We measured the minimal inhibitory concentrations (MICs) and minimal fungicidal concentrations (MFCs) of micafungin (MCFG), amphotericin B (AMPH-B), flucytosine (5-FC), voriconazole (VRCZ), itraconazole (ITCZ), miconazole (MCZ), and fluconazole (FLCZ) for 57 Candida strains isolated byblood cultures. In the experiment of viable cell counting, polysorbate 80 was added to the sterile saline in order to inhibit the aggregation of fungus cells, and to Sabouraud agar media, in combination with lecithin and histidine, to overcome the carryover effect of antifungal agents. MFC was defined as the lowest concentration of the drug that could kill 99% of viable cells. The MFC⁹⁰ values of MCFG and AMPH-B for C. albicans (14 strains), C.tropicalis (11 strains), and C.glabrata (14 strains) were 0.03 and 1 μg/mL, 0.125 and 0.5 g/mL, and 0.5 and 2 μg/mL, respectively. Furthermore, MCFG and AMPH-B exhibited superior fungicidal activity against azole-resistant C.albicans (one strain) and azole-resistant C.tropicalis (one strain). While theMIC₉₀ of VRCZ for 16 C. parapsilosis strains was 0.008 μg/mL, showing thegreatest growth-inhibitory activity, the MFCs of VRCZ for C. parapsilosis ranged from 0.03 to≥32 μg/mL, and the MFC of VRCZ was 32 μg/mL or more. In contrast, AMPH-B and MCFG showed marked fungicidal activity, and the MFC₉₀ of AMPH-B and MCFG for C.parapsilosis was 2 and 8 μg/mL, respectively. As compared to MCFG, AMPH-B showed more marked fungicidal activity against two C.guilliermondii strains. The MFC₉₀ of the azoles for Candida strainsbelonging to the five Candida species isolated could not be defined at the concentrations tested. Our results demonstrated that MCFG and AMPH-B exhibit superior fungicidal activity against medically important Candida strains isolated by blood cultures.

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Oral cephem antibiotics are commonly used to treat children with acute upper respiratory tract infection. We studied the efficacy, safety, and compliance of afive-day three-dose regimen of cefdinir (CFDN) fine granules at 15 mg/kg daily or cefcapene pivoxil (CFPN-PI) finegranules at 9 mg/kg daily. Because a new improved formulation of CFPN-PI fine granules was introduced by the manufacturer during the study, period we divided the study into period I from January to September 2004, and period II, from October 2004 to April 2006. In period I, CFDN fine granules were administered to 33 patients and CFPN-PI to 36 patients. In period II, each drug was administered to 50 patients. Therapeutic efficacy was calculated based on changes in body temperature and the rate of improvement in clinical symptoms. Efficacy was 100% for period I and 92% for period II in the CFDN group. and 100% for period I and 86% for period II in the CFPN-PI group. No significant difference was seen between groups. Soft stool and diarrhea were side effects noted in both groups. For the CFDN group, the incidence of side effects was 12% for period I and 18% for period II. For the CFPN-PI group, the incidence was 14% for period I and 32% for period II, with no significant difference between groups. When we examined compliance, all doses were taken without problem in 81% of the CFDN-treated patients in period I and 83% in period II, and in 57% of the CFPN-PI-treated patients in period I and 67% period II. Although the improved CFPN-PI fine granule formulation demonstrated better compliance than the older formulation, compliance was significantly better in the CFDN group than the CFPN-PI group (p<0.05). We therefore confirmed the high efficacy and safety of both CFDN fine granule and CFPN-PI fine granule formulations for the treatment of acute upper respiratory tract infections in children. We concluded that CFDN fine granules was a particularly useful therapy because compliance is an important consideration when treating younger children.

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This study retrospectively evaluated the influence of malignancy on the pharmacokinetics of arbekacin in 20 patients with malignancies (including 14 patients with lung cancers and 6 patients with other malignancies) as compared with that in 36 patients without malignancy. The pharmacokinetic parameters of arbekacin were estimated by the one-compartment model. No differences in arbekacin pharmacokinetics were seen in patients with malignancies as compared with that in those with no malignancy. No differences in arbekacin pharmacokinetics were seen in patients with one type of malignancy as compared with that in those with other types of malignancies. However, significant differences in arbekacin clearance were found between patients with no malignancy and those with lung cancers (0.0648±0.0355 versus 0.0828±0.0281 L/hr/kg [kmean±standard deviation], respectively; P<0.05).
Our data suggest that a pharmacokinetic difference exits for arbekacin in patients with lung cancer.

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The susceptibilities of Pseudomonas aeruginosa isolated from lower respiratory tract infections (402 strains) and urinary tract infections (215 strains) against various antibacterial agents were examined. The strains were clinically isolated between 2004 and 2005 at Toho University Omori Hospital.Susceptibility Rates (SR) were calculated according to break point of Clinical and Laboratory Standards Institute (CLSI). The SR tended to elevate overall compared to those we reported in 2003. The SR of major agent against strains isolated from lower respiratory tract infections and urinary tract infection (2004/2005, respectively) was: ceftazidime, 94.0%/91.6 % and 90.0%/81.9%; imipenem, 67.5%/75.5% and 80.9%/69.5 %; ciprofloxacin, 81.5%/85.6% and 76.4%/78.1 %; amikacin, 99.0%/99.0% and 94.5%/98.1 %. The decrease of SR of cephem antibiotics and the increase of multiply-resistant organism mainly isolated from urinary tract infection can be the subject of future discussions, which requires appropriate intervention.

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[in Japanese]

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