For macrolide antibiotic resistance on the clinical isolates, it is enough to remember only that (1) macrolide antibiotics come to be unable to bind to ribosome and become resistant due to the modification of the ribosomal target site in the 23 Sr RNA in the 50 S subunit of 70 S ribosome by N6, N6dimethylase, before 30 years. Recently, however, the macrolide resistance mechanism has diversified due to the various kinds of macrolide development starting from erythromycin. Macrolide-resistant strains have evolved extremly by using large amounts of macrolides and new macrolides. The details of the dimethylational mechanism and new resistance mechanisms come to light together with the advance of recent study using biotechnology. Addition to these resistance mechanism are known as follows.:(2) basic mutation of multiple sites in the 23 Sr RNA, (3) mutation of ribosomal protein in the 50 S subunit and elsewhere, (4) macrolide efflux protein, (5) changes in macrolide permeability, (6) inactivation of erythromycin esterase, (7) macrolide 2'-phosphotransferase, (8) inactivating mechanism due to the macrolide 2'-glycosylation, (9) reduction of macrolide formyl group, and (10) resistance due to macrolide deacylation. There are many subgroups, and they are specific to each strain and also to each bacterial species. Faced with the problem of the emergence of various kinds of macrolide resistance, it is expected that new macrolides (15-memberring macrolide such as azithromycin and 14-member-ring macrolide such as ketolide) will appear in the future. A new battle between the new macrolides and resistant strains showing the new mechanism is now going to start over again, and then macrolide resistance strains must be obliged to generate newly evolution of macrolide resistance mechanism (s).

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A clinical investigation of a new cephem antibiotic, cefoselis (CFSL), was carried out. The tissue concentration of this drug was examined in plasma, gingiva, and cortical bone of mandible. Intravenous injection of 1g CFSL was administered for 60 minutes to 10 volunteer patients. Assessment was completed in 9 patients with 1 drop out. The mean value of plasma concentration was 32.6, μg/mL and ranged from 22.0 to 46.0, μg, /mL immediately after injection. However, the mean concentration value was 18.3 μg/mL and ranged from 8.82 to 29.2 μg/mL one hour after injection. The half time noted was 79.05 minutes. The mean value of mandibular gingiva concentration was 17.3 μg/g and ranged from 8.34 to 27.10 μg/g one hour after injection. The overall concentration ratio of gingiva/plasma was 99.5%. Alternatively, the mean value of mandibular cortical concentration was 2.8 μg/g and ranged from 0.45 to 7.25 μg/g one hour after injection. The overall concentration ratio of the mandible/plasma was 21.2%. These results indicate a superior value in tissue concentration of CFSL compared to other cephems, and no major postinjection complication. Furthermore, the present study suggests that CFSL attains a high mandibular tissue concentration. In conclusion, CFSL is effective in the treatment of oral and maxillofacial infections.

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Between January 1999 and August 1999, 87 children were treated with cefozopran (CZOP), ages ranging from 5 months to 13 years. CZOP was administered by intravenous injection every 8 hours 54.6 to 78.9 mg/kg in a daily dose for 2 to 10 days. Out of 87 patients, in 42 were detected pathogenic organisms, including 34 with bronchopneumonia and 8 with both bronchopneumonia and acute otitis media. These 42 patients were evaluated for clinical and bacteriological efficacy. The clinical efficacy rate was 100%. The bacteriological eradication rates for Haemophilus influenzae and Streptococcus pneumoniae were 92.3% (24/26) and 85.7% (18/21). Five patients had pneumonia or acute otitis media 7 to 14 days after the cessation of CZOP treatment. The clinical efficacy rate for an additional 29 patients who were suspected of bacterial infection but in whom pathogenic organisms were not detected, was 100%. Safety investigations were performed for all 87 subjects. Diarrhea was observed in 4 infants (4.6%).

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A large-scale, multicenter randomized trial was performed to evaluate the efficacy of intravenous immunoglobulin (IVIG) in combination therapy with antibiotics for severe infections, compared with antibiotics monotherapy, as part of the reevaluation of drugs required by the Ministry of Health and Welfare. Patients whose symptoms specific for infection did not improve sufficiently after receiving broadspectrum antibiotics for three consecutive days were randomly allocated to the IVIG group or control group. The antibiotics were discontinued in both groups, and imipenem/cilastatin (IPM/CS) and amikacin (AMK) were administered consecutively for seven days from the day of the allocation (day 1). In the IVIG group, IVIG 5 g/day was concomitantly given for three days starting on day 1. Efficacy was assessed mainly on the basis of the number of days required to become afebrile and for symptom eradication as end-points. The proportion of cases excluded from the efficacy evaluation was 26.1% (178/682). There were no significant imbalances between the two groups in regard to gender, age, disease category, colony-stimulating factor (CSF) usage, baseline albumin level, baseline IgG level, or time course of neutrophil counts. The proportion of patients obtaining defervescence by day 7 estimated by the Kaplan-Meier method, was 54.8% in the IVIG group and 37.2% in the control group (the generalized Wilcoxon test: p=0.002), and the proportions of patients whose symptoms were eradicated by day 7 were 57.3% and 39.4%, respectively (the generalized Wilcoxon test: p=0.002). The “response rates”, defined as the proportion of patients whose outcomes was assessed as “excellent” or “good” based on computerized objective criteria, were 61.5% (163/265) and 47.3% (113/239), respectively (x²test: p<0.001). Intravenous immunoglobulins are considered to be effective for severe infections when used as combination therapy with antibiotics.

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To objectively evaluate the clinical value of biapenem (BIPM) a new parenteral carbapenem, in the treatment of complicated urinary tract infections, We perfoirmed a prospective, randomized, double-blind comparative study using imipenem/cilastin (IPM CS) a control drug. Patients were randomly assigned to receive either 300 mg b. i. d. of BIPM or 500mg/500mg b. i. d. of IPM/CS for 5 days by intravenous drip infusion. All patients were shown to have pyuria of at least 5 WBCs/HPF, bacteriuria of at least 10⁴CFU/mL and an identifiable underlying urimiry tract disease. Overall clinical efficacy was evaluated on the basis of criteria proposed by the, Japanese UTI Committee as “exccllent”, “moderate” or “poor” Of the 151 patients evaluated for clinical efflicacy, 75 patitents received BIPM and 76 received IPM/CS. No significant differences were observed in the background characteristics of the patients between the two treatment groups except that the age distrlution was higher in the IPM/CS group than in the BIPM group (p<0.15). Excellent and moderate rsponses were obtained in 94.7% of the 75 patients in the BIPM group and in 93.4% of the 76 patients in the IPM/CS group. The 90% confidence interval the difference between the 2 groups was between-6.4 and 8.9%. and the clinical comparability of BIPM to IPM/CS was verified. The overall bacteriological eradication rate Was 95.0% of 121 strains in the BIPM group and 94.4% of 124 strains in the IPM/CS group, with no statistically sinificant difference. Clinical adverse reactions were experienced in 2.2% of the 92 patients in the BIPM group and in 4.4% of the 90 patients in the IPM/CS group. Laboratory advers, reactions were, observed in 14.8% of the 88 patient in the BIPM group and in 15.7% of the 89 patients in the IPM/CS group. No statistically significant differences in the incidences of both clinical and laboratory adverse reactions were noted.The clinical value was evaluated as significantly higher in the BIPM group (p<0.05). Based on the results obtained in study, we concluded that the treatment of complicated urinary tract infect, with 300mg b. i. d. of BIPM is as effective and is tolerated as well as 500mg/500mg b. i. d. of IPM/CS.

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