Haernophilus inituenzae numbering 215 clinical isolates were classified into 6 groups based on amino acid mutation in penicillin-binding protein 3, associated with β-lactam resistance. MICs of 24 β-lactam agents were determined for these isolates, and geomettic mean MICs were determined for each of six PBP 3 mutation groups. Cluster analysis was conducted for these 24 β-lactam agents using geometric mean MICs and agents were classified into three clusters reflecting antibacterial activity against H.influenzae including PBP3 substituted strains. Agents with strong activity against H.influenzae, i. e., meropenem, tazobactam piperacillin, and cefditoren, were classified into the same cluster. Increased ratios of geometric mean MICs involved with PBP 3 mutations were determined and modified as variables for cluster analysis. From the result of this analysis, many of β-lactam agents were classified into several clusters reflecting their chemical skeletons. Side chains at the C-7 position may be related to the clustering of cephalosporins. Cefditoren was uniquely ranked in this evaluation because its antibacterial activity would be barely affected by PBP: 3 mutations. Cluster analysis based on drug resistance mechanisms is thus useful for evaluating β-lactam agents.

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Antimicrobial susceptibility testing by chemiluminescence ATP assay is a new method for determining of minimum inhibitory concentrations (MICs) by the broth microdilution method.In this method bacterial ATP is measured by the luciferin-luciferase reaction.We tested 30 Staphylococcus aureus strains consisting of 15 methicillin-sensitive S.aureus (MSSA) strains, and 15 methicillin-resistant S.mimics (MRSA) strains for susceptibility to 12 antimicrobial agents and 15 Pseudomonas acruginosa strains for susceptibility to 7 antimicrobial agents and compared the results to those obtained by the standard broth microdilution method.chemiluminescece ATP assays were performed after incubating inoculated microdilution trays for 6 hr at 35°C.
In the result of the testing for MSSA, the rate of agreement between the results of the tests for ampicillin was only 60.0%. In addition to the result, the rate of agreement for ofloxacin was only 20.0%.The rates of agreement for MICs by the chemiluminescence ATP assay and standard broth microdilutionmethod for MSSA was high for all antimicrobial agents except ampicillin and ofloxacin.The rate of agreement for MICs by the same two methods for MRSA was also high. On the other hand, the rate of agreement for MICs by the two methods for P.aeruginosa was low.The MIC determination method by the chemiluminescence ATP assay was more rapidly than the standard broth microdilution method.The chemiluminescence ATP assay may be the most sensitive testing when we choose the combination a sort of bacteria and antimicrobial agent.

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The efficacy of gatifloxacin (GFLX) in acute bacterial sinusitis was examined based on drug sensitivity, clinical efficacy, safety, and tissue penetration. Prior to administration of GFLX, specimens were collected and the antibacterial activities of GFLX against 17 clinical strains of Streptococcus pneumoniae that were isolated from these specimens were inspected. Gatifloxacin was found to have a minimum inhibitory concentration (MIC₉₀) of 0.5μg/mL, indicating that GFLX has greater antimicrobial activity as compared to levofloxacin (LVFX), clavulanic acid/amoxicillin (CVA/AMPC), and cefcapene (CFPN), which have an MIC₉₀ of 1μg/mL. Fluoroquinolone antimicrobials-GFLX and LVFX-with an MIC₉₀μ0.06μg/mL, demonstrated the greatest bactericidal activity against 10 strains of Haemophilus influenzae. These fluoroquinolone antibiotics were also found to be the most active against 11 strains of Morafella catarrhatis (0.06μg/mL). An examination of the clinical efficacy revealed that GFLX was very effective with an actual efficiency of 21.6% and a significant efficacy of 86.3%. In addition, the safety of GFLX was established because none of the cases developed hypoglycemia and no serious adverse drug reactions were observed. The concentration of GFLX in nasal discharge was measured 1 to 12 h after GFLX was administered. The concentration ranged from 0.69 to 7.04μg g, indicating that GFLX had migrated into the pus at a concentration that was well over the of the S.pnotmoniac, H.influenzae, and M.catarrhalis isolates. Thus, GFLX has good tissue penetration ability. Our results suggest that GFLX is clinically very effective in treating acute bacterial sinusitis.

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Between February 2003 and May 2003, we conducted a clinical trial to evaluate the clinical efficacy of Gatifloxacin (GFLX) in acute sinusitis in adults. Subjects were 98 acute sinusitis patients, in 82 of whom clinical efficacy was evaluated. Based on the clinical conclusion, we administered GFLX for 7 days, with the following results:
1. Clinical efficacy was 78.6% in mild cases, 92.5% in moderate, and 78.6% in severe, with excellent good efficacy observed in 85.4%. Overall efficacy was assessed as excellent in 58 cases, good in 12, fair in 7, and poor in 5 cases.
2. Efficacy based on X ray findings was assessed as excellent in 35 cases, good in 20, fair in 13, and poor in 14, with efficacy rated as 82.9%(68/82).
3. MIC₉₀ of GFLX for main bacteria associated with acute sinusitis was 4μg/mL for Staphylococcus aurens, 0.5μg/mL for Streptococcus pneumoniae, 0.03μg/mL for Haemophilus influenzae, 0.5μg/mL for Streptococcus pyogenes, and 0.12μg/mL for Moraxella catarrhalis.
4. No side effects were observed.
We therefore conclude that GFLX is useful in treating acute sinusitis in the presence of bacterial resistance.

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Early postmarketing phase vigilance for pazufloxacin mesilate (PZFX) was conducted from September 2002 to March 2003 based on “Guidelines for Implementation of Early Postmarketing Phase Vigilance Surveillance for Prescription Drugs, etc.(December 27, 2000).”
We first organized information delivery to provide monthly updates on adverse drug reactions to physicians and pharmacists working at all hospitals where PZFX was used.
A total of 203 adverse drug reactions in 180 patients were reported. Serious adverse reactions (43), most of which were already reported for other new quinolones, such as ciprofloxacin and ofloxacin, were observed in 40 patients.
That is; the main serious adverse reactions were convulsion (5), tonic convulsion (1), interstitial lung disease (2), pseudomembranous colitis (2), hepatic function abnormal (4), liver disorder (3), hepatic failure (1), dermatitis medicamentosa (3), rhabdomyolysis (2), acute renal failure (2), amnia (1), renal failure (1), platelet count decreased (3) and thrombocytopenia (1).

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