Patients with severe pulmonary and urinary tract infections who had responded poorly to a prior chemotherapy were treated with minocycline in combination with aminoglycoside. The efficacy of the combined therapy in treatment of these patients was evaluated.
Sixteen patients with pulmonary infection and one patient with urinary tract infection were included in this study. In all of these patients the prior chemotherapy was interrupted, because of the lack of response or side effects. To these 17 patients 100mg of minocycline and a conventional dose of aminoglycoside (dibekacin, amikacin or gentamicin) were given by intravenous drip infusion and intramusculary twice a day, respectively.
Clinical response to the above combination therapy was excellent in 5 patients, good in 9 patients and fairly good in 2 patients. In the remaining one patient response was poor. Thirteen strains of pathogenic microorganisms were cultured from the specimen of these patients; 3 strains each of S. pneumoniae and E. coil, 2 strains of Acinetobacter and 1 strain each of H. influenzae, S. marcescens, K. pneumoniae, P. aeruginosa and Alcaligenes. Eleven of the 13 pathogens were eradicated from the specimen and 2 pathogens markedly decreased in number.
Then in vitro combined effects of minocycline plus gentamicin on a strain of Serratia marcescens from the sputum of a patient included in this study was examined. When these two drugs were combined, a remarkable synergistic potentiation of antimicrobial activity was found, as evidenced by a fractional inhibitory concentration index of 0.094.
The elevation of low grade of serum transaminases was found in three patients and that of alkaline phosphatase in one patient. But the results of liver function tests turned to be normal upon cessation of the combined therapy.
It is concluded that the combination of minocycline and aminoglycoside is of value in the treatment of patients who had severe infections of the lung or urinary tract and had poorly responded to or had not tolerated the prior treatment with β-lactam alone or with β-lactam plus aminoglycoside.

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Fusobacterium (43 strains) isolated from human oral cavity, including 24 strains of Fusobacterium nucleatum and 19 strains of Fusobacterium sp., were tested for susceptibility against 34 antibacterial agents. Minimum inhibitory concentration (MIC) were determined by agar dilution method with GAM agar as a basal medium.
The distribution pattern of MIC showed single peak in most of drugs tested. Both of F. nucleatum and Fusobacterium sp. were very susceptible to agents except aminoglycosides and chemotherapeutics. Penicillin G, cephapirin, hetacillin, amoxicillin, ampicillin, piperacillin, cephalothin and cefazolin were markedly effective, and 90% of the strains were susceptible at MIC<0.1μg/ml. 90% of the strains were inhibited at MIC 0.1-1.0μg/ml of cloxacillin, methicillin, carbenicillin, cephaloridine, cephalexin, cefmetazole, lincomycin, minocycline, doxycycline, tetracycline and chloramphenicol. In the concentration of 1.0-10μg/ml of mecillinam, erythromycin, mitomycin C, polymyxin and rifampicin, and 10-100μg/ml of cephaloglycin and colistin, 90% of the strains were inhibited. Aminoglycosides, gentamicin, dibekacin, streptomycin and fradiomycin, and chemotherapeutics, nalidixic acid, piromidic acid, pipemidic acid and sulfamethoxazole-trimethoprim, were not so effective as other agents and could not inhibit 90% of the strains at MIC> 100μg/ml.

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Intrauterine infection was induced experimentally in rats, and the therapeutic effects of antibiotics (CTX and cefazolin (CEZ)) on the infection were determined to examine the availability of such animals as the experimental model.
Virgin rats, and rats delivered the day before and 4 days before the test were used. The cervix of each animal was ligatured, and E. coli suspension mixed with 5% mucin was injected into both uterine horns. Among such infected uteri, the uterus in the group delivered 4 days before the test was in optimal conditions for bacterial growth. Histologically, the uterus of these cases showed inflammatory changes in the endometrium and neutrophil infiltration into the lumen and gland.
When the two antibiotics were intravenously administered to the animals infected as above, therapeutic effects were shown apparently with both drugs, and CTX was more effective than CEZ. Thus, such animals may serve as the model with which in vivo effects of antibiotics can be estimated.

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In this study, AM-715 was administered to 13 typhoid patients and 12 asymptomatic typhoid carriers.
Of the typhoid patients 8 cases were adults and the remaining 5 cases were children. All of the carriers were adults, and in 4 cases gall stone were observed.
Daily doses of AM-715 were administered to the adult typhoid fever patients: 1, 600 to 3 patients and 2, 000 mg to the other. Three of the children were administered 1, 200 mg and 2 were given 1, 600 mg of the drug. Except in the case of one adult patient who showed no sign of improvement with the administration of the drug, duration of the treatment extended over 14 days. Clinical and bacteriological effects were observed in all cases with the exception of the above-mentioned case.
For the typhoid carriers, daily doses of the drug were: 1, 200 mg in one case, 1, 600 mg in 10 cases and 2, 000 mg in one. Treatment was continued for over 14 days in these cases too. One female carrier relapsed 5 months after her discharge.
No major adverse reaction was recognized, but the following slight abnormalities occured in laboratory findings: elevated transaminase activity in 2 cases, eosinophilia and elevation of serum bilirubin value in one case, granulocytopenia in one case, granulocytopenia with thrombocytopenia in one case and thrombocytopenia in one case. One of the cases of thrombocytopenia still showed abnormality after 2 weeks, but in the other case abnormalities disappeared in a week.
The results of further follow-up study of 8 cases formerly reported were also described.

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Minimum inhibitory concentrations (MICs) of eight antibiotics for 448 Klebsiella isolates were examined to study the relationship between the antimicrobial susceptibilities of Klebsiella species and their productions of indole and pigment. There were no major differences in the susceptibility patterns of the indole-negative strains and the indole-positive, pigment non-producing strains. Pigment non-producing strains were almost similar to the pigment producing strains in susceptibilities to cefoxitin, ceftizoxime, kanamycin, gentamicin, and tetracycline but differed in showing greater susceptibilities to ampicillin, cephalothin, and cefazolin. At an inoculum of 10⁶ colony-forming units, 228 strains (97.0%) were inhibited by cefazolin at a concentration of 12.5μg/ml, as compared with 84 strains (94.4%) of indole-positive, pigment non-producing strains and 104 strains (83.9%) of pigment producing strains. The concentration of cefazolin required to inhibit the growth of 90% of total number (MIC₉₀) of the pigment producing strains were 100μg/ml, whereas the MIC₉₀ of cefazolin against the indole-negative strains and the indole-positive, pigment non-producing strains were 3.13, and 6.25μg/ml, respectively.
Of the 32 cefazolin-resistant Klebsiella strains, 14 were isolated from urine and 11 from feces. There were no evidence of epidemics of infection due to the cefazolin-resistant strains during the investigation period.

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We have already reported the newly developed local chemotherapy of cancer, in which intratumoral conversion of 5-FC to 5-FU by extrinsic cytosine deaminase (CDase) implanted to the tumor is expected to induce antineoplastic activity at a local site with minimal systemic toxicities. Determination of the tissue concentration of both 5-FC and converted 5-FU is, therefore, very important for evaluating the antineoplastic effects of this local chemotherapy. In this report, we discussed the usefulness o the microbiological assay (Thin layer cup method) using 2 test organisms for the differential quantitation of the drugs in the same material and investigated the tissue concentrations of the drugs in the tumor and the serum.
In vitro studies; The standard curves for 5-FC and 5-FU were obtained by measurement of the zones of inhibition using standard solutions of the drugs. In the used bacteria and the fungi, Micrococcus luteus ATCC 10240 was found to be the most sensitive organism to 5-FU (MIC=0.025 μg/ml). On the other hand, Saccharomyces cerevisiae AKU 4100 was sensitive to 5-FC (MIC=0.4 μg/ml), but had the same sensitivity to 5-FU. The standard curve of M. luteus was affected only by the concentration of 5-FU under the various combinations with 5-FC and 5-FU. On the contrary, the standard curve of S. cerevisiae was affected by the concentration of the sum of both drugs. The concentration of 5-FC (C) in the sample mixed with 5-FC and 5-FU, therefore, could be determined by the difference between the value (A) obtained by S. cerevisiae and that (B) obtained by M. luteus (C=A-B), although the concentration of 5-FU was calculated as (B).
In vivo studies; based on these results, we have made the differential quantitation of the drugs in the practical experiments. 5-FC were administered intraperitoneally to the rats bearing subcutaneous tumors which were previously implanted with the CDase containing capsule at the tumor bed. The pattern of 5-FC concentration curves of the serum and the tumor tissue showed a close similarity. At 1 hour after the administration, 5-FC attained to maximum and were estimated to be 96μg/ml in the serum and 85 μg/g in the tumor. The converted 5-FU attained to maximum at 2 hours and were estimated to be 8μg/ml. 5-FU passed into the blood stream was only 2.5% of that in the tumor.

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Correlation between sensitivity to cefazolin (CEZ) and that to cefmetazole (CMZ) in Staphylococcus aureus was investigated. It was indicated that CMZ gave lower MICs against the strains with higher MICs for CEZ and that CMZ exerted a stronger bactericidal effect on the strains with similar MICs for CEZ and CMZ. Although CEZ-rcsistant strains were induced by treatment with CEZ or penicillin G, the treatment had no influence upon the antibacterial activity of CMZ.
MICs were correlated with penicillinase activities produced in CEZ-resistant strains, suggesting some relation between acquisition of the resistance and production of the enzyme.

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Significance of coagulase-negative staphylococci (CNS) as pathogens of the urinary tract was studied both bacteriologically and clinically. Results were summarized as follows;
1) In the study of acute uncomplicated cystitis in the female, CNS were regarded as pathogens only when isolated with bacterial count of 10⁵ bacteria per ml of urine or more as a single organism with significant pyuria of 10 cells per high power field or more. CNS which agreed with this criteria were isolated from approximately 10% of the patients with acute uncomplicated cystitis and were second commonest cause after Escherichia coli.
2) CNS occured predominantly in younger age group as compared with E. coli and were more frequent in summer than in winter season.
3) Urinary CNS disappeared by adequate treatment simultaneously with the disappearance of pyuria and symptoms. This could be regarded as a strong evidence that CNS had pathogenic role in acute uncomplicated cystitis.
4) Whereas, in most cases with complicated urinary tract infections, CNS were isolated with bacterial count of less than 10³ bacteria per ml of urine in polymicrobial infections without significant pyuria. These findings suggested that significance of CNS was rather low at least in complicated urinary tract infections.
5) When CNS were classified by BAIRD-PARKER'S method, Staphylococcus subgroup II was most predominant in acute uncomplicated cystitis, followed by Staphylococcus subgroup IV. But in chronic complicated urinary tract infections, Staphylococcus subgroup II, subgroup V and Micrococcus subgroup 3 were predominant. When KLOOS & SCHLEIFER's classification was employed, S. saprophyticus was most prevalent and S. epidermidis was second in acute cases. Whereas in chronic cases, most strains were classified as S. epidermidis.
6) Most strains of S. saprophyticus were novobiocin resistant but some strains were sensitive, whereas 57% of S. epidermidis strains were novobiocin sensitive and 43% were resistant. Therefore, novobiocin sensitivity test seemed unsuitable for the differentiation of S. saprophyticus from S. epidermidis.
7) Difference of distribution in biovar, species or novobiocin susceptibility between acute and chronic cases suggested that source or mode of CNS infection in acute cases might be different from that of chronic cases.

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Apart from immunological response in vivo when combined dose of antibiotics and immunoglobulin is given, the effect of antibiotics upon in vitro antibacterial activity resulting from the addition of pepsin-treated human immunoglobulin (GGP) was studied on eight strains of gram positive cocci and gram negative bacilli. An enhanced antibacterial activity due to GGP addition was comfirmed in either cases of minimum inhibitory concentration (MIC), number of bacterial colony, and proliferation curve. It was very interesting phenomenon, in particular, that the effect was also seen in each case of Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae, being moderately or more resistant to antibiotics. This phenomenon also was verified through microscopic morphological observation.

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Norfloxacin (AM-715), a new oral antibacterial agent, was evaluated clinically for the patients with urethritis and the following results were obtained.
(1) Thirty-five patients with gonococcal urethritis and 25 patients with non-gonococcal urethritis were administered at daily dose of 600mg divided 3 times for a duration of 3 to 7 days. Overall clinical efficacy rate was 94.3%(33/5) in patients with gonococcal urethritis and 83.3%, (20/24) in patients with non-gonococcal urethritis except for one case.
(2) MIC values of AM-715 against clinical isolated gram-positive coccus were distributed from 0.2μg/ml to 25μg/ml. These MIC values were superior to those of NA and PPA.
(3) Side effect was observed in only one case as complaint of diarrhoea. It was concluded that AM-715 was an useful agent for the treatment of urethritis.

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