We used PCR to survey 247 clinical Haemophilus influenzae isolates from the nasopharynx of 190 infants and children with acute otitis media between October 2001 and December 2001 and reviewed the isolates for transmutation of penicillin-binding proteins and the TEM-1 type β-lactamase gene. The genes that we reviewed were (1) the TEM-1 type β-lactamase gene, (2) the pbp 3-1 gene, and, (3) the pbp 3-2 gene. The H.influenzae detected consisted of 162 BLNAS strains (60.0%), 27 low-BLNAR strains (10.0%), 39 BLNAR strains (15.0%), 23 BLPAR strains (9.0%), 10 BLPACR-I strains (4.0%), and 6 BLPACRII strains (2.0%). The majority of strains isolated showed age-related peaks. BLNAS or sensitive strains were detected in every age group; low-BLNAR peaked at 2 years; and BLNAR yielded multiple peaks, at 1, 4, and 5 years. The BLPAR peak was distributed between 1 and 2 years. BLPACR-I and BLPACR-II were frequently detected in children under than 3 years and peaked at 2 years and 1 year, respectively. However, no TEM-1 type gene or pbp genetic variations were detected in children aged 7 years and older. In addition, the percentage of tolerant strains among those isolated peaked at 2 years, 1 year, and 4 years of age. Findings differed for Streptococcus pneumoniae, and at young ages, the ratio of sensitive strains still accounted for more than 50%, but careful monitoring is needed, because the ratio of tolerant S.pneumoniae strains seemed to be increasing. The PCR method was used to determine the tolerance of these strain, because the results the provided more information in a shorter time than measurement of conventional MIC values.

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The antitumor effects of 5-fluorouracil (5-FU) by dosage schedule were studied using a human colon cancer (Exp-388) serially transplanted subcutaneously into nude mice. Change in F-RNA (5-FU incorporated into RNA of tumor cells) was measured over time after 5-FU administration. To determine the time and concentration dependence of the 5-FU antitumor effect, a collagen gel droplet embedded culture drug sensitivity test (CD-DST) was conducted using tumor cell suspension. The antitumor effects of 5-FU in intermittent administration were significantly stronger than those in daily dosage. The change in F-RNA after intermittent administration of 5-FU was slow and significantly higher than after daily dosage. CD-DST showed that the antitumor effect of 5-FU against Exp-388 was equally dependent on exposure time and drug concentration acting as a type I b drug.

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The antitumor effect against the cell line of human breast carcinoma, MX-1, R-27, and MCF-7, of the combination therapy, 5-fluorouracil (5-FU) and cisplatin (CDDP), or S-1 and CDDP, were tested in vivo and in vitro. In vivo, S-1 (10mg/kg) and CDDP (3mg/kg) were administered to nude mice 5 times a week for 3 weeks orally and every 4 days for a total of 3 times intraperitoneally, after a subcutaneously inoculated tumor started exponential growth. The treated/control ratio (T/C) of relative mean tumor weight was calculated and values under 50% were determined to be effective. T/C with the combination for MX-1 was 0%, which was lower than that of S-1 and that of CDDP, enhanced the antitumor effect. For R-27 and MCF-7, T/C was not under 50% in all treated groups. In vitro, the SDI test showed an increased inhibition index (%) especially for MX-1, R-27. Therefore, the antitumor effect was enhanced when the 2 drugs were administered simultaneously. We also examined the sequence dependence of anticancer activity of this combination therapy using the SDI test, suggesting CDDP followed by 5-FU was more effective than 5-FU followed by CDDP in classical isobolography. This combination therapy, thus appears to be useful in the treatment with breast cancer.

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We analyzed drug susceptibility of 72 strains of Haemophilus influenzae isolated from children during 2001.β-lactamase positive ampicillin (ABPC)-resistant strains accounted for 4 (5.6%), β-lactamase-negative ABPC-resistant strains for 5 (BLNAR, MIC>4μg/mL) 7%, low BLNAR for 22 (31%), and β-lactamase-positive AMPC/CVA-resistant strains for 1 (1.4%). Cefditoren was the most effbctive oral antimicrobial agent. Among Parenteral antimicrobial agents, ceftriaxone was most effbctive. Although 5 cases contracted invasive diseases, no deaths nor sequelae were reported.

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The widest possible variety should be provided for selecting antibiotics for the outpatient treatment of community-acquired pneumonia while inhibiting the accumulation of resistant bacteria. A new ketolide antibiotic agent, telithromycin (TEL), was marketed in December 2003, giving a wider selection of antibiotics. An outpatient treatment model of community-acquired pneumonia was develoed to evaluate the medical treatment strategy for outpatients in view of health economics by referencing TEL. The model was provided as parameters with data collected prospectively in double-blind comparative studies in which levofloxacin (LVFX) was used as a comparator for TEL and those estimated from the results of questionnaires distributed to physicians. In addition to basic analysis of basic values of the parameters, sensitivity analysis was done to validate the effects of individual parameters. The expected medical cost in 7-day TEL administration was calculated at ¥32, 981, which was further evaluated cost-specifically, showing that the cost of clinical laboratory tests accounted for the greatest percentage. Sensitivity analysis for parameters were confirmed that the 3 parameters having the greatest effect were (1) hospitalization rate at the changing of antibiotic treatment, (2) cure rate at initial examination for antibiotic treatment, and (3) dropout rate due to insufficient initial antibiotic effect. The 4 parameters were confirmed greater in the effect of cost were, (1) examination cost at initial diagnosis, (2) cost of drugs for alleviating underlying disease, (3) cost of antibiotics at the initial treatment, and (4) cost of examinations at revisit. We also confirmed that shoter initial antibiotic treatment reduced the expected medical cost. Based on these results, we concluded that 3 points are important in treating community-acquired pneumonia in view of health economics:(1) shorter antibiotic treatment, (2) reduced hospitalization as much as possible and (3) avoidance of unnecessary concomitant antibiotic use.

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