Antibacterial actions have been investigated in vitro and in vivo with a cephamycin antibiotic, CS-1170. As the results, the drug had antibacterial action against various species of Gram-positive and Gram-negative bacteria, besides against indole positive Proteus (Proteus vulgaris, Proteus morganii, Proteus rettgeri and Proteus inconstans) and Serratia to which the existing cephalosporins had only a weak sensitivity. CS-1170 was more stable than other cephalosporins to β-lactamase produced by E. coli, Citrobacter and Klebsiella, and its antibacterial activity was superior to cephalothin (CET)-and cephaloridine (CER)-resistant E. coli and Klebsiella. To the contrary, antibacterial activity of CS-1170 was weaker than existing cephalosporins against Gram-positive bacteria, and the drug was ineffective similarly to cephalosporins against non glucose fermentative Gram-negative bacilli. From the above results, in comparison with analogous cefoxitin (C-FX), CS-1170 was similarly stable to β-lactamase, while it showed slightly stronger antibacterial activity than CFX against most of bacteria species.
In vivo experiment demonstrated that the therapeutic effect of CS-1170 was similar or slightly superior to CFX in the infections due to Staphylococcus aureus, Proteus mirabilis and E. coli, while it was inferior to CEZ. And yet, the therapeutic effect of CS-1170 was superior to that of CEZ in the infections due to CEZ resistant E. coli.

View full abstract

CS-1170, sodium (6R, 7S)-7-(2-(cyanomethylthio) acetamido)-7-methoxy-3-(((1-methyl-1H-tetrazol-5-yl) thio) methyl)-8-oxo-5-thio-1-azabicyclo (4. 2. 0) oct-2-ene-2-carboxylate is a new semisynthetic cephamycin derivative that possesses a broad spectrum of in vitro antibacterial activity against Gram-positive and Gram-negative bacteria. CS-1170 is more effective than cefoxitin (CFX) and cefazolin (CEZ) against Klebiella pneumoniae, indole-positive Proteus and Serratia marcescens. CS-1170, like CFX, was not hydrolyzed by penicillinase and was stable to cephalosporinase, moreover, inhibited the cephalosporinase activity.

View full abstract

Antibacterial activity of CS-1170 was determined to compare with that of cefoxitin (CFX) and cefazolin (CEZ) on Streptococcus faecalis, E coll. Klebsiella, Enterobacter, Serratia, Proteus 5 species, Bacteroides fragilis, totalling 806 strains which we have isolated from various clinical materials in this hospital from 1977 to March 1978.
The activity was compared also on some species with other antibiotics including cephalosporins.
1. CS-1170 exhibited a fairly strong antibacterial activity against E. coli, Klebsiella, Proteus vulgaris, Proteus mirabilis and Proteus inconstans, while a slightly strong antibacterial activity against Proteus rettgeri. The activity was slightly weak against Proteus morganii and Bacteroides fragilis, while fairly weak against Streptococcus faecalis, Enterobacter and Serratia.
2. Antibacterial activity of CS-1170 was weaker than that of CEZ and other usual cephalotporins against Streptococcus faecalis, while it was stronger than that of CEZ against Gram-negative bacilli.
3. Antibacterial activity of CS-1170 was slightly weaker than that of CFX against Bacteroides fragilis, though it was strong against other species. Cross resistance was observed fairly well between these two drugs.

View full abstract

The in vitro antibacterial activity of CS-1170 against anaerobes was determined by agar dilution method. Anaerobic cocci and Gram-positive rods were sensitive to the concentration of 3.13μg/ml or less of CS-1170, whereas many strains of gram-negative rods were resistant to 6.15μg/ml or more of this drug.
The spontaneous resistant mutants were not detected.
Rise in the level, of CS-1170 resistance by serial subculture was slow.
CS-1170 has been found effective, on the experimental subcutaneous abscess with Fusobacterium necrophorum as well as cefazolin.

View full abstract

The in vitro and in vivo antibacterial activity of CS-1170 was compared with that of cephalothin (CET) and cefazolin (CEZ). The following results were obtained.
1) Studies on the antibacterial activity of CS-1170 in vitro showed the compound to be, active against a wide range of Gram-positive and Gram-negative bacteria.
2) Sensitivity distribution of clinical isolates to CS-1170 exhibited stronger activity than CET and CEZ against not only cephalosporin sensitive Escherichia coli and Klebsiella pneumoniae but also most strains of cephalosporin-iesistant Escherichia coli, Klebsiella pneumoniae, indole-positive Proteus sp. and Serratia marcescens, while slightly inferior to those of CET and CEZ against Staphylococcus aureus.
3) It was cleared that the antibacterial activity of CS-1170 against Gram-negative bacteria was enhanced at high pH, on the contrary, those of CET and CEZ were rather increased at low pH. The antibacterial activity of CS-1170 was influenced by inoculum size to lesser degree as compared with those of CET and CEZ.
4) Bactericidal action of CS-1170 was observed at the level of MIC against cephalosporin-sensitive or resistant Escherichia coli.
5) After subcutaneous administration of CS-1170 to, mice at a single dose of 50mg/kg, the tissu level at the peak was highest in the liver and kidney, followed by the serum, lung and spleen in descending order.
6) CS-1170 was more effective than CET and CEZ in experimental mice infections caused by Gramnegative bacteria, including cephalosporin-resistant Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris, Proteus morganii and Serratia marcescens.

View full abstract

As an aid for seeking an optimal method for dosing a new cephamycin antibiotic, CS-1170, against E.coli ST-0198 and Klebsiella pneumoniae infections in mice, both in vitro and in vivo antibacterial actions of CS-1170 were examined, and the following results were obtained.
1) CS-1170 showed dose-dependent bactericidal action on E.coli ST-0198 and Klebsiella pneumoniae in vitro.
2) Growth inhibition time (lag) of E.coli ST-0198 damaged by 10 MIC of CS-1170 was about 1 hour. However Klebsiella pneumoniae damaged by CS-1170, when the drug was free, immediately began to regrow in vitro.
3) The therapeutic effect of CS-1170 on E. coli ST-0198 infection in mice seemed to be superior in single dose in a few large doses than in multiple in jections. On the other hand, the therapeutic effect of CS-1170 on Klebsiella pneumoniae infection in mice found to be superior in multiple injections than single administration.
4) An important factor to decide the therapeutic efficacy of CS-1170 was the highness of drug concentration rather than the total duration time of the effective concentration in Klebsiella pneumoniae infection.

View full abstract

The effects of CS-1170 and cefazolin (CEZ) on the morphology of Escherichia coli No.29, Proteus morganii 101 and Serratia marcescens T-55 were examined with light microscope, phase contrast microscope and scanning electron microscope. The following results were obtained.
1) Exposure of E. coli No.29 to CS-1170 revealed the formation of long filaments and spheroplastlike structures. The degree of morphological change was related to the concentrations of CS-1170 used. The filamentous forms were observed when the concentration of CS-1170 was low. Where the concentration of CS-1170 was high, the cells formed spheroplasts.
It seemed that these morphological alterations of E. coil No.29 treated with CS-1170 were similar to that seen with CEZ.
2) The filamentous forms, spheroplast-like structures, and cell lysis were observed when CS-1170 was allowed to act on Proteus morganii 101 and Serratia marcescens T-55 (β-lactam antibiotics resistant strains)
When effected with CEZ, most cells grew similarly to untreated controls in Proteus morganii 101 and Serratia marcescens T-55.

View full abstract

CS-1170 is a semisynthetic cephamycin derivative having good activity against both Gram-positive and Gram-negative bacteria. The activity was bactericidal and was little influenced by changes in pH of the medium and in inoculum size and by co-existence of human serum in the medium up to 50%.
The susceptibility of more than 900 clinical isolates to CS-1170 was determined by agar dilution method. At a concentration of 3.12μg/ml, over 80% of the pathogens belonging to the following genera were inhibited: Staphylococcus, Streptococcus (except enterococci), Escherichia, Klebsiella, Protein, and Haemophilus. At a concentration of 25μg/ml, three-fourths or more of Serratia and Yetsinia were also inhibited. Enterococci and pseudomonads were resistant to CS-1170.
CS-1170 was highly resistant to hydrolysis by β-lactarnases derived from strains of E. coli and indole-positive Proteus, and moreover inhibited competitively the activity of the enzymes to the substrates at very low concentrations.
Model infections in mice caused by several strains of β-lactamase producing and non-producing pathogens such as Staphylococcus aureus, Streptococcus, E. coli, Klebsiella piieumoniae, both indole-negative and-positive Proteus, and Serratia marcescens responded well to therapy with subcutaneous doses of CS-1170.
Thus we believe CS-1170 can be considered to be a prominently powerful candidate for further studies aiming to clinical trials.

View full abstract

Pharmacokinetics and metabolic fate of CS-1170 were studied in mice, rats, rabbits, dogs and monkeys. It was found that there is a large species variation in the blood levels and urinary excretion and that monkey is the most suitable model for human pharmacokinetics.
After subcutaneous or intramuscular administration (50mg/kg), the urinary recovery was lowest in rats (22%) followed by mice and dogs (60%) and rabbits (64%), while highest in monkeys (77%).
The peak plasma concentration was also lowest in rats (27gg/ml) and highest in monkeys (150gg/ml).
The species difference was found to be mainly due to that in the participation of biliary excretion and the excretion in cannulated animals was in the order: rabbits (1.3%) < dogs (15%) < rats (60%).
The concentration in the bile was significantly higher in CS-1170 as compared to cefazolin in all animals tested.
The distribution studies in rats and mice showed that the concentration of CS-1170 was high in the liver and kidney, followed by the plasma and lung, while low in the muscles, pancreas and spleen and none in the brain.
The fate of CS-1170 in monkeys was studied in detail by bio-and radioassay with 7α-rnethoxyl-¹⁴C-labeled drug. The plasma level of radioactivity after intramuscular injection reached the maximum after 10 min and declined afterward with half-life of 48 min. In the plasma extracts, a single radioactive spot corresponding to CS-1170 was detected on TLC. Over 75% of the intravenous or intramuscular dose was recovered in the urine by both radio-and bioassay, the most part being excreted during the first 3 hr. In the TLC autoradiogram of urine, the main radioactive spot was observed corresponding to CS-1170. The counting experiment revealed that over 97% of the urinary radioactivity in the 3 hr urine is intact CS-1170. In the feces, about 15% of the radioactive dose was recovered in which 30-40% was detected as intact CS-1170. In the respiratory air, only about 1% of the dose was excreted as ¹⁴CO₂, indicating that 7-methoxyl moiety is stable in the body.

View full abstract

General pharmacology of CS-1170, a new semisynthetic cephamycin antibiotic, was studied.
On the central nervous system, CS-1170 potentiated thiopental anesthesia in mice at an i. v. dose of 2000 mg/kg and caused seizure discharge in EEG, clonic convulsion and enhancement of spinal reflexes in cats at an i. v. dose of not less than 800mg/kg. The convulsive effect of CS-1170 was one tenth as that of cefazolin sodium. CS-1170 gave no significant influence on gross behavior, locomotor activity, conditioned avoidance response and bodytemperature and showed no anti-convulsant, muscle relaxant and analgesic effects.
On the respiratory, cardiovascular and autonomic nervous systems, CS-1170 caused slight transient increase of respiratory rate, slight hypertension, slight decrease of heart rate and transient increase of femoral, carotid and coronary blood flow in anesthetized dogs at an i. v. dose of not less than 800mg/kg. Blood pressure responses to carotid artery occlusion and biogenic amines and contraction of nictitating membrane induced by electrical stimulation of cervical sympathetic nerves in cats and movements of isolated guinea pig atria were not influenced by CS-1170.
Movements and tone of stomach, ileum, pregnant and nonpregnant uterus, seminal vesicle and tracheal muscle in situ and in vitro and oxytocin-induced contraction of isolated pregnant rat uterus were not influenced by CS-1170.
CS-1170 showed no spasmolytic effects against acetylcholine, histamine, serotonin, nicotine and adrenaline.
Gastric secretion in rats and intestinal propulsion and defecation time in mice were not influenced by CS-1170.
CS-1170 caused dose-dependent increase of urine volume and sodium excretion in rats at i. v. doses of 1000 and 2000 mg/kg. Furosemide-induced saliuresis was little influenced by CS-1170.
CS-1170 gave no significant influence on isolated phrenic nerve-muscle preparation, carrageenin edema, blood sugar level, blood clotting time and platelet aggregation and showed no antitussive, hemolytic and local anesthetic effects.
As shown above, significant pharmacological actions of CS-1170 were observed only at 800mg/kg i. v. or more but not at 400mg/kg, which would be assumed 20 to 40 times as that of the single clinical dose. This suggests that CS-1170 would not cause any adverse effects clinically.

View full abstract

Determination method of tissue distribution of CS-1170, a new semisynthetic cephamycin group antibiotic, was studied wih use of serum and urine of the phase one study. Thin layer cup-plate method in which Micrococcus luteus ATCC 9341 was used as test organism was proved to be the best way to determine the low level of CS-1170 in body, fluid. The sensitivity of this method for CS-1170 in human serum was 0.6 μ g/ml. Conuenient thin layer disc-plate method was not different from thin layer cupplate method, though the former showed somewhat larger deviation as compared with the latter. The sensitivity of thin layer disc-plate method for CS-1170 in human serum was 1 μ g/ml. The body fluid level of CS-1170 obtained by these bioassay methods was in good agreement with that obtained by HPLC method. Serum level of CS-1170 was 30-40% lower, if Moni-Trol I or Consera was used in place of human serum as the diluent for preparing standard solution in the thin layer cup-plate method. It was confirmed that serum level of CS-1170 was not affected if serum samples were diluted with serum or buffer solution when the standard solution of serial dilution was prepared with the diluent of the same composition as that of test sample solutions. Furthermore measured serum value of CS-1170 was not affected when Micrococcus luteus ATCC 9341 or Bacillus subtilis ATCC 6633 was used as test organism. The sensitivity of the thin layer cup-plate method for CS-1170 in human serum was 10 μ g/ml when Bacillus subtilis ATCC 6633 was used, test organism.
CS-1170 was stable in buffer solution, human serum and human urine when it was kept in frozen state. Although CS-1170 was somewhat unstable in human bile, it showed no decrease of the potency when it was kept frozen with addition of the equal volume of pH 6.0 phosphate buffer solution.

View full abstract

CS-1170 was studied in rabbits on its immunogenicity and cross-reactivity with the related antibiotics. It was shown that CS-1170 and cefazolin (CEZ) stimulate the production of hemagglutination antibody by immunization of respective antibiotic with Freund's complete adjuvant, while not by multiple intravenous immunization of each antibiotic without adjuvant. CS-1170 showed the cross-reactivity with other beta-lactam antibiotics to a minimal extent, as it was with CEZ. No positive Coombs' reaction was induced by CS-1170.

View full abstract

CS-1170, a new cephamycin preparation, has been investigated to give following results.
1) Pharmacokinetics: The mean peak serum concentrations in 6 male healthy volunteers were 103.2 μg/ml in 15 minutes following administration of 1 g intravenously. The mean of half life in the serum was found to be 54 minutes and the urinary recovery rate was 83.9% in 6 hours.
2) Clinical evaluation: Thirty four patients with various infection were treated with CS-1170 receiving, 1 to 5 g per day for 4 to 16 days intramuscularly or intravenously (one shot and drip infusion).
Two of 34 patients were cured excellent, 19 were good, 7 were fair and 6 were failure. No side effects were occurred. However, ten of 11 patients administered intramuscular injection had the pain of injection site.
On the laboratory findings, 4 eosinophilia and 3 elevated of GOT were occurred.

View full abstract

CS-1170 (Sodium (6R, 7S)-7-(2 (cyanomethylthio) acetamido)-7-methoxy-3-(((1-methyl-1H-tetrazol-5-yl) thio) methyl)-8-oxo-5-thio-1-azabicyclo (4. 2. 0) oct-2-ene-2-carboxylate) is a new antibiotic, developed from a cephamycin by Sankyo company.
Thirty-one cases in total, including 24 respiratory infectious diseases, of which 11 were chronic pneumonitis cases, and 13 were acute pneumonia cases; and 6 cases of acute or chronic urinary infectious diseases, were treated by CS-1170 intramuscularly (0.5 g, 2 or 3 times a day, within 5 days), one shot intravenously (0.5 or 1.0 g, 1 or 2 times a day, within 7 days) or by drip venous infusion (1.0 or 2.0 g, 2 or 4 times a day, within 17 days). As the results, 26 of 30 cases (86.7%) showed over fair effects, and 70% of effective cases were observed within dosage of 30 g in total. As to the side effects of the agent, one case complained of nausea in 2.0 g one shot intravenous injection, and one headache and cold sweat after 14 days of the treatment, while no case revealed any unfavorable effects on hepatic and renal functions in laboratory findings.

View full abstract

The treatment was made with CS-1170, to evaluate its clinical response, in 14 cases of infections including 3 of acute suppurative lung disease, 4 of acute pneumonia and 6 of urinary tract infection. As the result, 4 cases were cured with excellent clinical response, 9 were good, and 1 showed poor. All cases of acute urinary tract infection responded well to the treatment, and Escherichia coil was found in these cases as causative organism. In conclusion, CS-1170 treatment was proved to respond well clinically for the urinary tract infection, acute pneumonia and acute suppurative lung disease.
As to the side effects of CS-1170, rash was noticed in 1 patient, and increments of serum transaminases and BUN in another patient.

View full abstract

Laboratory and clinical investigations were performed on CS-1170 and the results were obtained as follows.
1) Susceptibility and clinically isolated strains to CS-1170 was determined by ager plate dilution method, and compared with that to cephaloridine, cefazolin and ceftxitin. Minimum inhibitory concentrations of CS-1170 were examined against 54 strains of Haemophilus influenzae, 64 of Kkbsielk, 33 of Serratia and 26 of E. coli, and values counted 6.25 μg/ml (90.7%), 0.78 μg/ml (71.9%), 12.5 μg/ml (75.8%) and 1.56 μg/ml (84.6%) respectively.
2) Eleven patients of respiratory tract infections were treated by CS-1170, and 9 cases showed effective clinical results.
Any side effects were not observed in all 12 patients, except that 1 case showed exanthem on the body skin.

View full abstract

CS-1170 was administered to 4 patients of pneumonia, 4 of lung abscess, 6 of superinfection of bronchogenic carcinoma and 1 of superinfection of systemic lupus erythematosus for therapeutic purpose. Streptococcus pneumoniae was isolated from sputum in 5, Klebsiella pneumoniae in 4, and coagulase (+) Staphylococcus aureus, E. coli, Enterobacter aerogenes, Citrobacter freundii, α-hemolytic Streptococcus and gram (-) bacill i in one each.
CS-1170 was infused intravenously twice daily at a dose of 1-3g in 300 to 500 ml of 5% glucose or xylitol in water for mean 20 days.
Three patients developed nausea, vomiting and serious headache on the 2nd or 3rd day of administration, and 3 others skin rash on the 10th to 13h day. Serum GOT levels were elevated in 4 patients but returned to normal range in 1 to 2 weeks after the withdrawal of medication. During and after the administration of CS-1170, sputum culture showed α-hemolytic Streptococcus in 7, Klebsiella pneumoniae, Enterobacter aerogenes, Enterobacter cloacae, Proteus mirabilis and Citrobacter freundii in one each.
Two patients were dropped out of the study because of either untoward effect or unrelated death. Of the remaining 13 patients, remarkable therapeutic effect was observed in 4, moderate effect in 4, minimum effect in 2 and no effect in 3 patients. A unique characteristic of CS-1170 was the effect on Klebsiella pneumoniae; the organism was either eradicated or did not grow during the administration of CS-1170.

View full abstract

CS-1170 was applied to the following infections, and the results are as shown below:
CS-1170 was effective in total 14 cases consisting of 3 cases of bacterial pneumonia, 1 case of bronchitis, 3 out of 4 cases of acute pyelonephritis, 6 out of 9 cases of chronic pyelonephritis, and a case of cholecystitis. The effective rate was 63.6%.
As bacteriological results CSr1170 was effective in 8 out of 9 cases of E. coli, a case of Proteus mirabilis, and a case of Haemoplilus parainfluenzae, but was ineffective in a case of Klebsiella, 2 cases of Citrobacter and a case of Enterobacter.
Side effects were observed in 3 cases: induration of the site of injection in 2 cases, and shock-like symptom in one case.
No adverse effect of CS-1170 was found in hemogram nor in urinalysis.

View full abstract

On a new cephamycin group antibiotic, CS-1170, several basic and clinical studies were performed and the following results were obtained.
1) The sensitivities to CS-1170 were determined about clinical isolates belonging to gram negative bacilli comparing with those to cefazolin (CEZ). In general the antibacterial activity of CS-I170 markedly exceeded that of CEZ.
2) The phase one study of CS-1170 was performed in our clinic. CS-1170 was administered in gradually increasing doses by three routes to a total of 24 volunteers, confirming the safety of this agent.
3) At above mentioned study, blood level, urinary recovery and metabolism were also investigated. The blood level rose relatively high, and sustained well. Urinary recovery was also high. There found no bioactive metabolite from urine.
4) The blood level in drip infusion of CS-1170 was compared with that of cefoxitin (CEX) and CEZ in cross over fashion. When standard curve was drawn by serial dilution of the drug using buffer, the blood level of CS-1170 was maintained in the highest value among them.
5) At a patient who had been built external biliary fistula, biliary excretion of CS-1170 was compared with that of CFX in cross over fashion. CS-1170 was superior to CFX in both of biliary level and excretion rate.
6) Clinically CS-1170 was administered to 7 patients with various infections. As a result, 4 were good, one was poor and 2 were impossible in judgement. No side effect was observed.

View full abstract

CS-1170, a new semisynthetic cephamycin antibiotic, was studied on its antibacterial activity, absorption, excretion and clinical effect, and the following results were obtained.
1) Antibacterial activity
Susceptibility of CS-1170 was distributed among 0.39-100 ≤μg/ml with E. coli, and 45 of 50 strains were inhibited at 6.25 μg/ml or less: 0.78-100 ≤μg/ml with Klebsiella pneumoniae, and 41 of 50 strains were inhibited at 6.25 μg/ml or less: and 3.13-100 ≤μg/ml with Serratia marcescens. Antibacterial activity of CS-1170 was similar to cefazolin against gram-negative bacteria.
2) Serum levels and urinary excretion
CS-1170 was given by a single intravenous administration at a dose of 1.0 g in a case with normal renal, function, and serum level was 76.0 μg/ml after 15 minutes, 7.6 μg/ml after 4 hours, and serum half life of the drug was 1.1 hours. This serum half life was prolonged in proportion to the degree of impairment of renal function, and it was 9.3 hours in a case with 9.6 ml/min. of creatinine clearance. Urinary recovery of CS-1170 was 83.5% 6 hours after 1.0 g intravenous administration in a case with normal renal function, while it was only 26.1% in a case with 9.6 ml/min. of creatinine clearance.
3) Clinical results
CS-1170 was clinically applied to 10 cases of bacterial infection, including 7 cases of urinary tract infection and each 1 case of sepsis, cholecystitis and respiratory tract infection. The results obtained were good in 7 cases, fair in 1 case and poor in 2 cases.
No marked side effects were observed with CS-1170.

View full abstract

Studies were made of CS-1170 to obtain results as summarized below:
1. Antibacterial activity
The MIC s of CS-1170 onE. coliandKlebsiellawere measpred with the results that the agent showed a potent antibacterial activity against them, especially strains resistant to cefazolin.
2. Absorption and excretion
CS-1170 was administered intravenously in doses of 0.5 g and 1.0 g to show dose responses in the blood level. The urinary recovery amounted almost to 100% in 6, hours.
3. Clinical trial
CS-1170 was administered to one patient with subacute bacterial endocarditis, two patients with urinary tract infection and one patient with localized peritonitis to prove effective in 3 cases.
No side effects were observed.

View full abstract

Antimicrobial activity of CS-1170 was determined on 42 strains ofBacteroides fragilisIt was found that 12.5μg/ml of the drug inhibited about two thirds of the strains.
Clinical evaluation of CS-1170 was performed on 7 elderly patients. Satisfactory response was obtained in 3 patients ofE. colisepticemia and 2 patients of urinary tract infection, while efficacy was not determined in other 2 patients of urinary tract infection. Prothrombin time was prolonged during these treatment in a patient with impaired renal function.

View full abstract

1) Antibacterial activity of CS-1170 was stronger than that of cefoxitin (CFX) and cefazolin (CEZ) againstE. coli, KlebsiellaandCitrobacter freundii.CS-1170 was equally effective to CFX and more effective than CEZ againstSerratia marcescensandProteus morganii. Proteus mirabiliswas susceptible to all three of the drugs tested, whereasEnterobacter cloacaewas mostly resistant to these drugs. Antibacterial activity of CS-1170 was slightly weaker than that of CFX againstProteus rettgeriandProteus inconstansB, while it was stronger than that of CEZ. Strains resistant or nearly resistant to CER and CEZ (MIC: 25μg/ml or more) showed mostly stronger sensitivty to CS-1170, and CS-1170 was found to be superior to CFX in MIC against these strains.
2) Blood concentration of CS-1170 was higher when diluted with serum than with buffer solution and its urinary recovery rate was high.
3) CS-1170 was excreted more rapidly into bile than CEZ, besides the drug showed higher biliary concentration than CEZ.
4) CS-1170 was administered clinically in 7 cases of respiratory tract infection, 4 cases of bile duct infection and 2 cases of urinary tract infection, and the results obtained were good clinical response in 11 cases and no response in 2 cases. From bacteriological viewpoint, pathogens were eradicated in 5 cases, microbes were substituted in 4 cases, no change was caused in 1 case, and the result was undetermined in 3 cases.
5) No side effect was observed in any case treated by CS-1170. Hematological and hematochemical analyses did not show any change which would have been attributed to CS-1170. From the results mentioned above, CS-1170 may be considered to be a clinically useful antibiotic of cephamycin group.

View full abstract

The efficacy of CS-1170, a new antibiotic agent, in the treatment of 12 cases of relapsed chronic bronchitis, 10 cases of pneumonia and 3 cases of urinary tract infections was studied.
With relapsed chronic bronchitis, excellent response was observed in a case, good response in 7 cases, poor in 4 cases (efficacy rate: 67%); with pneumonia excellent response in 3 cases and good response in 7 cases (efficacy rate: 100%); and good response in all three cases of urinary tract infections.
In view of the above, CS-1170 appears to be a clinically useful agent against these infections, and is worth further studies.

View full abstract

1) Sensitivity of 5, 4 and 3 strains ofE. coli, Serratia marcescensandPseudomonas aeruginosa isolatedfrom patients, respectively, to CS-1170 was compared with that of cefazolin (CEZ), cephalothin (CET) and ampicillin (ABPC) The antibacterial activity of CS-1170 againstE. coilandSerratia marcescenswas superior to that of CEZ, CET and ABPC. However, all strains ofPseudomonas aeruginosawere insensitive not only to CS-1170, but also to other three antibiotics.
2) Blood level and urinary recovery of CS-1170 were determined in two patients.
Peaks of blood level by single intravenous injection of 1.0g of CS-1170 and a subsequent intramuscular injection of 0.5g were 78μg/ml at 15 min. and 15.5μg/ml at 30 min., respectively.
Dose was recovered at 77.8% in urine within 2 hours after intravenous injection, and at 111.4% within 4 hours after intramuscular injection.
3) Ten patients other than with mycoplasma infection responded well to CS-1170 therapy.
With regard to haematological findings, erythrocyte counts, haemoglobin and haematocrite decreased in one patient, and eosinophile counts elevated in 2 patients.

View full abstract

CS-1170, a new derivative of cephamycin, was used clinically and the following results were obtained:
1) As compared with cefazolin (CEZ), fewer strains of clinically isolatedE. coliandKlebsiellaa were resistant to CS-1170.
2) Favorable responses were observed only in two of the five clinical cases, probably due to the advanced stages of the underlying diseases in the patients.
3) Rash was observed in one case, although not determinable as the side effect of CS-1170.
4) No abnormal value attributable to CS-1170 was found in clinical examinations.
5) CS-1170 would be a clinically useful antibiotic agent if used selectively for appropriate cases.

View full abstract

The nephrotoxicity of CS-1170 was compared with that of.cephalothin or cefazolin in experimental animals. Rabbits were injected intravenously with lg/kg of CS-1170, cephalothin or cefazolin for 5days. In rabbits treated with CS-1170 or cephalothin, changes in renal tubular cells were not found, while the kidneys of animals receiving cefazolin had degeneration and necrosis in tubular cells. In addition, rabbits treated intravenously with 2g/kg of CS-1170 or cephalothin for 10 days had no notable lesion in tubular cells.
Clinical application of CS-1170 was attempted in 26 patients with various infectious diseases. The good responses were demonstrated in 24 patients, and there was no side effect nor toxicity observed, except for one patient who showed a transient elevation of transaminase.

View full abstract

1) After an intravenous injection of 1 g of CS-1170 into patients with various enal functions, serum levels were measured. The half-life of serum levels prolonged in relation to the degree of renal impairements. In dialized uremic patients, serum levels were lower than those of non-dialized one. 2) CS-1170 was administered to 25 patients with respiratory (11 cases), both biliary and ab dominal (5cases), and urinary tract infections (6 cases), and with fever derived from peritoneal or hemodialysis. Clinical results were excellent in 3, good in 15, fair in 3, and poor in 3 cases, but the result of 1 patient could not be determined. Liver damage occurred in 1, and eosinophilia in 1, but no significant side effects were recognized in another cases.

View full abstract

Pharmacokinetics of CS-1170 was studied in healthy adult volunteers and patients with impaired renal function.
1) The concentrations of CS-1170 in the sera were assayed by an agar diffusion method (thin layer cup method) with Bacillus subtilis PCI 219, in the range between 200 and 12.5 μg/ml, and Micrococcus luteus ATCC 9341 below 12.5 μg/ml as the test organism. By using Bacillus subtilis as the test organism, the serum specimens were not required to be diluted in the high concentrations of CS-1170. The serum specimens having the concentration of about 12.5 μg/ml were assayed both by Bacillus subtilis and Micrococcus luteus as the test organism and the concentrations obtained by using two organisms have coincided in the range of error of biological assay.
2) Four healthy adult volunteers were received 2 hours intravenous continuous infusions of 1g, 2g, and 4 g of CS-1170. The average concentrations of CS-1170 in the serum at the end of infusions were 51.51, 07 and 203.75 μg/ml respectively, and showed apparent dose responses. The avarage elimination rate constant was 0.723 ± 0.085, biological half life in the serum was 0.97 ± 0.10 hours, and recovery rate in urinary excretion untill 4 hours after the end of infusion of the drug was 83.28 ± 8.13 %. The renal clearance of CS-1170 was 103.7 ± 28.02 ml/min.
3) The biological half lives of CS-1170 in the serum showed prolongation in the patients with impaired renal function, accounting 3.08 and 27.11 hours in whom creatinine clearance revealed 37.2 and 2.8 ml/min. The correlation between elimination rate constant (Kel) and creatinine clearance (Ccr) was significant, and the linear relationship was observed giving formula of Kel=0.07 + 0.006·Ccr.

View full abstract

Laboratory and clinical investigations have been carried out on CS-1170, a new semisynthetic cephamycin, and following results were obtained.
1) CS-1170 exhibited a growth inhibitory action against wide range of Gram-positive and Gram-negative bacilli, and stronger antibacterial activity than cephalothin (CET) and cephaloridine (CER) against E. coli, Klebsiella, Serratia and Proteus.
2) CS-1170 was injected intravenously by drip infusion singly as chemotherapeutic drug for respiratory tract and urinary tract infections, and favorable result was obtained in 12 cases (85.7%) out of 14 respiratory tract infections, while marked improvement was obtained in 6 cases (100%) of urinary tract infections.
3) Side effect was observed in 2 cases; eosinophilia was shown in one, and BUN elevated slightly in another with renal dysfunction.

View full abstract

Laboraotory and clinical investigations were performed on CS-1170 and the following results were obtained.
1) In vitro antibacterial activity was examined on standard strains and clinical isolates of Staphylococci and Gram-negative bacilli (E. coli, Klebsiella pneumoniae, Proteus and Pseudomonas aeruginosa). Although the activity of CS-1170 was somewhat inferior to that of cefazolin (CEZ) against Staphylococci, it was several grades superior against Gram-negative bacilli, and no resistant bacteria was noticed. CS-1170 was ineffective against Pseudomonas aeruginosa as it was with CEZ.
2) After CS-1170 was administered subcutaneously in rat, concentrations in blood and organs were ranged liver>kidney>blood>lung in order. Both levels demonstrated a peak 30 minutes after the administration, and they were not detected after 6 hours.
3) CS-1170 was administered clinically in 11 cases of internal infections of moderate or more severe grade, and the results obtained were good in 6 cases, poor in 1 case, and undetermined in 4 cases. As to the side effects of the drug, eruption and pain at the injected site were noticed respectively in 1 case.

View full abstract

CS-1170 was administered by intravenous drip infusion to a total of 12 clinical cases consisting of 6 respiratory tract infection, 4 urinary tract infection, a bile duct infection and an acute enteritis. Either excellent or good responses were obtained in all of the cases.
The present study indicates that' a relatively minor dosage of CS-1170, i.e., 1000 mg/day, should be sufficiently effective against moderate and uncomplicated infection. Complicated cases and aged patients have tolerated the administration of CS-1170 over extended periods, and this suggests that CS-1170 is clinically safe drug.
Side effects such as drug eruption and vascular pain were not observed in our study, however, an elevation of GOT for a short duration was noted in one case.

View full abstract

Clinical studies on CS-1170, a new cephamycin antibiotic, were carried out, and the following results were obtained.
1) CS-1170 was administered intramuscularly or intravenously by drip infusion at a daily dose of 0.5-2.0g for 7 to 23 days to 5 patients consisting of 2 pneumonia, 1 bronchopneumonia, 1 of lung abscess and 1 cavitary lesion of uncertain etiology.
Clinical response was good in 2 patients of pneumonia, slightly good in 1 patient of lung abscess, and not assessable in remaining 2 patients due to uncertain etiology.
2) Side effects of CS-1170 were noticed in 2 patients. One patient of pneumonia complained of pain, redness and induration at the site of intramuscular injection.
Another patient of bronchopneumonia complained of general malaise during, the intravenous drip infusion. The drug was administered thereafter safely.

View full abstract

Laboraory and clinical sudies have been carried ou on CS-1170, a new cephamycin anibioic developed in our counry, and he following resuls were obained.
1) MICs of CS-1170 to Staphylococcus aureus, E.coli, Klebsiella, Proeus mirabilis and Proeus vulgaris isolaed clinically, demonsraed a peak a 1.56μg/ml, 1.56μg/ml, 3.12μg/ml, 6.25μg/ml, and 12.5μg/ml respecively, and MIC lowered to 1/2-1/4 when he inoculum size was reduced. Anibacerial aciviy of CS-1170 to hese baceria was superior to cefazolin (CEZ) excep to Staphylococcus aureus, and CEZ resisan srains showed mosly good sensiiviy to CS-1170. However, he drug exhibied no anibacerial aciviy agains Pseudomonas aeruginosa similarly to CEZ.
2) CS-1170 was adminisered inramuscularly or by inravenous drip infusion at a daily dose of 1.5-4.0g to 8 cases of respiraory rac infecion, 2 cases of biliary rac infecion 5 cases of urinary rac infecion, 2 cases of sepicemia, oalling 17 cases. Clinical resuls obained were excellen in 4 cases, good in 7 cases, fair in 1 case, and poor in 5 cases. No side effec was observed wih he drug, excep ha BUN, blood creainine, and blood sugar value increased in a paien wih renal insufficiency.

View full abstract

Basic and clinical studies were made on CS-1170, a new cephamycin derivative developed by Sankyo Company. The results obtained were as follows.
1) Antibacterial activity in vitro: Cs-1170 was found to be more potent against Gram-negative bacilli (E.coli, Klebsiella and Proteus) than cefazolin and ampicillin, while less potent against Staphylococcus aureus than cefazolin.
MIC was influenced to some extent by the inoculum size in regard to these Gram-negative bacilli.
2) Distribution and excretion: CS-1170 was administered by intravenous drip infusion for 2 hours at a dose of 500mg in a patient of leukemia, and the blood level attained a peak of 68μg/ml, then fell to 2.1μg/ml 6 hours after the termination of infusion. Urinary recovery was 59.2% in this patient.
CS-1170 was administered intramuscularly at a dose of 100mg/kg in rats, and tissue concentrations were estimated by serial method. Kidneys showed the highest concentration among the organs, closely followed by liver. Concentrations were lower in order of blood, lungs, muscle and spleen. This distribution pattern was similar to that of cefazolin.
In vitro recovery rates of CS-1170 were nearly 100% from rat organ emulsions.
3) Clinical trials: Five patients of various infections were treated with CS-1170 by drip infusion, intramuscularly or intravenously at doses of 1.5-4.0g per day. As for the results, response was good in 4 out of 5 cases, including sepsis (Staphylococcus epidermidis, leukemia underlying), respiratory tract infection (leukemia underlying), acute exacerbation of chronic bronchitis (Staphylococcus aureus), and acute pyelonephritis (Proteus, apoplexy, catheter indwelled), while the effect was not so distinct in the remaining 1 case of chronic bronchitis (Streptococcus).
No patients revealed any side effects nor abnormal laboratory data which would be attributable to the drug.

View full abstract

A quantitative observation of clinical effect of antibiotics was carried out using CS-1170, a new broad spectrum antibiotic, in spinal cord injury patients with chronic complicated urinary tract infection. A standard procedure was employed for this purpose. A clean-catch mid-stream specimen of urine was observed first in the morning. Bacterial counts and differentiation of bacterial species were performed daily on the clean-catch specimens for 1 week. MIC was also determined on the strains before CS-1170 treatment. The results were obtained as follows.
Quite the same tendency was shown in the patterns of response of 73 strains obtained from 28 patients under CS-1170 treatment. Bacterial strains from urine specimens (100μg/ml or lower MIC) were completely eradicated within 3 days after CS-1170 treatment (daily dose 0.5g twice). The bacterial specimens eradicated were mainly gram-negative bacilli; Serratia marcescens 16, Ptoteles rettgeri 18, Proteus morganii 10 and other 5 species 7. Dose response was observed between intramuscular administration of CS-1170 0.5g twice daily and that of 1.0g.
The antibacterial effect following CS-1170 administration was observed to be remarkable and constant throughout the present study, and CS-1170 was considered to be one of the most effective antibacterial agents.
The above procedure can quantitatively estimate suppression and eradication of organisms isolated from urine following the administration of adequate antibacterial agent.
It was clarified further that this is a method by which the drug effect may be judged objectively with relationship between viable count, bacterial species, and dose response by comparing with MIC of the drug against strains.

View full abstract

Laboratory and clinical investigations were performed on CS-1170, and the results obtained were as follows.
1) Sensitivity of clinically isolated strains to CS-1170 was tested by agar plate dilution method, and compared with that to cefazolin, cephaloridine and cefoxitin.
Minimum inhibitory concentrations of CS-1170 were 0.78 to 6.25μg/ml, and 0.4 to 6.25μg/ml respectively against 50 strains of Staphylococcus, and 52 strains of E.coli. Inhibition was noticed at the range of 0.78 to 25μg/ml of CS-1170 in 45 out of 51 strains of Klebsiella pneumoniae and 43 out of 50 strains of Proteus group.
Antibacterial activity of CS-1170 was found to be superior to that of cefazolin and cefoxitin against most of clinically isolated gram-negative bacilli.
2) CS-1170 was administered by intravenous infusion at a dose of 1.0g, and serum concentration reached a peak 1 or 2 hours after, levels being ranged from 58 to 70μg/ml. At a dose of 2.0g, serum levels attained a peak 2 hours after, levels being ranged from 130 to 150μg/ml.
3) Effective clinical result was obtained with CS-1170 in 5 of 8 patients treated. No side effect was observed in all patients.

View full abstract

CS-1170 was administered intramuscularly or intravenously in 7 patients of bacterial infection. These patient, consisted of 4 of pulmonary infection, 2 of cystitis and 1 of cholecystitis. CS-1170 was effective in 5 of 7 patients, while it was no effective in 2 paitents of neoplasic disease. No side effect was noted in any case.

View full abstract

Laboratory and clinical studies were carried out on CS-1170, a new synthetic antibiotic of cephamycin group, and the following results were obtained.
1) Minimum inhibitory concentration (MIC) of CS-1170 was determined against clinically isolated bacteria. As to the strains of Staphylococcus aureus, MIC of CS-1170 ranged mostly from 1.6 to 3.1μg/ml, being slightly inferior to that of cephaloridine (CER) or cefazolin (CEZ) while superior to that of cefoxitin (CFX).
Against the strains of E.coli and Klebsiella, MIC of CS-1170 demonstrated mostly from 1.6 to 6.3μg/ml, being superior to that of CEZ, CER or CFX. CS-1170 exhibited an increase of antibacterial activity against Enterobacter and Serratia, though the degree was not remarkable. Pseudomonas and Streptococcus faecalis were found to be highly resistant to agent.
2) MIC was measured with the inoculum size of 10⁶/ml, and it improved by more than a grade concentration compared with that of 10⁸/ml. Distinction became thus more clear between sensitivity and resistance.
3) CS-1170 was drip infused intravenously at a dose of 1 g, and serum concentration reached a peak of 84μg/ml after the completion of administration, decreased then rapidly to 27μg/ml and 1.2μg/ml 1 hour and 4 hours after the infusion respectively, and no amount was detected in blood 6 hours after. The agent was excreted in urine at 73% of the dose within 2 hours, while at 84% within 6 hours.
4) CS-1170 was administered clinically at a daily dose of 1 to 6 g for 5 to 17 days to 3 cases of septicemia, 5 cases of pneumonia, 1 case of bronchitis, 2 cases of biliary tract infection, and 2 cases of other disease, totalling 13 cases. The response obtained was good in 4 cases, fair in 2 cases, none in 5 cases, and undetermined in 2 cases. There was no side effect attributable to this drug.

View full abstract

CS-1170 was used in the treatment of 10 cases of respiratory infections: 5 cases of lung abscess, 4 cases of bronchopneumonia and 1 case of chronic bronchitis. The drug was administered by intravenous drip infusion at a daily, dose of 2 to 4g. Six cases of respiratory infections complicated with severe underlying disease were combined with a drug of aminoglycoside agents as amikacin, gentamicin and tobramycin; The results obtained were as follows; good in 9 cases and unknown in 1 case. The last patient showed a weak allergic reaction as skin eruption, and CS-1170 treatment was discontinued on the 5th day.

View full abstract

Fundamental and clinical studies on CS-1170, a new semisynthetic cephalosporin were carried out and the results were as follows.
1) Antibacterial activity: The in vitro antibacterial activity of CS-1170 was tested by the serial agar dilution method. The minimal inhibitory concentrations (MICs) against 22 standard strains and 830 clinical isolates (Staphylococcus aureus 54, Salmonella 36, Citrobacter freundii 38, Citrobacter diversus 32, Citrobacter amalonatica 11, E.coli 54, Shigella 45, Klebsiella aerogenes 53, Enterobacter aerogenes 54, Enterobacter cloacae 54, Serratia marcescens 54, Proteus vulgaris 12, Proteus mirabilis 42, Proteus rettgeri 22, Proteus inconstans 16, Proteus morganii 43, Aeromonas 20, Pseudomonas aeruginosa 54, Pseudomonas putida 31, Pseudomonas maltophilia 33, Pseudomonas putrefaciens 14, Flavobacterium 50 and Acinetobacter anitratus 8.) were compared with those of cefazolin (CEZ) MICs against 22 standard strains were *lost same as those of CEZ with the exception of those of Staphylococci. MICs against clinical isolates were 2-4 times lower than those of CEZ in almost all bacteria except for Staphylococcus.
2) Serum levels in man: Two patients with pulmonary infections were injected 1 gram of CS-1170 by intravenous drip infusion with normal saline solution for 1-2 hours. Peak serum levels were 120-130μg/ml at the end of infusion. A 74y.o. male patient with pulmonary infection was given 2 grams of CS-1170 by drip infusion for 2 hours and peak serum level was 270μg/ml at the end of injection. Serum levels were around 10μg/ml even six hours after drip infusion.
3) Penetrations into sputum: A 46y.o. male patient with lung abscess who had purulent sputum was given 1 gram of CS-1170 by drip infusion for 2 hours with 5% glucose solution. Peak sputum level of the drug was about 3.8μg/ml at 3 hours after injection.
4) Biliary excretion: A 63y.o. female patient with common bile duct cancer was injected 1 gram of CS-1170 by drip infusion for one hour. Peak biliary level was 20μg/ml 2 hours after injection, The drug was still detected in small amount at seven hours after administration.

View full abstract

Laboratory and clinical studies on CS-1170 were performed with the following results.
1. MIC values of CS-1170 against respiratory pathogenic organisms were measured. 96.3% of MICs of CS-1170 against 54 strains of Haemophilus influenzae was 3.13 to 6.25μg/ml. Two strains of the organism revealed MIC value of 25-50μg/ml and they were resistant to CS-1170.
The distribution of MICs against 7 strains of E.coli was divided into two groups. They were the susceptible group (6 strains) with MIC values lesser than 0.78 μg/ml and the resistant group (1 strain) with MIC value more than 100μg/ml.
MICs against 19 strains of Klebsiella pneumoniae were 0.39 to 1.56μg/ml.
Five strains of Haemophilus influenzae and one strain of Haemophilus parainfluenzae were ampicillin resistant strains isolated from the patients with meningitis in England, and MICs of CS-1170 against these strains were 1.56 to 3.13μg/ml.
2. After intramuscular administration of CS-1170 500mg/kg to rats, the tissue concentrations reached peak in 15 minutes. The levels in tissues were high in kidney, liver, serum and lung in order of concentration. CS-1170 was not detected in lung one hour after the administration and two hours after in other tissues.
3. Serum concentrations in one patient with chronic bronchitis after intravenous administration of 0.5g CS-1170 were measured. The peak level was 107μg/ml immediately after the administration and the half-life was about 32 minutes. Sputum concentrations in this patient were ranged 2.9 to 3.6μg/ml.
Serum concentrations in other patient with acute bile duct infection after instillation of 2g CS-1170 over 1.5 hours were measured. The peak level was 41.5μg/ml and the half-life was 42 minutes.
4. CS-1170 0.25 to 6g per day was administered against 16 patients and following results obtained. In 14 patients this antibiotic was effective. Two patients died before the appearance of effect.
There was no adverse reaction in any case.

View full abstract

1) Antibacterial activity, blood concentration and sputum concentration of CS-1170 were measured on 49 strains of Staphylococcus aureus, 44 strains of E.coli, 50 strains of Klebsiella pneumouiae, 21 strains of Proteus and 30 strains of Serratia marcescens, all of which were isolated clinically.
Antibacterial activity of CS-1170 against Gram-negative bacteria was superior to that of cefazolin (CEZ)
Blood concentration of the drug attained a peak in 1 hour, and the peak value was higher with 2g administration than with lg administration, showing thus a dose response.
Sputum concentration of the drug was rather superior to that of CEZ.
2) CS-1170 was administered at a dose of 1 g twice daily in 11 cases of various respiratory tract diseases, and the results obtained were excellent in 1 case, good in 8 cases, poor in 1 case, and unjudged in 1 case, effective rate being thus 90%.
3) No side effect was observed with CS-1170 administration.

View full abstract

Fundamental and clinical studies on CS-1170 were investigated and the following results were obtained.
1) Antibacterial spectrum
CS-1170 showed excellent antimicrobial activity against both gram-positive and -negative bacteria exceptStreptococcus faecalis, Bacillus cereus, andPseudomonas aeruginosa.
2) Antimicrobial activities against clinically isolated strains
CS-1170 exhibited reasonable antimicrobial activity against clinical isolates ofStaphylococcus aureus, coli, KlebsiellaandProteus mirabilis.However, againstStaphylococcus aureus, CS-1170 was less active than other cephalosporins such as cephalothin, cephaloridine, cefazolin, cephapirin and ceftezole tested.
The strains ofE. coli, KlebsiellaandProteus mirabiliswere the most susceptible to CS-1170 among 9 cephalosporins investigated.
3) Pharmacokinetic parameters
Pharmacokinetic parameters were calculated using computer by way of one compartment open model method and the following results, that is Ka (h^-1): 6.5, Vd (1): 12.6, Kel (h^-1): 0.70 and T_1/2 (h): 0.99 were obtained.
4) Serum and urinary concentrations
Serum concentrations were assayed with cup-plate method using Moni-trol serum for the standard curve. CS-1170 was administered intramuscularly at a dose of 500 mg and serum concentrations attained a peak after 30 minutes with the mean value of 28.8μg/ml respectively.
Urinary concentration attained a peak after 1 hour with the mean value of 3, 085μg/ml respectively. Mean recovery rates in urine during 6 hours were 65.9% respectively.
5) Tissue concentraions
Twenty mg/kg of CS-1170 given intramuscularly to SD strain rats revealed that the tissue concentrations in radioassay were the highest in kidney, followed by liver, serum and lung, with the almost same order as that in bioassay.
6) Metabolism
Metabolism of CS-1170 was examined in human urine after given CS-1170 as well as rat urine after given ³⁶S-labelled CS-1170. The results of bioautogram, and radioscanning on samples obtained by thin-layer chromatography revealed that CS-1170 was excreted in urine without being metabolizedin vivo.
7) Clinical results CS-1170 was administered to 20 cases of surgical infections. Clinical response was excellent in 1 case, effective in 16 cases, and failure in 3 cases with effectiveness of 85%. Adverse reactions were observed in 1 case of increased GOT and GPT, and elevated BUN value in another case including 5 cases of prevention of infection.

View full abstract

1) Serum, biliary and pancreatic juice concentrations of CS-1170 following the intravenous administration were studied.
2) Seven cases of surgical infections were treated with CS-1170 and clinical effect was observed in 3 out of 4 cases evaluated. Prophylactic administration of CS-1170 in 7 cases after gastrointestinal surgery resulted in effective prevention of postoperative infections in 6 cases.
3) Daily dosages were 2 g in 5 cases, 4 g in 8 cases and 10 g in one case. The maximum total dosage and period of administration were 100 g and 16 days, respectively. There was no side effect on hematological examination, hepatic, renal and circulatory functions nor allergic reaction with the exception of transient leukopenia in one case.

View full abstract

Fundamental and clinical studies were conducted on CS-1170, and the following results were obtained.
(1) Antibacterial activity
The minimum inhibitory concentration of CS-1170 against ll strains ofE. colitested was 12.5μg/ml or less, which was far superior to that of cefazolin (CEZ). CS-1170 also demonstrated appreciable antibacterial activities againstSerratia.
(2) Absorption and excretion
Excretion of CS-1170 into bile was considered to be of the moderate group.
(3) Clinical results
CS-1170 was administered to 7 patients of surgical infections, and excellent response was observed in 1, case, good response in 4, fair in one and poor in one case. No subjective side effect was noted in any of the cases. As a result of the clinical examinations, a slight increase in Al-p value was found in one case, however, we could not determine whether this was attributable to CS-1170.

View full abstract

CS-1170, a new derivative from cephamycin C, was investigated on its serum level, urinary excretion, clinical effectiveness and side effects.
1) Following the intramuscular injection of 500mg of CS-1170, the average serum level reached its peak of 41.4μg/ml in 30 minutes, gradually decreased thereafter and the average serum level 8 hours after the administration was 0.8μg/ml. The average excretion in urine within 2 hours after injection was 286.3 mg (57.3% of the dose) and within 8 hours following the injection, 480.0 mg, or 96.0% of the dose, was excreted in urine.
2) The average serum level upon completion of 15-minute intravenous drip infusion of 1 g of CS-1170 was at its peak, of 53.4μg/ml. The serum level decreased rather rapidly.and by 6 hours, thereafter no measurable amount was found in the, serum. The average excretion in urine within 2 hours after the infusion was 671.6 mg (67.2% of the dose), and by the end of 8 hour period following the administration, 879.0mg (87.9% of the dose) was excreted in urine.
3) CS-1170 was administered to 23 patients with infection in the field of surgery. The result obtained was outstanding: excellent response in 4 cases, good response in 11 cases and fair response in 8 cases. They include excellent response in a case of parotitis; good and fair responses each in 2 cases of postoperative pneumonia; an excellent response, 4 good responses and 3 fair responses among 8 cases of bile duct infection; one excellent, 3 good and 2 fair responses among 6 cases of peritonitis; 2 excellent and 2 good responses among 4 cases of wound infection; and an excellent and a good response in 2 cases of anal fistula and periproctal abscess.
4) Side effects of nausea in one case, elevation of GOT and GPT in 3 cases, and elevation of BUN in another case were observed, however, they were not serious and cessation of the administration was not required in any of the cases.

View full abstract

The advent of CS-1170, a new antibiotic of the group of cephamycin which is stable against cephalosporinase, is considered rather timely as there is the possibility of the increased number of bacteria becoming resistant to cephalosporin due to R-plasmid infection.
Others have reported about the excellent antibacterial activity of CS-1170 against clinically isolated bacteria, and our results are in agreement wih them: Of 9 clinical cases treated with CS-1170, we have observed good response in 5 cases, fair response in 3 cases, while response in one case was undeterminable.
Excretion of CS-1170 into bile was favorable and was equal to or better than that of cefazolin (CEZ), as the maximum concentration within 2 to 3 hours after its administration was from 3.8μg/ml to 40.5μg/ml.
Based on the above evidences, our conclusion is that CS-1170 is a clinically useful agent adequately effective in the treatment of biliary tract infections where cephalosporins have failed.

View full abstract

Patients with postoperative choledocholithiasis who were undergoing choledochol drainage were given 1.0 g of CS-1170 intravenously, and time-course of serum concentraion and biliary concentration levels were determined. The results were satisfactory, as the blood level reached its peak of 128μg/ml 30 minutes after the drug administration, while excretion in bile reached a high concentration of 224μg/ml 3 to 4 hours after the administration of CS-1170.
Eleven cases of postoperative infection were given 2.0 g of, CS-1170 daily for 4 to 11 days by intravenous injection and drip infusion, and the result was that excellent response in 2 cases, good response in 7 cases and no response in 2 cases. The effective rate was 81.8%.
No side effect was noted other than elevation of GOT and GPT in 2 cases.
The above findings indicate the satisfactory antibacterial effect of CS-1170 against infections in the surgical field.

View full abstract

1. Consecutive transfer of CS-1170 in bile was investigated on 2 groups of patients, the one with disorder of hepatic function and the other without these disorders.
2. In the group of normal hepatic function, concentrations of the drug showed a peak of more than 20 μg/ml after 1 g drip infusion, while a peak of 35.5 μg/ml after 2 g drip infusion.
3. In the group of disordered hepatic function, scattering was noticed from 4.2 μg/ml to 2 μg/ml after 1 g drip infusion.
4. CS-1170 was drip infused to 5 cases of biliary tract infection at a daily dose of 4 g divided into 2 times, and the results obtained were remarkably effective in 3 cases, effective in 1 case and ineffective in 1 case. No side effect was observed with the drug throughout all cases.

View full abstract