AC-1370 a new cephalosporin with strong antimicrobial activity against a broad spectrum of Gramnegative bacteria, especially P. aeruginosa was administered intravenously 1-2 g 2 times a day to 8 patients with pulmonary infections to evaluate therapeutic efficacy. The results obtained as follow:
1) Excellent and good clinical responses were obtained in 6 to 8 patients (75%).
2) No marked side effects were observed.

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Antimicrobial activities of AC-1370 were compared with that of CTX and CEZ against 279 clinically isolated strains. Against Gram positive cocci CEZ showed the strongest activity, and against Gram negative bacilli, CTX was the best one in general. But against P. aeruginosa and P. maltophilia, the activity of AC-1370 was superior to other two antibiotics.
Of 11 cases of respiratory tract infection who were treated with AC-1370, efficacies were observed in 7 cases. Especially in two cases of S. pneumoniae infection, clinical and bacteriological effects of AC-1370 were excellent.
As the adverse reactions associated with the administration of AC-1370, slight elevation of transaminase activity in one case and the eruption in another case were observed.

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The clinical effects of AC-1370, a new cephalosporin antibiotic, was studied in 7 patients; 6 with respiratory tract infections, one with choleduct infection. Four patients had various underlying diseases.
This antibiotic was administrated 1.0-2.0g a day by intravenous injection for 7-25 days.
Clinical efficacy was observed in 5 out of 6 patients with respiratory tract infections and in one patient with choleduct infection.
The rate of effectiveness was 85.7%.
In one case, rash and eosinophilia developed on 23 therapeutic day, but alleviated 9 day after cessation of the therapy.
No laboratory abnormalities were observed in other cases.

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Laboratory and clinical studies were performed on AC-1370, a new cephalosporin antibiotic, and the results were as follows.
1) Antimicrobial activity
MICs of AC-1370 against various clinical isolates were determined with the inoculum size of 10⁶ cells/ml. Percentages of strains susceptible to 12.5 μg/ml or less were 82% for S. aureus, 3% for S. faecalis, 55% for E. coli, 79% for K. pneumioniae, 67% for E. cloacae, 60% for E. aerogenes, 20% for S. marcescens, 100% for P. mirabilis, 67% for indole-positive Proteus, and 74% for P. aeruginosa. Most of S. aureus was inhibited by 12.5μg/ml and most of Enterobacteriaceae were inhibited by 1.56 6.25 Especially, AC-1370 had an excellent activity for P. mirabilis.
2) Clinical efficacy
Four patients with pneumonia, 1 with interstitial pneumonitis, and 1 with chronic bronchitis were treated with AC-1370 in daily doses of 1-6 g for 3-15 days. Clinical response was good in 2, fair in 1, poor in 1, and unknown in 2 patients. No side effect was observed, but GOT and GPT elevation was seen in 2 patients.

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Laboratory and clinical studies on AC-1370, a newly developed cephalosporin antibiotic, were carried out with the following results.
results. 1) Antibacterial activity: The minimum inhibitory concentrations (MICs) of AC-1370 was determined against 341 clinical isolates consisted of 11 different species and compared with those of cefmetazole (CMZ), cefazolin (CEZ) and cefoperazone (CPZ). Antibacterial activity of AC-1370 against S. aureus, S. faecalis, E. coli and K. aerogenes were less potent than those of CEZ, CMZ and CPZ, but that against P. aeruginosa and H. influenzae was superior to those of CEZ and CMZ and ranked next to CPZ.
2) Absorption and excretion: AC-1370 was administered to four patients with chronic respiratory tract infections at a dose of 1 gram or 2 gram by intravenous drip infusion for one hour. The peak serum levels were 58.0±2.31 μg/ml with the dose of 1 gram and 92.0μg/ml with the dose of 2 gram at the termination of infusion. The peak sputum levels were 1.85-4.6 μg/ml at two or four hours after. Urinary recovery rates at six hours after at a dose of 1 gram were 65.8-75% (71.1±8.43%).
3) Clinical results: AC-1370 was given to 59 patients with various respiratory tract infections. That clinical results were excellent in 15, good in 33, fair in 5 and poor in 4 patients. The over all clinical efficacy rate was 84.2%. Bacteriologically, all strains of S. pneumoniae and H. influenzae were eliminated and the elimination rate of P. aeruginosa was good. The over all bacteriological efficacy rate was 83.8%.
Total 12 patients showed the following adverse reactions; eruption in 3, eosinophilia in 1, liver disfunction in 6, mild elevation of BUN, and Creatinine in 2 patients.

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The laboratory and clinical studies on AC-1370, a new broadspectrum cephalosporin antibiotics, were performed in the lower respiratory tract infections and examined in vivo effects for rat air-pouch inflammation.
The in vitro antibacterial activities of AC-1370 against respiratory pathogens were measured as the MICs values (inoculum size: 10⁶cfu/ml). The peak MICs of AC-1370 were 0.39μg/ml against Haemophilus influenzae, 0.78μg/ml against Streptococcus pneumoniae, 50μg/ml against Pseudomonas aeruginosa, 1.56μg/ml against Klebsiella pneumoniae and >100μg/ml against Staphylococcus aureus. Generally, in vitro antibacterial activities of AC-1370 against main respiratory pathogens were less active than those of other new cephalosporins.
After intravenous instillation of 0.5g, 1g and 2g AC-1370 over a one hour period, peak serum concentrations in patients with respiratory infections were 59.9μg/ml, 107.9μg/ml and 196.4ug/ml, respectively and showed good dose-response relationship. The serum half-life of AC-1370 in a patient was approximately two hours. The ratio of peak sputum level to peak serum level was 0.93% in a patient with chronic bronchitis and bronchiectasis. In the same case, the ratio of maximum intrabronchiolar secretion level to peak serum level was 1.51%. After intramuscular administration of AC-1370 20mg/kg in rat, tissue concentrations reached peak value in 15 minutes. Tissue levels in order of concentrations were in kidney, serum, lung and liver.
An experiment on rat air-pouch inflammation under Zymosan and Klebsiella pneumoniae B-54 stimuli showed some influences to diapedesis, phagocytosis and killing of neutrophils, vascular permiability and antiinflammatory action.
Seventeen patients with respiratory infections were treated with AC-1370. As the rate of clinical therapeutic efficacy was 82.4%, it was confirmed that AC-1370 had good in vivo effects compared with in vitro antibacterial activities. Although skin eruption was obserbed in one patient, there was no other side effect.
From the above results, it is concluded that AC-1370 is a useful antibiotics with good in vivo effects.

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A laboratory and clinical study on a third generation cephem antibiotic, AC-1370, was carried out, and the results obtained were as follows:
1. Antibacterial activity: The minimum inhibitory concentrations of AC-1370, CEZ, CMZ, CTM and CZX against a total of 650 isolates from recent clinical materials, i.e., S. aureus, coagulase-negative staphylococci, S. faecalis, E. coli, C. diversus, K. pneumoniae (biovar aerogenes), E. aerogenes, E. cloacae, S. marcescens, P. mirabilis, P. vulgaris, M. morganii, P. rettgeri, P. aeruginosa, P. fluorescens, P. maltophilia, P. putida, A. calcoaceticus, Flavobacterium sp. and B. fragilis, were measured by the method according to the Japan Society of Chemotherapy, and compared with each other.
The antibacterial activity of AC-1370 was ranked at about the middle of all antibiotics tested, and it was shown that this drug was the most active against P. aeruginosa.
2. Concentrations in the serum and penetration into bronchial tree: Four patients with respiratory infections (weighting 42 to 64 kg, and aged 54 to 64) were administered with 1 g of AC-1370 by intravenous drip infusion for one hour. The serum concentration of AC-1370 reached a peak of 64.5ug/ml on an average at the end of the drip, and then decreased steadily. It reached 7.2μg/ml 6 hours after the drip, with a halflife of 1.6 to 2.1 hours. The sputum concentration was measured in three of the patients. It reached a peak level of 1.6 to 3.1μg/ml two to four hours after the end of the drip.
3. Treatment of respiratory infections with AC-1370: A total of 15 patients, consisting of eight patients with chronic respiratory tract infections, 6 with bronchopneumonia and pneumonia, and one with lung abscess, were treated with 2 g daily, divided into two equal parts, every day, for 7 to 19 days. The efficacy of the treatment was evaluated as good in nine, fair in four and poor in one, and it was not evaluable in one patient because of adverse reaction.
4. Side effects: Out of the 15 patients, one complained of rashes and itching; one complained of nausea and vomiting; and slight elevation of GOT and GPT was found in one patient. These adverse reactions were quickly improved after discontinuance of the drug.

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AC-1370, a new cephalosporin antibiotic, is reported to have an unique characteristic that this drug has more antimicrobial potency in vivo than in vitro.
AC-1370 is active against both Gram-positive and negative bacteria, including Pseudomonas aeruginosa. AC-1370 is stable to β-lactamases.
A total of 14 patients with bacterial infections, consisting of 8 pneumonia, 1 acute bronchitis, 3 chronic bronchitis and 2 urinary tract infections, were treated with this drug. One to two grams of AC-1370 was administered twice a day intravenously with a proper amount of iv-fluids.
Eleven out of 14 cases evaluated responded satisfactorily to the treatment and efficacy rate was 78.6%.
Two strains of Streptococcus pneumoniae, 2 strains of Haemophilus influenzae, 1 strain of Proteus mirabilis, Streptococcus faecalis, β-Streptococcus, Staphylococcus aureus and Acinetobacter calcoaceticus were eliminated by this drug. However, Pseudomonas aeruginosa was not eliminated.
One patient out of 14 had fever accompanied with eosinophilia (0 → 17 → 6%) during the administration of the drug.

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The usefulness of AC-1370, a new cephalosporin antibiotic, was studies in the surgical field, especially in the biliary tract infections.
AC-1370 was given intravenously at a dose of 1 g, and its levels in bile were determined periodically after administration: the levels at 3 hours after administration were in the range of from 50 to 120 μg/ml with the mean level of 38.84±17.46μg/ml. The bile levels at 6 hours were slightly lowered, but still effective. In the patients with malignant tumor the bile levels of AC-1370 at 6 hours were lowered to 10 μg/ml. The rate of excretion into the bile was 0.04-0.18%.
Clinical efficacy of AC-1370 were examined. Of 11 patients having infection symptoms at the time of surgical operation, it was excellent in 3 cases, good in 6 cases, fair in 2 cases, and thus all patients were relieved from the infection. AC-1370 was administered for the purpose of preventing postoperational infections in 15 patients who had no infection symptoms at the surgical opeartions, and all of the patients received the surgical operations left the hospital without infection. However, skin rush was observed as the side effect in 1 case.
From the results, AC-1370 was considered to be an effective antibiotic agent in the surgical treatment of biliary tract diseases.

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A new antibiotic semisynthesized drug of cephalosporin group, AC-1370 for parenteral use, having marked resistance to β-lactamase, and a broad spectrum of antibacterial activity against various bacterial species, including Pseudomonas aeruginosa. AC-1370 has higher activity in vivo than in vitro. AC-1370 was administered intravenously before or during operation in a dose of 1 g to 5 cases with biliary tract infection, 7 cases with acute localized peritonitis and 3 cases with others, and tissue specimens and body fluid samples were taken during the operation. The AC-1370 concentrations were determined by bioassay using Klebsiella pneumoniae IFO 3317 as the test organism.
The AC-1370 concentration in the common duct bile ranged from 5.4 to 76.0 μg/ml at 66 to 160 minutes after intravenous bolus injection. The level in the gall bladder bile ranged from 3.0 to 115.0 μg/ml, and that in the gall bladder wall showed 39.1 to 88.6 μg/g. AC-1370 concentration in the infected appendix wall ranged from 11.2 to 82.6 μg/g at 3 to 84 minutes after injection. These level in purulent ascites ranged from 19.0 to 45.0 μg/ml at 30 to 82 minutes after administration. These values were superior to the MICs of almost all of the organisms which were isolated from these cases.
For therapeutic purposes, AC-1370 was given in a daily dose of 1g (1×1) to 2 cases of acute appendicitis (outpatient, not operated), 2g (1×2) to 17 cases (5 of biliary tract infection and 10 of acute localized peritonitis and 2 of periproctal abscess), and 4 g (2×2) to 1 case of panperitonitis, for 4 to 8 days. The clinical response was rated excellent in 5 cases, good in 14 cases and fair in one case. No adverse effect was observed.
Therefore, AC-1370 appears to be a very useful drug when used for chemotherapy of acute peritonitis, biliary tract infection and other abdominal infectious diseases.

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AC-1370 was studied in 10 cases with surgical infections (urinary tract infection 3, intraperitoneal abscess 2, periproctal abscess 1, perityphlic abscess 1, wound infection 1, cholangitis 1, acute peritonitis 1) and administered 1 g twice a day for 5 days.
The results were good in 7 cases, poor in 3 cases with effective rate 70%.
Bacterial effects with 16 strains in 10 species were as follows: 3 strains of B. fragilis, 2 strains of P. morganii, each one strain of E. coli, S. pyogenes, S. epidermidis were eradicated and each one strain of E. coli and S. pyogenes decreased but each one strain of P. morganii, Enterobacter, P. putida, Serratia, P. inconstans, S. faecalis persisted.
No side effects were observed, and in laboratory findings, no abnormal elevations of transaminase, BUN and creatinine were found.

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In vitro and in vivo studies were conducted on AC-1370.
AC-1370, a new cephalosporin antibiotic, has a broad antibacterial spectra against both gram-positive and gram-negative organisms: especially it shows strong antibacterial activity against P. aeruginosa.
Blood levels and urine concentrations of AC-1370 were determined with bioassay and HPLC in three healthy volunteers who intravenously injected by a single 1, 000 mg dose.
The results indicated that average peak serum levels of 121 μ/ml (bioassay) and 122 jig/ml (HPLC) were attained 5 minutes after the dose. The peak urine levels were 8, 167 μg/ml (bioassay) and 7, 867 lig/ml (HPLC) after dosing and 89.8% (bioassay) and 87.1% (HPLC) were recovered in urine within 8 hours.
Pharmacokinetic parameters obtained from the HPLC assay data were as follows; K₁₂ (hr^-1): 2.86, K₂₁ (hr^-1): 2.79, Kel (hr^-1): 0.93, T1/2 (β)(hr): 1.64, Vd (liter): 12.6, AUC (hr·μg/ml): 173.
Analysis of metabolites in human urine by TLC and bioautography demonstrated that AC-1370 was excreted without being metabolized.
A single 20 mg/kg dose of AC-1370 was intramuscularly administered to SD strain rats and kidney level was the highest, followed by those in serum, lungs, heart and liver.
Clinical response to AC-1370 in 13 cases of surgical infections was evaluated as excellent in 1 case, effective in 8 cases, and failure in 4 cases.
No side effect was observed in all patients.

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Clinical effect and excretion into peritoneal exudate of AC-1370, a new cephalosporin, were studied.
AC-1370 was given in five cases of surgical infections including pelvic abscess, urinary tract infection, subphrenic abscess, combination of mediastinitis and pleuritis, and septicaemia. AC-1370 was administered intravenously 1g × 2/day. The clinical effect of AC-1370 was evaluated in four cases, the results being good in two cases, fair in one case and poor in one case. The concentrations of AC-1370 in intraperitoneal exudate were above 12 pgiml for the three days following gastrectomy when AC-1370 was given 1 g bid intravenously. The concentration was higher than the minimal inhibitory concentrations of the AC-1370 against most pathogenic bacteria.
Out of 12 cases including 7 cases of prophylactic use, no subjective and objective adverse effects were noticed except for the elevations of s-GOT and s-GPT seen in one case.

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Fundamental and clinical studies of AC-1370 on the surgical fields were performed and following results were obtained.
1) Antibacterial activities
Against E. coli and Klebsiella , MIC levels of AC-1370 were slightly higher than those of CPZ, but againstP. aeruginosa those of AC-1370 were similar to CPZ.
2) Bile excretion
On the three cases with biliary truct disorder, the bile excretion of AC-1370 were measured. As a results, the bile excretion of AC-1370 were low levels on the three cases. The recovery rates of the bile till 6 hours after single intravenous injection of 1 g of AC-1370 were from 0.07% to 0.27%.
3) Clinical results
AC-1370 were administered to 7 patients with surgical infections and the clinical results were excellent in 1, good in 2, fair in 2 and poor in 2 cases. Adversed reaction due to AC-1370 could not be found on any cases.

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AC-1370, a new cephem antibiotic, is characterized by increasing the phagocytic activity of neutrophils and also by a much more potent activity in vivo than its in vitro activity. It may be anticipated therefore that this antibiotic will prove clinically effective in treating peritonitis for which not only a bactericidal activity but also a pathogen-eradicating activity is required. We clinically used AC-1370 in the treatment of 44 patients with acute purulent peritonitis, 2 cases of biliary tract infections and 1 case of abdominal wall infection following appendectomy, and the following conclusions were obtained:
1) The primary cases of peritonitis were as follows; 22 due to perforation in appendicitis, 8 due to perforation of gastroduodenal ulcers, 8 due to perforation of the intestine, 6 due to biliary peritonitis. All of the above 44 cases were treated with 1 g of AC-1370, twice daily, by intravenously bolus or drip infusion, for a mean period of 7.7 days, and the mean total dose was 15 g. The clinical response to the treatment was evaluated on the 7th day of treatment; and a response rate of 87.5% was achieved in the patients with peritonitis due to perforation of gastroduodenal ulcers, 77.3% in those with peritonitis due to perforation in appendicitis, and 75.0% in those with peritonitis due to perforation of the intestines, while a low response rate of only 62.5% was achieved in patients with binary peritonitis.
2) When these patients were classed by the involved area and severity of peritonitis, the efficacy of the treatment was evaluated as excellent in 1 (5.9%) and good in 15 (88.2%) of 17 patients with moderate diffuse peritonitis, with the response rate being as high as 94.1%.
3) According to the “Indices for Peritonitis” which has been proposed by us as the clinical indices for the recovery process of peritonitis, the disappearance rate of muscle guarding on the 3rd day of treatment with AC-1370 was 84.6%, which was higher than 60.9% with CMZ and 72.1% with CTT as described in the previous papers.
4) The level of AC-1370 in ascitic fluid was 33.5, μg/ml one hour after intravenously bolus injection of 1 g, and the mean daily level of the agent in purulent ascitic fluid during the period of medication with 1 g twice daily was 22.9μ/ml the day following the operation.
5) Bacteriologically, 57 isolate strains disappeared; 11 remained, and 14 appeared, with an eradication rate of 84%. The treatment was associated with the following side effects: rashes in one, phlegmagia in another, and elevation of GOT and GPT in another patient.

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AC-1370, a new synthetic cephalosporin C derivative, was investigated on its serum level, biliary concentration and clinical effectiveness.
Following one shot intravenous injection of 1g of AC-1370 in 3 patients after cholecystectomy and T-tube drainage, the peak level of biliary concentration showed no definite distribution: in one patient the peak level reached 80 μg/ml but in the other 2 patients it revealed 31.0 and 17.5 μg/ml respectively. Serum level was investigated in 2 of the 3 patients, showing a peak level of 97 and 51 μg/ml at one hour.
AC-1370 was administered on 30 patients with various surgical infections. The results obtained were excellent in 11, good in 14, fair in 4, and poor in 1 patient and total efficacy rate was 83.3%.
There was no serious side effect without slight elevation of GOT, GPT, ALP and γ-GTP in one patient.

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The new antibacterial agent, AC-1370, was studied clinically. The results were as follows:
1) AC-1370 was administered by intravenous one shot or drip infusion to 30 patients with infection in the field of surgery, such as 7 cases of peritonitis, 5 cases of postoperative wound infection, 3 cases of phlegmon, 3 cases of abscess, 2 cases of carbuncle, 2 cases of periproctal abscess, 2 cases of subphrenic abscess and 6 cases of other infections. The results obtained were excellent in 5, good in 12, fair in 6, poor in 5 and unknown in 2 cases, then total efficacy rate was 61%.
2) Side effects were noted in two cases. One was drug eruption and the other was anaphylactic shock. Drug administration was stopped when these side effects were appeared. These cases did not become to severe diseases. These patients become good when drug was stopped.
3) There were no liver disturbance nor renal disturbance.

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We made preclinical and clinical studies of a new, injectable cephem antibiotic, AC-1370, and drew the following conclusions:
1. Antibacterial activity: The antibacterial activities of AC-1370 against S. aureus and S. faecalis were weak, but those against E. coli, Klebsiella sp., P. mirabilis, Enterobacter sp. and P. aeruginosa were relatively potent.
2. Transfer into bile: When two patients with surgical bile fistula were injected intravenously with AC-1370, the level of the agent in bile reached the peak values of 39.5 and 10.5 mcg/ml 2 hours after the injection. Even in patients with no impaired bile outflow, the level of the agent in bile remained relatively high, or 18.5 mcg/ml, for a long time, i. e., even 6 hours after intravenous injection of the agent.
3. Fourteen patients with surgical infections were treated with AC-1370, and the efficacy of the treatment was evaluated as good in 10, fair in 3 and poor in the other patient, with a relatively high response rate of 71.4% achieved. No side effects of the agent were observed in particular.

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AC-1370, a new cephalosporin, was studied in surgical field. The drug was administered 2g a day for 4-10 days to ten in-patients with surgical infection-4 patients with postoperative wound infection, 4 with postoperative intraabdominal abscess, 1 with perineal infection after Miles's operation and 1 with multiple fistula in gluteal region.
The results were as follows:
1. The clinical effect were excellent in 1, good in 5 and poor in 4 cases. The effective rate was 60.0%.
2. Bacteriologically, 8 strains out of 11 were disappeared after treatment with this drug.
3. 2 out of 3 strains of P. aeruginosa were eradicated with this drug.
4. No side-effect was observed.

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The new antibacterial agent, AC-1370 was studied experimentally and clinically.
The results were as followed:
1) Antibacterial activity
P. mirabilis and P. aeruginosa were sensitive but, E. coli, K. pneumoniae, Indole (+) Proteus sp., Enterobacter sp., Citrobacter sp. and S. marcescens were resistant to AC-1370.
2) Clinical effects
Six patients with chronic complicated urinary tract infection were treated with AC-1370. Clinical response was good in 3, poor in 3, and therefore the efficacy rate was 50%.
3) Side effects
The peripheral blood test and liver and renal function test were performed before and after the administration. These tests showed no objective side effects. No subjective side effect clearly due to this drug was observed.

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Clinical studies on AC-1370, a new synthetic cephalosporin antibiotic, were performed and following results were obtained.
Thirty-nine patients with genitourinary tract infections (4 acute simple pyelonephritis, 31 complicated urinary tract and 4 genital organ infections) were given AC-1370 at a daily dose of 1g, 2g or 4g by intravenous injection or infusion for 5 days.
Clinical results of the patients with acute simple pyelonephritis were all excellent, complicated urinary tract infections were excellent in 2, good in 21 and poor in 8, and genital organ infections were excellent in 1, good in 2 and fair in 2. The effectiveness rates were 100%, 74.2%, and 75.0%, respectively.
In bacteriological response of the patients with complicated urinary tract infections, eradication of organisms resulted in 26 (57.8%), persistence in 19 (42.2%) out of 45 strains.
Any side effect was not observed except one case of vascular pain. However, as abnormal clinical laboratory values, a decrease in WBC was observed in one case and decrease in RBC and slight increase of s-GOT in one case. But they were not so severe that they improved without treatment.

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A total of 16 patients with urinary tract infections (UTI)were treated with AC-1370, a cephalosporin antibiotic for injection, and their clinical responses to the treatment were evaluated. AC-1370 was administered on a dose of 1 or 2 g daily, for 5 days, and the responses to the treatment were then evaluated. The responses of 13 patients with complicated UTI out of these subjects were evaluable according to the criteria of UTI for clinical evaluation; and the overall clinical efficacy were evaluated as “excellent” in 6, “good” in 3, and “poor” in 4 of the patients, with an overall effectiveness rate of 69%. The clinical effectiveness rate by disease classification was 67% in Group 1, and 100% in Group 3: in other words, an overall effectiveness rate of 78% was achieved in 9 patients with single infections. An overall effectiveness rate of 50% was achieved in 4 patients with mixed infections. Bacteriologically, 17 of 20 clinical isolates were eradicated with the treatment, while 2 new strains appeared, with an eradication rate of 77%. None of the patients showed any subjective or objective side effect of the treatment, and no abnormalities were found by laboratory studies

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Clinical evaluation of AC-1370, a new cephem antibiotic, was performed in genitourinary tract infections.
Thirteen patients with urinary tract infections and two with epididymitis were given AC-1370 at a daily dose of 2 g twice a day by intravenous bolus injection.
One of two cases with acute simple pyelonephritis was evaluable by the criteria of UTI committee and the response resulted in excellent. As for 11 cases with complicated urinary tract infections, 6 cases were evaluable by the criteria and the response was moderate in 4, and poor in 2 with effectiveness rate of 66.7%. Meanwhile, the response by doctors' evaluation were excellent in 1, good in 4, fair in 3 and poor in 2, the effectiveness rate being 50.0%. The response in 2 cases with epididymitis were good.
As for side effects, rash was observed in 2 cases and AC-1370 treatment was discontinued. The transient elevation of serum transaminases was noted in 2 cases, but the elevation was considered not to be due to the AC-1370 treatment.

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A new cephalosporin agent, AC-1370, was evaluated in the urological field and the following results were obtained.
AC-1370 was administered intravenously to 2 cases with acute simple pyelonephritis and 35 cases with acute and chronic complicated urinary tract infections.
AC-1370 was effective in 2 cases with acute simple pyelonephritis.
Effectiveness rate for 33 patients with acute and chronic complicated urinary tract infections was 55%. None of these patients recognized the side eect for AC-1370.
Slight transient elevation of laboratory findings in 3 cases (eosinophilia, GPT, GOT and GPT, respec-tively) were observed after the administration.

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Clinical effects of AC-1370, a new cephalosporin antibiotic, were studied in 16 patients with chronic complicated urinary tract infections.
AC-1370 was administered at a daily dose of 1-4 g by one shot iv injection or drip infusion for 5 days.
The overall clinical efficacy was excellent in 2 cases, moderate in 7 cases, and poor in 7 cases. Thus overall effectiveness rate was 56%.
Bacteriologically, AC-1370 was active against all of 5 strains of S. faecalis, all of 3 strains of S. epidermidis, two of 3 strains of E. coli, two of 3 strains of Klebsiella and one of 1 strain of P. aeruginosa.
Organisms were all eradicated except for each one strain of E. coli, strain of Klebsiella, strain of Serratia, strain of Citrobacter and strain of P. vulgaris.
Overall bacteriological response rate was 62%.
No serious side effect was observed.

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AC-1370, a new cephem analogue, was administered to 10 cases diagnosed as chronic complicated urinary tract infections. All cases except two 0.5 g×2/day received drip infusion of 1 g × 2/day for 5 days. Overall clinical efficacies were good in 4 (40%) and poor in 6 patients (60%). Eradication rate was 46.7% and yet all of two rods of P. aeruginosa persisted. These poor results were caused mainly high MIC levels of bacteria.
In above mentioned 10 cases, serious side effects were not observed. However, we have experienced ashock in another case in his first administration.

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For the studies of absorption and excretion, AC-1370 was given to 5 healthy volunteers at a dose of 1g or 4g in a cross-over manner by 1 hour intravenous drip infusion. The Cmax and T 1/2 of AC-1370 were 117.4 μg/ml and 1.45 hours for 1g injection, and 278.9 μg/ml and 1.63 hours for 4g injection. The urinary recovery rates within 8 hours were 90.8% for 1g injection, and 94.4% for 4g injection. AC-1370 was also administered to each two dehydrated and hydrated rabbits at a dose of 500mg/3 kg by a single intravenous injection, and the levels in serum and various organ tissues were measured. The every level for dehydrated rabbits was higher than the corresponding level for hydrated ones.
For clinical evaluation, AC-1370 was given to 9 patients with urinary tract infections at a daily dose of 2 to 4g twice a day. Six of these 9 cases were evaluated by the criteria of UTI committee, and the clinical response to AC-1370 treatment was excellent in 3 cases and poor in 3 cases with 50% of effectiveness rate.
No remarkable side effect was observed except for one case that showed slight elevation of BUN and serum creatinine with slight decrease of WBC. This was transient, but could not be denied to be due to the AC-1370 treatment.
When considering the report that in vivo antimicrobial activity of AC-1370 is more potent than in vitro, AC-1370 is expected to be useful against pyelonephritis rather than chronic complicated cystitis.

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Diffusion into human prostatic fluids and clinical evaluation of AC-1370, a new parenterally active cephalosporin antibiotic, were performed and the following results were obtained:
(1) The average diffusion into human prostatic fluid was 0.88 μg/ml (n=3) at 1 hour after one shot I. V. administration of 1 g, the average ratio of the diffusion v. s. serum level being 1.4%.
(2) Seven patients with acute simple pyelonephritis were treated with AC-1370 at a daily dose of 1 to 2 g for 5 days. All the patients were responsive to the treatment with the effectiveness rate of 100%.
(3) Twenty eight patients with complicated urinary tract infections were treated with AC-1370 principally at a daily dose of 2 g for 5 days. The clinical efficacy was evaluated in accordance with the criteria of UTI committee, and was excellent in 6 cases, moderate in 10 cases and poor in 12 cases with the effectiveness rate of 57.1%.
(4) The AC-1370 was more effective for the treatment of pyelonephritis than cystitis in the field of complicated urinary tract infections, and its efficacy for cases with polymicrobial infection or catheter indwelt was rather poor.
(5) No remarkable side effects were observed except for transient nausea during drip infusion of AC-1370 in one case. As for abnormal laboratory findings, slight elevation of GOT in 1 case and of GOT and GPT in 1 case, and slight decrease of WBC in 1 case were noted.
(6) AC-1370 is considered to be effective for the treatment of pyelonephritis caused by bacteria sensitive thereto.

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AC-1370, a new cephalosporin derivative, was used for 5 days in a daily doses of 1g or 2g. Four of 8 patients with complicated urinary tract infection received 1g, and other 4 patients received 2g daily of AC-1370. Seven of 8 patients responded to the therapy. No complication attributable to the therapy was observed.

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The morphological changes in urinary microbes as well as the clinical evaluation were investigated after intravenous administration of a new cephalosporin antibiotic, AC-1370. The following results were obtained.
1. It was observed that E. coli in the urine is changed morphologically to spheroplast, ovoid cells and filament, which are known on the way to lysis. In S. marcescens, the formation of filamentous cells was induced by the antibiotic.
2. Clinical evaluation
The effective rates were 100% for simple UTI and 50% for complicated UTI cases.

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AC-1370, a new cephem antibiotic agent with a potency promoting the function of phagocytosis, was studied in vitro and clinically. The results were summarized as follows;
1) Antibacterial spectrum of AC-1370 was broad against standard strains including P.aeruginosa. MICs AC-1370 and cefoperazone (CPZ) for 93 strains of ampicillin-resistant E. coli and 47 strains of P. aeruginosa isolated from patients with urinary tract infection (UTI) were also determined. MICs of AC-1370 were considerably higher than that of CPZ for strains of ampicillin-resistant E. coli and almost equal or slightly higher than that of CPZ for P.aeruginosa.
2) Plasma half-life after intravenous injection of 0.5 g of AC-1370 to healthy volunteers was 1.37 hour. Urinary recovery rate was 68% within 6 hours of administration.
3) Sixteen patients with complicated UTI were treated with AC-1370 at the dose of either 0.5 g or 1g twice a day for 5 days. Overall effectiveness rate was 31%. Eradication rates of P. aeruginosa and S. faecalis were fairly good but those of S. marcescens and E. cloacae were poor.
4) The subjective side effects were not observed in any patients by AC-1370 administration. No abnormal value in the laboratory examinations was also observed.
5) In conclusion, AC-1370 was suggested to be a useful and safe drug in the treatment of UTI with causative organisms other than S. marcescens and Enterobacter.

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We administered a lately developed cephem antibiotic, AC-1370, to 25 patients with complicated urinary tract infection and studied its clinical efficacy in 12 of them (6 with chronic pyelonephritis and the other 6 with chronic cystitis); and the following were found:
1. Overall clinical efficacy
The efficacy of the treatment was evaluated as excellent in 2, good in 8, and poor in 2 out of the 12 patients, with the effectiveness rate of 83.3%.
2. Efficacy by disease classification
A response rate of 100% was achieved in the patients of groups 1, 3 and 6; 75% in those of group 4, and 0% in those of group 5.
3. Bacteriological response
Out of 15 isolates from the urine, including 4 strains of E. coli, 14 were eradicated with the exception of 1 strain of S. marceseens.
4. Side effects
Out of the 25 patients treated with AC-1370, 2 complained of nausea. The drug was withdrawn from one of the 2, while the complaint disappeared from the other on switching the modality to intravenous drip. GOT, GPT and Al-P rose in another patient, but restored normal after withdrawal of the drug.

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Clinical studies on AC-1370, a third generation cephem antibiotic, were performed.
Nineteen patients with urinary tract infections and one with genital infection were given AC-1370 at a daily dose of 2 g twice a day by intravenous drip infusion for 5 days. These infections were classified into acute simple pyelonephritis (2 cases), acute complicated pyelonephritis (5 cases), chronic complicated pyelonephritis (2 cases), chronic complicated cystitis (10 cases), and acute epididymitis (1 case).
Thirteen cases out of 19 urinary tract infection cases were evaluable by the criteria of UTI committee, and the clinical response were excellent in 1 case, moderate in 4 cases and poor in 8 cases with effectiveness rate of 38%. Meanwhile, the clinical response by doctors' evaluation were excellent in 6 cases, good in 7 cases and poor in 7 cases with effectiveness rate of 65%.
As for bacteriological response 7 out of 19 bacterial species isolated from the urine before AC-1370 treatment were eradicated, its rate being 37%.
Neither side effect nor abnormal clinical laboratory finding was observed except one case of slight elevation of GOT.

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Preclinical and clinical studies of a new cephem antibiotic, AC-1370, were made; and the following were found:
1) In vitro antibacterial activity: the MICs of AC-1370 against 8 clinical isolates of gram-negative rods were measured in comparison with those of CPZ, LMOX, CTX, CTM and CEZ. The in vitro antibacterial activity of AC-1370 was superior to that of CEZ, and it was more potent against P. aeruginosa but less potent against the other isolates than that of CTM. Its in vitro antibacterial activity was generally inferior to those of CPZ, LMOX and CTX.
2) Pharmacokinetics: Three normal subjects were treated with 2g of AC-1370 by intravenous oneshot injection, respectively. The AC-1370 level in the blood reached 303.3μg/ml in 5 minutes, with a T^1/2 of about 2 hours. Its excretion in the 0-2 hour urine amounted to 15, 400μg/ml, with 91.7% of the injected dose recovered from the urine in 8 hours. The level of AC-1370 in prostatic adenoma was 48.2 and 66.6 μg/g (30 minutes after intravenous one-shot injection of 1g), and its level in the effusion of hydrocele was 8.7 μg/g (90 minutes after intravenous one-shot injection of 1g).
3) Clinical findings: Thirty patients with complicated urinary tract infections were treated with AC-1370; and the treatment was evaluated as having exerted an “excellent” effect on 6, and “good” effect on 11 of the patients, with a response rate of 57%, and a (pathogen) eradication rate of 70%. Neither subjectivenor objective side effects were noted in any of the patients; however, laboratory studies revealed that GOT, GPT and ALP were transiently elevated in one of the patients.

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Bacteriological and clinical evaluation of a new cephem AC-1370, was performed, and following results were obtained.
1. MICs of AC-1370 against 152 clinical isolates were determined according to the method of Japan Society of Chemotherapy.
AC-1370 was more effective than LMOX and CEZ against P. aeruginosa. Against S. marcescens AC-1370 was more effective than CEZ, but less effective than LMOX. Against E. coil and K. pneumoniae AC-1370 as less effective than LMOX and CEZ.
2. Twenty-four cases with genitourinary infections were treated with 2.0 g of AC-1370 daily for 5 to 7 days.
Excellent or good effects were obtained in 8 of 20 cases (40%) according to the criteria of the UTI committee.
3. Concerning bacteriological response, 22 of 34 strains isolated before AC-1370 treatment were eradicated, and 15 strains appeared after treatment.
4. No side effect associated with the administration of AC-1370 was observed in this trial.

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Three patients with simple urinary tract infection and 19 complicated urinary tract infection were treated with AC-1370, a new cephalosporin having high antibacterial effects and accerelating effect of host defense mechanism, on a dose schedule of 1g by intravenous one-shot injection twice a day for 5 consecutive days, and the followings were found:
1) Intravenous one-shot injection of 1g AC-1370 once only was followed by its peak blood level of 123 mcg/ml in 15 minutes, with T1/2 of 2.0 hours, 53.2% of the injected dose was recovered from the urine within the first 6 hours.
2) The global clinical effectiveness of 20 of the treated patients on whom the efficacy of the treatment was evaluable according to the criteria for drug efficacy for UTI was detected excellent effect on 8, moderate effect on 6, and poor effect on 6, with an overall effectiveness rate of 64.7%.
3) Bacteriological, 16 (64%) of 25 clinical isolates were eradicated, but 9 remained.
4) One of the patients complained of slight headache as side effect of the treatment, while none of the posttreatment laboratory findings were abnormal.

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AC-1370 was administered to 25 patients with complicated urinary tract infections. All 25 patients were treated with 1g of AC-1370 intravenously by drip infusion every 12 hours for 5 days. Clinical evaluation was made in 25 patients according to 2nd Edition of Criteria for Clinical Evaluation of Antimicrobial Agent on Urinary Tract Infections. The clinical results of AC-1370 were excellent in 5 cases, moderate in 9 cases and poor in 11 cases, the overall efficacy rate was 56%.
Antibacterial activities of CPZ, LMOX, CTM, CEZ and AC-1370 against 16 strains causing urinary infections were determined. Antimicrobial activities of AC-1370 were almost equal to those of CTM and CEZ, while clearly inferior to those of CPZ and LMOX. Ten of 16 strains causing urinary infections were resistant to AC-1370 (MIC, ≥100 μg/ml). Of the 7 strains which had been eradicated during 5 day therapy, only 4 strains were sensitive to AC-1370 (MIC, 0.39-3.13 μg/ml), while the other 3 strains were resistant (MIC, 50-μ800). The MIC data of resistant strains were not always useful in predicting the outcome of AC-1370 therapy.
In 27 patients in whom pre-and post-therapy liver, renal, and hematopoietic function studies were obtained, slight alteration of laboratory values was observed in 9 patients. However, the alteration was of equivocal significance. There was no evidence of subjective adverse reactions in this clinical study.

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A total of 26 patients with complicated urinary tract infections were treated with AC-1370, and the following were found:
1) AC-1370 was administered on a dosage schedule of 0.5, 1 or 2g twice daily, in the morning and the evening, by intravenous one-shot injection (except in 1 patient who received it by intravenous drip), every day, for 5 days.
2) The efficacy of the treatment was clinically evaluated as excellent in 8, good in 11 and poor in 7 of the 26 patients, with a response rate of 73.1%.
3) Bacteriological responses of 36 isolates were such that 26 (72%) were eradicated; 5 decreased, and the other 5 remained unchanged.
4) No side effects were observed.
From these findings, AC-1370 was proved to be a clinically effective and safe drug.

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Eleven inpatients diagnosed as complicated urinary tract infections at the Department of Urology in the Kyushu University from April to September in 1982 were treated with AC-1370 at a daily dose of 1 or 2 g intravenously for 5 consecutive days.
The clinical effects were excellent in 3 cases, good in 2 cases and poor in 4 cases out of 9 cases except for 2 cases of dropout, the efficacy rate being 56%.
Bacteriologically, out of 12 strains of bacteria isolated 8 (66%) disappeared, 4 (44%) persisted. Four strains newly appeared after AC-1370 treatment.
Side effects did not occur in any cases and any abnormalities attributable to AC-1370 in laboratory tests were not recognized.

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We administered AC-1370 to a total of 15 patients, consisting of 14 with chronic complicated urinary tract infections and the other with acute simple urinary tract infection, and achieved the following results:
1) The global clinical efficacy of the drug was evaluable in 8 of them: excellent in 2, good in 5 and poorin the other, with a response rate of 88%.
2) The disease classification of the 8 patients indicated that group 4, comprising 3 patients, accounted for the greatest part of the subjects. The drug was not administered to patients with indwelling catheterization of groups 1 and 5.
3) Bacteriological study revealed that 9 out of 10 isolates were eradicated, with an eradication rate of 90%.
4) No abnormalities were found in any laboratory parameters, while one of the 15 patients complained of mild anorexia as a subjective side effect of the drug.

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AC-1370, a new cephalosporin antibiotic, was investigated on pharmacokinetics and clinical evaluation. The following results were obtained.
1) Absorption and excretion
The peak serum levels, biological serum half life and urinary recovery rate with in 8 hours were 76.9±10.3 μg/ml, 1.35±0.66 hrs, 84.5±2.9% at a dose of 0.5 g in 3 healthy volunteers and were 84.5±10.1μg/ml, 1.35±0.21 hrs, 80.6±5.7% at a dose of 1 g in 3 healthy volunteers and 54.0-67.7 μg/ml, 11.9-14.3 hrs, 10.9-17.7% at a dose of 1 g in 2 patients with renal failure.
2) Clinical evaluation
AC-1370 was administered to 21 cases with complicated urinary tract infection and clinically evaluated to be excellent in 5 cases (23.8%), moderate in 8 cases (38.1%) and poor in 8 cases (38.1%), the efficacy rate being 61.9%. In bacteriological study, out of 28 strains, 17 strains (60.7%) were eradicated.
No side effect was observed in any cases.

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Nine patients with chronic complicated UTI and 4 patients with male accessory sex organ infection were treated with AC-1370. The results were moderate in 4 (44%) and poor in 5 patients (56%) with chronic complicated UTI and moderate in 4 patients (100%) with other infections. Nausea was found in one out of 13 patients treated with AC-1370.

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AC-1370 is a new semi-synthesized cephalosporin derivative developed in Japan.
Minimum inhibitory concentration of AC-1370, CPZ and CMZ against 250 bacterial strains isolated from patients with urinary tract infection in our hospital and affiliated hospitals were measured by agar dilution method. AC-1370 revealed two or three folds weaker antibacterial activities against S. epidermidis, E. coli, K. pneumoniae, Enterobacter and Proteus than other two drugs. Antibacterial activity of the drug against S. faecalis, C. freundii and S. marcescens seemed to be as same as that of CPZ. Many cross resistant strains seemed to exist. However, the drug revealed three or four folds stronger antibacterial activity against P. aeruginosa than that of CPZ. Sensitivity peak of the drug against P. aeruginosa distributed 12.5μg/ml with inoculum size of 10⁶/ml and 25μg/ml with 10⁸/ml.
One patient with acute simple pyelonephritis and 37 cases with chronic complicated UTI were given daily dose of 1 to 2g of AC-1370 for 5 days. Clinical effectiveness was evaluated by a criterion recommended by Japanese UTI committee. A case of acute simple pyelonephritis was judged to be moderate despite of bacterial replacement. In cases with chronic complicated UTI overall clinical efficacy was evaluated to be 67.7%; excellent in 4 cases, moderate in 17 cases and poor in 10 cases. Bacteriological response of the drug to P. aeruginosa was excellent, while response to S. marcescens was poor.
One patient suffered from drug eruption on the first administration day. Rising of GOT and GPT values were found in this case for about ten days. Transient eosinophilia was recognized in other case. No other abnormal laboratory findings were noticed.

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We made preclinical and clinical studies of a new injectable antibiotic developed in Japan, AC-1370, in obstetrics and gynecology.
In its antibacterial activity tests, the MICs of AC-1370 for P. mirabilis were similar to those of cefoperazone (CPZ), and it also proved active against Pseudomonas aeruginosa. The drug was efficiently transferred through the placenta and also into female genital tissues. In other words, the intravenous injection of 1g of the drugwas followed bgby its transfer into the umbilical cord serum to a level corresponding to 36.8 to 20.3% of the level in the mother serum, and its transfer into the amniotic fluid tended to increase with time until 2 hours 30 minutes after the injection. Its levels in female genital tissues (ovary, oviduct, myometrium, endometrium and portio vaginalis) were also high from one hour after the injection onward.
We clinically administered 2.0g daily of AC-1370 to a total of 12 patients with pelvic infections (endometritis adnexitis, pelvic peritonitis, parametritis and adnexa abscess) and urinary tract infection (pyelonephritis) by one-shot intravenous injection or intravenous drip, and evaluated as effective in 11 of them (with a response rate of 91.7%). No side effects calling for attention in particular were observed.

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AC-1370, a new cephem antibiotic, was studied fundamentally and clinically in the field of obstetrics and gynecology, and the following results were obtained:
1) MICs of AC-1370 against 241 isolates of 8 species clinically isolated in the field of obstetrics and gynecology were measured.
The peak values in the MIC distribution curves ranged widely;<100μg/ml for S. epidermidis, 12.5μg/ml for S. aureus, 1.56μg/ml for E. coli, 0.78μg/ml for K. pneumoniae, <100μg/ml for C. freundii, 3.13μg/ml for E. cloacae, 6.25μg/ml for P. aeruginosa, and <100μg/ml for S. marcescens.
2) Serum level of AC-1370 following an intravenous injection of 1 g was 50.3μg/ml at 30 minutes with the half-life of 2.1 hours. The urinary excretion rate was 73.3% within 8 hours.
3) Penetration of AC-1370 into intrapelvic organs following an intravenous injection of 1g was measured. The concentration in every organ reached maximum at 50 minutes after injection with the range of 31.2 to 46.5μg/g. The concentration was decreased thereafter like the tendency of serum concentration, the concentration showing 3.6 to 1.3μg/ml at 7 hours after injection.
4) Transfer of AC-1370 into intrapelvic dead space exudate was measured periodically after an intravenous injection of 1g. The transfer was fairly good, showing 60μg/ml of maximum concentration at 4 hours and 15.5μg/ml at 9 hours after injection.
5) AC-1370 was administered at a dose of 1 to 2g twice a day to a total of 9 patients; 3 patients with endometritis, 1 patient with endometritis and adnexitis, 1 patient with parametritis, 2 patients with pyelonephritis and 2 patients with complicated urinary tract infection. Seven out of these 9 cases responded to the AC-1370 treatment with the clinical efficacy rate of 77.8% and the eradication rate of causative organisms of 80%. Neither remarkable side effects nor abnormal laboratory findings were observed except for vomiting and nausea in one case. In accordance with the above results, AC-1370 is considered to be useful in the field of obstetrics and gynecology.

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Antibacterial activity of AC-1370 was determined by agar plate methods against clinical isolates from obstetrical and gynecological infections including urinary tract infections. Against about 80 percents of E. coli used this chemotherapeutic agent showed less than 50μg/ml in MIC. This drug required 50μg/ml to inhibit 80% of 107 strains of genus Staphylococcus.
It also required 50μg/ml to inhibit 80% of 106 strains of anaerobic Gram positive cocci and Bacteroides of 62 strains (63.9%) was susceptible to this concentration of this drug.
Nine out of ten patients with obsterical or gynecological infections (one case of adnexitis, Bartholine's abscess intrauterine infection and cystitis and 6 cases of acute mastitis) responded well to the administration of AC-1370. This new chemotherapeutic agent did not cause any noteworthy adverse reactions or laboratory data abnormalities throughout this clinical trials.

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Fundamental and clinical studies on AC-1370, a new cephalosporin antibiotic, were performed with the following results.
1. Concentration of AC-1370 was examined in serum, internal genital organs and retroperitoneal fluid after single intravenous administration of 1.0g dose.
The transfer of AC-1370 to the internal genital organs was very good and it's ratio to venous serum level was about 39.0-112.
The transfer of AC-1370 to retroperitoneal fluid was also good and it's ratio to venous serum level was about 23.7-128.5%.
2. In clinical trial, AC-1370 was given to 7 patient with obstetrical and gynecological infection.
Efficacy was excellent in 3 cases, good in 3 cases, poor in 1 case and efficacy rate was 85.7%.
Neither side effect nor abnormal laboratory findings was observed in any of the patients studied.

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We made preclinical and clinical studies of a new cephalosporin derivative AC-1370 in obstetrics and gynecology, and found the following:
1) In the study of MICs of AC-1370, the antibiotic was not so effective against S. aureus, while the peak MICs for gram-negative microbes (1-fold diluted inocula) were such as 1.56 to 12.5μg/ml for E. coil, K.pneumoniae and P. mirabilis; and the MICs for P. vulgaris and S. marcescens were slightly better than those of the standard drug CTM, and the MIC for P. aeruginosa was comparable to that of CPZ.
2) When mothers were injected with 1g of AC-1370 by one-shot intravenous injection, the maximum level of AC-1370 in the mother serum was 125μg/ml, and the level in the umbilical cord serum reached a peak of 27.0μg/ml 33 minutes after the injection, and the level in the amniotic fluid reached a peak of 29.0μg/ml 4 hours 10 minutes after the injection. The remaining level of the drug in the neonate blood was found to be in the range from 3.8 to 2.8μg/ml 3 to 6 hours after the injection only in one baby after delivery, and remained below the detectable limit in other babies. The level of the antibiotic in the mother's milk was below the detectable limit in all mothers.
3) A total of 3 patients, comprising 1 patient with puerperal fever, another with pyelonephritis and the other with asymptomatic bacteriuria, were injected with 1 g of AC-1370 by one-shot intravenous injection or intravenous drip twice a day for 4 to 7 consecutive days; and the drug was clinically evaluated as effective in 2, and its efficacy was unknown in the other patient. Laboratory studies revealed the following abnormalities: the elevation of S-GOT, S-GPT and Al-P in one, and elevation of Al-P in another.

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From the laboratory and clinical studies on AC-1370, the following results were obtained.
1) Antibacterial activity; The antibacterial activity of AC-1370 was compared with those of cefazolin and ceftizoxime against clinical isolates. It was very inferior to cefazolin against S. aureus and very inferior to ceftizoxime against P. mirabilis. Against P. aeruginosa, the MIC level was from 6.25μg/ml to 100μg/ml.
2) Tissue concentration; The concentration of palatine tonsil was 10.4μg/g at 1hr after 1g intravenous injection.
3) Clinical results; AC-1370 was used clinically in 22 cases of various infections in otorhinolaryngological field. The results were excellent in 18 cases, effective in 2 cases and poor effective in 2 cases. Its effectiveness rate was 90.9%.
4) Adverse reaction; Adverse reactions noted were eruption in 2 cases, increase of GOT and GPT in 2 cases and anorexia in 1 case.

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We made preclinical and clinical studies of a new cephalosporin antibiotic, AC-1370, for application in ophthalmology.
The agent proved to have a broad antibacterial spectrum including not only gram-positive but also gramnegative organisms. The antibacterial activity of the agent was found to be weak against gram-positive microbes, but potent against gram-negative microbes compared with that of CEZ. S. aureus was susceptible to 1.56 to 25μg/ml of AC-1370, with a peak of MIC at 6.25μg/ml. Pseudomonas aeruginosa was susceptible to 12.5 to 50μg/ml, with a peak at 25μg/ml. When white mature rabbits were injected intravenously with 50mg/kg of AC-1370 once only, the level of the agent in the aqueous in the anterior chamber reached a peak of 7.1μg/ml 1 hour after the injection, but was no longer measurable 6 hours after the injection. The aqueous: blood ratio of AC-1370 was 15.4%. Half an hour after the intravenous injection, the agent was transferred into the external eye tissues at as high as 10 to 60μg/g, and in the internal eye tissues at 4 to 20μg/g. A total of 11 patients with lidabscess, acute dacryocystitis, corneal ulcer, scleral abscess, purulent iridocyclitis, and orbital infection were treated with 1.0 or 2.0g of AC-1370, once or twice daily, by intravenous drip, respectively. The efficacy of the treatment was evaluated as excellent in 4, good in 6 and fair in the other patient. No allergic reaction was observed as a side effect of the treatment, nor any abnormalities were found on hematology, hepatic and renal function test.

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