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Lytic action of cefminox (CMNX) against slowly growing Escherichia coli (E. coli) K-12 JE1011 was compared with that of the related cephamycin cefmetazole (CMZ) or ampicillin (ABPC). The growth rate in doubling time was 30 min. at 37 degrees C. Minimal concentrations of CMNX, CMZ and ABPC showing clear lysis were 0.39, 3.13 and 12.5 micrograms/ml, respectively, under these conditions. When E. coli was cultured at 12 degrees C, the doubling time was 720 and 816 min. which were 24 and 27.2 fold as slow as those at 37 degrees C, respectively. In 12 degrees C culture, the minimal concentrations showing clear lysis were 0.78 (2 fold at 37 degrees C), 25 (8 fold) and 100 micrograms/ml and higher (8 fold or more) with CMNX, CMZ and ABPC, respectively. Therefore, it appeared that the lytic activity of CMNX was not significantly affected by bacterial growth rate and was demonstrated effectively against slowly growing bacteria at a low concentration. We determined release activity of cell wall peptidoglycan fragments by 5 beta-lactam antibiotics in addition to the above-mentioned 3 antibiotics. The results showed that the release activity was not proportional to the MIC and that of CMNX was the strongest among those antibiotics. The rapid and strong bactericidal action of CMNX against bacteria at the early stationary phase was suggested to result from the characteristic lytic action against slowly growing bacteria.

A study was done to determine susceptibilities of Haemophilus influenzae that were obtained in our laboratory in 1994 to new quinolones (NQ) and other drugs. The results were as follows; 1. Among the 300 isolates, the detection frequency of NQ-resistant strains was 8.7% (26 strains), including isolates from chronic lower respiratory tract infections (22 strains) and those from middle meatus of nose (2 strains), etc. NQ-resistant strains were not isolated from children. 2. The cross resistance was studied for different NQs against NQ-resistant strains. Clavulanic acid/amoxicillin, cefteram, cefpodoxime, cefditoren, cefodizime (CDZM) and cefpirome showed strong antimicrobial activities against NQ-resistant strains. MIC90 of CEPs against all isolated strains including NQ-resistant strains and beta-lactamase producers was low. And the MIC90 of CDZM was < or = 0.025 microgram/ml, which was the lowest among all the antibiotics tested. 3. We found 47 strains (15.7%) of beta-lactamase producers among the 300 isolates, the frequency of beta-lactamase producing strains was high among strains obtained from children.

Against main clinical isolates at our center in 1990 to 1992, the minimum inhibitory concentrations (MICs) of cefminox (CMNX) and some other comparable cephems were determined. The results are summarized as follows. 1. As to the strains resistant to cephems including CMNX, annual increases were observed for Streptococcus pneumoniae among Gram-positive bacteria and Proteus vulgaris among Gram-negative bacteria. Moreover, cephem-resistant strains of Escherichia coli were constantly isolated, and there were signs indicating that cephem-resistant strains would increase among strains of Klebsiella pneumoniae. 2. The annual increases in cephem-resistant strains of S. pneumoniae and P. vulgaris may respectively reflect the recent increases in the incidence of benzylpenicillin (PCG)-insensitive strains of S. pneumoniae (PISP) and multi-drug resistant strains including oxime type cephems and new quinolones introduced into clinical use in the latter half of the 1980s. 3. Concerning antimicrobial activities of CMNX against recent clinical isolates, the same problems as described above will remain. However, these tendencies have been observed only with regard to MIC90. No remarkable changes have been noted for MIC50 or MIC80 at this time.

Combined antibacterial effects of imipenem (IPM)+arbekacin (ABK) and cefminox (CMNX)+ABK against methicillin-resistant Staphylococcus aureus (MRSA) were examined and the obtained results are summarized below. 1. Either combination, IPM+ABK or CMNX+ABK, showed a strong antibacterial effect against MRSA when blood concentration of ABK were sustained at MIC as could be expected in clinical situations. While at sub MICs of ABK the antibacterial effect of these combination was slightly less than those of the previously reported combinations of ABK and other antibiotics. 2. Antibacterial effects of the combinations against MRSA were strongly dependent on the concentration of ABK and less dependent on the concentration of IPM or CMNX. As were observed in the previously tested combinations of ABK with other antibiotics, the antibacterial effect of the combination appeared to be highly dependent on the antibacterial activity and the concentration of ABK. 3. As IPM has potent antibacterial activities against Gram-negative bacteria (GNB) including Pseudomonas aeruginosa while CMNX has potent antibacterial activities against GNB except P. aeruginosa, it is likely that the combinations of IPM+ABK or CMNX+ABK are useful for treatment of infections with MRSA together with GNB.

Cefminox (CMNX), one of newly developed cephamycin antibiotics, was administered to 7 cases of diffuse peritonitis associated with infantile acute appendicitis to determine its concentrations in the blood, the appendiceal tissue and the purulent ascites and simultaneously to investigate its clinical efficacy. CMNX was intravenously injected at a dose of 20 mg/kg (at a maximum amount of 1.0 g/body) before operation and intravenously by bolus injection or by drip infusion twice daily after operation for 3 to 11 days in a total dose of 2.36 to 14.06 g. Fourteen strains of bacteria were isolated from the purulent ascites: Escherichia coli was isolated from 6 cases but superinfections in 5 cases. MICs of CMNX against these isolated organisms were at or lower than 3.13 micrograms/ml for 12 out of 14 strains. CMNX penetrated into the appendiceal tissue and the purulent ascites very well. The concentrations in the pus reached higher than those in the tissue in about 1 hour after administration and were found to reach as high as 9.63 micrograms/ml in 5 hours after administration. Its clinical efficacies were excellent in 4 cases, good in 2 cases and poor in 1 case. No subjective or objective adverse reactions were observed nor any abnormalities were found in laboratory examinations.

Fundamental and clinical studies were carried out to objectively evaluate the effectiveness and safety of cefmetazole (CMZ) in the treatment of S. aureus infections of the skin, and the following results were obtained. 1. Blisters are induced with cantharis ointment to determine transfer of CMZ and cefazolin (CEZ) into the sclerosity and skin. The sensitivity of clinically isolated S. aureus was measured to these drugs. 2. In case of CMZ, antibacterial activity, exudate and tissue transfer were favorable, and the sclerosity and skin concentration of the drug was such that it covered the major portion of MIC distribution of the clinically isolated S. aureus. 3. In the crossover test following one shot intravenous injection of CMZ and CEZ at the doses of 1 g, drug concentrations in the serosity and skin were higher after CMZ as compared with those after CEZ. 4. Clinical effect of this drug in the treatment of S. aureus infections of the skin in 10 cases was such that it was markedly effective in 4 cases, moderately effective in 4 and slightly effective in 2 cases. Bacteriological, effect of CMZ was eradication of the bacteria in 9 cases and change of bacterial flora in 1 case. In addition, the clinical effect of the drug in 2 cases in which cephalexin had been ineffective was that it was markedly effective in 1 and slightly effective in the other. 5. Side effect was not observed in any of the treated cases. From the above, it was concluded that CMZ is highly useful drug in the treatment of S. aureus infections of the skin.

Fundamental and clinical studies in the pediatric field on 6059-S, a newly synthesized oxacephem antibiotics, were carried out, and following results were obtained. 1) MIC of 6059-S for K. oxytoca (40 strains), recently isolated from patients, were mostly more less than 0.2 mcg/ml, and that for H. influenzae was 0.05 mcg/ml, but that for non-group A-beta-Streptococcus (2 strains) were 12.5 mcg/ml. 2) In 9 infants, the serum concentration of 6059-S in a dose of 10 approximately 37.5 mg/kg/day with intravenous drip infusion method was measured. The peak serum concentration were 32.8 approximately 241 mcg/ml at end of injection, and serum concentration were 0.6 approximately 3.19 mcg/ml 7 hours after administration. The excretion rates in urine for 12 hours after administration were distributed between 55.8 approximately 89.6%. 3) Clinical evaluation of 6059-S was performed in evaluated 29 cases: 24 cases of respiratory tract infection, 2 cases of cervical lymphadenitis, 2 cases of urinary tract infection, 1 case of enteritis. The overall efficacy rate was 96.6%. 4) Side effects observed during this therapy were 1 case of diarrhea, 2 cases of adverse effect (eosinophilia, elevation of GOT, GPT).

We compared the in vitro antibacterial activities of ceftizoxime (CZX), cefotaxime (CTX), cefmenoxime (CMX), cefoperazone (CPZ), ceftazidime (CAZ), latamoxef (LMOX) and cefotetan (CTT) against 2,729 strains of 11 organisms freshly isolated from 10 medical institutions in Japan between June 1983 and January 1984 and obtained the following results: Against S. pyogenes, LMOX and CTT, which have the methoxy group at the 7 position, were less active than the other drugs. LMOX inhibited 80% of S. pyogenes at 0.78 micrograms/ml; CTT, at 1.56 micrograms/ml; but CZX and CTX inhibited 100% at 0.025 micrograms/ml or lower; CMX, at 0.05 micrograms/ml; and CPZ and CAZ, at 0.20 micrograms/ml. Against H. influenzae, E. coli, K. pneumoniae, P. mirabilis and indole-positive Proteus, these test antibiotics, especially CZX, CTX and CMX, which have the aminothiazolyl methoxyimino group, were potently active. Against S. marcescens CZX and CAZ were more active than the other drugs and against P. aeruginosa CAZ was more active than the other drugs. The test organisms did not tend to acquire resistance to these cephems when our results were compared with the results obtained at the development period.

Studies on T-1982 (cefbuperazone), a new cephamycin antibiotic, were carried out in the field of pediatrics, and the following results were obtained. 1. Peak MIC of T-1982 against S. pyogenes (group A) lately isolated was 0.39 micrograms/ml, and the drug was active even against highly resistant strains of macrolides, lincomycin, tetracycline and chloramphenicol. 2. Peak MICs of T-1982 were 0.78 microgram/ml against B. pertussis, 0.2 microgram/ml against E. coli and less than or equal to 0.05 microgram/ml against K. oxytoca, and the drug was also active against ampicillin-resistant bacteria. 3. Serum levels and urinary excretions of T-1982 were investigated in 6 cases. When given at a dose of 20-28 mg/kg by 1 hour intravenous drip infusion, serum concentrations of T-1982 attained the peak level of 63.5-75.9 micrograms/ml at the end of administration and sustained the level of 0.9-2.6 micrograms/ml at 6 hours, the serum half-life (T 1/2) ranging 70-82 minutes. Approximately 20-72% of the dose were excreted in the active form into urine within 6 hours. 4. Twenty-seven cases of acute pediatric infections were treated with T-1982 mainly by intravenous drip infusion, and satisfactory clinical results were obtained in all the cases of angina lacunaris, bronchitis, bronchopneumonia, pertussis, sepsis caused by Serratia and acute urinary tract infections caused by ampicillin-resistant E. coli. The efficacy rate was 96.3%. In this study the drug was administered chiefly at a daily dose of 50-70 mg/kg 2-3 times a day for 2-12 days. 5. Gram-positive cocci (S. aureus, S. pneumoniae, S. pyogenes) and Gram-negative rods (H. influenzae, H. parainfluenzae P. vulgaris, B. pertussis, S. marcescens, E. coli) were eradicated by the treatment with T-1982. 6. No noticeable side effects were observed, except for temporary increase of eosinophil in 2 cases and slight elevation of GOT in 1 case.

Laboratory and clinical studies were performed on cefminox (CMNX, MT-141), a new cephamycin antibiotic, and results were as follows. Antimicrobial activities. MICs of CMNX against various clinical isolates were determined with the inoculum size of 10(6) cells/ml. Percentages of strains susceptible to 12.5 micrograms/ml or less were 4% for S. aureus, 0% for E. faecalis, 100% for E. coli, 81% for K. pneumoniae, 3% for Enterobacter sp., 18% for S. marcescens, 90% for P. mirabilis, 88% for indole-positive Proteus sp. 100% for S. flexneri, 100% for Salmonella sp., 0% for Citrobacter sp. and 0% for P. aeruginosa. Most of those sensitive strains were inhibited by 0.39-0.78 microgram/ml. These activities were better than those of cefmetazole and cefazolin, but were not as good as those of cefoperazone. Clinical efficacy Three patients with pneumonia, 1 with pneumonia and sepsis, and 1 with urinary tract infection were treated with CMNX daily dose of 1-4 g for 7-31 days. Clinical responses were excellent in 1, good in 3, poor in 2 patients (contained a double case). Bacteriological effects were good for E. coli, K. pneumoniae and S. liquefaciens, poor for P. aeruginosa and P. mirabilis. C. freundii, A. calcoaceticus and E. faecalis were cultured after treatment. No side effect and no abnormal change of laboratory findings were seen in our cases.

Cefmetazole was investigated on stability to beta-lactamases produced by Bacteroides fragilis and on therapeutic effects in mice infected with B. fragilis. 1. Cefmetazole, like other cephamycins, was found extremely stable to beta-lactamases obtained from B. fragilis. 2. Cefmetazole showed good antimicrobial activities to 50 strains of B. fragilis and extremely high stability to their beta-lactamases. 3. Cefmetazole showed an excellent protecting effect to infections due to beta-lactamase producing B. fragilis. 4. Cefmetazole exhibited an excellent chemotherapeutic effect against polymicrobial infections in mice due to E. coli (beta-lactamase -)and B. fragilis (beta-lactamase +).

A series of studies was performed on the use of cefotetan (CTT) in the field of pediatrics. The results that were obtained are described below. The minimum inhibitory concentrations (MICs) of CTT against strains of E. coli and K. oxytoca that were recently isolated from child patients were found to mostly be 0.78 micrograms/ml or less. Even strains that were highly resistant to the action of ABPC were sensitive to CTT. CTT was administered to pediatric patients by intravenous drip infusion or by one shot intravenous injection, and then the concentration of the drug in the serum was monitored. The same procedures and dosages were employed for CFX and CMZ. In comparison with these 2 antibiotics, CTT showed a higher peak concentration in the serum, and it was retained in the blood for a longer time. The half-life of the CTT serum concentration was 2 hours or more in most of the subjects. When CTT was administered in a dosage of 10 mg/kg by intravenous drip infusion, the drug could still be detected in the serum as long as 12 hours later in some cases. Repeated intravenous drip infusion administration of CTT was not found to result in any accumulation of this antibiotic in the serum. During the 8-hour period following intravenous injection of CTT, about 50 to 80% of the administered dose was found to be excreted in the urine in its active form. During the acute phase of meningitis, intravenously injected (one shot) CTT was found to be transferred to the cerebrospinal fluid in a concentration that was sufficient to kill those bacteria that were sensitive to the action of this antibiotic. It was proven that, following the intravenous injection of CTT, the concentration of this drug in the feces was sufficient to inhibit the growth of Salmonella, Campylobacter, etc. CTT was administered by intravenous drip infusion as therapy to a total of 37 child patients diagnosed as having acute infections; these infections consisted mainly of upper and lower respiratory tract infections, urinary tract infections, intestinal tract infections and suppurative diseases. The dosage of CTT used in the treatment of these diseases ranged almost from 20 to 40 mg/kg/day, given as 2 doses per day (at intervals of 10-12 hours). The efficacy rate of this therapeutic regimen was 97%.(ABSTRACT TRUNCATED AT 400 WORDS)

The authors have carried out the laboratory and clinical studies of T-1982 (cefbuperazone). The results were as follows: The sensitivity was estimated by the plate dilution method on 28 strains of S. aureus 26 strains of E. coli, 27 strains of K. pneumoniae, 25 strains of S. marcescens and 14 strains of Proteus sp. isolated from patients. The distribution of susceptibility of S. aureus was 1.25-25 micrograms/ml and the peak of distribution was 12.5 micrograms/ml. The strains of 84.6% of E. coli were inhibited at concentration of less than 0.39 micrograms/ml. The strains of 77.8% of K. pneumoniae were inhibited at concentration of less than 0.2 microgram/ml. The strains of 96% of S. marcescens was inhibited at concentration of less than 3.13 micrograms/ml. The distribution of susceptibility of Proteus sp. was 0.39-25 micrograms/ml. T-1982 was given to intravenous administration for 5 minutes and drip infusion for 30 minutes a single dose of 20 mg/kg of T-1982 to 2 and 2 children respectively. After intravenous administration of T-1982, the mean serum level was peak 88.4 +/- 8.7 micrograms/ml at 15 minutes, 52.5 +/- 2.7 micrograms/ml at 1 hour, 4.6 +/- 0.15 micrograms/ml at 6 hours respectively. Half-life was 89 minutes. And after drip infusion of T-1982, the mean serum level was 75.5 +/- 3.5 micrograms/ml at 30 minutes and 3.1 +/- 0.6 micrograms/ml at 6.5 hours respectively. Half-life was 82 minutes. The mean urinary excretion rate was 94.7%, 57.4 +/- 11.0% up to 6 hours after intravenous administration and drip infusion respectively. T-1982 was effective in 13 cases out of 13 cases with bacterial infections. No side effects were observed except for 1 case with elevation of serum GOT, 1 case with elevation of serum GPT and 2 cases with eosinophilia.

1. Cefmetazole (CMZ) exerted excellent antibacterial effect in vitro for E. coli, Klebsiella spp. and Staphylococcus spp. bacteria isolated from clinical specimens in high yield (more than 40%). The effect was better than that of the conventionally used cephalosporin antibiotic agents. CMZ was also effective for anaerobic bacteria, such as Bacteroides spp., and the antibacterial spectra were broader than those of CEZ and CET. 2. Clinical effects of CMZ were examined for the postoperative traumatic infections and postoperative peritonitis in the field of surgery, and it was found that the effect of CMZ was seen in more than 80% in the both A and B groups; that is, CMZ was administered to the A group as the first choice, and CMZ was administered to the subjects to which CEZ and CET and other penicillin antibiotics were administered in vain (B group). 3. No side effects and influence on the laboratory test values were observed, and it may be said that CMZ is a safe antibiotic agent in the field of surgery.

Antibacterial activities of cefmetazole, a new preparation of cephamycin antibiotic, were determined against selected clinical strains of Escherichia coli (27 strains), Klebsiella sp. (27 strains) and Bacteroides fragilis (27 strains). Activities were evaluated at bacteriostatic and also bactericidal levels with particular reference to time of exposure of microbes to the drug. The minimal drug concentrations producing minimal reduction of colony-forming units at time intervals of 3, 6 and 24 hours after exposure to the drug--approximations to the theoretical bacteriostatic concentrations--were designated as 3-h, 6-h and 24-h MRCs, respectively. Conventional MIC yielding no turbidity after incubation of antibiotic-containing broth for 24 hours was also determined. The minimal concentrations of the drug producing 99.9% killing at time intervals of 3, 6 and 24 hours after exposure to the drug were designated as 3-h, 6-h and 24-h MLCs, respectively. Assuming that the apparent mode of action of a drug is bactericidal when the ratio of bactericidal-bacteriostatic concentrations is low (less than or equal to 4) and bacteriostatic when high (greater than or equal to 8), then cefmetazole appeared to be a bactericidal drug to a considerable number of Gram-negative strains when the exposure time exceeded a period of 6 hours. The data that the mode of action of this drug is bactericidal with such relatively brief exposure times--indicating rapid decrease of colony-forming units--would suggest cefmetazole is an excellent antibacterial agent and would be a useful drug in treatment of bacterial infections.

In vitro and in vivo antibacterial activities of MT-141, a new cephamycin, against anaerobic bacteria were compared with those of cefmetazole (CMZ), cefoxitin, cefotaxime, ceftizoxime, latamoxef and cefazolin to obtain the following results. MT-141 showed high activity against a wide variety of anaerobic bacteria including B. fragilis and C. difficile except for Eubacterium lentum, E. aerofaciens and B. furcosus. Antibacterial activity of MT-141 against anaerobic bacteria was almost independent of inoculum size, medium, pH and serum addition. In vitro development of resistance of MT-141 against P. variabilis and B. fragilis was comparable to that of CMZ. Successive parenteral administration of MT-141 into mice did not cause abnormal proliferation of C. difficile. MT-141 showed excellent therapeutic effect against experimental subcutaneous abscess in mice caused by B. fragilis.

Laboratory and clinical studies were performed on a new oxacephem antibiotic, flomoxef (FMOX, 6315-S). In vitro antibacterial activity of FMOX was evaluated in comparison to latamoxef (LMOX), cefmetazole (CMZ), cefazolin (CEZ) using clinically isolated strains of Gram-negative and Gram-positive bacteria. Antibacterial activities of FMOX were stronger than LMOX, CMZ, CEZ against Escherichia coli, Klebsiella but only slightly effective against Staphylococcus aureus. This antibiotic drug was administered to 5 patients consisting of 2 cases with pneumonia, one each with pyelonephritis, chronic bronchitis and urinary tract infection. The drug was given in 1 g drip infusion twice a day for 8 to 13 days. Clinical efficacies of FMOX were excellent in 1 case, good in 2, fair in 1, and unevaluable in 1. As for bacteriological effect of FMOX, organisms were eradicated in 3 cases. No side effect was noted and there was no abnormal change in laboratory findings.

Antibacterial activity of cefmenoxime (CMX) against clinically isolated organisms was examined in comparison with that of 4 other antibiotics and concluded as follows: Antibacterial activity of CMX was markedly stronger than those of cefazolin (CEZ), cefmetazole, latamoxef and ampicillin against E. coli, K. pneumoniae, S. marcescens, H. influenzae, P. mirabilis and indole positive Proteus. But the MIC level of CMX against S. aureus was higher than that of CEZ.

Clinical studies on cefminox (CMNX, MT-141) were conducted and the following results were obtained. Twelve cases of bacterial infections were treated with CMNX with a satisfactory result of "excellent" in 9 and "good" in 3. Antibacterial activity was examined in 7 cases. Pathogenic organisms which were S. aureus, beta-Streptococcus, H. influenzae, S. pneumoniae and P. morganii were eradicated in all the cases. Mean maximum serum concentrations of CMNX after intravenous injection of 10, 20 and 40 mg/kg were 54.5 mcg/ml, 102.3 mcg/ml and 202.4 mcg/ml, respectively which were obtained 15 minutes after each injection. Mean half-lives of each dose group were 1.60, 1.13 and 1.51 hours, respectively. Mean urinary excretion rates of CMNX at 6 hours after intravenous injection in 10, 20, 30 and 40 mg/kg groups were 73.5%, 80.9%, 92.6% and 66.5%, respectively. Side effects were not observed clinically, but anemia in 1 case and eosinophilia in 2 cases were noted in laboratory examination.

Cefminox (CMNX), a new cephamycin, was administered by one shot intravenous injection twice daily with a dose of 1,000 mg each time for 5 days to seven healthy male volunteers whose ages ranged from 21 to 28 years (mean: 25 years) and body weights were from 60 to 92 kg mean: 72 kg). The effect of the drug on fecal bacterial flora was investigated and the concentrations of the drug in feces were measured on 5th day before the treatment, on 0, 3rd, and 5th day (the final day of the treatment) during the treatment, and on 3rd, 5th, and 10th day after the treatment. Antibiotic susceptibility tests of CMNX, cefmetazole (CMZ) and cefotaxime (CTX) against several strains of organisms isolated from feces of the seven volunteers were performed. Clinical adverse reactions and effect on laboratory examinations were also investigated. The results of the study are described as follows. Among Enterobacteriaceae, populations of E. coli, Klebsiella sp. and Citrobacter sp. temporarily disappeared during the treatment of CMNX. After 5-day-treatment, that of Citrobacter sp. transiently increased and the isolation of Enterobacter sp. increased during treatment and up to 5 days after treatment, while those of Proteus sp., H. alvei, or Serratia sp. did not show a definite change. The mean Enterobacteriaceae population in general was 10(8) to 10(9) cells/g feces, showing almost no variation, on all examination days except 5th day during treatment when these organisms were not isolated from only one subject. No remarkable change was not found in populations of other isolated organisms including Gram-negative bacilli; Aeromonas sp., Pseudomonas sp. and Acinetobacter sp., and Gram-positive bacteria; Staphylococcus sp., Enterococcus sp., Micrococcus sp. and Candida sp. Among anaerobes, the mean population of Bacteroides sp. was 10(10) to 10(11) cells/g feces, showing almost no variation, and C. difficile was not isolated from any subject, however the toxin was detected in samples from 5 of 7 subjects; one subject showed always positive for toxin on all examination days; 1 on 5th day during treatment to 10th day after treatment; 2 on 5th and 10th day after treatment, and 1 only on 10th day after treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Cefminox sodium (CMNX, MT-141), a new semisynthetic cephamycin, having marked resistance to beta-lactamase, and a broad spectrum of antibacterial activity against various bacterial species, including Haemophilus influenzae, Serratia marcescens and Citrobacter freundii, CMNX has higher activity in vivo than in vitro. For therapeutic purpose, CMNX was given in a daily dose of 0.5 g (0.5 g X 1) to 2 g (1 X 2) by intravenous drip infusion for 4 to 8 days to 24 cases with acute peritonitis (17 cases with acute appendicitis, 1 with localized peritonitis after gastrectomy, 1 with diffuse peritonitis due to perforative duodenal ulcer and 5 with panperitonitis due to intestinal obstruction). The clinical response was rated excellent in 9 cases, good in 14 cases and fair in 1 case and poor in none. No adverse effect was observed. There were 29 strains isolated organisms included 12 Escherichia coli, some Enterococcus faecalis and Pseudomonas aeruginosa. These isolated organisms were eradicated after CMNX treatment, except a strain of E. faecalis was decreased. In 19 cases of them, 16 cases with acute peritonitis due to acute appendicitis and 3 cases with acute panperitonitis due to intestinal obstruction, CMNX was administered intravenously in a dose of 1 g (1 case was 0.5 g) before or during the operation, and tissue specimens and body fluids samples were taken during the operation. CMNX concentration was determined to a bioassay with Escherichia coli NIHJ or Vibrio vercolans ATCC 8461 as the test organisms. CMNX concentrations in purulent ascites were 47.2 +/- 38.5 micrograms/ml (n = 23), those in infected appendix wall were 32.2 +/- 21.7 micrograms/g (n = 16), that in pus in appendix were 22.1 +/- 24.3 micrograms/ml (n = 8) and that in other non infected tissues were 24.3 +/- 22.0 micrograms/g (n = 8). CMNX concentrations in infected tissues were higher than the non infected tissues. In the 3 cases with empyemic appendicitis, CMNX levels in pus in appendix were more higher than that in appendix wall itself. Therefore, CMNX sodium appears to be a very useful drug when used for chemotherapy on acute peritonitis.

Experimental and clinical studies were carried out on cefmetazole (CMZ), a synthetic antibiotic of cephamycin group, and the following results were obtained. 1) The minimal inhibitory concentrations (MICs) of CMZ against Gram positive cocci (30 strains) isolated from the patients with oral infections showed slightly inferior to those of ABPC, CEZ, while MICs against Gram negative bacilli (166 strains) of CMZ exhibited stronger activity than ABPC, CEZ. 2) The mean serum concentration of CMZ at 60 minutes after drip infusion showed 65.6 micrograms/ml. The concentration of CMZ in oral tissues varied in 4--60% of serum level at 60 minutes after drip infusion. The concentration in pus showed 15.2 micrograms/g at 60 minutes after drip infusion. 3) CMZ was administered by the drip infusion to 22 patients with various infections in the oral surgical field. The efficacy rate was 90.9%. 4) No side effect was observed.

Preclinical studies were carried out on cefotetan (CTT), together with clinical studies in the field of pediatrics. The following results were obtained. A total of 114 clinical isolates that have been stored in the authors' department was employed to determine the minimum inhibitory concentrations (MICs) of CTT against various bacterial species. Against E. coli, Salmonella, K. pneumoniae and P. mirabilis, the MICs of CTT showed a peak at 0.78 micrograms/ml, and most of the strains were inhibited by a CTT concentration of 6.25 micrograms/ml or less. The MICs for S. marcescens strains showed a peak at 25 micrograms/ml, with 25% of the strains having MICs of 3.13 micrograms/ml or less, and 67% having MICs of 25 micrograms/ml or more. All of the P. aeruginosa strains had MICs of over 100 micrograms/ml. Against all of the tested strains of S. aureus, a Gram-positive bacterium, CTT showed MICs of 12.5 micrograms/ml or more, while all of the strains of S. faecalis were found to have MICs of over 100 micrograms/ml. CTT was administered intravenously to pediatric patients as a bolus injection, and then the concentration of the antibiotic in the serum was determined as a function of time. When the dosage rate was 10 mg/kg, the mean serum levels were as follows; 58.2 micrograms/ml at 30 minutes, 45.5 micrograms/ml at 1 hour, 33.6 micrograms/ml at 2 hours, 18.0 micrograms/ml at 4 hours and 11.7 micrograms/ml at 6 hours after the injection. The half-life of CTT in the serum at this dosage was thus 2.40 hours. Similarly, at a dosage rate of 20 mg/kg, the mean values at the various times were; 98.6 micrograms/ml at 30 minutes, 75.6 micrograms/ml at 1 hour, 57.8 micrograms/ml at 2 hours, 35.5 micrograms/ml at 4 hours and 23.2 micrograms/ml at 6 hours subsequent to the injection. The half-life of CTT in the serum in these cases was 2.73 hours. CTT was drip-infused intravenously over a period of 1 hour, and then the serum concentration of the drug was monitored with the passage of time. Subsequent to the administration of 10 mg/kg, the mean serum concentrations were as follows; 48.8 micrograms/ml at 30 minutes, 81.5 micrograms/ml at 1 hour, 42.2 micrograms/ml at 2 hours, 23.6 micrograms/ml at 4 hours and 14.8 micrograms/ml at 6 hours subsequent to the injection. The half-life of CTT in the serum after this intravenous drip infusion was thus 2.13 hours.(ABSTRACT TRUNCATED AT 400 WORDS)

Cefotetan (CTT), a new cephamycin antibiotic, was administered to 21 pediatric patients, 1 year and 1 month to 9 years of age, with moderate or severe infections. CTT was intravenously administered 3 times a day at daily doses of 26.5 to 120 mg/kg for 2 to 14 days, and 0.75 to 31.0 g of the drug were totally given. Total of 21 cases, 12 cases of respiratory tract infections (each 1 case of acute pharyngitis, acute tonsillitis and asthmatic bronchitis, 6 cases of acute pneumonia, 1 case of lung fibrosis and 2 cases of primary atypical pneumonia), 2 cases of urinary tract infections, 1 case of acute appendicitis, 1 case of perianal abscess, 2 cases of sepsis, 1 case of MCLS, 1 case of ReYE's syndrome and 1 case of meningoencephalitis, were received CTT. Five cases were excluded for the evaluation of clinical efficacy, and good response were obtained in 11 cases (effective rate of 68.8%), fair in 1 and poor in 4. Out of 3 strains of causative organisms isolated before the treatment, H. influenzae and K. pneumoniae were disappeared after the CTT treatment, S. faecalis which was resistant against CTT persisted. Neither adverse effects nor abnormal laboratory findings were observed except 1 case of eosinophilia.

The authors treated 415 patients, with injection of 4 g cefmetazole (CMZ) per day after operation of the digestive tract. In these cases, the prevention of postoperative wound infections was investigated and the following results were obtained. Out of 415 cases, 11 cases (2.7%) had postoperative wound infections; 6 cases of which were superficial wound infections and 5 cases deep wound infections. In relation to the degree of infection of the surgical field of them, 10 cases were performed with the contamination by bowel organisms and 1 case was in infected surgical field. Bacteriological examination was carried out. Twenty-four strains of bacteria were isolated and identified. The major bacterial strains identified were 6 strains of S. faecalis, 4 strains of E. cloacae and 4 strains of P. aeruginosa. These organisms were rarely sensitive to CMZ. The results suggest that the organisms causing postoperative wound infections are changing compared with the organisms of previous reports and that the use of CMZ as a postoperative medication is useful in the prevention of wound infections.

The 868 strains of S. aureus were isolated at the Department of Pediatrics, Third Hospital and Aoto Hospital, The Jikei University, School of Medicine and the Kanagawa Prefectural Nursing and Hygienic School Hospital during 6 months from May to October in 1981. From them 66 strains not sensitive to CEZ were selected by a 3-concentration disk method. A total number of 54 strains except for 12 isolated from the same infant patient was examined for their MIC's for 6 drugs, CMZ, CEZ, CTM, CXM, MCIPC and GM. Moreover, phage typing and beta-lactamase activity determination were carried out in them. 1. Antibacterial activity Sixty-six (7.6) of 868 strains were not sensitive to CEZ. The MIC's of CMZ against these resistant strains were between 1.56 and 50 micrograms/ml with a peak between 3.13 and 6.25 micrograms/ml when the 10(5) cells/ml bacterial suspension were inoculated. CMZ was superior in antibacterial activity to CEZ and CXM by about 4 degrees and to CTM by about 3 degrees. MCIPC and GM has higher antibacterial activity against a few strains than CMZ. However, the number of strains with MIC higher than or equal to 50 micrograms/ml was 17 for MCIPC and 40 for GM, but only 2 for CMZ. Thus, the former 2 drugs were far inferior to the latter one. 2. Phage type (1) Nineteen strains (35.2%) had MIC's for CEZ greater than 50 micrograms/ml and CMZ less than 6.25 micrograms/ml. Seventeen of them belonged to the nontypable. (2) Fourteen (25.9%) had MIC's for CEZ greater than 100 micrograms/ml. Of them 9 were allocated to the group III, 3 to the mixed (I + II + III, I + III) group and 2 to the nontypable. (3) Of 20 strains (37.0%) which had MIC's for CEZ greater than 100 micrograms/ml and CMZ less than 6.25 micrograms/ml 5 belonged to the group I, 3 to the group III and 12 to the nontypable. (4) Five strains classified into the group I were all isolated at the Kanagawa Perfectural Nursing and Hygienic School Hospital. (5) Eleven of 15 strains belonging to the group III were isolated at the Third Hospital, The Jikei University, School of Medicine. (6) Seventeen of 21 strains isolated at the Aoto Hospital, The Jikei University, School of Medicine belonged to the nontypable. (7) Phage type was considered to be influenced by difference in areas, infection within hospitals, etc., 3. beta-Lactamase activity beta-Lactamase activity was demonstrated at levels between 0.07 and 3.26 mumol/min/mg in all 54 strains. There was no correlation between MIC for CEZ or CEZ and beta-lactamase activity. It was suggested that beta-lactamase might not contribute to mechanism of resistance of S. aureus to each drug examined.

The results on pharmacological effects of MT-141 were as follows. MT-141 did not exert effect on central nervous system in mice and rabbits but potentiated the anesthetic effect of thiopental at doses above 800 mg/kg i.v. MT-141 slightly raised a level of blood pressure in dogs and also caused a slight increase in the blood flow and heart rate when intravenously given more than 400 mg/kg. This compound did not affect the spontaneous contraction of isolated guinea pig atria and the blood vessels in perfused rabbit ears. MT-141 did not significantly affect the spontaneous contraction and coronary flow in isolated hearts of guinea pig. The body temperature was raised slightly by an injection of more than 400 mg/kg of MT-141. These results suggest that MT-141 does not possess specific effect on central nervous system but at a high dose slightly affects the autonomic nervous system such as blood pressure, body temperature, heart rate and blood flow in experimental animals.

The changes in the fecal flora and their correlation with the fecal drug concentrations were studied, employing 4 volunteers (healthy adult males) to whom 1 g of cefotetan was intravenously administered daily for 6 days. 1. In all of the subjects, the total counts of fecal organisms were slightly decreased 1 day after administration of cefotetan, then showed gradual increase, and recovered to the normal level on 8 days after the withdrawal of the drug. 2. Cefotetan caused drastic suppression of normal aerobic and anaerobic flora during the administration period, except streptococci that remained unchanged at all. The bacterial groups suppressed were bacteroidaceae, eubacteria, bifidobacteria, peptococcaceae, lactobacilli, enterobacteriaceae, lecithinase-positive clostridia, and staphylococci. Yeasts were found to increase during the administration period. 3. The changes in flora well correlated with the fecal level of the drug concentrations. This is in accordance with the in vitro antibacterial activity of the drug. 4. A period of more than 15 days was required after the withdrawal of cefotetan to recover the normal fecal flora. 5. Loss of body weight and diarrhoea were not observed in any of the subjects.

Cefminox (CMNX, MT-141) was evaluated for its safety and efficacy in children. Fifteen cases of bacterial infections were treated with intravenous bolus injections of 30 to 100 mg/kg/day of CMNX. Each 5 cases of acute respiratory tract, urinary tract, and gastrointestinal infections were included. All the cases were cured after the CMNX therapy. No adverse reactions were encountered with the therapy. The serum half-life was approximately 1.5 to 2 hours after intravenous bolus injection in children. The data suggest that CMNX is a safe and effective antibiotic when used in children with susceptible bacterial infections.

A perinatal and postnatal study of MT-141 was performed in SD rats. The dams were administered intramuscularly (i.m.) with MT-141 at the dose levels of 400, 800 and 1,600 mg/kg/day from the day 17 of gestation until the day 21 post delivery. The results are summarized as follows. No significant adverse effects of MT-141 were observed on the body weight gain, food consumption and water intake in dams of all groups treated with the drug during the perinatal and postnatal period. MT-141 did not change parameters of reproductive study in birth, development, physiological function and behavior of F1 rat. This compound had no effect on the fertility in F1 rats and also did not caused significant defects in the external appearance, viscera and skeleton of fetuses from dams (F1). It is concluded from these results that the maximal "no effective" dose of MT-141 is above 1,600 mg/kg/day i.m. for dams and the offsprings.

T-1982 (cefbuperazone), a new cephamycin antibiotic, was fundamentally and clinically studied. The following results were obtained. Serum and internal genital tissue levels of T-1982 were measured following intravenous injection or intravenous drip infusion of 1 g. High serum levels of more than 10 micrograms/ml and tissue levels of more than 5 micrograms/g were maintained for 3 hours after intravenous administration. Favourable transfer of T-1982 into the pelvic dead space exudate was observed. The exudate level attained its peak at 2 hours and was 14.6 micrograms/ml on average even at 8 hours after intravenous infusion. With its MIC values, T-1982 was considered to be bactericidal against many Gram-negative bacteria except Pseudomonas sp. A total of 4 cases comprising 2 with pyometra, 1 with pelveoperitonitis and 1 with endometritis complicated with pelveoperitonitis was treated with T-1982 at a dose of 1-2 g twice daily by intravenous drip infusion. The clinical response was excellent in 1 case and good in 2 cases. A case with pyometra due to S. faecalis did not respond to the therapy. Side effects and abnormal laboratory findings due to the drug were not noted.

Susceptibility of 100 clinical isolates of H. influenzae (84 beta-lactamase non-producing strains and 16 beta-lactamase producing strains) to 5 cephamycin antibiotics was studied in comparison with 3 reference antibiotics. In MIC90 against beta-lactamase non-producing strains, LMOX and ABPC were the most excellent, followed by T-1982, CTT, CTM, CMZ, CFX and CEZ. Against beta-lactamase producing strains, all the cephamycin antibiotics were as active as against beta-lactamase non-producing strains, whereas ABPC was extremely less active with the MIC90 of greater than 100 micrograms/ml. CTM and CEZ were about 1 tube less active than against beta-lactamase non-producing strains. Thus, it was confirmed that the cephamycin antibiotics were stable to beta-lactamase.

T-1982 (cefbuperazone), a new cephamycin antibiotic, was clinically and bacteriologically studied in 25 children with bacterial infections. The following results were obtained. 1. The antibacterial activity of T-1982 was determined against clinically isolated bacteria. T-1982 demonstrated excellent activity against Gram-negative bacilli, the MICs being less than 0.39 microgram/ml against E. coli and K. oxytoca, less than 1.56 microgram/ml against H. influenzae. 2. Clinical response was excellent or good in all 24 cases evaluated. The efficacy rate was 100%. 3. As for side effects associated with T-1982, slight and transient elevation of GOT, GPT and eosinophil, slight decrease of platelet and eruption were observed. From these results, T-1982 is considered to be a useful antibiotic for treating bacterial infections in children.

The antibacterial activities of Staph. aureus isolated in 1980 and 1981 at all districts in Japan to ABPC, CEZ, CMZ and GM were tested. Numbers of test strains were 587 strains in 1980 and 700 strains in 1981, respectively. The frequencies of ABPC and CEZ resistant strains of Staph. aureus (MIC: greater than or equal to 25 micrograms/ml) were clearly increased in annual variation. The percentage of CEZ resistant strains in 1981 tested by 10(8) CFU/ml inoculum size was 12.3%, but the same of CMZ was only 0.6%.

T-1982 (cefbuperazone), a new 7 alpha-methoxycephem antibiotic, was fundamentally and clinically studied, and the following results were obtained. The antibacterial activities of T-1982 against clinical isolates of S. aureus, E. coli, K. pneumoniae, S. marcescens, P. mirabilis and P. aeruginosa were determined in comparison with those of CER, CEZ, CMZ and CTT. Against S. aureus, CER and CEZ exhibited excellent activity, whereas T-1982 was less active with the peak MIC of 12.5 micrograms/ml even with the inoculum size of 10(6) cells/ml. The activity of T-1982 was equal to that of CTT and by far superior to that of CER, CEZ and CMZ against E. coli, K. pneumoniae and P. mirabilis, the peak MICs with the inoculum size of 10(6) cells/ml being less than or equal to 0.1-0.2 microgram/ml, less than or equal to 0.1-0.2 microgram/ml and 0.2-0.39 microgram/ml, respectively. Against S. marcescens, T-1982 was superior to CMZ and CTT and 48% of the strains were inhibited by 3.13 micrograms/ml or less, whereas all the strains were resistant to CER and CEZ. The MIC of T-1982 against most strains of P. aeruginosa was more than 100 micrograms/ml. 10 mg/kg or 20 mg/kg of T-1982 was administered by one shot intravenous injection or 1 hour drip infusion to 23 pediatric patients to measure serum levels and urinary recovery. At 30 minutes after one shot injection of 10 mg/kg and 20 mg/kg, the highest serum levels of 22.0-38.8 micrograms/ml and 52.4-80 micrograms/ml were observed, the half-lives being 1.32 hours and 1.76 hours. When given by 1 hour drip infusion, the serum levels attained the peaks of 29.2-42.6 micrograms/ml and 49.0-75.6 micrograms/ml at the end of infusion, the half-lives being 1.24 hours and 1.19 hours. The urinary recovery rates within 6 hours were 74.2-92.5% and 50.2-66.5% by one shot injection and 63.4-84.2% and 53.9-79.0% by drip infusion. T-1982 was administered at a dose of 50 mg/kg by 30 minutes drip infusion to a child with purulent meningitis. The levels of T-1982 in the cerebrospinal fluid at 1 hour after administration were 4.8-6.7 micrograms/ml with the CSF/serum ratios of 4.4-8.4%. A total of 36 pediatric patients (21 cases of respiratory tract infection, 9 cases of urinary tract infection and each 1 case of purulent cervical lymphadenitis, scarlet fever, purulent meningitis, acute colitis, peritonitis and sinusitis) was treated with 40-80 mg/kg/day of T-1982 (252.6 mg/kg/day in purulent meningitis). The response was excellent in 27 patients and good in 7 patients, the efficacy rate being 94.4%. Diarrhea or eruption were observed in each 1 case. No abnormal laboratory findings were noted in any cases.

Cefotetan (CTT) is a new parenteral semisynthetic cephamycin-type antibiotic with a broad antibacterial spectrum against both Gram-positive and Gram-negative bacteria. Against wide varieties of Gram-negative bacteria, particularly including indole positive Proteus, S. marcescens, Enterobacter sp. and C. freundii CTT was more highly active than cefmetazole, cefoxitin and cefazolin. The 50% inhibition doses (ID50) of CTT against E. coli, K. pneumoniae, P. mirabilis, indole positive Proteus and S. marcescens were by far superior to those of the 3 other antibiotics. The antibacterial activities of CTT were bactericidal and were little affected by addition of horse serum and by variation in pH of the medium, in inoculum size and in type of culture media. Model infections in mice against Gram-positive and Gram-negative bacteria were studied. The therapeutic effects after subcutaneous injection of CTT against various Gram-negative bacterial infections were superior to those of cefmetazole, cefoxitin and cefazolin.

Clinically isolated 741 strains of 10 bacterial genus (except for Pseudomonas aeruginosa) which are frequent causal pathogens of infection in the otorhinolaryngological field were examined for their sensitivity to second-generation cephem agents, CTM, CXM and CMZ using the first-generation agent, CEZ, as a control. 1) The antibacterial activity of CTM, CXM, and CMZ was expanded to H. influenzae and Proteus spp. (indole positive) as compared with the first-generation agent, CEZ. CTM and CXM and strong antibacterial activity against H. influenzae. CMZ was slightly inferior to them in this activity. In contrast, against Proteus spp. (indole positive) CMZ was most effective and CTM was more effective than CXM. 2) The proportion of strains of S. aureus resistant to CEPs was 6.5% in CEZ, 4.8% in CTM, 8.1% in CXM, and as low as 1.6% in CMZ.

The time course of the concentration of cefmetazole (CMZ) in the serum and in skin and intestinal tissues was determined after a single intravenous injection of 2 g of the drug. CMZ moved into them well. Furthermore, 41 patients with postoperative wound infection (superficial in 29 and deep in 12) were treated with CMZ 2-4 g daily. Bacteriological examination of the lesions with simultaneously carried out. As a result, 101 strains of bacteria were isolated and identified. Mixed infection was found in 27 cases (65.9%). Fifteen strains (14.9%) of E. coli, 15 (14.9%) of B. fragilis, 7 (6.9%) of Klebsiella sp. and 7 (6.9%) of Proteus sp., were the main bacteria isolated. Eight cases (19.5%) had mixed infection of E. coli and B. fragilis. The committee (3 members) evaluated CMZ to be effective in 75.6% (31 of 41 cases) and bacteria disappeared in 60.5% (23 of 38 cases). The side effects observed were pyrosis and feeling of gastric malaise in 1 case. The results suggest that CMZ is useful, which exerts an excellent effect on postoperative wound infections.

A new cephamycin antibiotic, cefotetan, was administered intramuscularly to 45 patients with female genital infections including 2 cases with abscess of Bartholin's gland, 14 cases with endometritis, 23 cases with adnexitis and 6 cases with pelvic peritonitis. The daily doses of the drug were 1 to 3 g, with 2 g daily being the most frequent regimen. The treatment was given twice daily in most patients. All cases responded to the drug, and marked response was seen in 22 cases and moderate response in 23. The eradication rate for causative organisms was 64.3%. In 16 cases of S. faecalis, it was rather low at 37.5%. Neither side effects nor abnormalities in clinical laboratory findings attributable to the drug were seen.

Experimental and clinical studies in the pediatric field on 6059-S, a newly synthesized broad spectrum parenteral antibiotics, were carried out, and the following results were obtained. Antibacterial activities of 6059-S against S. pyogenes, S. aureus, E. coli and P. aeruginosa, recently isolated from patients, 50 strains respectively was compared with that of cefazolin (CEZ), cefmetazole (CMZ), ceftizoxime (CZX), cefotiam (CTM) and ticarcillin (TIPC). 6059-S was less active than the other compound against S. aureus and S. pyogenes, but was about 1-5 times more active than other CEZ, CTM, CMZ and CZX against E. coli, and 6059-S had a activity against P. aeruginosa. It was equal or slightly more activity than that of TIPC. Serum concentrations were measured in 14 infants (3 y 3m-12 y) by one shot or intravenous drip infusion with 10 mg/kg or 20 mg/kg. By one shot intravenous infusion, the peak of serum concentrations of 6059-S with 10 mg/kg and 20 mg/kg were 40.4-44.2 mcg/ml, 79.1-90.8 mcg/ml at 30 minutes after administration respectively, and that's half life were 1.5, 1.4 hours. By intravenous drip infusion, the peak of serum concentration was 89.9 mcg/ml at the end of administration, 13.7 mcg/ml at 5 hours after administration, and half life was 1.5 hours. The urinary recovery rate of 6059-S were 97.4, 67.4% during 6 hours in 2 cases. The cerebrospinal fluid concentration of 6059-S were 2.4-3.6 mcg/ml at 90 minutes after intravenous infusion administration, and the CSF/serum ratio were about 7-8%. Clinical studies of 6059-S was performed in total of 27 cases (25 patients); 8 cases of urinary tract infection, 15 cases of respiratory tract infection, 1 case of staphylococcal scalded skin syndrome, 1 case of peritonitis, 2 cases of purulent meningitis, with the dose of 6059-S 150 mg/kg/day in purulent meningitis, 40-80 mg/kg/day in other disease. That's efficacy rate was 85.2%. Side effect observed in this therapy were 2 cases (exanthema 1, diarrhea 1), and 2 cases of rise of GOT, GPT.

Cefmetazole (CMZ), an antibiotic agent of the cephamycin group, is resistant to beta-lactamase and has a broad antibacterial spectrum covering Gram-positive cocci and Gram-negative bacilli. However, it has not been indicated for Gram-positive cocci. We examined its clinical, bacteriological and side effects in 2 infants with pneumonia and 2 with pyothorax, which had been suggested to be caused by CEZ-resistant and CMZ-sensitive Staphylococcus aureus or other inflammatory organisms by a disc sensitivity test, for 2 years and 3 months from January, 1981 to March, 1983. The patients aged 1 to 22 months, and a mean daily dose of 108 to 115 mg/kg was divided into 2 to 4 equal doses and injected into the vein at one shot for a mean fo 19 days. The following results were obtained: The clinical effect of CMZ was evaluated to be good in 1 and fair in 1 of 2 infants with pneumonia, and excellent in 1 and good in 1 of 2 with pyothorax. Bacteriologically, S. aureus was removed in an infant with pneumonia and in 2 with pyothorax. Bacteriological test was not conducted in the remaining 1 with pneumonia. No side effects were found in any cases. Eosinophilia appeared as an abnormal clinical test value in a case, but the number of eosinophils became normal after termination of the medication. As mentioned above, CMZ manifested an excellent clinical effect in infants with pneumonia or pyothorax caused by S. aureus although the number of the patients was small. From the results the antibiotic agent can be expected to be effective in these disease.

Experimental and clinical studies of T-1982 (cefbuperazone), a new cephamycin antibiotic, were performed in the field of obstetrics and gynecology, and the following results were observed. T-1982 was determined for its in vitro activity against 180 recent clinical isolates in comparison with cefmetazole (CMZ) and cefazolin (CEZ). The activity of T-1982 was superior to that of CMZ against E. coli (101 strains) and B. fragilis (19 strains), and similar to that of CMZ and CEZ against Peptococcus (34 strains). High concentrations of T-1982 exceeding the MIC values against various bacteria were maintained for a few hours in the female genital organs and postoperative retroperitoneal exudate after intravenous drip infusion of 2 g. T-1982 was administered to a total of 6 patients in daily dose of 2 approximately 3 g for 2 approximately 10 days. The clinical results were excellent or good in 5 cases. Drug eruption was observed in 1 case. These results suggest that T-1982 is highly effective for the treatment of bacterial infections in this field.

Fifteen children with acute bacterial infections, including pneumonia (8), pharyngitis (2), cervical lymphadenitis (1), perforative peritonitis (1), gastroenteritis (1) and urinary tract infection (2), were treated with cefotetan. This drug was effective to all of the patients. In 2 patients the result was excellent and in 9 it was satisfactory. No adverse reactions were observed in the above cases and 2 other patients, during and after the dosage of 30-60 mg/kg/day for 4-11 days.

Cefmetazole was studied experimentally in the field of dermatology. The following results were obtained. 1. The in vitro antibacterial activities of cefmetazole against S. aureus and S. epidermidis were studied. Most strains of both staphylococci were inhibited by 1.56 micrograms/ml or less of cefmetazole. 2. Serum and skin concentrations of cefmetazole in rats were studied after intramuscular administration of 20 mg/kg of cefmetazole. Mean serum concentrations were 40.3, 21.5, 7.1, 0.56 micrograms/ml respectively at 0.25, 0.5, 1 and 2 hours, and the corresponding skin concentrations were 12.5, 6.1, 0.62, 0.61 micrograms/g (n = 4).