 Pseudomonas aeruginosa, were eradicated except for P.aeruginosa. No side effects or abnormal laboratory findings were observed in any of these cases.

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We performed laboratory and clinical studies on cefotiam hexetil (CTM-HE), a new cephalosporin and pro-drug of cefotiam, with the following results.
1) Antimicrobial activity
The minimum inhibitory concentrations (MICs) of cefotiam (CTM) for a total 134 strains, consisting of 12 standard strains and 122 clinical isolates, were determined and compared with those of cefaclor (CCL). The activity of CTM against Klebsiella pneumoniae, Staphylococcus aureus, Haemophilus influenzae and Branhamella catarrhalis was superior to that of CCL. The activity of CTM against Streptococcus pneumoniae was equally potent to that of CCL. MICs of both antibiotics against strains of Pseudomonas aeruginas were more than 100 μg/ml.
2) Clinical efficacy
CTM-HE 300 or 600 mg/day was given to 4 patients with pneumonia, 3 with acute bronchitis and 3 with acute exacerbation of chronic bronchitis for 5 to 14 days. Clinical response was excellent in 1, good in 4, fair in 4 and not assessable in 1 patient. Vomiting as a side effect was observed in one patient. Altered laboratory findings were observed in 2 patients with transient elevation of GOT and in one case with an increase in eosinophils.

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We performed a pre-clinical, clinical and epidemiological study on cefotiam haxetil (CTM-HE), a new oral cephalosporin antibiotic, with which we treated 43 men with gonorrheal urethritis in the city of Asahikawa. The patients ranged in age from 18 to 70 years, with a peak in the 20s. The major sources of infection in 80% of the patients were non-professional contacts aged up to 25 years, and bar hostesses and prostitutes, in the majority of those over 25.
The MICs of cefotiam against Neisseria gonorrhoeae were between 0.05μg/ml and 0.39μg/ml, with a peak at 0.2μg/ml. PPNG was found in 5 (12.2%) of 41 strains, all of which showed an MIC of 0.39μg/ml. Cefotiam hexetil given in doses of 600mg for 7 days showed an efficacy rate of 100% at day 3 and was thus highly useful as a chemotherapeutic agent against gonorrheal urethritis. The 16 patients in whom Chlamydia trachomatis was also detected exhibited a higher residual rate of secretion following the treatment with cefotiam hexetil than did the patients without this bacterium, requiring continued chemotherapy. Cefotiam hexetil was thought to be a safe drug with no side effects.

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Cefotiam hexetil (CTM-HE), an oral ester pro-drug of cefotiam, was used in the treatment of urological infections, and its therapeutic efficacy and safety were evaluated.
Nineteen patients with acute uncomplicated cystitis and 20 with complicated urinary tract infection (UTI) were treated with CTM-HE at the Department of Urology, Faculty of Medicine, University of Tokyo and affiliated hospitals.
The clinical effect in 13 patients with acute uncomplicated cystitis and 13 with complicated UTI was assessed according to the 3rd Edition of the Japanese UTI Committee's Criteria for Clinical Evaluation of Antimicrobial Agents in Urinary Tract Infections.
Overall clinical efficacy in the 13 patients with acute uncomplicated cystitis was excellent in 10 and moderate in 3, an efficacy rate of 100%. Clinical efficacy in the 13 patients with complicated UTI was assessed as excellent in 4 patients, moderate in 6 and poor in 3.
No adverse effect during therapy was observed. An abnormal laboratory finding after treatment was slight anemia in 1 case.
Thus CTM-HE appears to be a safe and effective drug for the treatment of UTIs.

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1. Cefotiam hexetil (CTM-HE) was administered to a total of 45 patients visiting the Department of Urology, Tokai University Hospital, and the Asaka Kosei Clinic, during the period from May through December 1986, comprising 29 with acute, simple and 16 with complicated urinary tract infection.
2. The patients with acute, simple urinary tract infectionwere medicated with 100-200 mg of CTM-HE 3 times daily for 3 days, and those with complicated urinary tract infection with the same dose but for 5 days as a rule.
3. The response to the medication was evaluated according to the Japanese UTI Committee's Criteria for Evaluation of Clinical Efficacy of Antimicrobial Agents in UTI. The response was excellent in 13, and moderate in 5 of 18 patients with acute, simple cystitis (a response rate of 100%), and moderate in 1 patient with acute, simple pyelonephritis. The response was also excellent in 2, moderate in 2, and poor in 2 of 6 patients with complicated urinary tract infection (a response rate of 66.7%)
4. Bacteriologically, CTM-HE proved very active against Escherichia coli and Staphylococcus epidermidis, eradicating all strains of the species, while enterococci and candidas were not so susceptible to the drug.
5. No adverse reactions to CTM-HE were observed in any patients: the drug proved very safe.

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The following findings were obtained for a new oral cephalosporin derivative, cefotiam hexetil (CTM-HE).
1. Diffusion into human prostatic fluid
The concentration of cefotiam (CTM) in the prostatic fluid at 1 hour after administration of 200mg of CTM-HE was 0.05 μg/ml in 2, and less than 0.05 μg/ml in another 2 human subjects. The mean drug concentration in the blood was 3.3 μg/ml (n=4).
2. Clinical study
(1) Acute uncomplicated cystitis (AUC): 22 female patients were given 300 mg daily of CTM-HE for 3 to 8 days. The response, after 3 days, was evaluated according to the Japanese UTI Committee's criteria, and was excellent in 18 patients and moderate in 4, with a response rate of 100%.
(2) Chronic complicated urinary tract infection (CC-UTI): 13 patients were given 600 mg daily of CTM-HE for 5 to 14 days. The response, after 5 days, was evaluated according to the Japanese UTI Committee's criteria, and was excellent in 4 patients, moderate in 6 and poor in 3, with a response rate of 76.9%. A bacteriological study revealed an eradication rate of 15/18 pathogens, or 83.3%.
(3) Urethrogenital infection: patients with urethrogenital infection were given 600 mg daily of CTM-HE for 5 to 12 days. The response was excellent in 1 patient with gonorrhea. Of 4 cases of bacterial prostatitis, the response was good in 2 caused by Escherichia coli, and fair in 2 caused by Gram-positive cocci.
3. Safety
Neither subjective or objective adverse reactions nor abnormal changes in laboratory findings were observed in any patients.

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We evaluated the clinical efficacy of the new oral cephem, cefotiam hexetil (CTM-HE), an esterified pro-drug of cefotiam, in 22 cases of complicated urinary tract infection. The following results were obtained.
1) The clinical efficacy rate was 60%(9/15) in 15 cases which met the criteria of the Japanese UTI Committee.
2) With a 200 mg dose, the clinical efficacy rate was 50%(4/8). The rate for the 400 mg dose was 71%(5/7).
3) Bacterial eradication rates were 70%(7/10) for Gram-positive bacteria and 72.7%(8/11) for Gram-negative bacteria.
4) Concerning side effects, 1 case of rash and 1 of enterogastric disorder were observed. Abnormal clinical laboratory findings of elevated GOT and GPT were found in the case where a rash was observed.

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