Although the prognosis of pulmonary tuberculosis has become fairly good with the recent development of antituberculous agents, there have been still a few number of patients who showed aggravation ...during the treatment or relapse after discontinuation of antituberculous therapy. The criteria of aggravation and relapse, however is so far not clearly defined, and discrepancy is seen among various research workers. In this paper, 1, 024 patients with pulmonary tuberculosis who has/had been admitted to the nine institutions in both Nagasaki and Saga Prefectures during the period from January 1970 to March 1976 were surveyed and the patients showing roentgenologically new shadows were mainly analysed in relation to the differential diagnosis between bacterial infections and true tuberculous aggravations. Moreover, patients with reappearance of A. F. B. in sputum after consecutive three months negative cultures were investigated. The results were as follows: 1) Seventy (6.8%) out of 1, 024 patients surveyed developed “new shadows” on chest X-ray, i. e. enlargement of shadow (4a according to the Gakken Standard) 24, appearance of new shadows (4b) 27, cavitation (4c) 16, and development of pleural effusion (4d) 3. 2) Sixteen (22.3%) out of 70 patients with development of new shadows seemed to have ordinary bacterial infection (bacterial pneumonia). Most of these patients had high fever of more than 38°C at the onset of infection and the laboratory examination revealed leukocytosis with the shift to left, accelerated ESR, positive CRP and increased mucoprotein. Escherichia coli and Pseudomonas aeruginosa were isolated from each two patients and Staphylococcus aureus was from one patient. No remarkable pathogenic organisms were detected from the sputum of the remaining 11 patients. These shadows disappeared within two months by antibacterial drug's treatment in all 16 cases. Hence, it is suggested to set the two-month observation period as target for differential diagnosis between bacterial pneumonia and aggravation of pulmonary tuberculosis. It was also found that the tuberculous patient with low pulmonary function were easily infected by pyogenic organisms. 3) Seven patients showing cavitation of tuberculoma without enlargement of shadows had good clinical course, but almost all the patients with cavitation accompanyed with enlargement of shadows showed no improvement even after 6 months treatment. 4) From the above mentioned results, it is questionable to judge the cavitation without enlargement of shadows on roentgenogram or the appearance of new shadows as aggravation of pulmonary tuberculosis according to the present Gakken Standard for Evaluation of Course of Pulmonary Tuberculosis, and the cavitation without enlargement of shadows and the appearance of new shadows which disappears within two months could be excluded from the aggravation of tuberculosis.
During the period from July 1970 to February 1975, the minimum inhibitory concentration (MIC) of 15 chemotherapeutic drugs (gentamicin, amikacin, dibekacin, tobramycin, streptomycin, kanamycin, ...chloramphenicol, minocycline, cefazolin, cephaloridine, cephalexin, ampicillin, sulbenicillin, furatrizine and nalidixic acid) to 200 Serratia marcescens strains isolated from various clinical materials was investigated by using agar plate dilution method, and the results were as follows. 1. Most strains of pigment-nonproducing were more resistant to 15 chemotherapeutics than pigmentproducing strains, whereas 6 pigment-nonproducing strains (amikacin 1, gentamicin 1, sulbenicillin1, nalidixicacid3) were inhibited by the MIC of lesst han 0.20μg/ml On the other hand, only onepigment-producing strain (kanamycin) was inhibited under the same concentration. 2. In the susceptibility test of S. marcescens strains isolated from various clinical materials, resistant strains to the all chemotherapeutics tested were found mainly in isolates from urine and most of them were pigment-nonproducing. 3. S. marcescens strains were most sensitive to gentamicin and furatrizine, followed to amikacin, tobramycin and dibekacin, while not sensitive to penicillins, cephalosporins and chloramphenicol
Laboratory studies have been performed on ceftezole (CTZ), a newly developed cephalosporin antibiotic, and this drug has been applied clinically to various infections of respiratory organs. Results ...obtained were as follows. 1) Antibacterial activity : Minimum inhibitory concentrations of CTZ were determined by means of standard method of the Japan Society of Chemotherapy on 519 strains in total including 22 strains preserved in our department as standard and 497 strains isolated from various clinical materials (Staph. aureus 64, β-Streptococcus 32, Salmonella 16, Shigella 15, E. coli 64, Kl. aerogenes 64, Ent. aerogenes 32, Ent. cloacae 32, Serratia marcescens 64, Pr. vulgaris 20, Pr. mirabilis 30 and Ps. aeruginosa 64). Compared these results with those of cefazolin, antibacterial activity of two drugs was almost the same. 2) Distribution in organs of rat : CTZ was injected intramuscularly to male Wistar rats at a dose of 20 mg/kg, and the drug concentrations in various organs were measured. Peak was attained in 30 minutes, and levels were arranged in order of kidney > serum > lung > liver. Ratios of organs level to serum level were kidney 5.017, lung 0.569 and liver 0.353. 3) Blood level in human : CTZ was injected intramuscularly by drip infusion for 2 hours at a dose of 3 g with 5% glucose, and blood concentrations of the drug were measured. Peak value of 78-85 μg/ml was shown at termination of drip infusion, and no blood activity was noticed 6 hours after completion of the infusion. Half life time was about 30 minutes. 4) Level in sputum : CTZ was administered similarly to 3) to the cases of bronchiectasis expectorating purulent sputum, and CTZ activity of 0.8 μg/ml was noticed in sputum. Ratio of sputum level to maximum blood level was 0.01. 5) Clinical results of respiratory infections : CTZ was injected intravenously by drip infusion at a dose of 3 g once daily to 6 cases of respiratory infections. Results obtained were excellent in 3 cases of bacterial pneumonia, fair in 1 case of lung abscess, and failure in 2 cases of bronchiectasis. 6) Side effect : Slight elevation of GOT and GPT was observed in 1 case out of the above 6 cases, though the values were normalized after interruption of the drug administration. No abnormality was noticed in other subjective symptoms and hemato-biochemical findings.
Bacampicillin (BAPC) is a newly developed derivative of ampicillin which is well absorbed when given orally and is hydrolyzed to ampicillin in the body to give peak levels of ampicillin higher than ...those obtained with ampicillin itself. Fundamental and clinical studies on this drug were carried out and the results were as follows: 1) Absorption and excretion in man Three healthy male adults volunteers were given orally 250 mg of BAPC after fasting and peak levels of BAPC in the blood of two volunteers were 3.5μg/ml and 4.8μg/ml one hour after administration of BAPC. Residual one has 2.1μg/ml of peak level two hours afterwards. Urinary recovery rate during the initial two hours after administration of BAPC was 40-50 percent and 59-67 percent, 62 on the average were excreted by the end of the study for 6 hours. 2) Clinical study Thirty one patients with pulmonary infection including one case with lung cancer and one with pulmonary tuberculosis respectively, were treated with one gram of BAPC daily for 3-21 days and good results were obtained in 21 cases with efficacy rate being 75 percent. In five cases out of six patients with chronic bronchitis due to Haemophilus influenzae, this organism was eliminated completely with BAPC. 3) Adverse reaction Two patients complained of mild diarrhea and one heart burn. Eosinophilia was seen in one case.
Cefsulodin (SCE-129, CFS), a newly developed anti-pseudomonal cephalosporin was studied basically and clinically. Following results were obtained. 1) Antimicrobial activity: Minimum inhibitory ...concentrations (MICs) of CFS against 22 standard strains subcultured in our department and 856 clinical isolates (Pseudomonas aeruginosa 106, Staphylococcus aureus 54, Salmonella 36, Citrobacter freundii 38, C. diversus 30, C. amalonatica 10, E. coli 53, Shigella 45, Klebsiella pneumoniae 53, Enterobacter aerogenes 54, E. cloacae 54, Serratia marcescens 54, Proteus vulgaris 12, P. mirabilis 41, P. rettgeri 22, P. inconstans 16, P. morga Following results were obtained. 1) Antimicrobial activity: Minimum inhibitory concentrations (MICs) of CFS against 22 standard strains subcultured in our department and 856 clinical isolates (Pseudomonas aeruginosa 106, Staphylococcus aureus 54, Salmonella 36, Citrobacter freundii 38, C. diversus 30, C. amalonatica 10, E. coli 53, Shigella 45, Klebsiella pneumoniae 53, Enterobacter aerogenes 54, E. cloacae 54, Serratia marcescens 54, Proteus vulgaris 12, P. mirabilis 41, P. rettgeri 22, P. inconstans 16, P. morganii 43, P. putida 31, P. maltophilia 33, P. putrefaciens 14, Flavobacterium spp. 50 and Acinetobacter anitratus 7) were determined by agar plate method. MICs of CFS against 106 Pseudomonas aeruginosa were compaied with those of Sulbenicillin (SBPC) and Piperaciliin (PIPC). MICs of CFS against 86 out of 106 P. aeruginosa were determined in combination with Gentamicin (GM). MICs of CFS against 22 standard strains and clinical isolates excluding P. aeruginosa were compared with those of Cefazolin (CEZ). CFS had 1-4 tubes higher activities against P. aeruginosa than SBPC and PIPC and it was more than 4 tubes stronger than CEZ. On the contrary, MICs of CFS against 84 P. aeruginosa were around one tube weaker than those of GM. MICs of CFS against standard strains and clinical isolates excluding P. aeruginosa were almost the same as those of CEZ or higher. 2) Serum levels in man: A 46 year-old 53 kg male patient with chronic diffuse panbronchiolitis and a 68 year-old 49kg female patient with chronic bronchitis were given 1, 000mg of CFS by intravenous drip infusion with 300ml solution foi two hours. Peak serum levels were 18μg/ml and 38μg/ml at the end of injection in both cases. Six hours after injection 1-2μml of the drug was measurable. 3) Urinary excretion and trends of bacteria in urine: Urinary recovery rates of CFS in the above mentioned male patient were 65% at 2 hours and 87% at 8 hours after the end of injection respectively. A 37 year-old 40 kg female patient with chronic cystitis and viral meningitis was treated with 1, 000mg intravenous drip infusion of CFS a day. CFS was excreted in urine at the concentration of 340μg/ml 2 hours after injection, and numbers of P. aeruginosa and E. coli which were cultured more than 105 ml and 10 mlin number respectively at the beginning started to decrease around 3 hours. Both bacteria were less than 102/ml at 8 hours after injection and were eliminated from the urine from the second day. MICs of CFS against each P. aeruginosa strain isolated hourly were constant.
Laboratory and clinical studies were made on cefuroxime, a new cephalosporin C injectable antibiotic showing resistance to beta-lactamases. Cefuroxime was compared with cefazolin in antibacterial ...activity against total 852 strains-22 standard strains and 830 routine clinical isolates. The minimum inhibitory concentration (MIC) of cefazolin against Staphylococcus aureus was 1-2 times higher than that of cefuroxime. As for gramnegative organisms, cefazolin showed higher MICs against some strains, cefuroxime showed higher MICs against some other strains, and the both drugs had almost same activity against the other strains. Cefuroxime was administered to a patient at a dose of 750 mg by intravenous drip infusion for 1 hour, and the peak serum concentration of 62 μg/ml was assayed at the end of infusion. His expectorated sputum was collected, and the peak sputum level of 0.15 μg/ml cefuroxime was assayed 1 hour after the end of infusion. Streptococcus pneumoniae was eliminated from the patient's sputum by repeated administration. Cefuroxime was given to total 22 patients-21 with respiratory infection and 1 with chronic pyelonephritis-intravenously or by intravenous drip infusion for 8-16 days. Ten out of the 22 patients responded effectively to the cefuroxime treatment (efficacy rate of 55. 6%). Such clinical results are considered attributable to the fact that a majority of patients studied had underlying diseases. Total 3 cases showed the following adverse reaction of the drug; an elevation of S-GOT in 1 case, that of alkaline phosphatase in 1 and eosinophilia in 1.
1. Antibacterial activity: Minimum inhibitory concentrations (MICs) of mezlocillin for 797 strains in totalincluding 20 strains preserved in our department as standard and 777 strains isolated from ...various clinical materials (Staphylococcus aureus 53, Salmonella 36, Citrobacter freundii 53, Shigella 46, Escherichia coli 90, Klebsiella aerogenes 54, Enterobacter aerogenes 43, Enterobacter cloacae 43, Serratia marcescens 104, Proteus mirabilis 52, Proteus vulgaris 25, Proteus rettgeri 22, Proteus inconstans 15, Proteus morganii 42, Pseudomonas aeruginosa 99), were determined by means of the standard method of the Japan Society of Chemotherapy and compared with those of carbenicillin (CBPC). In most cases mezlocillin demonstrated the same antibacterial activities as CBPC. In several species it was slightly more effective than CBPC. 2. Blood concetration: Two dosages of mezlocillin were diluted with 500 ml of 5% glucose each and drip infusion was carried out for 2 hours in 2 patients with respiratory infections. After administration of 4 g, peak level of 160μg/ml was shown at termination of drip infusion, 1.2 μg/ml was noticed 6 hours after termination of the infusion. Half life time was 0.75 hour. After administration of 2 g, peak level of 64μg/ml was shown at termination of drip infusion, 0.5 g/ml was noticed 6 hours after termination of the infusion. Half life time was 0.85 hour. 3. Clinical results of respiratory infections and side effects: Mezlocillin was administered at a dose of 4 g once or twice daily to 10 cases of respiratory infections (bronchopneumonia 7, lung abscess 1, chronic bronchitis 2). Results obtained were excellent in 4 cases, good in 3 cases, fair in 2 cases and failure in 1 case. Adverse reactions noted were eruption in one patient and increase in eosinocyte in two patients, though the values were normalized after discontinuation of the drug administration. No abnormality was noticed in other subjective symptoms and hemato-biochemical findings.
Fundamental and clinical studies on AB-206, a new antimicrobial agent, were carried out and the following results were obtained: 1. Antimicrobial activity: Minimal inhibitory concentrations (MICs) of ...AB-206 against 22 standard strains which had been subcultured in our department and 664 strains (Staphylococcus aureus 54, Salmonella 36, Citrobacter freundii 38, C. diversus 24, C. amalonatica 10, E. coli 53, Shigella 45, Klebsiella aerogenes 53, Enterobacter aerogenes 54, Ent. cloacae 54, Serratia marcescens 54, Proteus vulgaris 13, Pr. mirabilis 41, Pr. rettgeri 22, Pr. inconstans 16, Morganella morganii 43, Pseudomonas aeruginosa 54) isolated from the various clinical materials were determined in comparison with those of nalidixic acid (NA). MICs of AB-206 were 2 to 4 times lower than those of NA in almost all bacteria. 2. Absorption and excretion in man: Three healthy male adults were given 500 mg of AB-206 orally at fasting time and the peak serum levels were 5.3 to 6.25μg/ml 1 to 2 hours after administration. Two healthy male adults were also given 500 mg of AB-206 orally after meal and the peak serum levels were 3.8 to 6.25μg/ml 2 to 4 hours afterwards. A 54 years old female patient with chronic bronchitis was administered 500 mg of AB-206 after meal and its peak level of the drug was 5.8μg/ml 4 hours after medication. Urinary recovery rates within 6 hours were 5.4 to 7.8%. 3. Clinical effect: Five patients with pulmonary infections (Bronchopneumonia 2, Bronchiectasis 1, Chronic bronchitis 1, Acute bronchitis 1) were treated by 1, 500 mg of AB-206 per day. Clinical and bacteriological effectiveness was poor in all five cases. 4. Adverse reaction: Subjective and objective symptoms and hematological, biochemical data and renal function were checked up after administration of AB-206. No side effect was observed.
Comparative studies between amoxycillin (AMPC) and penicillin G (PCG) were carried out in order to clarify whether AMPC can take place of PCG in the chemotherapy of subacute bacterial endocarditis ...(SBE). The results were as follows : 1) The minimal inhibitory concentration (MIC) of AMPC against Streptococcus mitis isolated was 0.2 μg/ml. Serum levels of AMPC from 30 minutes until 6 hours after oral administration to 5 healthy adult volunteers at the dose of 1 ranged from 1. 0 μg/ml to 7. 8 μg/ml on the average, which were 5 to 40 times higher than MIC of AMPC against S. mitis. 2) The serum bactericidal activities after oral administration of AMPC at the dose of 1 to a patient with SBE were compared with those of PCG after intramuscular injection at the dose of 400, 000 or 600, 000 units. Reciprocal titer of bactericidal activities of AMPC against S. mitis was 4 to 60 times and it was higher than those titers after 400, 000 units PCG injection, being almost same as those of 600, 000 units injection. From the above mentioned results, it is considered to be useful to give AMPC orally at the dose of 1 g 6 hourly in a day to patients with SBE instead of PCG injection.
A new aminoglycoside antibiotic, Sisomicin was investigated fundamentally and clinically. The results were as follows: 1. Antimicrobial activity: Twenty three standard strains subcultured at our ...department and 81 Gram positive cocci (Staphylococcus aureus81) and 844 Gram negative bacilli (Salmonella33, Citrobacter freundii57, Shigella48, E. coli81, Enterobacter aerogenes42, Erwinia herbicola9, Klebsiella aerogenes81, Ent. cloacae39, Serratia marcescens162, Proteus vulgaris26, Prot. mirabilis51, Prot. rettgeri22, Prot. inconstans17, Morganella morganii42, Aeromonas22, Vibrio parahemolyticus24, Pseudomonas aeruginosa88) were investigated for determination of Minimum Inhibitory Concentrations (MICs) of Sisomicin in comparison with those of Gentamicin (GM). MIC of Sisomicin againstStaphylococcus aureus was lower than that of GM. In regard to Gram negative bacilli, Sisomicin had higher MICs againstE. coliandSerratiathan GM. On the other hand, Sisomicin had about two-fold lower MICs againstPseudomonas aeruginosa, Proteus rettgeri, Proteus inconstansandMorganella morganii. AgainstKlebsiella aerogenesandSalmonella speciesboth drugs had almost same MICs. 2. Absorption and Excretion: Serum concentration of Sisomicin after intramuscular administration of 50 mg to three healthy adult volunteers reached peak levels ranging from 2.7 to 2.1μg/ml within 30 min. to 60 min. and at 6 hours following injection average serum level was 0.5μg/ml. Average urinary recovery rate within 6 hours was 73.9%. 3. Organ distribution in Rat: Organ concentrations in rat after intramuscular injection of Sisomicin 20 mg/kg was the highest in serum followed by kidney, lung and liver in order. 4. Penetration into purulent pleural effusion: A 46 y. o. male patient with lung abscess and pyothorax was given 75 mg of Sisomicin intramuscularly. Peak serum level was 11.3μg/ml at 30 min. and peak level in pleural effusion was 1.9μg/ml at 2 hours after injection. 5. Clinical effects and adverse reaction: Eleven patients with respiratory infections (Bronchopneumonia 6, Lung abscess 1, Lung abscess+Pyothorax 1, Bronchopneumonia+Bronchiectasis 1, Chronic bronchitis 1 and Mucoid impaction 1) were given 75-150 mg/day for 7-21 days and the efficacy rate was 70%. Adverse reaction was noticed in only one case with slight elevation of S-GOT and S-GPT.
