We examined the susceptibilities to antimicrobial agents of Streptococcus pneumoniae (200 strains) isolated from children in Kurume University Hospital (UH), riferring hospitals (RH) and practitioner's offices (P0) from January 1981 to December 1992. Seventy four strains (37.0 %) were resistant to benzylpenicillin (PCG)(MIC≥0.1Eug/ml) and highly-resistant strains (MIC≥1.56μg/ml) a ccounted for 22.5% of the total. No strains were resistant to four carbapenems (imipenem, meropenem, panipenem, biapenem), vancomycin and rifampicin. The first strain of penicillin-resistant strain in UH was isolated in 1985, and those were progressively increased, withyears.There were no significant differences in the ratio of the resistant strains among specimens or among institutions (UH, RH, P0). From our results it is cinsidered that antibiotics for bacterial meningitis due to penicillin-resistant S. pneumoniae at present time are either panipenem/betamipron or combination of cefotaxime or ceftriaxone plus vancomycin.

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The effect of a sub-minimum inhibitory concentration (sub-MIC) on infectious activity of type I pili-bearing Escherichia coli in murine pyelonephritic infection was studied. The infectivity dropped when the TUH 9501 strain of E. coli was incubated with 1/4 MIC of quinolones such as ciprofloxacin, fleroxacin, sparfloxacin and levofloxacin. The level of decrease in infectivity was highest following treatment with fleroxacin and levofloxacin. A siginificant reduction in the level of type I pili and in resistance to phagocytosis and the killing activity of human polymorphonuclear leucocytes were associated with these drug treatments at sub-MIC, which decreased in murine pyelonephritic infectivity comparing to untreated control. In murine pyelonephritic infection the therapeutic effect of levofloxacin was decreased due to longer administration interval, however, the therapeutic effect of fleroxacin was almost unaffected by an increase in the administration interval. Analysis of the pharmacokinetic parameters of 4 test drugs in kidneys indicates that area under the curve in sub-MIC area may influence the therapeutic effect.

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Staphylococcus aureus N 315 is a preMRSA which is relatively sensitive to many β-lactam antibiotics owing to its possesion of the mec regulator genes mecRI and mecI, which encode a signal transducer and repressor, respectively, upstream from mecA, which encodes penicillin-binding protein (PBP) 2'. This strain harbors a β-lactamase plasmid which contains blal and blaZ, repressor and structural genes, respectively, of β-lactamase. S. aureus N 315-LR 5 P, a derivative of N 315, has a mutation in mecI and lacks blaI and blaZ. It was found to be resistant to methicillin (DMPPC), imipenem (IPM) and ceftizoxime (CZX). S.aureus N 315-HR 3 P, which has an additional unknown mutation, was resistant to cefpirome (CPR) and cefepime (CFPM) as well as DMPPC, IPM and CZX. Both mutants, however, showed almost the same sensitivity to cefozopran (CZOP) as N 315. CZOP inhibited [¹⁴C] benzylpenicillin binding to PBP 2' of S.aureus N 315 P-ZR, which lacks β-lactamase and produces PBP 2' constitutively; the IC₅₀ value was 43μg/ml. The affinity of CZOP for PBP 2' was equal to that of CPR, 6 times higher than that of CFPM and IPM, and more than 70 times higher than that of CZX. CZOP had a bacteriostatic effect on S. aureus N 315-HR 3 P at 1 and 10μg/ml, concentrations lower than the IC₅₀ for PBP 2', and was bactericidal at more than the IC₅₀. These findings suggest that preMRSA becomes resistant β-lactam antibiotics with low affinity for PBP 2' by the mecI mutation converting the organism to a constitutive producer of PBP 2', and that additional mutations are necessary to become resistant to antibiotics with higher affinity for PBP 2'.

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The clinical efficacy of pazufloxacin (PZFX) on the treatment of patients with bacterial pneumonia and/or lung abscess were evaluated in double-blind study by multi-institutional system in Japan with tosufloxacin (TFLX) as the control drug. PZFX was given orally at a daily dose of 600mg, and TFLX at a daily dose of 450mg three times daily for 14 days as a rule. The following results were obtained.
1. The test drug were administered to a total of 193 patients with bacterial pneumonia or lung adscess, consisting of 95 in the PZFX group and 98 in the TFLX group. The clinical efficacy was evaluated in 75 of the PZFX group and 87 of the TFLX group, the overall gafety was evaluated in 90 of the PZFX group and 93 of the TFLX group, and the usefulness was evaluated in 77 of the PZFX group and 87 of the TFLX group. There was no significant bias among patient's background factors between the two groups except “duration” and “chest X-ray findings”. However, no influence on the drug evaluation from these bias was verified from the viewpoint of statistical analysis test.
2. The clinical efficacy rates for bacterial pneumonia and lung abscess were 94.7% in the PZFX group (71/75) and 93.1% in the TFLX group (81/87), with no statistically significant difference in x²-test between both groups. However the clinical equivalency of PZFX to TFLX was demonstrated atΔ=5%.
3. The bacteriological elimination rate of isolated bacteria was 90.0% in the PZFX group (27/30) and 93.8% in the TFLX group (30/32). There was no significant difference between both groups.
4. Side effects were noted in 6 patients (6.4%) in the PZFX group and 5 patients (5.2%) in the TFLX group, and the main symptoms were central nervous system disorders (1 case in the PZFX group, 2 cases in the TFLX group) and gastrointestinal symptoms (5 cases in the PZFX group, 2 cases in the TFLX group).
5. Abnormal changes in laboratory findings were seen in 15.7% in the PZFX group (14/89) and 21.7% in the TFLX group (20/92), and showed no significant difference between both groups. Main items of them were eosinophilia (5 cases in the PZFX group, 8 cases in the TFLX group) and GPT and/or GOT elevation (5 cases in the PZFX group, 6 cases in the TFLX group).
6. “Safe” in overall safety was 80.0% in the PZFX group (72/90) and 74.2% in the TFLX group (69/93). There was no significant difference between both groups.
7. “Useful and better” judged in each case was 92.0% in the PZFX group (69/75) and 89.7% in the TFLX group (78/87), indicating a high usefulneess in both groups, and no significant differences was observed between both groups.
From aboves, it may be concluded that PZFX is one of the highly effective drugs for the treatment of bacterial pneumonia.

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As an objective assessment of the efficacy of pazufloxacin (PZFX), a double-blind study between tosufloxacin (TFLX) and PZFX for chronic airway infections was performed by multi-institutional system in Japan. Six hundred mg daily dose of PZFX or 450 mg daily dose of TFLX was orally given for the patients with acute exacerbation of chronic airway infections for 14 days as a rule.
The following results were obtained.
1. The total number of patients enrolled in the study was 100 for PZFX group and 102 for TFLX group, and 13 patients were excluded from evaluation on clinical efficacy.
2. The clinical efficacy rates were 87.1% in the PZFX group (81/93) and 78.1% in the TFLX group (75/96), with no significant differences between both groups. However the clinical equivalency of PZFX to TFLX was demonstrated at Δ=10%.
3. The bacteriological elimination rate of isolated bacteria was 67.6% in PZFX group (25/37) and 83.3% in TFLX group (40/48). There was no significant difference between both groups.
4. Side effects were observed in 4.1%(4 cases) in the PZFX group (4/97) and in 4.0%(4 case) in the TFLX group (4/101). The main symptoms were mild headache (1 case in the PZFX group), giddiness (1 case in each two groups) and gastrointestinal symptoms (2 cases in the PZFX group, 3 cases in the TFLX group). However no severe side effects were seen.
5. Abnormal changes in laboratory findings were seen in 2.3% in the PZFX group (2/88) and 8.4% in the TFLX group (8/95). Most of them were mild GPT or GOT elevation (2 cases in the PZFX group, 3 cases in the TFLX group). There was no significant difference between both groups.
6. “Virtually safe and better” in overall safety was 100% in the PZFX group (88/88) and 96.9% in the TFLX group (93/96). There was no statistical significance.
7. “Useful and better” judged in each case was 87.1% in the PZFX group (74/85) and 76.8% in the TFLX group (73/95). However, there was no significant difference between both groups.
From aboves, it may be concluded that PZFX is one of the most effective oral antimicrobial agents for the treatment of patients with chronic airway infections, without any remarkable side effects as well.

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