Mechanisms of resistance to fluoroquinolones in oral streptococci such as Streptococcus sanguis and Streptococcus anginosus were studied. S. sanguis QS-951 and S. anginosus QS-701, susceptible to ofloxacin, were serially transferred on agar, with each sample containing gradually increased concentrations of ofloxacin or DU-6859a. Although the resistances of these strains to fluoroquinolones were markedly induced with both drugs, MIC values of DU-6859a-induced resistant strains of S. sanguis QS-951 and S. anginosus QS-701 were 4-8 fold higher than those of ofloxacin-induced strains. The gyrA was analyzed to elucidate the mechanisms of resistance to fluoroquinolones in these strains. The mutation of serine at codon 83 to phenylalanine or tyrosine was found in each of the resistant strains and occurred by inductions with either ofloxacin or DU-6859a, and the additional mutation of glutamic acid at codon 87 to lysine was found in high-level resistant strains by induction with DU-6859a. Marked differences in types of gyrA mutation and in levels of resistance were found in the in vitro resistant strains of oral streptococci, when different kinds of fluoroquinolones were used as the inducers.

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We used agar-dilution MIC determinations to assess the activity of 41 antibacterial agents against various clinical isolates (19 Gram-positive cocci, 920 strains), which were isolated in 1996 at 16 facilities in Japan, and compared the results with those of similar studies in 1992 and 1994. We found that 60.4% of the strains of Staphylococcus aureus were methicillin-resistant S. aureus (MRSA). This high level frequency was equivalent to those found in 1992 and 1994. Vancomycin (VCM), arbekacin (ABK) and sulfamethoxazole-trimethoprim (ST) proved to have the highest antibacterial activity against these MRSA with an MIC₉₀ of less than 1.56μg/ml. The agants which showed higher antibacterial activity against Staphylococcus epidermidis were VCM, ABK and minocyclin (MIC₉₀≤1.56μg/ml). Most of the agants tested, includingβ-lactam antibiotics, demonstrated good antibacterial activity against Streptococcus pyogenes and Satreptococcus agalactiae. The rate of penicillin-resistant Streptococcus pneumoniae (PRSP) was 38.6%, which was equivalent to those rates reported in 1992 and 1994. We noted that carbapenems, VCM, cefpirome, cefditoren and cefcapene displayed a high level of antibacterial activity against PRSP (MIC₉₀≤0.39μg/ml). Also the agents which showed higher antibacterial activity against Enterococcus faecalis were ampicillin, ST, VCM and imipenem (MIC₉₀≤3.13μg/ml), while VCM proved to have the highest antibacterial activity against Enterococcus faecium with an MIC⁹⁰ of 0.78μg/ml. Finally, we found no strain highly resistant to VCM among any of the isolates of Gram-positive cocci tested including MRSA and Enterococcus species.

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We used agar-dilution MIC determinations to assess the activity of various antibacterial agents against clinical isolates (20 Gram negative aerobic bacteria, 1, 178 strains), which were isolated in 1996 at 16 facilities in Japan and compared the results with those of similar study in 1992 and 1994. Most cephems, carbapenems (CBPs), aztreonam, aminoglycosides (AGs) and new quinolones (NQs) exhibited high antibacterial activity against Escherichia coli, Klebsiella spp., Proteus spp. and Morganella morganii with an MIC₉₀ of less than 3.13 μg/ml. However, several strains highly resistant to NQs appeared among most bacterial species. One strain of β-lactamase non-producing Proteus mirabilis proved a resistance against most β-lactam antibiotics. NQs showed low activity against Providencia spp. with an MIC₉₀ of more than 25 μg/ml. The agents which demonstrated higher antibacterial activity against Citrobacter spp. and Enterobacter spp. were cefpirome (CPR), cefozopran (CZOP), CBPs, AGs and NQs. While CBPs, CPR, CZOP, and ceftazidime (CAZ) showed high antibacterial activity against Serratia marcescens with MIC₉₀ of 0.1-1.56μg/ml. Most agents exhibited high antibacterial activity against Haemophilus influenzae, Branhamella catarrhalis and Neisseria gonorrhoeae. However, the rate of NQs-resistant N. gonorrhoeae strains was accounted a high level at 62.5%.β-lactamase producing H. influenzae strains were detected at the rate of 18.8%, which was an increase compared with the 10.0% in 1992 and the 7.0% in 1994. The agents which demonstrated the highest antibacterial activity against Pseudornonas aeruginosa were tobramycin, ciprofloxacin, meropenem (MEPM), tosufloxacin (TFLX) and arbekacin with an MIC₈₀ of less than 6.25μg/ml. The rate of P. aeruginosa strains which showed sensitivity to all of the 11 anti-pseudomonal agents came to 14.1% in 1996, compared to 24.3% in 1992 and 32.8% in 1994. However, P. aeruginosa strains resistant to all eleven agents were detected in 4 strains, and strains resistant to 10 agents were detected in 6 strains. These fi ndings indicate an increase in the number of resistant agents against P. aeruginosa in 1996 as compared to 1992 and 1994. Agents which showed high antibacterial activity against Burkholderia cepacia with an MIC₉₀ of less than 6.25 μg/ml were CAZ and MEPM. Minocycline and TFLX exhibited the highest antibacterial activity against Stenotrophomonas maltophilia and Acinetobacter spp. with MIC₉₀ of 1.56μg/ml and 0.2μg/ml, respectively.

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We synthesized antisense oligonucleotides toward to immediate early pre-mRNA4/5 of herpes simplex virus type I (HSV-I). We've found that complementary sequences of splicing site possessed potent anti-herpetic activities in in vitro assay. Since sequences contatining consecutive G sequences showed sequence non-specific anti-herpetic activities, it might involve another mechanism other than antisense manner. In this study, we studied inhibitory effect of oligonucleotides on virus absorption onto the cell membrane. Virus yeild absorped onto the cell membrane were measeured by PCR technique. It was obviously recognized that phosphorothioate oligonculeotides showed inhibitory effect on virus absorption onto the cell membrane in the early phase of infection. This inhibitory effect was recognized in a range of 0.5-10 μM concentrations.

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