The susceptibilities of Candida parapsilosis (ATCC 90019), Candida glabrata (ATCC 90030) and Candida krusei (ATCC 6258) to five antifungal agents (amphotericin B, flucytosine, fluconazole, itraconazole and miconazole) were investigated by the frozen microplate method of antifungal susceptibility testing. The testing microplate was designed according to the method proposed by the Japanese Society for Medical Mycology. This method is similar to M27-T proposed by the National Committee for Clinical Laboratory Standards. The endpoints of the five antifungal agents against three reference strains in the microplate were determined by the usual visual and spectrophotometric methods. The microplate was incubated for 48 hours in air at 37°C. Areas and numbers of colonies at the bottom of the microplate well were determined by a microcomputer and the endpoints of the agents against the reference strains were also determined by image processing. The endpoints obtained by image processing were almost the same as the values obtained by the visual method and similar to the values obtained by the spectrophotometric method. These results suggest that it is possible to determine the endpoint by image processing automatically and objectively.

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IQI mice (ICR, 5 weeks old) were orally challenged with verotoxin-producing strains of Escherichia coli 0157: H7 NK2 or R29. The viable cells, at 10¹⁰-10¹¹ CFU/g, excreted into the feces were collected from the non-treated mice for 1-6 days after infections with both strains, which indicates stable inoculation in their intestinal tracts. No mice died in the non-treated groups during or after the dosing period. Norfloxacin was given orally at a dose of 3mg/kg twice/day for 6 days to three mice each which were infected with NK2 or R29 strains. VT2 of 625-2, 500mg/g was found in the feces of the infected mice for 15 hours after two doses on the first day of norfloxacin dosing, and large amounts of VT1 (1, 250-5, 000mg/g) and VT2 (40, 000mg/g) were also found in the feces for 15 hours after dosing on the second day. Although a marked decrease in the viable cell count was found in the feces of the mice given norfloxacin, all the mice died within 4-5 days after onset. On the other hand, when fosfomycin was given to the infected mice at a dose of 25mg/kg twice/day for 6 days, no verotoxins were found in any feces of the mice and no mice died of infection with either E. coli 0157: H7 NK2 or R29. Very high concentrations of VT2 were found in the contents of the lower intestines of mice which died after norfloxacin dosing. Bleeding was detected in the intestines of 4 of the 6 dead mice, and a positive occult reaction was observed in feces of the other 2 mice. No such changes were observed in the mice given fosfomycin. This intestinal infection model in mice infected with E. coli 0157: H7 may be useful for evaluating the in vivo production or liberation of verotoxins by antibacterial drugs and their toxic effects on mice infected with this bacterial strain.

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We evaluated the clinical efficacy and safety of sulbactam/ampicillin (SBT/ABPC), β-lactamase inhibitor, for patients with respiratory tract infections who had visited our hospital as Kasaoka Daiichi Hospital for treatment and as Kawasaki Medical School Hospital and compared the two patient groups. More patients who visited our hospital as Kawasaki Medical School Hospital had already received treatment with different antibiotics, had underlying diseases (especially respiratory diseases), and were in a poor nutritive state as compared with those visiting our hospital as Kasaoka Daiichi Hospital. Regarding the relationship between efficacy rate and infectious type, 22 were of the community acquired infectious type, and 11 cases (12 episodes) were of the nosocomial infectious type and the efficacy rate was lower (71%) for patients for whom our hospital was Kawasaki Medical School Hospital. The efficacy rate for patients at Kawasaki Medical School Hospital with infection of community acquired type only was 82%. Most patients who visited our hospital as Kasaoka Daiichi Hospital had infections of the community acquired infectious type, and the efficacy rate was high (96%). As to side effects, drug-induced pneumonitis and drug fever, respectively, were observed in two patients for whom our hospital was Kawasaki Medical School Hospital. In laboratory tests, transient slight transaminase elevation or eosinophilia was observed in four patients visiting our hospital as Kawasaki Medical School Hospital, and in six patients visiting it as Kasaoka Daiichi Hospital. Sulbactam/ampicillin is an effective initial therapy for respiratory tract infections of the community acquired infectious type, but careful observation is also necessary for patients during the administration of sulbactam/ampicillin.

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In this prospective study of the efficacy of postoperative immunochemotherapy after mastectomy, which we started to use in 1977, we compared outcomes after mastectomy only, after mastectomy and chemotherapy, and after mastectomy and immunochemotherapy. In chemotherapy, carboquone was given intravenously in a daily dose of 3 mg on the day of operation and the next two days; and for the next five years, carboquone was given orally in a daily dose of 0.50 or 0.75mg for 40 days and withheld for the next 56 days. In immunochemotherapy, with a same scheduled intravenous carboquone, a static hemolytic streptococcal vaccine, OK-432, was injected intramuscularly two times a week at an initial dose of 0.2 KE. The dose was increased gradually to 2.0 KE during the first two months after the operation. Then, instead of OK-432, a polysaccharide preparation (PSK) from a boiled Basidiomycetes extract was given a daily dose of 3.0g on the days of carboquone administration. In all, 150 patients agreed to random allocation (envelope method) of one of the three groups. As of April 1997, 91 were alive without recurrence, 11 were alive with recurrence, 37 had died of recurrence, and 11 had died of other causes. The fifteen-year overall survival rate was 61% for the control group with mastectomy only, 80% for group with mastectomy and chemotherapy, and 75% for the group with mastectomy and immunochemotherapy. The fifteen-year relapse-free survival rates in these three groups were 58%, 75%, and 66%, respectively. The results with chemotherapy, added were better than with mastectomy only (p=0.04, log-rank test). When adjusted with Cox regression analysis, overall survival was 72%, 74%, and 74%, respectively, and the relapse-free survival rate was 66%, 68%, and 67%, respectively. Both number of metastatic lymph nodes and carboquone administration were factors in survival (p<0.05 and p<0.05, respectively). Cancer of the contralateral breast was diagnosed, one in each group. Cancer of another organ was observed in seven patients: two were in control group, two were treated by mastectomy and chemotherapy, and three were treated by mastectomy and immunochemothrapy. Compared with the number expected (calculated by a governmental group in Osaka), the number observed was 1.8-2.2 times for all malignancies and 3.1-4.5 times for breast cancer. Carboquone as a postoperative adjuvant improved overall survival and relapse-free survival, but OK-432 or PSK did not. As a standard drug for postoperative treatment of breast cancer carboquone should be useful.

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