Antimicrobial activity of 6 macrolides was determined using a micro-broth dilution method, against 535 clinical isolates of 22 species, which were isolated in 1996 from 325 facilities in Japan. Results were as follows.
1. In general, antimicrobial activities of 14-membered macrolides were higher than those of 16-membered macrolides. The antimicrobial activities of 14-membered macrolides were in the order of clarithromycin (CAM), erythromycin (EM), roxithromycin (RXM). Among 16-membered macrolides, rokitamycin (RKM) was the most potent, josamycin (JM) was next potent followed by midecamycin (MDM).More numbers of highly-resistant strain of >100μg/ml were recognized in 14-membered macrolides than in 16-membered macrorides.
2.Most of S. pyogenes (group A) strains were distributed in the susceptible range and almost none was found in the resistant range.
3. S. pneumoniae strains were distributed widely from the susceptible range to the highly resistant range, and as high as 37.1% fell into the high resistance of >100 iug/ml range.
4. Against Peptostreptococcus spp. and MRSA, 16-membered macrolides were more effective than 14-membered macrorlides, and their antibacterial activities were in the order of RKM, JM, MDM.Ratio of high-resistant strains of >100μg/ml against 14-membered macrolides was much higher than that against 16-membered macrolies.
5. Most of M.(B.) catarrhalis strains were distributed in the susceptible range of ≤1.56μg/ml, and most of H.influenzae strains were distributed within the moderately resistant and the resistant ranges.
6. In M.(B.) catarrhalis and H. influenzae, no correlation between macrolide resistance and betalactamase production was recognized.
7.Most of C. jejuni strains were susceptible to all macrolides used in this study.

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The mechanism of resistance was studied with vancomycin-resistant Staphylococcus aureus (VRSA) strain Mu50.It was demonstrated that the incorporation of ¹⁴C-N-acetylglucosamine into the cell wall of Mu50 was not suppressed in the presence of 8μl/ml of vacomycin, whereas it was completely suppressed in vancomycin-susceptible strains FDA 209P and H-1. Increased binding of vancomycin to the wall of Mu50 was observed compared to the control strains: 1.7×10¹⁶ (Mu50), 6.1×10¹⁵ (209P), and 6.7×10¹⁵ (H-1) vancomycin molecules/mg cell wall, respectively.Remarkable proportion of the cell-wall component muropeptides were non-amidated in the cell wall of Mu50.In concordance with this phenomena, peptidoglycan cross-linkage decreased strikingly in the Mu50strain.Free D-Ala-D-Ala residues at the end of muropeptides in the pre-existing cell wall generated by decreased cross-linkage seems to account for increased vancomycin binding.The increase of vancomycin-resistance level is presumably caused by sequestration of vancomycin molecules from primary target point on cell membrane.
It was considered that at least two phenotypic changes are required for the vancomycin resistance in the Mu50strain.First, as we have described previously, is the activated cell wall synthesis, and second, the reduction of cross-likage of peptidoglycan by production of non-amidated muropeptide precursors.

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Between January 1995 and March 1997, 78 Helicobacter pylori strains were isolated from patients with gastritis and gastric ulcer and their drug-susceptibilities to8antimicrobial agents and3anti-ulcer drugs were determined.Imipenem was the most active agent and its MICs to all the strains tested were lower than 0.013μg/ml. Amoxicillin, cefaclor and minocycline were active against H.pylori with MIC₉₀s of 0.05μg/ml, 0.78μg/ml and 0.39μg/ml, respectively, and no resistant strains against these drugs were isolated.However, resistant strains to clarithromycin (isolation frequency: 9%), erythromycin (13%), ofloxacin (8%) and metronidazole (13%) were isolated.
Triple, double and single resistant strains to above 4 antimicrobial agents were noted. No quadruple resistant strain was isolated. Frequencies of those resistance patterns were14.3% (triple), 28.6% (double), and57.1% (single), respectively.
Seven erythromycin-resistant strains were shown to be cross-resistant to clarithromycin but 3 erythromycin-resistant strains were susceptible to clarithromycin. It seems likely that this phenomenon is caused by the fact that clarithromycin is more active to H.pylori than erythromycin.
The MIC₉₀ value of lansoprazole was lower than those of omeprazole and famotidine.

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Following its introduction into the market, PAPM/BP (panipenem/betamipron) was clinically studied in 188 evaluable cases out of 207 cases primarily of respiratory infectious diseases treated at the pediatric departments of 15 hospitals.
In the clinical evaluation, the drug provedeffective in three of three cases of sepsis;three of three cases of suppurative meningitis;nine of ten cases of laryngopharyngitis, six of seven cases of tonsillitis, 56 of 63 cases of acute bronchitis, 90 of 98 cases of pneumonia, and one of one case of phyothorax, all of which are respiratory infectious diseases;one of one case of secondary infection of a chronic respiratory disease; and two of two cases of lymphadenitis, which is a disease of the soft dermal structure.The overall efficacy rate was91.0% (171/188cases).
In the bacteriological study, Gram-positive bacteria were eliminated in five of five strains of S. aureus, 30 of 31 strains of S.pneumoniae (96.8%), and three of three strains of S. pyogenes. Gramnegative bacteria were eliminated in 15 of 17 strains of H. influenzae (88.2%), three of four strains of M. catarrhalis, and two of two strains of K. pneumoniae. The overall elimination rate was92.1% (70/76 strains).In the 23 strains of S. pneumoniae that were examined, penicillin-resistant strains accounted for 56.5%, showing an elimination rate of100%.
No serious adverse effects were observed, and the incidence of adverse effects was1.45%. As for abnormalities in laboratory tests, levels of GOT and GPT increased in eight cases (3.88%), LDH increased in one case (0.48%), and neutropenia occurred in one case (0.51%).
These results suggest that PAPM/BP could be considered the first choice in the treatment of infectious diseases in pediatrics, due to its effectiveness and high level of safety.

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Cefpirome (CPR) and amikacin (AMK) were used concomitantly to treat infections complicated by hematological diseases.A total of 100 subjects were evaluated, and the allover efficacy rate was 72.0%. Acute leukemia was found in the largest number of patient, 55, followed by 12 cases of malignant lymphoma and 6 cases of chronic myelogenous leukemia.By type of infection, patients having suspected sepsis were the largest in number, being 50, and the efficacy rate was 68.0%.The efficacy rates for sepsis and pneumonia were 57.1% (7 cases) and 61.1% (18 cases), respectively.The efficacy rates by neutrophil counts before administration of CPR and AMK and at 7 days after administration were both 71.9% in the group of less than 500/μl, both 60.0% in the group of less than 100/μl. The efficacy rate was 75.0% in the group of granulocyte colony stimulating factor (G-CSF) concomitant usage, and 70.0% in the non-concomitant usage group.Concomitant treatment with CPR and AMK exhibited a high level of safety and efficacy rates in infections complicated by hematological diseases and high.

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