Enterococcus faecalis and Enterococcus faecium isolates that are resistant to vancomycin have recently been identified in North America and Europe. We investigated the susceptibility to antimicrobial agents against 51 clinical isolates of enterococci (9 vancomycin-resistant E. faecalis, 16 vancomycin-resistant E. faecium and 26 vancomycin-susceptible E. faecalis). Ampicillin, piperacillin, imipenem, minocycline and teicoplanin were more effective than other antibiotic agents against vancomycin-resistant E. faecalis. RP 59500, minocycline chloramphenicol were more effective than other antibiotic agents against vancomycin-resistant E. faecium. Among 25 strains of Enterococcus spp., either vanA or vanB gene was detected in 9 and 16 strains, respectively, by the PCR method. The strains possessing vanA gene are resistant to vancomycin (MIC; 50-800μg/ml) and teicoplanin (MIC; 6.25-100μg/ml). The strains possessing vanB gene are resistant to vancomycin (MIC; 6.25-200μg/ml) but susceptible to teicoplanin (MIC;<0.2-0.39μg/ml).

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Arbekacin (ABK)-highly resistant mutants were isolated from methicillin-resistant Staphylococcus aureus (MRSA) of clinical isolates which showed low resistance (1.56μg/ml of MIC) or sensitivity (0.78μg/ml of MIC) to ABK. The mutants derived from gentamicin (GM)(25μg/ml to 100μg/ml of MIC) and tobramycin (TOB) resistant strains expressed ABK resistance at a level of 12.5μg/ml or 25μg/ml of MIC, and at highly GM resistant levels equal to or exceeding 200μg/ml. Plasmid pMS 91 is a laboratory plasmid and confers GM (100μg/ml of MIC) and TOB (800μg/ml of MIC) resistances but is sensitive to ABK (0.78μg/ml of MIC) in S. aureus, and encodes a determinant for bifunctional aminoglycoside modifying enzymes of 6'-aminoglycosides acetyltransferase (AAC (6')) and 2''-aminoglycosides phosphotransferase (APH (2'')). ABK resistant mutants were isolated from S. aureus MS353 carrying pMS91, and the mutants expressed ABK and GM resistances at a level of 25μg/ml, and at levels equal to or exceeding 200μg/ml of MIC, respectively. The amount of the aminoglycoside modifying enzyme AAC (6')/APH (2'') in the mutant strain was six times more than that of the parent strain. The relative enzyme activities to ABK of the parent and mutant strains were 2% that of kanamycin (KM). These results indicate that the ABK-highly resistant mutant of GM-TOB resistant S. aureus resulted from an increased amount of the aminoglycoside modifying enzyme of AAC (6')/APH (2'').

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The distribution of β-lactam-antibiotic-resistant bacteria among normal oral microbial flora and the transfer of β-lactam-resistance factor were examined to assess the mechanism of occurrence of β-lactam-resistant bacteria in odontogenic infection. When an attempt to detect β-lactam-resistant bacteria among the normal flora was made in saliva by culturing on selective medium containing 32μg/ml cefaclor (CCL), they were found in all subjects tested. Ninety-one isolates of gram-negative rods isolated from the saliva were almost all black-pigmented gram-negative rods and included Prevotella melaninogenica and Prevotella intermedia, and 88 strains (96.7%) of β-lactamase producers were detected. The MIC₉₀s of CCL and Eunpicillin against anaerobic gram-negative rods were the highest among the β-lactams used, ≥256μg/ml. The MIC₉₀s of ceftizoxime, cefteram, cefazolin and latamoxef were moderate, 16-128μg/ml, and those of cefmetazole and imipenem were 2 and ≤0.25μg/ml, respectively.β-lactam-resistance factor was transferredfrom β-lactamase producer/β-lactam-resistant P. intermedia T5001 isolatedfrom odontogenic infection to β-lactamase non-producer/β-lactam-sensitive Bacteroides capillosus K8085 by the filter-mating procedure. The frequency of transfer was 7.9×10^-5. Five transconjugants isolated were β-lactamase producers and exhibited β-lactam-resistance. However, it was impossible to detect the donor, recipient and transconjugants with plasmids. These findings suggest that the presence of β-lactam-resistant bacteria among normal oral microbial flora, and the transfer of β-lactam-resistance factor from β-lactam-resistant strains to sensitive strains are involved in the occurrence of β-lactam-resistant bacteria in odontogenic infection. It also appears that β-lactam-resistance factor is present in the chromosomal DNA.

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Lomefloxacin (LFLX) concentrations in human serum, gingiva, mandibular bone, and dental follicles following a single oral administration of LFLX (200 mg) were studied. The mean concentrations in serum, gingiva, mandibular bone, and dental follicles peaked at identical times, 3 h after administration, and were 1.37μg/ml, 2.24, 0.77, and 1.77μg/g, respectively. The mean concentration ratios of gingiva/serum, mandibular bone/serum, and dental follicles/serum at the peak time were 1.60, 0.58, and 1.22, respectively. All or most of the lomefloxacin concentrations in gingiva.(2/3 cases), mandibular bone (all), and dental follicles (4/5 cases) did not exceed the MIC₈₀ of clinically isolated strains of oral streptococci. As the present results were obtained after a single dose study, however, higher concentrations of LFLX in oral tissues would be expected after a multiple dose study.

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We studied the clinical efficacy of sparfloxacin (SPFX), a new quinolone antibacterial agent, in patients with chlamydial respiratory infection. The results obtained were as follws:
1) SPFX was administered orally to 97 patients suspected of having chlamydial respiratory infection at a dosage of 200 mg divided into 1-2 times a day for 3 to 14 days. Out of the 97 patients enrolled in this study 21 were confirmed to have chlamydial infection.
2) Of these 21 patients 18 with pneumonia, acute bronchitis, or bronchial asthma with infection were evaluated for clinical efficacy, and the clinical efficacy rate was 88.9%(16/18).
3) The cumulative clinical efficacy rates of “excellent” and “good” against Chlamydia pneumoniae, Chlamydia trachomatis and Chlamydia sp. were 77.8%, 100% and 100%, respectively.
4) C. pneumoniae was isolated from one patient and eradicated after administration of SPFX.
5) Side effects such as nausea, vomiting, headache, diarrhea and fever were observed in 11 (11.6%) out of 95 cases evaluated for safety.
6) Abnormal laboratory findings, such as elevation of S-GPT and eosinophiles were observed in 8 (8.9%) out of 90 cases evaluated. However, all side effects and abnormal laboratory findings were mild or moderate and transient.
Based on these results, we conclude that SPFX is a very useful quinolone for chlamydial respiratory infections.

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A dose-finding study on pazufloxacin (PZFX), a new quinolone antibacterial agent, was conducted to determine the optimal dose of PZFX using ofloxacin (OFLX) as the active control for treatment of complicated urinary tract infections without indwelling catheters and a history of prostatectomy. PZFX was orally administered at doses of 100 mg t. i. d.(PZFX-300 group) and 200 mg t. i. d.(PZFX-600 group) for 7 days, while OFLX was given at a dose of 200 mg t. i. d.(OFLX group). The clinical efficacy of the drug was evaluated according to the criteria proposed by the Japanese UTI Committee.
1) Of a total number of 108 patients (36 in the PZFX-300 group, 39 in the PZFX-600 group and 33 in the OFLX group), 85 patients (31, 28 and 26 in the PZFX-300, PZFX-600 and OFLX groups, respectively) were evaluated for dinical efficacy.
2) The overall clinical efficacy rates were 84%(26/31), 89%(25/28) and 77%(20/26) in the PZFX-300, PZFX-600 and OFLX groups, respectively.
3) Bacteriological elimination rates of isolated bacteria were 87%(4V47), 90%(35/39) and 82%(32/39) in the PZFX-300, PZFX-600 and OFLX groups, respectively.
4) Adverse drug reactions were found in 2 cases (6%) out of 36 cases in the PZFX-300 group and in 2 cases (6%) out of 33 cases in the OFLX group, and there were no adverse reactions in the PZFX-600 group. Abnomal laboratory changes were found in 1 case (3%) of 32 cases in the OFLX group. However none of the adverse reactions were serious.
5) The rates of usefulness as determined by the presiding doctors, were 87%(27/31), 81%(21/26) and 89%(24/27) in the PZFX-300, PZFX-600 and OFIX groups, respectively. There was no significant difference in the overall clinical efficacy, bacteriological response and safety between PZFX-300 and PZFX-600 groups. From the above results, our conclusion is that the range of optimal daily dose of PZFX in the treatment of complicated urinary tract infections is 300-600 mgday (3 divided doses).

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