Norfloxacin (NFLX), a new quinolone antibacterial agent, was investigated for its antibacterial activity and clinical efficacy on respiratory tract infections.
The results obtained are summarized as follows:
1. Antibacterial activities were evaluated against 127 strains of various bacteria isolated from clinical sources. MIC₈₀'s of this drug were: against Staphylococcus aureus and Streptococcus pyogenes 1.56μg/ml; Haemophilus influenzae 0.05μg/ml or less; and Klebsiella sp. and Enterobacter sp. 0.10μg/ml. These antibacterial activities were superior to these of ampicillin and cephalexin, except against S. pyogenes.
2. Clinical responses to NFLX in a total of 32 cases with respiratory tract infections were excellent in 9 cases, good in 12, fair in 9, poor in 2, with an efficacy rate of 65.6%.
Neither adverse reactions nor abnormalities of laboratory test results were observed.

View full abstract

Concentrations of cefuroxime (CXM) in the skin and the serum of 24 patients were examined. CXM (0.75g, 1.5g) was administered to these patients intravenously in one shot.
The skin and the serum were collected at 30 and 60 minutes after the injection. Concentrations of CXM in the skin were following:
0.75g, 30min.; 11.4±5.3μg/g
60min.; 9.5± 4.7μμg/g
1.5g, 30min.; 17.1±6.8μg/g
60min.; 15.7±13.2μg/g
Concentration ratios (skin/serum) at 60 minutes after the injection were from 72.5% to 79.2%. The binding ratio of CXM to serum protein was 41%, which was lower than most other antibiotics.
High concentration levels of CXM were maintained in the skin for a long time. Based on this study, we consider that CXM is effective in the skin surgery.

View full abstract

Pharmacokinetic and clinical studies on cefuzonam (CZON) were performed to evaluate its usefulness in the field of obstetrics and gynecology. A summary of the results is as follows:
1. Concentrations of CZON in female genital organ tissues showed a little variance among organs. Mean concentrations were 3.34-7.83μg/g at 40 minutes, 0.523-1.08μg/g at 2 hours 15 minutes and 0.286μg/g (in the myometrium) at 3 hours 10 minutes after the end of drip infusion.
2. Mean concentrations of CZON in the pelvic dead space exudate were 31.0μg/ml immediately after the end of drip infusion ( 1 hour after the start of infusion), and 37.2μg/ml 1 hour after the end of infusion, then they gradually decreased to 25.6μg/ml after 3 hours and 21.4μg/ml after 5 hours.
Mean serum concentrations of CZON in concurrently collected samples from the peripheral vein were 30.0μg/ml immediately after the end of drip infusion, 14.4μg/ml after 1 hour, 4.00μg/ml after 3 hours and 1.84μg/ml after 5 hours. The T 1/21 β was 1.03 hours.
3. Clinical trial in 7 patients, with CZON administered at a dose level of 1g at a time, twice daily, showed “excellent” and “good” efficacy in all the patients. No side effects were noted.
From the results of the above studies, CZON seems to be highly useful for infections in the field of obstetrics and gynecology.

View full abstract

The antibacterial activity of cefminox (CMNX) was compared to those of cefotaxime (CTX) and latamoxef (LMOX) in human urine using 11 clinical isolates from complicated urinary tract infections.
When the inoculum size was increased from 10⁴ (or 10³) to 10⁸ (or 10⁷) CFU/ml, MIC values increased in general, but the increment of average MICs of CMNX was the smallest of the 3 drugs: 4-8 fold with CMNX, 32-64 fold with CTX and 8-32 fold with LMOX. MICs also increased when the urinary pH was altered from 8.5 to 5.5, but again the increment of MICs of CMNX was the smallest.
Using 5 clinical isolates of Gram-negative bacteria as test organisms, the bactericidal activity of CMNX was compared to those of CTX and LMOX. In spite of the inferior activity of CMNX as determined by the MIC values, CMNX showed killing activity equal to or better than CTX and LMOX, particularly at low concentrations (2-20μg/ml). The bacteriolytic activity of CMNX was also equal or superior to those of CTX and LMOX against 6 test organisms.
These results suggest the usefulness of CMNX in the treatment of urinary tract infections, particularly when dense bacterial populations are present.

View full abstract

Aspoxicillin (ASPC), a new injectable penicillin, was administered to 5 healthy male adult volunteers once a day at a daily dose of 4g for 5 consecutive days to study its absorption and excretion. The results of this study are summarized as folows:
1. In consecutive administration of ASPC for 5 successive days, no remarkable changes were observed in serum concentrations and urinary excretion after each administration of ASPC. Therefore, no tendency of accumulation of the drug was recognized.
2. The serum ASPC concentration showed its peak values ranged from 212.3 to 224.8μg/ml at completion of the intravenous drip infusion of ASPC.
3. Urinary recovery rates of ASPC ranged from 70 to 80%.
4. There were neither abnormal findings in subjective and objective symptoms nor abnormal values in physical and clinical laboratory test due to the administration of ASPC.

View full abstract

The present study was performed to investigate the distribution of β-lactam antibiotics, cefotiam (CTM) and cefmenoxime (CMX) in pulmonary tissue of sheep.
The animals were prepared to form chronic lung-lymph fistula for the collection of lung lymph. CTM and CMX were administered bolus-intravenously at doses of 20mg/kg and 40mg/kg, respectively, and serum and lymph levels of each drug were measured by bioassay method.
Antibiotic levels of serum or lymph increased to a peak within 15 minutes after injection and then decreased rapidly. Measurable concentrations persisted for 240 minutes after the injection. Ratios of lung lumph to serum concentrations of CTM and CMX within 1 hour after the injection ranged 0.7 to 1.3, and 0.9 to 1.3, respectively. In addition, CMX levels in serum, lung lymph and tissues of both right and left lung were compared in anesthetized sheep to which CMX 50mg/kg was given. Ratios of lung lymph and tissue concentrations of CMX in right and left lung to serum concentration were 0.76, 0.14 and 0.13, respectively.
These results indicate that CTM and CMX were well distributed in interstitial fluid (lung lymph), and the levels of CMX in tissues of both right and left lung were markedly lower than those of lung lymph.

View full abstract

Collaborated studies on species of respiratory tract infection (RTI)-related organisms for their identification and drug susceptibilities have been carried out since 1981 at about 20 centers in Japan.
On this occasion, the data obtained between 1982 and 1985 were reanalyzed to determine whether or not drug susceptibilities differed depending upon diseases, from which the organisms were isolated. The results summarized below were obtained in this study.
1. Among Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Klebsiella pneumoniae and Pseudomonas aeruginosa examined, differences in drug susceptibilities according to different diseases were found among S. aureus and also mucoid strains of P. aeruginosa.
2. Susceptibility to beta-lactam antibiotics was definitely lower in S. aureus strains isolated from pneumonia than in those isolated from chronic bronchitis and bronchiectasia.
3. The isolation frequency of methicillin-and cefazolin-resistant strains of S. aureus was 30.3% and 25.9%, respectively, and was especially high among strains isolated from pneumonia. The antibiotic potency of minocycline against S. aureus, including methicillin resistant S. aureus, was the strongest among 9 drugs examined; S. aureus maintained relatively sufficient sensitivity to dicloxacillin among beta-lactam antibiotics.
4. Mucoid producing strains of P. aeruginosa isolated from chronic bronchitis had slightly lower drug susceptibility than those isolated from bronchiectasia.
5. When drug susceptibilities of H. influenzae were compared among groups separated according to diseases using MIC₅₀, MIC₈₀ and MIC₉₀ as indicators, there were no clear differences. The isolation frequency of ampicillin (ABPC)-resistant strains, however, was clearly different among diseases; namely, resistant strains were the most and the least frequently isolated from chronic bronchitis and from pneumonia, respectively.
In addition, the drug susceptibility of H. infiuenzae isolated in 1985 was analyzed in relation to the production of beta-lactamase. As a result, it was suspected that some factors, other than beta-lactamase, participated in the mechanism of ABPC-resistance.
6. These results suggest that drugs to be used for the chemotherapy of RTI should be selected considering the fact that drug susceptibilities of the pathogens differ, even among the same species, according to diseases.

View full abstract

Susceptibility tests were carried out on a variety of clinically isolated pathogens using the susceptibility disc method at 197 hospitals in Japan between May, 1985 through March, 1986. These tests were organized by the Research Group for Testing Ofloxacin Susceptibility on Clinical Isolates, and the results were statistically analyzed.
This paper describes a comparison of susceptibilities of clinical isolates including Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Streptococcus pneumoniae, Neisseria gonorrhoeae, Escherichia coli, Enterobacter aerogenes, Enterobacter cloacae, Citrobacter freundii, Klebsiella pneumoniae subsp. pneumoniae, Proteus mirabilis, Morganella morganii, Serratia marcescens, Haemophilus influenzae, Pseudomonas aeruginosa, Acinetobacter calcoaceticus, Acinetobacter sp. and Campylobacter jejuni to ofloxacin (OFLX) and conventional antibacterial drugs. The results obtained were summarized as follows.
1. OFLX showed strong antibacterial activity against S. aureus, S. epidermidis, N. gonorrhoeae, E. coli, E. aerogenes, E. cloacae, C. freundii, K. pneumoniae subsp. pneumoniae, P. mirabilis, M. morganii, H. influenzae, A. calcoaceticus, Acinetobacter sp. and C. jejuni and only a few strains were resistant to OFLX.
Moreover, OFLX has superior antibacterial activity against many species compared not only to norfloxacin but also to most of the conventional antibacterial drugs.
2. When studied by sampled materials such as sputum, urine, abscesses and otorrhea, OFLX occasionally showed different actions against the same species from different sources. Almost species from the urinary isolates were less sensitive than those from the sputum.

View full abstract

In clinical chemotherapy with neocarzinostatin (NCS) against cancers, side effects such as leukopenia, anorexia, vomiting and nausea were mainly observed when parenteral administration was used. To prevent these adverse side effects without changing the anticancer activity of the drug, we attempted to apply the two-route-infusion chemotherapy using NCS and antidotes for the NCS treatment devised by BABA. This report presents the results of our study on effects of some antidotes on the acute toxicity of NCS in mice and also on the antitumor activity of NCS against Sarcoma-180 in mice (ICR-JCL strain) when used with tiopronin. The results are summarized as follows.
1. LD₅₀ values of NCS administered via intravenous route increased 2.3-to 3. 2-fold when 150, 300, 500 or 1,000mg/kg of triopronin was administered subcutaneously together with NCS, 1.3-to 1.4-fold when 50 or 100mg/kg of sodium thioglycolate was used, When antidotes were given prior to the administration of NCS, 1.8-to 5.4-fold increase in LD₅₀ values of NCS resulted with 300, 500 or 1,000mg/kg of tiopronin administered 1 hour prior to NCS, 2. 3-fold increase resulted with 2,000mg/kg reduced glutathione, 1.2-fold increase with 100mg/kg of sodium thioglycolate and 1.9-fold increase with 1,000mg/kg of L-cysteine monohydrochloride monohydrate. Furthermore, 4.8-to 13.1-fold increase in LD₅₀ of NCS occurred when 150, 300, 500 or 1,000mg/kg of tiopronin was administered 15 minutes prior to NCS. When these antidotes were administered 1 hour after the administration of NCS, however, no changes in the LD₅₀ value occurred.
2. The LD₅₀ value of NCS given intraperitoneally increased 1.6-to 5.8-fold when 150, 300, 500 or 1,000mg/kg of tiopronin was administered intravenously at the same time as NCS, 1.4-to 1.6-fold when tiopronin was given 1 hour prior to NCS, intraperitoneally and 1.3-to 1.7-fold when it was given 1 hour after NCS.
3. It was recognized that the acute toxicity of NCS was the most effectively reduced by tiopronin, but only slightly by glutathione, sodium thioglycolate or L-cysteine monohydrochloride monohydrate. The action of tiopronin was the most effective when it was given subcutaneously 15 minutes prior to NCS administered intravenously.
4. The combination chemotherapy on Sarcoma-180 in mice using NCS intraperitoneally and tiopronin intravenously was markedly effective when these agents were given simultaneously.

View full abstract