The MIC distribution, bactericidal activity and β-lactamase stability of cefditoren (CDTR). the active form of an oral cephalosporin cefditoren pivoxil (CDTR-PI), against a clinical isolate of Haemophilus influenzae, as well as its affnity for penicillin-binding proteins (PBPs) were compared with those of other reference compounds. The results were as follows.
1. The MIC₈₀ value of CDTR against 46 strains of H. influenzae was 0.025μg/ml, which was almost the same as that of cefteram (CFTM) but superior to that of cefdinir (CFDN), cefaclor (CCL), and cefpodoxime (CPDX).
2. The in vitro bactericidal activity of CDTR against H. influenzae PRC 2 was superior to that of CFDN and CCL at concentrations simulating human blood levels after 6 hours. Under these conditions, after 4 hours H. influenzae treated with CDTR in this model simulating the human blood level showed filaments, bulges and bacteriolysis by scanning electron microscopic observation.
3. The affinity of CDTR for PBP 4 and PBP 5 among the PBPs of H. influenzae PRC 2 was higher than that of CFDN and CCL. Its high affinity was paralleled by its strong antibacterial activity.
. The relative rate of hydrolysis of CDTR by β-lactamase was determined. CDTR as well as CFDN was very stable to β-lactamase derived from H. influenzae.

View full abstract

We previously studied the antitumor effect of 5-FU according to the dosage schedule using a human stomach cancer xenograft to nude mice (SC-1-NU), and reported that 5-FU might be more effective with given by intermittent dosage than by daily dosage, if the total dose of the drug was equal. In this report, we performed an additional study on 3 human gastrointestinal adenocarcinomas (St-4, Co-3 and Co-4) serially transplanted to nude mice to determine whether the above-mentioned phenomenon might happen in other tumors. Treatment was begun when the estimated tumor weight reached 100-300mg. 5-FU was administered intraperitoneally daily (10 and 20mg/kg qd×40) or intermittently (40mg/kg q 4d×10). The sensitivities of the 3 cancers to 5-FU were low; the minimum T/C ratios when 10 and 20 mg/kg of 5-FU was administered daily were 93.0% and 67.5%(St-4), 73.6% and 40.3%(Co-3), 96.7% and 98.7%(Co-4), respectively. The minimum T/C ratios when 5-FU was administered intermittently were equal to those of daily dosage: 88.5%(St-4), 69.1%(Co-3) and 103%(Co-4), respectively. A statistically significant correlation was found between the sensitivities of 4 cancers (SC-1-NU, St-4, Co-3 and Co-4) and the ratios of the effects obtained by intermittent dosage to those by daily dosage (r=0.971, P<0.05). It was considered that the antitumor effects of 5-FU on the 3 cancers were similar with intermittent and daily dosages, because the sensitivity of the tumors to 5-FU was low. Up to now we had experienced no tumor in which the effect of 5-FU given by daily dosage was significantly superior to that given by intermittent dosage. Although additional study is required, it was suggested that 5-FU might be more effective when given by intermittent dosage than by daily osage.

View full abstract

The efficacy of long-term chemotherapy with erythromycin (EM) orclarithromycin (CAM) for chronic lower respiratory tract infections (CLRTI) has been empirically substantiated. Several investigators suggest that cytokines may play an important role in this effect, but the kinetics of cytokine production in vivo upon treatment with these antibiotics remains to bedetermined. In the present study, interleukin (IL)-2 production by peripheral blood mononuclear cells (PBMNC) and serum IL-4 levels were measured to determine the effects of these antibiotics on cytokine production. PBMNC and sera were obtained from 15 and 17 patients with CLRTI both before and after treatment, for IL-2 and IL-4 assay, respectively. We also investigated the relationship between IL-2 production by PBMNC from 25 patients with CLRTIs on long-term EM therapy (1.5-8.5 years) and duration of EM administration. Culture supernatants of PBMNC obtained after 24 hours of stimulation by Con A were tested for IL-2 by radioimmunoassay, and serum IL-4 levels were measured by enzyme linked immunosorbent assay. The results were as follows:
1. IL-2 production by PBMNC and serum levels of IL-4 were higher in CLRTI patients than in healthy controls.
2. IL-2 production (mean±SD) by patients with CLRTI on day 28 of treatment with EM or CAM was 14.6±11.3 U/ml, which was significantly higher (P<0.05) than before administraiton of these macrolides (8.1±4.1 U/ml).
3. Serum IL-4 levels of patients with CLRTI on day 28 of treatment with EM or CAM was 155.0±63.7pg/ml, which was significantly higher (P<0.05) than before administration of these macrolides (118.8±54.6pg/ml).
4. IL-2 production in the patients with CLRTIs on long-term EM chemotherapy was negatively correlated with the duration of its administration (r=-0.46, P<0.05).
These results suggest that administration of EM or CAM increases IL-2 production by PBMNC and serum IL-4 levels in the early phase, which is considered to be one of the mechanisms of effectiveness against CLRTI, and after that IL-2 production gradually decreases to the levels of healthy controls.

View full abstract

This study examined the effects of ferrous sulfate, an H₂ antagonist (famotidine), an antacid (magnesium oxide), and a gastroprotectant (troxipide) on the absorption of fleroxacin (FLRX) in 5 healthy male volunteers. When ferrous sulfate were coadministrated with FLRX, the relative bioavailability of FLRX was slightly decreased (C_max 2.21→01.69 μg/ml, not significant). Other coadministrated drugs did not influence on the absorption of FLRX. The urinary excretion rates (0-24 h) of unchanged FLRX, demethyl FLRX, FLRX N-oxide and the overall rate showed no significant difference in several cases. The bioavailability of FLRX was not influenced by the concurrent administration of ferrous sulfate, famotidine, magnesium oxide, or troxipide.

View full abstract

A multicenter clinical trial was conducted to determire an appropriate dosing of azithromycin (AZM), a new 15-membered antibiotic macrolide, in the treatment of skin and skin structure infections. AZM at 250 mg a day for three days (L-group), AZM at 500 mg a day for three days (H-group) and cefaclor at 250 mg t. i. d. for 7-10 days were compared. Patients were assigned randomly to a drug group after informed consent had been obtained. The L-group and H-group were given AZM in a double-blind fashoon. The C-group was not blinded. The infections treated were (1)deep-seated hair follicle infections: furuncle, furunculosis and carbuncle;(2)diffuse deepseated infestions: cellulitis, erysipelas, lymphangitis, and lymphadenitis:(3)miscellaneous abscesses: subcutaneous abscess, suppurative hidradenitis, and infected atheroma. The total number of patients enrolled was 76 (L-group, 24; H-group, 25; C-group, 27). Clinical efficacy was evaluated in 68 patients (L-group, 22; H-group, 22; C-group, 24). Safety was analyzed in 74 patients (Lgroup, 22; H-group, 22; C-group, 24). Clinical usefulness was evaluated in 68 patients (L-group, 22; H-group, 22; C-group, 24). Clinical efficacy rates were 77.3% for the L-group, 90.9% for the H-group, and 66.7% for C-group. Differences were not statistically significant. The overall clinical improvement rates on days 3 and 5 were in descending order of H-group<L-group≥Cgroup. Differences were not statistically significant. Safety rates were 83.3% for the L-group, 87.5% for the H-group, and 88.5% for the C-group. Differences were not statistically significant. Usefulness rates were 77.3% for the L-group, 90.9% for the H-group, and 66.7% for the Cgroup. Differences were not statistically significant. Bacteriologic response rates were 80.0% for the L-group, 93.8% for the H-group, and 69.2% for the C-group. The incidence of adverse reactions and abnormal laboratory findings were low in all three groups, and were all mild. These results suggest that the appropriate dosage of azithromycin is 500 mg once a day for 3 days in the treatment. of skin and skin structure infections.

View full abstract