Cephacetrile (CEC) was intravenously administrated to 18 patients with pulmonary infections at a daily dose of 2-4g for 7-47 days, and the following results were obtained:
1) 18 patients treated were 16 with pneumonia and 2 with lung abscess.
Clinical responses were excellent in 4 patients, good in 11 and fair in 3, with a response rate of 83.3%(15 of 18 patients).
As for bacteriological responses, the organisms were eliminated in 8 patients, unchanged in 1 and replaced in 1, with an elimination rate of 80.0%(8 of 10 patients).
Overalll responses were excellent in 4 patients (22.2%), good in 11 (61.1%) and fair in 3 (16.7%), with a response rate of 83.3%.
2) As for side effect, skin eruption occured in 3 patients. Abnormal laboratory findings were observed in 2 patients with elevation of serum GPT and in other 2 patients with elevation of serum GOT and GPT.

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Clinical investigations on Ceftizoxime, a new parenteral cephalosporin derivative, were made in the orthopedic field.
Twenty-eight patients with osteomyelitis and 5 patients with arthritis were treated with Ceftizoxime administered by intravenous drip infusion at a dosage of 1.0g twice daily, as a rule. The duration of administration ranged from 7 to 52 days, 16 days on the average.
Of 23 cases of acute osteomyelitis or arthritis including recurrent acute stage of inflammation, the clinical response to the drug was excellent in 12 cases, good in 8 cases and poor in 3 cases. Of 9 chronic osteomyelitis cases, the results of the treatment were rated as excellent in 4, good in 4 and poor in 1; one chronic arthritis case was categorized as having an excellent result. No significant difference was thus observed between ac ute and chronic cases of infection in therapeutic efficacy of the drug.
From 26 cases of entire 33, 16 species (37 strains) of causative organisms were detected. Measurement of MICs of Ceftizoxime, Cefazolin and Cefotiam against 16 strains of these 37 showed that Ceftizoxime was remarkably active against E. coli, Proteus, Serratia and Enterobacter (with MICs being as low as ≤0.025-0. 78 μg/ml), though relatively less effective against S. aureus and S. epidermidis.
Undesirable side effects encountered were fever, itching and a sensation of abdominal inflation seen in one case each.

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A new cephalosporin derivative, ceftizoxime (FK 749, syn) and its anti isomer, FR 14060 were compared in antibacterial activity, outer membrane permeability, stability to β-lactamases and affinity for penicillin-binding proteins using Escherichia coli NIHJ JC-2 and Enterobacter cloacae strain 58-5 as the test organisms. Although ceftizoxime was superior in antibacterial activity to FR 14060, no marked differences between the two agents were found in outer membrane permeability and stability to cephalosporinase. However, the affinity for penicillin-binding proteins (PBPs) and stability to penicillinase of ceftizoxime and FR 14060 differed significantly. Concentrations of ceftizoxime required to reduce [¹⁴C] penicillin-G binding by 50% were below 1μg/ml for PBP 1a and 1bs of E. cloacae strain 58-5 and below 3.2μg/ml for PBP la and lbs of E. coli NIHJ JC-2. A more than ten-fold higher concentration of FR 14060 was required for 50% reduction of [¹⁴C] penicillin-G binding to PBP 1 bs of the strains tested. Ceftizoxime was several-fold more stable than FR 14060 to penicillinase, but the antibacterial activity of both drugs against penicillinase-producing E. coli was as strong as against non-penicillinase-producing E. coli because of the large K_m value of FR 14060. These results indicate that the difference between the two compounds in antibacterial activity is likely to be mainly due to differences in their abilities to inhibit peptidoglycan-polymerization.

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The therapeutic efficacy and safety of apalcillin (APPC) were objectively compared with those of carbenicillin (CBPC) in patients with acute or chronic respiratory tract infections in the well controlled study at 30 institutions in Japan.
One hundred eighty seven patients were given daily 4g of APPC or CBPC in 2 divided doses by intravenous drip-infusion for, in principle, 14 days.
The therapeutic effects were analyzed statistically in 159 patients (79 administered APPC, 80 administered CBPC) after excluding those in whom the initial suspicion of infection was not confirmed or the medication was not performed in accordance with the rule of protocol. The adverse reactions were also analyzed statistically in 182 patients (APPC 93; CBPC 89) in whom the judgement was possible.
The results obtained were as follows:
1) Significantly more patients in the APPC group had highly eleveted body temperature than that in the CBPC group, on the other hand, significantly more patients in the CBPC group had severe infection than that in the APPC group. However, there was no other significant intergroup difference in the background factors of the patients.
2) In total 159 patients therapeutic effects of APPC (83.5% for good to excellent response) was significantly superior to that of CBPC (55.0% for good to excellent response)(P<0.001). Efficacy rate in the patients treated with APPC was also significantly higher than that with CBPC in the group of chronic respiratory tract infections. When patients were classified into three groups (severe, moderate and mild) with respect to severity, statistically significant differences in clinical efficacy were observed in the moderate or mild cases (APPC>CBPC) while no difference was observed in the severe cases.
3) No significant difference was observed between the two drug groups in bacteriological efficacyagainst causative organisms isolated from patients.
4) The improvement of fever, volume of sputum and erythrocytes sedimentation rate was significantly better in the APPC group than in the CBPC group.
5) Significantly more patients in the CBPC group had elevated blood urea nitrogen after treatment than that in the APPC group. However, there was no other significant intergroup difference in incidence of adverse reactions.
6) From these comparative results on therapeutic effects and side effects of these two drugs, it is thought that APPC is more useful than CBPC in the treatment of chronic respiratory infections.

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The tested sera were obtained from patients who showed some allergic symptoms by administration of β-lactam antibiotics such as penicillins and cephalosporins. Antibodies in the tested sera were detected by passive hemagglutination test (PHA test) and passive hemagglutination inhibition test (PHI test) using sheep red blood cells coated with hapten conjugated bovine gamma globulin.
(1) PHA and PHI titers for penicillins and cephalosporins were observed in the tested sera. (2) The drug which showed the highest titer in PHI test accorded with one that induced allergic symptoms. (3) PHA and PHI titers were also observed in the sera obtained from patients of skin test negative, who showed some allergic symptoms. (4) Antigenic specificities were determined concerning the sera which showed the high PHA and PHI titers for penicillins. One serum reacted with the acyl side chain moiety and penam structure moiety, but other two sera reacted only with acyl side chain moiety.

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This study was conducted to investigate the relationship between the in vitro susceptibility of the organisms and the outcome of treatment in urinary tract infections. The results achieved in the treatment of 256 patients with acute simple cystitis and 450 patients with complicated urinary tract infections in well controlled study. Summaries were as follows.
1. Clinical response to antibiotic treatment was categorized as either ‘ eradicated ’ or ‘persistent’ by bacteriological response.‘ Replaced ’ was defined as ‘ eradicated ’ when bacteria of identical species to the origin strain were not isolated after treatment.
2. Significant correlations between bacteriological response to treatment and MIC of the given drug to causative organism were obtained in the cases with acute simple cystitis treated with ABPC 1g, 0.5g, and 0.2g daily and in the cases with complicated urinary tract infections.
3. CELs; clinically effective levels, the critical levels of antibiotics which are the minimum necessary to eradicate the urinary organisms, were determined as 209μg/ml, 241μg/ml, and 50μg/ml for the cases with acute simple cystitis treated with ABPC 1g, 0.5g, and 0.2g daily respectively. CELs were determined as 439μg/ml, 79 μg/ml, and 21.8μg/ml for the cases with complicated urinary tract infections treated with CBPC 4g, i. v., CIPC 2g, p. o., and PPA 2g, p. o. daily respectively. The difference in eradication rates of causative organisms in these sensitive and resistant groups was statistically significant.
4. Significant agreement between in vitro and in vivo results was obtained despite any host factor influencing the outcome of treatment. In evaluation for differentiation of host factor modifying the bacteriological response, the frequent discrepancy between in vitro and in vivo results can't be attributable in the sensitive group. The significantly excellent eradication rate of resistant strains in female cases may be attributed to the differences in characteristics of the causative organisms between male and female cases.
5. The persistency, despite treatment, of sensitive strains in P. aeruginosa infection and the eradication of resistant strains in indole positive Proteus spp. infection were observed.
6. No attempt was made to define the relation of urinary concentrations to CEL. But antibacterial activity in the urine was considered as a prerequisite for eradication of bacteria.
7. In investigating the relationship between in vitro susceptibility and response of urinary organisms to antimicrobial therapy, CEL was considered as more reasonable critical level of urinary tract infections.

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The in vitro antifungal activity of tolciclate was compared with that of tolnaftate and clotrimazole. The following results were obtained.
1) The antifungal activity of tolciclate against Ascomycetes was superior to those of tolnaftate and similar to those of clotrimazole, and against Fungi imperfecti was similar to those of tolnaftate and superior to those of clotrimazole.
2) The in vitro antifungal activity of tolciclate against clinical isolates of Trichophyton mentagrophytes and Trichophyton interdigitale was superior to those of tolnaftate and clotrimazole, but was inferior to tolnaftate against Trichophyton rubrurn.
3) Influence of medium pH, the addition of horse serum, inoculum size and incubation time on in vitro antifungal activity of tolciclate showed the same tendency with tolnaftate and clotrimazole.
4) Development of resistance of Aspergillus niger to tolciclate, tolnaftate and clotrimazole in vitro was not observed.
5) Antifungal action of tolciclate against Aspergillus niger and Trichophyton mentagrophytes was similar to that of tolnaftate and clotrimazole.
6) Tolciclate and clotrimazole released cellular potassium ion.
7) With a light microscopy, exposure of Aspergillus niger to tolciclate, tolnaftate and clotrimazole resulted in the swelling of spore and the extention of hypae following abnormal budding.

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To 312 patients with complicated urinary tract infection due to single pathogen, gentamicin (GM), tobramycin (TOB), amikacin (AMK) and KW-1062 were administered for five days, and the relations between bacterial susceptibility to those drugs and the clinical efficacies were studied. The susceptibility to GM of all isolates were also tested, and the relation of the susceptibility to GM and the clinical efficacies of GM, TOB, AMK and KW-1062 were studied.
The results were as follows:
1) All those antibiotics had the almost equal antimicrobial activity against urinary pathogens.
2) GM resistant strains heve been increasing recently.
3) Clinical efficacy of GM was well correlated with the susceptibility to GM.
4) Clinical efficacies of TOB, AMK and KW-1062 against GM resistant strains were superior than 40 per cent, and, in the case of KW-1062, the efficacy was correlated significantly with the susceptibility to GM.
5) Concerning to the clinical efficacies of those drugs other than GM and the susceptibilities to each drugs administered, the efficacy of KW-1062 was also correlated significantly with the susceptibility to KW-1062, however TOB and AMK did not show the significant correlation between them.
6) In this study we followed the generally accepted conception that the boundary concentration of aminoglycosides separating resistant strains from sensitive ones was between 3.13 and 6.25μg/ml (10⁶ cells/ml), however, in the view point of clinical efficacy, the boundary concentration of these drugs (TOB, AMK and KW-1062) seemed to be more higher than 6.25μg/ml.

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Because of the fact that the conventional sensitive-resistant boundary concentration of aminoglycosides is not always fit for the clinical efficicacy, we tried to seek for the fittest one by analyzing the clinical efficacy obtained from well controlled studies. 312 patients with complicated urinary tract infections were treated with usual dosage of gentamicin (GM), tobramycin (TOB), amikacin (AMK) or KW-1062 for five days, and the relations between the efficacies of each drug group and the MICs of the drug for pathogens were observed statistically.
The patients were separated into two groups, so called sensitive and/or resistant group, at various levels of MIC for their pathogens, and the efficacies of both groups were compared statistically. The boundary concentration was determined from the level of MIC showing the most significant difference. The sensitive-resistant boundary concentrations were 1.56-3.13μg/ml (GM 40mg), 3.13-6.25μg/ml (GM 60mg), 3.13-6.25μg/ml (TOB 60mg), 6.25-12.5μg/ml (KW-1062 120mg) and 12.5-25μg/ml (AMK 200mg). Another method was to determine it from the cross point of the curve indicating effectiveness rate and the line indicating a certain expected effectiveness rate (for example 50%) for the patients group with sensitive pathogens. The cut off points for effectiveness rate above 50% revealed to be 3.13-6.25μg/ml (GM), 6.25-12.5μg/ml (TOB), 25-50μg/ml (AMK) and 6.25-12.5μg/ml (KW-1062).
In the present study, the following facts were observed. The most fittest boundary concentration was not always fixed but also changeable according to dosages, drugs and characteristics of subjects.

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