We studied the effect of recombinant human interferon-γ (IFN-γ) on the oxygen metabolite generation of human neutrophils in vitro. The incubation of whole blood with 1, 000 or 10, 000 units/ml of IFN-γ for 4 hours at 37°C significantly enhanced luminoldependent chemiluminescence (CL) stimulated by non-opsonized zymosan, phorbol myristate acetate (PMA) or Pseudomonas aeruginosa Nc-5. Four hours' incubation of neutrophils with IFN-γ enhanced CL. Preincubating neutrophils with 1, 000 units/ml of IFN-γ for 4 hours resulted in a 1.16-fold increase in zymosan-induced CL and a 1.75-fold increase in P. aeruginosa-induced CL. However, IFN-γ alone did not stimulate neutrophil CL. There was no significant enhancement during a 2 hours' preincubation with IFN-γ. Luminol-binding microsphere (lumispheres)-induced CL of neutrophils was also enhanced after incubation with 1, 000 units/ml of IFN-γ for 4 hours. In addition the effect of IFN-γ on the neutrophils obtained from elderly patients was evaluated. An increase in CL comparable to that obtained from healthy young adults was observed. These findings suggest that IFN-γ activates neutrophil function and may be clinically useful in immunosupportive therapy for intractable infections in elderly patients.

View full abstract

The effects of antibiotics on human neutrophil functions such as adherence, phagocytosis, hydrogen peroxide production, and enzyme release were examined. Piperacillin (PIPC), imipenem (IPM), flomoxef (FMOX), gentamicin (GM), amikacin (AMK), minocycline (MINO), josamycin (JM), lincomycin (LCM), chloramphenicol (CP), colistin (CL), rifampicin (RFP), and ciprofloxacin (CPFX) were used in this study. These drugs had no influence on neutrophil functions at their therapeutic concentrations. However, FMOX (>100μg/ml) was found to suppress neutrophil adherence to the plastic plate. High concentrations of CP (2, 50μg/ml) and MINO (500μg/ml) significantly impaired hydrogen peroxide production and phagocytosis. JM (300μg/ml) also inhibited PMA-induced hydrogen peroxide production. In contrast, PIPC (>100μg/ml) slightly enhanced adherence and hydrogen peroxide production. Results indicated that these antibiotics had little influence on neutrophil functions in the clinically relevant range.

View full abstract

Effects of cefditoren pivoxil (CDTR-PI) on dams and their fetuses were evaluated in Kbl-JW rabbits. CDTR-PI was administered orally to pregnant rabbits during the period of fetal organogenesis at doses of 2, 4, 7.5, 15 and 30mg/kg. One abortion each was observed in the 7.5 and 15mg/kg groups, and one premature birth and seven abortions were observed in the 30mg/kg group. Food consumption of dams decreased at 4mg/kg and higher. The suppression of body weight gain of dams, as the result of a dose-related decrease of food and water consumption, was observed at 7.5mg/kg and higher. The number of fetuses decreased at 7.5mg/kg and higher, and fetal body weight decreased in the 30mg/kg group. However, external, visceral and skeletal observations showed no anomalies and variations attributable to the administration of CDTR-PI. From these results, CDTR-PI may have no teratogenic effect in rabbits, and the no effect dose level of CDTR-PI for dams' reproductive performance and their fetuses is estimated to be 4mg/kg.

View full abstract

Bile samples were obtained from 310 autopsy cases at the Nagoya City Kosei-in Hospital, and submitted to bacterial culture and immunoglobulin measurements. The bacterial culture were performed in all samples, and immunoglobulin was measured in 138 cases. The culture was positive in 100 cases (32.3%), and 150 strains were isolated. Enterococcus faecalis was the most common organism, followed by Yeast like organism (YLO), Escherichia coli, Klebsielki spp., and Pseudomonas aeruginosa in this order. E.faecalis and YLO were predominant in those who recieved antibiotics and in those aged over 80, E. faecalis and E. coli in those bearing a gallstone and those whose time interval from death to autopsy were longer than 18 hours. The stone bearing rate was 19.0% (59/310), significantly higher in the females (p<0.05), and the culture positive rate was significantly higher in those bearing a stone (p<0.05). It was positive in 41.3% of those having the stone in the gallbladder, and in 61.5% when the stone was in the bile duct, but this difference failed to be significant. The number of those who waited more than 18 hours before autopsy were 90, and the culture was positive in 38 of them giving a significantly higher rate compared to the shorter group. The positive rate revealed no correlation with age. Antibiotics were administered in 194 cases, and the culture was positive in 27.3% of those under antibiotics, being significantly lower (p<0.05) compared to 40.5% in the others. The IgA levels was higher and the IgG and IgM levels were lower in the culture positive group, but it was not statistically significant. The IgG and IgM levels were higher in those younger than 79 compared to those over 80, but not significant, and there were also no difference in the IgA level between those two groups. These findings indicate that it is more advisable to treat biliary tract infection in the elderly according to the factors affecting positive bile culture.

View full abstract

The effects of various agents on biliary excretion of cefpiramide (CPM) were investigated to clarify the transport mechanism of CPM in the rat liver. Indocyanine green (ICG) (25mg/kg), bromosulfophthalein (BSP) (35mg/kg) or bilirubin (7.5mg/kg) administered 2 minbefore intravenous administration of CPM (20mg/kg) reduced the biliary excretion of CPM to the extent of 44.1, 39.4, and 64.8% respectively of the amount of CPM excreted for 120min without these agents. Propranolol and metoprolol, mainly excreted in bile and metabolized by mixed function oxidases, had no effect on biliary excretion of CPM. In the presence of CPM (45mM), the amount of BSP (0.02mM) bound to the glutathione S-transferase (GST) fraction on chromatography of the liver cytosol was reduced to 26.2% of the value obtained in the absence of CPM. The inhibition constant (Ki) of ICG, BSP, bilirubin and CPM to GST was, 0.12μM, 3μM, 39μM and 740μM respectively. Propranolol and metoprolol had no inhibitory effect on GST activity. Neither secretory IgA, which is transported via vesicles, nor colchicine, which inhibits movement of vesicles in the liver, had any effect on biliary excretion of CPM. Diethyl maleate, which reduces the amount of GSH in the liver had no influence on CPM excretion. The study showed that CPM shared a common hepatic transport system with ICG, BSP and bilirubin, and inhibited BSP binding to GST, suggesting an important role of GST in CPM excretion into bile.

View full abstract

To evaluate the efficacy, safety and usefulness of meropenem (MEPM), a new carbapenem antibiotic for injection, in chronic respiratory tract infections, amulticenter double-blind controlled study was conducted using imipenem/cilastatin sodium (IPM/CS) as the reference drug. Patients were given 1.0g of MEPM (the MEPM group) or 1.0g/1.0g of IPM/CS (the IPM/CS group) daily (b. i. d.) for 14 days as a rule. The results of evaluation by the committee were as follows:
1. Analyzed cases: Among a total of 136 cases, 115 cases were evaluated for clinical efficacy. These cases included 55 cases of chronic bronchitis, 43 cases of bronchiectasis with infection are 17 cases of pulmonary emphysema or fibroid lung with infection.
2. Clinical efficacy: The efficacy rate was 86.4% (51/59) in the MEPM group vs. 89.3% (50/56) in the IPM/CS group. There was no signifiant difference between the two groups.
3. Bacteriological response: The eradication rate was 63.4% (26/41) in the MEPM group vs. 73.2% (30/41) in the IPM/CS group. In cases of infection with Pseudomonas aeruginosa, the eradication rate was 38.1% (8/21) in the MEPM group vs. 30.8% (4/13) in the IPM/CS group. There was no significant difference between the two groups.
4. Safety: The incidence of side effects was 3.0% (2/67) in the MEPM group vs, 11.1% (7/63) in the IPM/CS group. There was no significant difference between the two groups. No severe side effects were noted. The incidence of abnormal laboratory findings was 29.7% (19/64) in the MEPM group vs. 27.9% (17/61) in the IPM/CS group. There was no significant difference between the two groups. Abnormalities were an increase in eosinophils, transient elevations of GOT, GPT and ALP, and elevation of BUN.
5. Usefulness: The usefulness rate was 86.4% (51/59) in the MEPM group vs. 86.2% (50/58) in the IPM/CS group. There was no significant difference between the two groups.
From the above results we concluded that 1.0 g/day of MEPM was as useful as 1.0g/1.0g/day of IPM/CS in chronic respiratory tract infections.

View full abstract

The efficacy of early miconazole (MCZ) use in infections associated with hematologic diseases was studied by the Tokai Infection Study Group on Hematological Disorders. Subjects consisted of 189 patients with hematologic disorders as underlying diseases, treated between July 1989 and December 1990. These subjects were suspected to have mycosis after a single course of antibiotic therapy had failed to relieve fever within 3 to 4 days. Subjects were randomized into the MCZ group or a control group using the envelope method. The MCZ group was given MCZ plus antibiotics, and the control group was given antibiotics alone. MCZ was administered at a dose of 400mg, two to three times daily, by intravenous drip infusion for a minimum period of 14 days. Selection of antibiotics for both groups was left to the attending physicians, and efficacy was evaluated by monitoring fever as well as by laboratory findings. To facilitate the diagnosis of mycosis, blood levels of β-D-glucan were measured, with 10μg/ml or more considered positive. Of the 189 patients studied, nine were ineligible, and 19 dropped out, leaving 84 patients in the MCZ group and 77 in the control group for efficacy evaluation. Among the patients in the MCZ group, excellent responses were observed in 27 and good responses in 24, a total of 60.7% (51/84). Among the control patients, excellent responses were observed in 29 and good responses in five, a total of 44.2% (31.77). Thus, significantly greater clinical responsiveness was observed in the MCZ group (p<0.05: x² test). In addition, the rate of positivity for β-D-glucan was 30.8% (8/26) in the MCZ group and 38.1% (8/21) in controls. The response rate in β-glucanpositive patients was 66.7% (4/6) in the MCZ group and 37.5% (3/8) in controls. The above findings indicate that concomitant use of this antimycotic agent and antibiotics resulted in an increased therapeutic effect in patients who had failed to respond to an initial 3-to-4-day course of antibiotic therapy.

View full abstract

Thirty six patients including 8 pregnant women with herpes simplex virus (HSV) infection were enrolled in the trial. Of these, 33 were treated with 5% acyclovir ointment 2-5 times daily and three were treated with gentamycin ointment as controls. Thirty one patients had recurrent genital herpes (HSV-1:6, HSV-2:25), four had acute genital herpes (HSV-1:1, HSV-2:3) and one had a recurrent HSV infection of the right hand (HSV-2). Treatment efficacy for the 33 treated patients was as follows. Very effective; 14 patients, effective; 16, and moderately effective in one case. The remaining two cases could not be evaluated. Twenty acycloir-treated patients with recurrent genital herpes, from whom virus cultures were taken, became negative within three days of commencing therapy. The treatment was very well-tolerated, with only mild irritation reported by one patient. All of the pregnant women had normal infants. In conclusion, acyclovir 5% ointment is a welltolerated and effective treatment for genital herpes.

View full abstract

A double-blind comparative study on cefditoren pivoxil (CDTR-PI) was carried out to evaluate objectively its efficacy, safety and usefulness in the treatment of bacterial pneumonia, using cefteram pivoxil (CFTM-PI) as the active reference drug. In principle, CDTR-PI at a dose of 300mg/day or CFIM-PI at a dose of 600 mg/day was administered in three divided doses for 14 days. The following results were obtained.
1. The efficacy rate as judged by the committee was 89.9% (62/69) in the CDTR-PI group and 87.7% (50/58) in the CFTM-PI group, with no significant difference between the two treatment groups.
2. The eradication rate of the causative organisms as confirmed by the committee was 92.3% (24/26) in the CDTR-PI group and 81.3% (13/16) in the CFTM-PI group, the difference between the two treatment groups not being significant.
3. The incidence of side effects was 9.1% (8/88) in the CDTR-PI group and 7.1% (6/85) in the CFTM-PI group. Laboratory abnormalities were observed in 22.4% (19/85) and 25.6% (20/78) of cases, respectively. There were no significant intergroup differences in the incidences of side effects or laboratory abnormalities.
4. The usefulness rate as judged by the committee was 82.9% (58/70) in the CDTR-PI group and 81.7% (49/60) in the CFTM-PI group, with no significant difference between the two treatment groups.
From these results it is indicated that CDTR-PI at a dose of 300 mg/day (in three divided doses) (one half the dose of CFTM-PI) is equally effective and safe to CFTM-PI at a dose of 600mg (in three divided doses) in the treatment of bacterial pneumonia, and we conclude that CDTR-PI is a useful drug with high efficacy for bacterial pneumonia.

View full abstract

A double-blind comparative study was carried out to determine the effficacy, safety and usefulness of cefditoren pivoxil (CDTR-PI), a new oral cephem, in the treatment of chronic respiratory tract infections, using cefteram pivoxil (CFTM-PI) as the reference drug. In principle, patients were treated by oral administration of either CDTR-PI or CFTM-PI at 200mg three times daily for 14 days. The following results were obtained.
(1) The Clinical effficacy rate as judged by the committee was 85.9% (73/85) in the CDTR-PI group and 85.9% (67/78) in the CFTM-PI group, with no significant difference between the two treatment groups.
(2) As to the bacteriological effifficacy as judged by the committee, the eradication rate was 84.2% (32/38) in the CDTR-PI group and 77.8% (28/36) in the CFTM-PI group. No significant difference was seen between the two treatment groups.
(3) The incidence of side effects was 9.3% (9/97) in the CDTR-PI group and 6.3% (6/95) in the CFTM-PI group, and the incidence of abnormal laboratory findings 12.4% (11/89) and 11.5% (10/87), respectively, as judged by the committee. There was no significant differeance between the two groups.
(4) The usefulness rate as judged by the committee was 80.2% (69/86) in the CDTR-PI group and 82.5% (66/80) in the CFTM-PI group, the difference not being significant.
From these results it is concluded that CDTR-PI is an oral antibiotic with high usefulness in the treatment of chronic respiratory tract infections.

View full abstract