The lipophilic yeast, genus Malassezia is a part of the normal cutaneous microflora of human and warm-blooded vertebrates. Species of the genera were re-classified to seven species; M. pachydermatis, M. globosa, M. furfur, M obtusa, M restricta, M. slooffiae and M. sympodialis. However, the means of species identification in conventional clinical laboratories have not been reported and the clinical significance of each species is not clearly understood. Species identifications of genus Malassezia which depend on the morphological, physiological characters are difficult and time-consuming. Recently, many molecular techniques have been developed for identification or typing of Malassezia. PCR-mediated methods, PCR-direct sequencing and nested-PCR using specific primers, are useful to identify the spices. The basic information obtained from these approaches have been contributing to the understanding of these pathogenic yeasts and related diseases.

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A questionnaire survey on the theory of postoperative infection prophylaxis was conducted to obtain the consensus on perioperative antimicrobial use among urologists in Japan in the period from April to July 2000. Sixty-three of the 87 urologists replied, and the following consensus was obtained. An antimicrobial prophyaxis (AMP) agent should be chosen based on their efficacy against the pathogens expected to be contaminants, such as Escherichia coli, Staphylococcus spp., Klebsiella pneumoniae and Bacteroides fragilis group. Use an AMP agent that achives a bactericidal concentrations in both the serum and operating site. Use an AMP agent that has little unfavourable side effects. The newer agents should be considered as a therapeutics for postoperative infections. The therapeutic antimicrobial agents having no cross-resistance to the AMP agents should be used, if postoperative infection is suspected or developed. The most commonly used agent for clean operations are cefazolin (CEZ), followed by cefotiam (CTM) and piperacillin (PIPC), in this order. For clean-contaminated operations, the most commonly used agent is CTM, followed by PIPC and CEZ.

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We examined antibacterial activities and PK/PD parameters of six kinds of aminoglycosides against seven bacterial species of clinical isolates in 2001. Aminoglycoseides examined were gentamicin (GM), dibekacin (DKB), tobramycin (TOB), amikacin (AMK), netilmicin (NTL), and isepamicin (ISP), and bacterial isolates used were each 50 strains ofEscherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Citrobacter freundii, Proteus spp., Serratia marcescens andPseudomonas aeruginosa.
All aminoglycosides showed good activities with low MICs against 6 species of Enterobacteriacea exceptS. marcescens. Eight strains (3.2%) among them were resistant to one or more aminoglycosides. Resistance to multiple aminoglycosides were detected in 16 strains (32%) ofS. marcescens, among which 13 strains were resistant to AMK but susceptible to ISP.
Three (6%) strains ofP. aeruginosa were resistant to multiple drugs, one of which was resistant to all six aminoglycosides, and others were moderately susceptible to AMK and ISP, and susceptible to GM, AMK and ISP.
Using a ratio of peak serum concentration to MIC₉₀ (C_max/MIC₉₀) or a ratio of area under the curve to MIC₉₀ (AUC/MIC₉₀) as a pharmacokinetic and pharmacodynamic (PK/PD) parameter, we estimated the efficacy of the drug.
An excellent effect of ISP, which was injected intramuscularly or intraveneously at a dose of 400 mg, was expected for strains of Enterobacteriacea exceptS. marcescens. The C_max/MIC₉₀ ratios forS. marcescens were comparably higher in GM and ISP and that forP. aeruginosa were rather high in TOB when compared to other aminoglycosides. Another PK/PD parameter, AUC/MIC₉₀ ratio, was high enough in NTL and ISP for Enterobacteriacea, suggesting good efficasy of these drugs. The (AUC/MIC₉₀) ratios forS. marcescens were comparbly high in GM and ISP, and that forP. aeruginosa were high in TOB, DKB, and ISP.

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We determined the minimum inhibitory concentration (MIC) of various antimicrobial agents against 108 strains of Streptococcus pneumoniae and 144 strains of Haemophilus influenzae isolated from respiratory organs in the First Department of Internal Medicine, Shinshu University, and affiliated hospitals between January 2000 and February 2001.
The following results were obtained.
1. Fifty-one (47.2%), 56 (51.9%), and 1 (0.9%) of 108 strains of S. pneumoniae were classified as penicillin-susceptible S. pneumoniae (PSSP), penicillin-intermediate S. pneumoniae (PISP), and penicillinresistant S. pneumoniae (PRSP), respectively.
2. Three carbapenems had potent antimicrobial activity against PISP and PRSP. Furthermore, none of the strains were highly resistant (MIC>2μg/ml) to benzylpenicillin, ampicillin (ABPC), sulbactam/ampicillin (SBT/ABPC), cefotaxime (CTX), or cefepime (CFPM).
3. Eleven (7.6%) and 6 (4.2%) of 144 strains of H. influenzae were classified as β-lactamase-producing ABPC-resistant strains and β-lactamase negative ABPC-resistant H. influenzae (BLNAR), respectively. Levofloxacin, sulfamethoxazole/trimethoprim, and meropenem had potent antimicrobial activity against these resistant strains.
4. BLNAR strains were more highly resistant to CTX, CFPM, SBT/ABPC, and cefaclor than β-lactamase-producing strains.
5. In our surveillance study regarding clinical isolates of S. pneumoniae and H. influenzae from respiratory organs in Nagano prefecture, there were regional differences in the isolation rate and antimicrobial susceptibility. The isolation rates of resistant strains were lower than those reported in a nationwide survey.

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From October 2000 to September 2001, we collected the specimen from 410 patients with lower respiratory tract infections in 16 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various antibacterial agents and antibiotics and patients' characteristics. Of 499 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in inflammation, 493 strains were investigated. The breakdown of the isolated bacteria were: Staphylococcus aureus 78, Streptococcus pneumoniae 73, Haemophilus infiuenzae 99, Pseudomonas aeruginosa (non-mucoid) 64, P. aeruginosa (mucoid) 14, Klebsiella pneumoniae 25, Moraxella subgenus Branhamella catarrhalis 21, etc.
Of 78 S. aureus strains, those with 4 μg/ml or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) occupied 53.8%. Vancomycin and arbekacin had the most potent activities against MRSA as observed in 1999. The frequency of S. pneumoniae exhibiting low sensitivity to penicillin (penicillin-intermediate S. pneumoniae: PISP+penicillin-resistant S. pneumoniae: PRSP) was 38.4% being consistent with that in 1999 (34.7%). PRSP accounted for 11.0% of the total, being more than that in 1999 (3.0%). Carbapenems had strong activities against S. pneumoniae. Especially, panipenem inhibited the growth of all 73 strains at 0.125 μg/ml. Generally, all drugs had strong activities against H. infiuenzae with MIC₈₀s of 8 μg/ml or less. The drug that had the strongest activity against H. infiuenzae was levofloxacin, which inhibited the growth of 94 of the 99 strains at 0.063 μg/ml. Tobramycin had a strong activity against P. aeruginosa (both mucoid and non-mucoid) with MIC₈₀ of 1 μg/ml. The mucoid strain was little isolated (14 strains) but the susceptibilities to all drugs were better than the non-mucoid strain. K. pneumoniae showed good susceptibilities to all drugs except ampicillin and the MIC₈₀s were 2 μg/ml or less. Particularly, cefpirome, cefozopran, and levofloxacin had strong bactericidal activities against K. pneumoniae with MIC₈₀s of 0.125 μg/ml, and cefotiam, second-generation cephems, also had a favorable activity being MIC₈₀ of 0.25 μg/ml. Also, all drugs generally had strong activities against M.(B.) catarrhalis. MIC₈₀s of all drugs were 2 μg/ml or less. The drug having the strongest activity was imipenem and levofloxacin inhibiting all 21 strains at 0.063 μg/ml.
Most of the patients with respiratory infection were aged 70 years or older, accounting for approximately a half of the total (44.4%). As for the incidence by the diseases, bacterial pneumonia and chronic bronchitis were the highest, being noted in 38.0% and 31.7% of all the patients, respectively. The bacteria frequently isolated from the patients with bacterial pneumonia were S. aureus (18.3%) and S. pneumoniae (16.1%). In contrast, H. infiuenzae (20.4%) and P. aeruginosa (both mucoid and non-mucoid: 16.7%) were frequently isolated from the patients with chronic bronchitis. Before the drug administration, the bacteria frequently isolated from all the patients were S. pneumoniae (24.3%) and H. infiuenzae (26.7%). The frequency of isolated S. pneumoniae tended to decrease with the increase in the number of administration days while that of isolated H. infiuenzae did not. The frequency of isolated P. aeruginosa tended to increase with the duration of administration. The isolated bacteria were comparable between the patients already treated with penicillins and cephems. In the patients treated with aminoglycosides, macrolides, and quinolones, P. aeruginosa was most frequently isolated (33.3 to 40.0%).

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The bacteria (Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Klebsiella spp. and Pseudomonas aeruginosa) isolated from patients diagnosed as having urinary tract infections (UTIs) in 10 institutions in Japan were supplied between August 2000 and July 2001. Then, the susceptibilities of these bacteria to various antimicrobial agents were examined, and the results were compared with those obtained between 1992 and 1999. Comparison was made by classifying strains isolated from patients into those in uncomplicated UTIs and those in complicated UTIs (including with or without indwelling catheter).
E. faecalis showed good susceptibility to ampicillin (ABPC) and imipenem (IPM), and the MIC₉₀s were 2 μg/ml. Also, E. faecalis showed good susceptibility to vancomycin (VCM). However, the MIC₉₀, which was 2 μg/ml between 1992 and 1999, rose to 4μg/ml in patients with complicated UTIs because the strains inhibited at 4μg/ml increased more than before. The low susceptibility of S. aureus to arbekacin (ABK) in complicated UTIs, as shown in 1998 and 1999, recovered in 2000, and no strains inhibited at_??_4μg/ml were detected. E. coli showed good susceptibility to CTM (MIC₉₀: 0.25-0.5μg/ml) and CZOP (MIC₉₀:_??_0.125μg/ml) and was not resistant to those. E. coli also showed good susceptibility to the other drugs except to penicillins. Decreases in susceptibility of E. coli to quinolones, ciprofloxacin (CPFX), and sparfloxacin (SPFX) were observed in the patients with complicated UTIs. The susceptibility of Klebsiella spp. to all drugs did not significantly change in 2000 and was generally good except to penicillins. Although the susceptibility of P. aeruginosa to carbapenems was notable, the MIC₉₀ went up from 4μg/ml to 16μg/ml in complicated UTIs compared with those observed in the previous year.

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Pharmacokinetics, clinical efficacy and safety of teicoplanin (TEIC) were evaluated in pediatric and neonate patients with MRSA sepsis in the dosages approved in overseas. The administrateddose for pediatrics patients was 10mg/kg once at hour 0, 12 and 24, followed by every 24 hours intervals. In neonates patients, first dose was 16 mg/kg, then 8 mg/kg every 24 hours intervals.
1. Pharmacokinetic results
All 17 patients (9 neonates and 8 pediatrics) who received TEIC were evaluated for pharmacokinetics. Trough concentrations were analyzed in 16 patients (9 neonates and 7 pediatrics) excluding one patient for lack of measurement of drug concentration at day 7. No patient with a concentration exceeding 60μg/mL in peak or trough concentrations were reported. Mean concentrations in trough at day 3, 4 and 7 in neonates were 15.2, 14.7 and 17.8μg/mL, and in pediatrics were 12.5, 12.2 and 13.1μg/mL, respectively. These results were similar to those reported in foreign pediatrics and neonates patients.
2. Efficacy and safety results
Since no patient was excluded, all patients were evaluated for efficacy and safety. Microbiological efficacy as well as clinical cure were secondarily evaluated in 2 patients for whom MRSA was isolated from blood.
Clinical efficacy rate was 76.5% (13/17) and number of cases in judgments of excellent, good, fairly improved and no change were 12, 1, 3 and 1 cases respectively. The patients for whom MRSA was isolated from blood were judged as MRSA eradicated case and cured without any additional anti-MRSA drugs.
Adverse events were reported in 2 neonates and 3 pediatric patients. Possibly related adverse events to study drug (adverse drug reactions) were: 1 case of respiratory disorder, thrombocythemia, γ-GTP increased, GOT increased and GPT increased in 3 pediatrics.
These results suggest that an application of overseas dose regimen of TEIC for neonate and pediatrics is appropriate in Japan.

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