Macrolides have been clearly demonstrated to have an excellent therapeutic effect in patients with chronic inflammatory diseases in lower respiratory tract. However, the mechanism remains controversial.We have reported that erythromycin increased serum glucocorticoid levels through the activation of the hypothalamo-pituitary-adrenal cortex axis. Then, we studied the effect of roxithromycin, a new macrolide with a 14-membered lactone ring, on serum glucocorticoid levels in mice. Roxithromycin increased serum glucocorticoid levels in a dose-dependent manner, and this increase in the glucocorticoid levels was completely suppressed by the pretreatment with dexamethasone. These results suggest that roxithromycin increase endogenous glucocorticoid levels through the hypothalamo-pituitary-adrenal cortex axis. Roxithromycin might be effective for the treatment of chronic inflammartory diseases.

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Rates of sensitivity to cefpirome of 19, 580 strains belonging to more than 46 bacterial species were determined by the one-concentration method, the three concentration method or the KB method.These starins were isolated at 60 hospitals all over Japan during the period from April 1995 to March 1996. Escherichia coli, methicillin-sensitive Staphylococcus aureus (MSSA) and Haemophilus influenzae were isolated from outpatients and Pseudomonas aeruginosa, methicillin-resistant S. aureus (MRSA), E. coli and Enterococcus faecalis were isolated from inpatients. Isolation frequencies of MRSA among all strains of S. aureus were 33.2% and 74.9% in outpatiens and inpatients, respectively. Rates of sensitivity to cefpirome were higher than 90% for MSSA, Streptococcus pneumoniae, S. pyogenes, S. agalactiae, Neisseria gonorrhoeae, H. influenzae, Moraxella subgenus Branhamella catarrharis, E. coli, Klebsiella pneumoniae, K. oxytoca, Proteus mirabilis, P. vulgaris, P. rettgeri, Morganellamorganii, Providencia stuartii, Enterobacter aerogenes, E. cloacae, Citrobacter freundii and Serratia marcescens by all three methods.The Rates of sensitivity of P. aeruginosa to cefpirome were 76% by the one-concentration and three-concentration methods and 72% by the KB method.The Rates of sensitivity to cefpirome were lower than 50% for MRSA, Enterococcus faecium, Xanthomonas maltophilia, Achromobacter xylosoxidans, and Bacteroides group.

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The effect of azithromycin (AZM), an azalide antibiotic, on the intestinal bacterial flora of pediatric pati-ents was investigated in inpatients, and outpatients.There were two boys and three girls, ranging in age from 14 months to 9 years and 2 months with body weights ranging from 9.99 to 24.8 kg. AZM was given orally once daily at dose levels of 10.0 to 19.6mg/kg for 3 or 5 consecutive days. Stool samples were collected from the patients before, during and after trea-tment for bacterial isolation and identification, and to determine counts per gram. Stool samples were also analyzed for AZM concentration and assayed for Clostridium difficile D-1 antigen titer. The MICs of AZM for the bacteria isolated were also determined.Although slight variability in flora was noted among the subjects, the counts of Enterobacteriaceae such as Escherichia coli were markedly reduced during and after treatment with AZM in all subjects. Intragenic alterna-tion of Enterococci was observed in some subjects otherwise no significant change was noted in total count of Enterococcus. The cell counts of aerobic bacteria decreased slightly in two patients. The predominant anaerobic bacteria in the intestine such as Bifidobacterium and Bacteroides were slightly decreased in two subjects, but the total anaerobe cell count did not change greatly. There were no abnormal increase in cell counts for glucose non-fermenting gram-negative rods or fungi, but Candida species became the predominant aerobe during treatment in one patient receiving AZM for 5 days. C. difficile and C. difficile D-1 antigen were identified in 3 subjects. There was no relationship between the C. difficile count and stool characteristics. One patient who received AZM for 5 days experienced mild diarrhea. AZM was recovered from stool samples collected from all subjects up to 25 days post-treatment.The AZM concentrations in the stool samples ranged from 0.6 to 2, 116.0μg/g. Drug sensitivity testing revealed that the MICs against Enterococcus and Bacteroides isolated from the stool samples became relatively high after treatment. The above results suggest that AZM is excreted in the feces for a long period, but has little influence on the intestinal bacterial flora of pediatric patients.

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Prulifloxacin (PUFX), a new quinolone antibacterial agent, was studied in 22 cases with biliary infections. PUFX was, in principle, administered at a dose of 400 mg/day b. i. d for 3 to 10 days. The clinical efficacy rate was 88.9%(16/18) with excellent in 9 cases, good in 7 cases, fair in 1 case and poor in 1 case. The bacteriological response was eradicated, partially eradicated and unchanged in 1 case each. Side effects were observed in 2 of 21 cases; eruption and diarrhea in 1 case each, but were rapidly resolved. No abnormal laboratory findings were observed in any of the 19 cases. From the above results, PUFX was considered to be a useful drug for the treatment of biliary infections.

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The minimum inhibitory concentration (MIC)(inoculum 10⁴ cells/well) of DU-6859 a was deter-mined for 97 strains of Staphylococcus aureus isolated from skin infection lesions. The MIC₈₀ value of DU-6859 a was 0.5μg/ml. Serum and skin levels of DU-6859 a after oral administration (30mg/kg) were determined in rats. Mean serum levels (n=5) 0.5, 1, 2, 4, and 8 hours after administration were 1.07, 1.19, 0.75, 0.57, and 0.23μg/ml, respectively, and the corresponding skin levels were 1.20, 1.92, 1.74, 1.44, and 0.63μg/g (wet skin weight).

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[in Japanese]

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