In Japan, the diagnosis and treatment of influenza virus infection has advanced dramatically. Rapid diagnosis of influenza is routine in many Japanese hospitals and clinics during winter. Influenza treatment using neuraminidase inhibitors is covered by National Health Insurance, so Japan has the world's highest neuraminidase inhibitor use, requiring careful monitoring of influenza viruses resistant to neuraminidase inhibitors and side effects. Japan is expected to achieve a pandemic plan based on stockpiling of neuraminidase inhibitors.

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The 6, 692 clinical samples in this study were collected from 187 medical institutions participating in the Community-Acquired Bacterial Infections Working Group between 1998 and 2000 in Japan. Of 4, 030 cases, duplicates excluded, acute otitis media (n=1, 425), acute upper respiratory tract infection (n=961), acute bronchitis (n=390), and pneumonia (n=175) prevailed. Streptococcus pneumoniae was most frequently isolated from the epipharynx (56.6%), followed by ear discharge (21.4%) and tympanotomy exudates (29.9%). The percentage of S. pneumoniae isolates from sputum in adults was 39.2%. For all isolates, PCR was conducted to identify S. pneumoniae species and to detect resistant genes (i) LytA gene, (ii) pbp1a gene, (iii) pbp2x gene, (iv) pbp2b gene, (v) mefA gene, and (vi) ermB gene. Capsular serotypes of these strains were also determined by quelling reactions with antisera. The in vitro activity of 14 oral antibiotics against these strains was determined by agar dilution. Correlation between the presence of abnormal pbp genes and MIC90 values of penicillin G in these strains (n=1, 945) was as follows: PSSP (n=304, 0.031, ug/mL), PISP with abnormal pbp2x gene (n=386, 0.063, ug/mL), PISP with abnormal pbp2b gene (n=13, 0.25μg/mL), PISP with abnormal pbp1a+pbp2x genes (n=179, 0.25μg/mL), PISP with abnormal pbp1a + pbp2b genes (n=3), PISP with abnormal pbp2x + pbp2b genes (n=106, 0.5μg/mL), and PRSP with abnormal pbp1a + pbp2x + pbp2b genes (n=954, 4μg/mL). Strains having either mefA gene or ermB gene, mediating macrolide resistances, were 635 and 796. Some 85 strains had both mefA and ermB genes. Distributions of serotypes showed distinctly different characteristics among PSSP, PISP, and PRSP. Various serotypes were found in PSSP. Serotypes 3 and 6 were predominant in PISP with abnormal pbp2x gene. Serotypes 14, 23, and 6 were most frequent in the other PISP. Serotypes 19, 6, and 23 accounted for 94.2% of PRSP.β-lactam antibiotic resistance appears to be evolving and PRSP having a new serotype was detected. In conclusion, continuous surveillance is required, based on molecular analysis of resistant genes for S. pneumoniae.

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We tested antitumoral activity of vinorelbine, a semisynthetic vinca alkaloid anticancer agent, against human breast carcinoma, in vivo and in vitro. The MCF-7 and R-27 tumors were positive for estrogen receptors and serially transplanted in female nude mice. The maximum tolerated dose of 16 mg/kg vinorelbine was administered intravenously to nude mice after a subcutaneously inoculated tumor started exponential growth. The treated/control (T/C) ratio of relative mean tumor weight was 26.7% for MCF-7 and 44.1% for R-27, showing that vinorelbine was equivalent or superior to other agents commonly used to treat breast cancer. An in vitro study using succinate dehydrogenase inhibition (SDI) showed that the 50% inhibitory concentration (IC₅₀) of vinorelbine was 2.4μg/mL for MCF-7 and 3.0μg/mL for R-27, much lower than for other vinca alkaloids, vindesin or vincristine. The combination chemotherapy experiment using SDI showed that adding 0.01μg/mL of vinorelbine greatly enhanced antitumor activity of 5-fluorouracil (5-FU), suggesting drug synergy. Vinorelbine thus appears to be a powerful second-or third line chemotherapy agent for patients with advanced or metastatic breast cancer.

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Piperacillin sodium (PIPC) was administered by intravenous drip to elderly (n=7) and non-elderly (n=7) subjects at a dose of 1.0 g over a 30-min period, to determine the drug's pharmacokinetics Analysis based on pharmacokinetic found the following:
(1) The mean peak plasma concentration (C_max) in the elderly tended to be 9% higher than in the non-elderly but not significantly.
(2) Systemic clearance (CL) in the elderly was lower than 70% in the non-elderly, was age-related, and tended to decrease with age.
(3) Renal (CL_R) and non-renal (CL_NR) clearance tended to decrease with age, as with CL, indicating that PIPC elimination through renal and non-renal pathways decreased with age.
(4) Accumulation is not anticipated in either group under a regimen of 2g of PIPC 4 times daily or 4g twice daily.
In the elderly, C_max tended to be higher and CL lower than in the non-elderly. Dosages in this study showed no accumulation in either group, indicating that similar dosages can be used in the elderly and non-elderly. In the elderly, however, the decreased PIPC elimination externally appears to be age-related, requiring that doses be reduced in some patients.

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To establish a dosage guideline for vancomycin (VCM) in hospitalized infants and neonates, we studied pharmacokinetic parameters. Subjects were 5 neonates and 16 infants undergoing vancomycin therapy to treat infections by MRSA during between August 1998 and August 2001 at our hospital. Pharmacokinetic parameters of vancomycin were estimated by the Sawchuk-Zaske method. A good correlation was obtained between VCM clearance (CL) and body weight (BW). Although good correlations were obtained between serum creatinine (Scr) and the CL and between Scr and elimination half-life, no good correlations were obtained between Vd and Scr and between Vd and BW. Vd in infants and neonates was significantly less than that in adults (0.499±0.199 versus 0.717±0.0249L/h/kg, P<0.05). These results suggested that BW and Scr are useful parameters for developing a dosage guideline.

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We conducted a multicenter postmarketing clinical study to obtain arbekacin sulfate (ABK) pharmacokinetic parameters in children younger than 6 years, with the following results: Patients were divided into group A; neonates and low-birth-weight (LBW) infants (n=7) and group B; infants and children (n=3). A dose of 2-3 mg/kg of ABK was administered intravenously by infusion for 30 min, and pharmacokinetic parameters were obtained. Two LBW infants and one neonate were excluded because of infusion errors and administration of a steroid drug that may affect ABK efficacy. Maximum plasma concentrations (C_max) were 6.64±1.13 (μg/mL) for group A (n=4) and 7.91±1.43 (μg/mL) for group B (n=3), indicating no significant difference (p=0.2429). Steady-state volume of distributions (Vdss) were 0.382±0.045 (L/kg) and 0.304±0.060 (L/kg), and plasma half-lives (t_1/2) 3.20±0.91 (h) and 1.73±0.43 (h) for groups A and B. Although these were not significantly different between groups (p=0.1049 and 0.0515), group A means were larger. Total body clearance (Cl_tot) was 0.091±0.017 (L/h/kg) and 0.154±0.030 (L/h/kg) for groups A and B. The group B mean was significantly larger (p=0.0148). Predicted plasma concentrations 12 h after infusion (trough), calculated with ABK pharmacokinetic parameters, were 0.42±0.25 (μg/mL) and 0.05±0.04 (μg/mL) for groups A and B. ABK plasma concentration profiles of these children were similar to those of adults, which were recommended in consideration of clinical effects and safety.

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