[in Japanese]

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[in Japanese]

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1) Cefoxitin (CFX). was administered to seven patients two with acute pneumonia, two with acute pyelonephritis, one with pyofiephrosis complicated to pyelolithotomy, one with acute cystitis and one with CONN syndrome complicated to liver cirrhosis.
2) Response to the CFX treatment was excellent in three patients, good in three, and poor in one.
3) No side effect was observed in all cases. In two patients in whom CFX and furosemide were concomitantly administered, no aggravation of the renal function was observed.

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Laboratory and clinical studies on PC-904, a new semisynthetic penicillin, were performed with following results. PC-904 in doses of 30-50 mg/kg body weight was administered intravenously. The maximum blood level was reached at the end of administration (both in drip infusion and one-shot), and a dose response was observed. In two cases of drip infusion, peak levels were 271.1μg/ml and 88.9 μg/ml. The half-life in serum was estimated to be 53.4 minutes and 80.4 minutes, and the urinary recovery was 25.751 within 3 hours in one patient and 25.5% within 6 hours in the other, respectively. In a case of one shot intravenous injection, the peak level was 330.9μg/ml, the half-life was 88.2 minutes, and the urinary recovery was 39.691 within 3 hours.
Clinical evaluation of PC-904 was attempted in seven patients. The diagnosis were urinary tract infections in four cases, acute brorichitis in two, and acute purulent thyroiditis in one. Of four cases with urinary tract infections, two were treated successfully, although bacteriological effect was negative in one, one patient failed to improve, and the other one -could not be evaluated because of discontinuance of drug due to severe anaphylactic reaction. In two patients with acute bronchitis, clinical effects were obscure. In one case of acute purulent thyroiditis, treatment with this drug was terminated in early period because ihe laboratory study indicated other antibiotic to be more effective to the causative organism.
In conclusion, this drug was regarded as A effective in two.cases, ineffective in one and in the other four cases distinct evaluation was impossible.

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A clinical study of PC-904 was performed and the following results were obtained.
1) PC-904 was intravenously administered at the daily dosage of 20-120 mg/kg to 13 children; urinary tract infection (10 cases), acute pueumonia (1 case), sepsis (1 case) and purulent meningitis (1case). The overall efficacy rate was 46.2%.
2) As to adverse reaction, eosinophilia was noted only in 2 patients. One neonate was treated with this drug, but no side effects were observed.
3) It was considered that PC-904 was a useful antibiotic drug for the second choice rather than the first.

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The following studies were carried out in pediatric patients.
1. Serum levels of PC-904 were examined in 3 patients by 1 hour intravenous infusion of 20mg/kg, reaching the peak of 22.5-25.5μg/ml at the end of infusion. Half life was 37-48 minutes.
2. Investigated in only 1 patient, the urinary excretion rate was 12.9% (0-6hours).
3. The effect of PC-904 on blood pressure was examined in 1 patient, and no effect was observed.
4. Clinical effects of PC-904 were examined in 9 patients; urinary tract infection (6 cases) and Salmonella enteritis (3 cases). The daily dose was 32.6-93.0mg/kg. The overall clinical effectiveness was 66.7%. As to causative organisms E.coli, Klebsiella and Salmonella were isolated. The clinical effects by the organisms were 100%, 0% and 66.7%, respectively.
5. Slight elevation of GOT and GPT and eosinophilia were observed in each one case but these abnormalities rapidly returned to pre-treatment levels when the administration was discontinued. No other side effects were noticed.

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Fundimental and clinical studies of PC-904, a newly developed penicillin with a broad spectrum, were performed and the following results were obtained.
(1) The serum levels of PC-904 after 1.5 hours drip infusion reached the peak at 1 hour or at the end of the infusion and the detectable levels of PC-904 were maintained up to 2 or 3 hours after the end of the infusion.
(2) The urinary excretion rates up to 6 hours after the onset of the infusion were 19.2-25.5%.
(3) Fourty-one patients were treated with PC-904 and the majority of the diseases were acute respiratory infections. The treatment by the drip infusion of 50-400 mg/kg/day resulted in good responses to whooping cough, and lacunar tonsillitis, lymphadenitis and staphylococcal scald skin syndrome resistant to the treatment by ampicillin and cephalexin.
The satisfactory results were also obtained by the treatment of almost the same dosage in the patients with acute bronchitis, bronchopneumonia and measles pneumonia.
(4) Staphylococcus aureus and Klebsiella pneumoniae were isolated from the sputum culture of the patients with bronchopneumonia and they responded well to the treatment with PC-904.
(5) The drip infusion of 60-70 mg/kg/day for 5-6 days was shown to be useful in the treatment of urinary tract infection of which the causative organism was E. coli.
(6) No side effects were observed except rubella-like eruption in one case.
(7) Clinical evaluation was examined in all cases except one patient of which the medication was withdrawn due to eruption, and the overall clinical efficacy was excellent or good in all of 40 cases.

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Clinical study of PC-904 was performed in 8 children with infectious diseases and the following results were obtained.
1) The patients treated with PC-904 were each one case of acute pharyngitis, lacunar tonsillitis, scarlet fever, phlegmone, acute bronchitis and lung abscess, and 2 cases of bronchopneumonia.
2) The adininistration methods were drip infusion, one-shot intravenous injection and the combined use of these administrations. The daily dosage varied from 30 to 49mg/kg in 3 cases and from 50 to 70mg/kg in 3 cases, and was 227 mg/kg in 1 case.
3) a Clinical evaluation was examined in 7 cases and 57.1% of effectiveness was obtained. Out of 2 cases of rineumonia, one case with the causative organism of My. pneunioniae was excluded from the clinical evaluation.
4) No side effects were observed in all 8 cases treated with PC-904.

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A clinical study of PC-904 was performed in children. The results were as follows;
1) Serum levels of PC-904 after single administration of 20mg/kg were studied in patients by one - shot intravenous injection or drip infusion for 1 hour or 2 hours. The results obtained in this fundamental study led to the suggestion that the proper dosage in bacterial infections would be 50-100mg/kg intravenously in 3-`4 divided doses daily.
2) A clinical study of PC-904 was performed in 16 patients including acute pharyngitis and bronchitis (3 cases), acute bronchopneumonia (3 cases), pertussis pneumonia.(1 case), lymphadenitis purulenta (2 cases), abscess with chronic granuloma (2 cases) and urinary tract infection (5 cases).
About 50-100 mg/kg of PC-904 were administered in 3-4 divided doses daily by one -shot intravenous injection. The clinical effects of 2 cases out of 16 were impossible to be evaluated, and these cases were excluded from the clinical evaluation. Ten cases out of 14 showed excellent or good responses (efficacy rate: 71.4%).
3) The bacteriological examinations were performed and the causative or isolated organisms were determined in 11 cases. The responses were “disappeared” in 6 cases, “decreased” in 2 cases and “notdi sappeared” in 3 cases.
4) No side effects were observed. Abnormalities of laboratory findings were not also noticed.

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PC-904 was administered to 3 pediatric patients, with serious infections resistant clinically to other antibiotics (2 cases of sepsis and 1 case of pseudormonal pneumonia).
Daily dosage was 100-150 mg/kg and intravenous infusions were carried out in 2 or 3 divided doses.
This drug showed clinically and bacteriologically good response in these patients without any side effect, and was considered to be a useful drug or worthwhile to use in the treatment of the serious infectious diseases such as sepsis or pseudomonal infections.

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PC-904 was administered to 16 pediatric patients and the following basic and clinical results were obtained.
(1) PC-904 was administered 20-30mg/kg. The serum peak level of PC-904 after drip intravenous infusion over 1 hour was 66.7μg/ml at 1 hour and T1/2 of PC-904 was 67.8 minutes. PC-904 was administered 25-30mg/kg intravenous one shot injection was 49.4-Eg/ml at 1 hour and Ti of PC-904 was 52.2 minutes.
(2) Urinary excretion rate was about 20% up to 6 hours after drip intravenous infusion of 20 mg/kg. In a case of intravenous one shot injection of 25-30 mg/kg, the excretion rate was 11.9-19.9%.
(3) PC-904 was administered 60-120 mg/kg/day for 3-48 days to 5 cases of sepsis and baterial endocarditis, 6 of pneumonia, 2 of sss syndrome (staphylococcal scald skin syndrome) and 3 of pyelonephritis. Clinical effects were excellent in 11 cases and good in 5 cases, effective ratio being 100%.
(4) Pseudomonas aeruginosa, Staphylococcus epidermidis, Streptococcus viridans, Acinetobacter anitratus and Hemophilus influenzae isolated from clinical specimens disappeared by the treatment of PC-904. Escherichia coli and Klebsiella pneumoniae reduced.
(5) As to the side effect by PC-904, s-GOT and s-GPT were elevated in 2 cases. Anemia, rash and fever were observed in each 1 case out of 16 patients though the causal relation with the agent was unknown.

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The authors have carried out the laboratory and clinical studies of PC-904. The results were as follows;
The sensitivity was measured by plate dilution method on 32 strains of Staph. aureus, 32 strains of P.aeruginosa, 12 strains of E. coli, and 15 strains of Kl.pneumoniae. The sensitivity distribution of P.aeruginosa was 0.78-6.25μg/ml and the peak was 1.56μg/ml. PC-904 inhibited the growth of all of P.aeruzinosa at less than 6.25μg/ml. The peak of sensitivity distribution of Staph.aureus was 0.78-1.56μg/ml and 50μg/ml. PC-904 inhibited the growth of 47% of E.coli at less than 50μg/ml but Kl.pneumoniae was not sensitive to this agent.
PC-904 was given by intravenous in or by drip infusion (for 1 hour) at dose of 25mg/kg body weight to 2 children. The serum levels of PC-904 were 204, 62 and 34 μg/ml at 0.5, 1 and 2 hours after intravenous administration, respectively, and. level at 6 hours was not detected. The serum level reached the maximum at 1 hour after drip infusion and the level at 1 and 2 hours were 62 and 34 μg/ml, respectively, and the level at 6 hours was not detected.
PC-904 was clinically effective in 7 of 9 cases with bacterial infections in infants and children.
No side effects were observed except for the abnormality of the laboratory findings; elevation of BUN in 1 case, elevation of GOT in 2, and elevation of both GOT and GPT in 1.

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PC-904 was administered to 24 patients: urinary tract infections (7 cases), bronchitis (2 cases), pneumonia (3 cases), brain abscess (1 case), septicemia and the suspected cases (10 cases), and buttock abscess (1 case). The daily dosage varied from 60 to 223.4 mg/kg and averaged 86.9 mg/kg. The drug was administered three times a day by 1-hour drip infusion, and the duration of the treatment averaged 11 days.
Clinical results were obtained as excellent responses in 5 cases, good in 13, poor in 4, and unknown in 2, giving 75%, of the clinical effectiveness.
Bacteriological responses were excellent in 7, good in 2, poor in 2, and unknown in 13, and the overall effectiveness was evaluated as excellent in 2, good in 17, and unknown in 5.
Antibacterial activities against clinically isolated bacteria were examined. MIC values of PC-904 were over 100μg/m; against 1 strain of E.coli and 2 strains of Klebsiella, however excellent sensitivities were observed in 3 strains of Ps. aeruginosa and MIC values varied 1.56 to 3.12 μg/ml at 10⁸ of inoculum size and 0.78 to 1.56μg/ml at 10⁸.
As to side effects, diarrhea was observed in 1 case, rash in 2, lowering of blood pressure in 2, elevation of GOT in 1, and elevation of LDH in 2.
Abnormal elevations of GOT (10 cases), GPT (5 cases), Al-P (1 case), LDH (7 cases), and BUN (1 case) were noticed in other patients, but it was considered to be due to underlying diseases.

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Fundamental and clinical studies were conducted on a new semisynthetic broad-spectrum penicillin PC-904 and the following results were obtained.
1. MICs were determined on the different inoculum size of the following clinical isolates, i.e., Staphylococcus aureus (14 strains), E.coli (9), Salmonella typhi (3), Salmonella B (1), Proteus mirabilis (2), P.morganii (1), Klebsiella pneumoniae (4), Enterobacter (5), Pseudomonas aeruginosa (8) and Klebsiella oxytoca (42). The antibacterial activity of the drug was found to be similar to that of T-1220 and BAY-f-1353 in respect of a marked reduction in MIC value with a decrease in inoculum size and antibacterial spectrum. When MICs of these three drugs were compared, PC-904 was almost equal to other two drugs in regard to some enteric bacteria but was superior in regard to Pseudomonas aeruginosa. When PC-904 and ampicillin were compared, antibacterial activity against Staphylococcus aureus was superior in ampicillin and that against E. coli in PC-904, respectively. However, there existed strains resistant to either antibiotic and these strains were also resistant to other broad-spectrum penicillins.
2. Following one shot intravenous injection of 100mg/kg of the drug to experimentally induced Staphylococcus aureus meningitis in rabbits, blood and cerebrospinal fluid (CSF) concentrations of the drug and CSF/serum ratio were determined at the indicated time as below, i.e., 1/2 1, 1 1/2 and 2 hours, respectively; blood concentrations (μg/ml), 265.8, 99.3, 53.4, and 38.5; CSF concentrations (μg/ml), 7.5, 6.5, 4.7 and 5.3; CSF/serum ratios (%), 2.8, 6.5, 8.8 and 13.8. Actual CSF concentrations were not so reduced when compared with other broad-spectrum penicillins, but markedly elevated blood concentrations of PC-904 made a CSF/serum ratio significantly lower and were equal to that of cloxacillin. Taking this observation into consideration, one should be prudent in clinical application of this drug in bacterial meningitis in humans.
3. A dose of 20-30mg/kg of the drug was given to 3 children by a continuous drip infusion over a period of 30-60minutes and blood concentrations (μg/ml) were determined using Moni-Trol I as a standard at the indicated time; 40-68 at the end of infusion, 19-43 at one hour and 11-30 at two hours after infusion, respectively. The blood concentration of more than 10 pg/ml was expected to be maintained for 3 hours after infusion. The recommended dosage in bacterial infections sensitive to the drug appears to be about 80mg/kg intravenously in 3-4 divided doses daily. However it is necessary to increase the dose in infections caused by moderately resistant strains of the organisms. A urinary excretion rate in one patient was 11.4% up to 6 hours.
4. The drug was given to 29 cases of following bacterial infections; pneumonia (13 cases), empyema (1), urinary tract infection (9), pyonephrosis (1), bacterial osteomyelitis (1), sepsis (2), Salmonella enteritis (1), typhoid fever (1). The dosage was 50-100mg/kg/day in 3 divided doses given intravenously over 30 minutes in most cases and for a period of 5-10 days. The overall efficacy rate was 79.3%, i.e., excellent in 10, good in 13 and failure in 6; pneumonia, excellent in 6, good in 6 and failure in 1; urinary tract infection, excellent in 4, good in 4 and failure in 1; failure in empyema, pyonephrosis, bacterial osteomyelitis and typhoid fever; good in sepsis (2 case) and Salmonella enteritis (1 case). The causative organisms included Pseudomonas aeruginosa (3 cases), Enterobacter (1) and Proteus morganii (1), and the drug was effective to these cases except for one case by Pseudomonas aeruginosa.

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