Given the importance of nationwide infectious disease control and prevention, the Japanese Society of Infectious Diseases and the Japanese Society of Chemotherapy are currently educating clinicians and medical staff to build up skill and knowledge. Evaluating the status of residents' education in infectious disease and chemotherapy is a key to this process, so we sent out questionnaires to major Kanto area hospitals. Results indicated that residents lacked satisfactory training in infectious disease and chemotherapy, making it necessary for societies to develop on going education by, for example, holding educational conferences, publishing standard texts on infectious disease and use of antimicrobial agents, and training specialists in infectious disease (ID doctors). To this end, Divisions of Infectious Diseases and Chemotherapy should made independent of other divisions in the clinical and education fields and their presence required in all medical schools and major hospitals.

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We isolated 83 Pseudomonas putida strains in the 5 years from January 1997 through December 2001 at Gunma University Hospital. The sample was free of patient duplication. Among them, 27 isolates were resistant to imipenem (IPM), 22 of which were of urine origin. None was isolated from respiratory specimens. Most IPM-resistant isolates were strains multiply resistant to piperacillin, ceftazidime, amikacin, and norfloxacin. The IMP metallo-β-lactamase gene (bla_IMP) was identified by PCR from all 27 IPM-resistant strains, which were derived from different 8 wards. We focused on 13 bla_IMP-bearing P. putida strains of a ward, 9 isolated from inpatients and 4 detected from around the water pipe. The longterm residence of bla_IMP-bearing P. putida strains, identified as the same strains with pulsed-field gel electrophoresis (PFGE) patterns and MIC patterns as for 10 drugs, was observed in both inpatients and the ward environment. From 9 of the 13 strains, the bla_IMP gene was effectively transferred to a recipient strain of Pseudomonas aeruginosa, conferring resistance to IPM and other β-lactams concomitantly with amikacin resistance; 4 of the 9 strains conferred additional resistance to gentamicin and tobramycin.

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Comparative antibacterial activities of several antimicrobial agents against 41 strains of Streptococcus pneumoniae were studied. The minimum inhibitory concentrations (MIC) of benzylpenicillin (PCG), cefotaxime (CTX), ceftriaxon (CTRX), cefditoren (CDTR), cefpodoxime (CPDX), cefdinir, imipenem (IPM), meropenem (MEPM), ofloxacin, ciprofloxacin, levofloxacin, sparfloxacin (SPFX), and linezolid were determined using the E-test and Mueller Hinton agar with 5% sheep blood. Variations in the genes for penicillin-binding protein were studied using polymerase chain reaction. The MIC of PCG ranged from 0.032μg/mL to 4μg/mL. Nine, twenty, and twelve strains were penicillin-resistant S. pneumoniae, penicillin-intermediate S. pneumoniae and penicillin-susceptible S. pneumoniae, respectively. The MIC of CTX ranged from 0.032μg/mL to 4μg/mL. The MIC of CTRX ranged from 0.016μg/mL to 1μg/mL. The MIC of CDTR ranged from 0.032μg/mL to 2μg/mL. The MIC of CPDX ranged from 0.032μg/mL to 8μg/mL. The MIC of IPM and MEPM ranged from 0.008μg/mL to 0.25μg/mL and from 0.008μg/mL to 0.5μg/mL, respectively. The MIC of SPFX ranged from 0.125μg/mL to 1μg/mL. Linezolid was the most active agent against these strains, with an MIC ranging from 0.5μg/mL to 1μg/mL. Twenty-one strains exhibited genetic variations at pbp 1a+2x+2b. Three strains exhibited genetic variations at pbp 1a+2x. One and 13 strains exhibited genetic variations at pbp 1a and pbp 2x, respectively. Three strains did not exhibit any genetic variations.

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Arbekacin sulfate (ABK), an aminoglycoside antibiotic, has been approved for use in pediatric patients, although its precise pharmacokinetics have not been evaluated due to patient growth and development. We analyzed ABK pharmacokinetics in infants and children by a pharmacokinetic analysis program with the Nonlinear Mixed Effects Model (NONMEM) to estimate population pharmacokinetic parameters. Data was collected retrospectively from 37 subjects 2 months to 17 years old, who received ABK on admission to the pediatric ward of Kitasato University Hospital and who underwent therapeutic drug monitoring. Population pharmacokinetic parameters were calculated and pharmacokinetic variation factors of ABK analyzed with clearance (CL_ABK) and volume of distribution (Vd_ABK) as pharmacokinetic parameters of the 1-compartment model, using ADVAN 1 and TRANS 2 subroutines. A relative deviation model was used to determine of intersubject variance, and an absolute deviation model for intrasubject variance. Blood concentration samples totaled 80. At a mean dosage of 3.5 mg/kg/dose, blood concentration at 1 hour after the start of drip infusion was 1.5 to 23.5 mg/L and the trough concentrations was 0.4 to 2.8 mg/L. The average CLABK for all subjects, obtained in a basic model of NONMEM analysis, was 0.140 ± 0.09 (L/h/kg), and the average Vd_ABK was 0.47±0.16 (L/kg). CL_ABK depended on serum creatinine (Scr), and CL_ABK changes due to aging correlated well with logarithmic function. VdABK started gradually decreasing in infants, which correlated well with exponential function, and ended up at 0.3 L/kg in adults. ABK population pharmacokinetic parameters were finally estimated at: CLABK=0.146Ln(wt)÷Scr(L/h), Vd_ABK=(0.334+0.11Age^0.536)×wt (L)

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Trichlosan (2, 4, 4'-trichloro-2'-hydroxy diphenyl ether) inhibited growth in all test fungus strains in vitro. Furthermore, the inhibitory effects of a combination therapy, consisting of trichlosan, urea and only a small amount of sulfate, were markedly more potent than those of trichlosan alone. These results suggest that bacteriostatic trichlosan enhances antifungal actions via its synergistic effects with urea.

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