Staphylocoagulase, an extracellular protein produced by staphylococci, specifically forms a complex with prothrombin. The staphylocoagulases are classified into eight serotypes based on the ability of antisera to cross-neutralize plasma clotting activity. We have developed a test based on the polymerase chain reaction (PCR) to detect the Staphylococcus aureus coagulase (coa) gene. The sequences of the oligonucleotide primers used in this assay were 5'-TAGGCGCATTAGCAGTTG-3' and 3'-CTCTGGTTCTAAGTTGTT-5'. We describe the coagulase typing of S. aureus based on the amplification and subsequent Dra I digestion of the PCR products of the coagulase gene. We ditermin'ed the coagulase types of 200 clinical isolates of S. aureus by antisera and PCR methods. The results suggest that the PCR method of coagulase typing was useful for the untypable strains by antisera methods. We also found variants of coagulase types II, V and VII. The variants were isolated at high frequency among 12 of 14 untypable strains by antisera methods.

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Erythromycin has now been thoroughly demonstrated to have an excellent therapeutic effect in the patients with chronic lower respiratory infection. However, the mechanism of action of the drug remains controversial. We studied the effect of macrolides on endogenous corticoids in mice. Erythromycin (100mg/kg, i. p.) significantly increased serum corticoid levels, but josamycin (100 mg/kg, i. p.) had little effect on them. The increase in the corticoid levels was completely suppressed by pretreatment with dexamethasone. These findings suggest that erythromycin increases corticoid levels through activation of the hypothalamo-pituitary-adrenal system. This increase in corticoid levels may be one of the mechanisms of the clinical efficacy of erythromycin in chronic lower respiratory infections.

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We examined the antitumor effect of 5-fluorouracil (5-FU) by daily oral (p. o.) administration of 20 mg/kg compared with that by daily intraperitoneal (i. p.) administration of 10 mg/kg. A 5-FU-sensitive human stomach cancer xenograft (SC-1-NU) was used for the experiment. We also measured the binding capacity of thymidylate synthase (TS) and 5-FU incorporated into RNA (F-RNA) for the effect on DNA and RNA, respectively. Antitumor effects of 5-FU by 20 mg/kg p. o. were significantly stronger than those by 10 mg/kg i. p., throughout the experimental period (P<0.05). The minimum TIC ratios were 9.97% for 20 mg/kg p. o. and 48.1% for 10 mg/kg i. p. The effects of a single dose of 5-FU on TS and F-RNA were transient, whereas the TS inhibition rate and F-RNA content were gradually increased after successive doses of 5-FU. In both cases, no differences were seen between the effects of 20 mg/kg p. o. and 10 mg/kg i. p. It was considered that the effect of a large dose of 5-FU given orally could be equivalent to that given intraperitoneally.

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Pazufloxacin (PZFX) and ofloxacin (OFLX) were administered as single oral doses of 200 mg to 6 male volunteers in a cross over fashion to compare their antibacterial effects on Staphylococcus aureus, Enterococcus faecalis, Escherichia coli and Pseudomonas aeruginosa in clinically isolated urine samples. The maximum mean drug concentration in urine was 763μg/ml in the PZFX group (0-2 hours after administration) and 281μg/ml in the OFLX group (after 2-4 hours). The urinary antibacterial titer in the PZFX group was revealed to be superior to that in the OFLX group up to 4 hours after administration. In particular, while the samples, even of the undiluted urine, in the OFLX group showed no antibacterial activity against quinolone-moderately resistant S. aureus, E. coli and P. aeruginosa, all samples in the PZFX group, including those of dilute urine, showed some antibacterial activity up to 4 hours after administration. Theses results appear to reflect the excedllent antibacterial effect and higher initial urinary concentration of PZFX as compared with that of OFLX. When the MIC in urine was compared with that in CAMHB, PZFX and OFLX showed decreased antibacterial activity in urine. A decrease in bacterial activity in urine, if present, was about 2 tubes in the case of PZFX. OFLX, on the other hand, showed decreased antibacterial activity especially against E. coli which exceeded 5 tubes.

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A 60-year-old man with double cancer of the esophagus and stomach and bilateral lung metastases and cervical lymph node metastasis was treated by combination chemotherapy with cisplatin, etoposide and 5-fluorouracil (PEF). Cisplatin (50 mg/m²) and etoposide (100 mg/m²) were administered by simultaneous drip infusion 8 times at two-week intervals, and 5-fluorouracil (300 mg/m²/day) was infused continuously for 105 days. Not only the cervical and lung metastases, but the primary lesions in the esophagus and stomach were markedly decreased in size after the second dose of cisplatin and etoposide, and the effects lasted for over 7 months. Mild and transient anorexia, hair loss and leucopenia (3, 300/mm³) were experienced during therapy.

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The (draft) “Guidelines for Indications for Antibacterial Drugs” published in 1987 have since been in effect as the guidelines for clinical trials of antibacterial drugs in Japan, and are associated with a variety of problems in conducting such clinical trials. The Guidelines Research Group organized by the Ministry of Health and Industry, Japan, for deliberating on the guidelines, decided to initially collect data relating to the problems associated with the currently enforced guidelines for clinical trials of antibacterial drugs in Japan, and then to compile new guidelines aimed at resolving the problems and taking into account consistency with similar guidelines already published for clinical evaluation of antibacterial drugs in Europe and the U. S. A. This paper describes the historyof the newguideline compilation with particular reference to differences between the guidelines in effect in Japan and those used in Europe and the U. S. A., the problems encountered in conducting such clinical trials in Japan, and the goals with which the compilation of the new guidelines has heretofore been carried out, including resolution of the aforementioned problems.

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