T-3262 (Tosufloxacin tosilate), a newly developed pyridone-carboxylic acid derivative, was administered to a total of 103 patients and carriers. In addition, in vitro antibacterial activity of T-3262 was determined against the clinical isolates, and compared with those of nalidixic acid (NA), pipemidic acid (PPA), enoxacin (ENX), norfloxacin (NFLX) and ofloxacin (OFLX). And when T-3262 was administered to the patients of acute infectious enteritis, fecal drug concentration and their correlation to the changes in the fecal microflora were investigated. The daily dose of 450 mg T-3262 was administered orally three times after meal for 7 days. A total of 63 cases were evaluated (one case of mixed infection caused by Shigella flexneri and Salmonella sp. was included). The clinical efficacy was good in all the enteritis (N=6). As the bacteriological effect, 60 out of 61 were eradicated, and eradication rate was 98.4% Adverse effects were observed in four of 102 cases (3.9%), consisting of one with skin rash, one with nausea, headache and stomatitis and two with soft stools. Deteriolations in laboratory findings were seen in 5 of 23 cases (17.4%), consisting of one with elevated GOT, two with elevated GOT and GPT, one with elevated BUN and one with increased eosinophiles count, although they were all slight in degree MICs of T-3262 which inhibited 90% of the isolates of Salmonella spp. was 0.0μg/ml, which was the lowest among the quinolone derivaties tested. The values of the fecal drug concentration of 7 cases of acute infectious enteritis, to which T-3262 administered, were higher than that of MIC90 and recovery rates of T-3262 were distributed from 2.85 to 46.3%. The degrees of changes of the drug concentrations were dependent on individual cases, and did not show the same trend. In addition, changes in the fecal microflora with in 24 hrs after T-3236 administration did not show the same trend.
The monosaccharide substances inositol hexasulfate (IHS) and inositol hexaphosphoric acid (Phytic acid, IHP) were investigated for their antiviral effect on the human immunodeficiency virus (HIV) in vitro. In MT-4 cells IHS completely inhibited the cytopathic effect of HIV and the HIV specific antigen expression at a concentration of 1.67 mg/ml. IHP moderately inhibited both of HIV effects as mentioned above.
SPF-BALB/c mice in which Mycoplasma pneumoniae cell proliferation accompanied by immunological responses had beenconfirmed, were immunized with live vaccines or with hyperimmune sera of M. pneumoniae FH-P24 and its mutant strains (P24-S1, P24-S11), were then assayed for infection-protection. Eight weeks after the last vaccination, 70 percent protection was obtained by inoculation once or twice with live FH-P24 and P24-S1 vaccines, respectively. After 12 weeks, 80% protection was achieved by FH-P24 and 60% by P24-S 1 live vaccine, while protectivity was not obtained by P24-S11 live vaccine. In case of passively immunized mice, IgG antibody titers and protective effect were not always found to be parallel. Namely, mice which were passively immunized with anti-FH-P24 serum, showed only 20% protection. However to get the above results, it was necessary that the anti-mutant strain serum be ten times higher than anti-FH-P24 serum in IgG titer. In the immunoblot anslysis, sera from patients infected with M. pneunoniae immunoblotted the 168-KDa (P1 protein) and the 85-KDa protein of FH-P24 and P24-S1, but not the 85-KDa protein of P24-S11.
To determine normal proportions of pharyngeal H. influenzae and H. parainfluenzae, qualitative and quantitative mapping of the species in the pharynx of 538 healthy children was carried out. The detection rates of H. influenzae rose to a peak at 4, 5 years, with a slow decline thereafter. In contrast to H. influenzae, the detection rates of H. parainfluenzae rose as the child became older in age. The rates of H. influenzae and H. parainfluenzae of the total cultivable flora showed the same tendency as the detection rates. No consistent seasonal fluctuations was found with H. influenzae. The pharyngeal swab was inferior to the nasopharyngeal swab in each age group, for detecting the carriage of H. influenzae and H. parainfluenzae in the upper respiratory tract. The rate of ampicillin-resistent H. influenzae was 17.7% in the nasopharynx
There is a trend of increase in the number of Staphylococcus aureus infection recently, and postoperative enterocolitis due to methicillin resistant strains is appearing. Because of this, a nation wide questionnaire survey on postoperative enterocolitis was conducted to clarify the status since 1980. Of the 875 major surgical institutes to which we sent the questionnarie, 370 (42.3%) replied and 67 case reports were obtained from 25 institutes. Twenty published reports were added to this and a total of 87 cases were evaluable. The number of postoperative enterocolitis incresed after the year 1985, and those resulting from MRSA infection were more frequent in the northern half of Japan including the Kanto area. It was more frequent in males and the mean age was 57.9. Their onset was suffen, beginning with diarrhea and/or fever between the second and fifth postoperative days. In most of the cases, the cepharosporin group of antibiotics, especially of the third generation, were administered preceeding the enterocolitis. Six of cases (24%) did not survive, and in some of the institutes they were considered to be hospital infections, as they appeared consecutively between a short period of time.
The effect of insulin on the incidence of experimental Serratia marcescens cystitis in alloxaninduced diabetic mice was studied. The symptoms in diabetes were improved by injection of insulin (1 I. U./b. i. d.) for 3 days. Diabetic mice treated with insulin showed lower susceptibility to cystitis with S. marcescens than non-treated diabetic mice, but slightly higher than normal mice. It was, therefore, suggested that the insulin treatment was important for prevention of S. marcescens cystitis. The prevention of cystitis in insulintreated diabetic mice was possibly due to the increase of urea nitrogen that inhibits the growth of S. marcescens in urine
Throat swab culture was compared with indirect hemagglutination (IHA) antibody detection for diagnosis of Mycoplasma pneumoniae infection. These two methods were tried on the patietns several times for a long term after onset of the disease. For five years from 1982 to 1986 in Kanagawa prefecture, a total of 566 patients were tested and 141 (25%) were diagnosed as M. pneunoniae infection by either of the two test methods. Both culture and antibody detection were performed on 110 patients out of 141, revealing that 96 patients (87%) were positive by culture and 89 (81%) were positive by antibody detection. Most of the patients with M. pneumoniae infection showed positive culture within a week after onset of the disease, and half of the patiens treated with antibiotics such as macrolides or tetracyclines showed positive for two or three months after the onset. Positive rate of IHA antibody detection in the patients with M. pneumoniae infection was 43% within a week after onset of the disease and reached the maximum (92%) in 15 to 21 days after the onset. The rate did not decrease to less than 70% three months after the onset. Geometric mean titer of the antibody reached the maximum at the same time as the antibody positive rate. Both antibody positive rate and geometric mean titer declined significantly four months after the onset. In general, IHA antibody of infants with M. pneumoniae infection increased satisfactorily day by day after onset of the disease. Nine percent of the patient with M. pneunoniae infection developed otitis media with effusion, and M. pneumoniae was isolated from two of six patient effusions.
Studies on the sputum organisms and their seasonal incidences were conducted on non-infected patients with pneumoconiosis. A total of 3318 organisms were isolated from 1427 sputum examina tions, an average of 4 examinations per patient.α-Streptococcus, GPC Neisseria and GNC were isolated in 74.1, 22.1, 64.8, 21.3% of the patients respectively. In addition, organisms to cause respiratory infection were isolated in the non-infected phase. S. pneumoniae, S. aureus, B. catarrhalis, H. influenzae, E. coli, K pneumoniae and P. aeruginosa were isolated in 1.5, 5.1, 2.5, 3.3, 2.9, 6.4, 2.8% of the patients respectively. Studies of the seasonal incidences in these organisms showed that H. influenzae, B. catarrhalis and S. pneumoniae were isolated mostly in winter, S. aureus mostly in spring, E. coli and K pneumoniae mostly in summer. On the other hand, P. aeruginosa showed no seasonal incidence. In relation to the causing organisms of respiratory infection with pneumoconiosis, it is very interesting that many organisms were isolated in the non-infected phase, and seasonal incidences were observed.
The gastric microflora of 21 cases receiving histamine H2-receptor antagonists (H2-blacker) were studied. Patients not given H2-blocker were also examined for gastric microflora. The gastric pH of patients who were receiving H2-blocker ranged from 1.91 to 6.51 (mean, 4.32). The gastric pH of over 5.00 was seen in 10 cases. Aerobic bacteria were isolated from 20 cases (95%). Aerobic bacterial counts per ml of gastric aspirates correlated positively with the pH of those aspirates but was little correlation between the pH of the gastric aspirates and the number of anaerobic bacteria of the samples, which were positive in 7 cases (33%). Candida and Staphylococcus were predominant isolates with positive rates of 82% and 41%, respectively. While Fusobacterium was isolated from 33% of the samples, none of the Bacteroides fragilis group organisms were isolated. It was also observed in the control group that aerobic and anaerobic bacteria were isolated from the gastric aspirates with high pH. These results suggest that in patients receiving H2-blocker anaerobes as well as aerobes may have the possibility to become pathogen for aspirate pneumonia and so on because of the overgrowth of anaerobic bacteria in the gastric fluid.
Epidemiology of rotavirus infection was studied from 1981 to 1988 mainly in three hospitals around Tokyo area. Major serotypes of rotaviruses in the three places were different from those in two hospitals around Kansai area in Japan (Ref. 6, 13), while, major serotypes were same among three hospitals. Both of serotypes 1 and 4 in group A were mostly found around Tokyo area. Frequencies of type 2, 3, and 9 in group A were low, although the frequencies were various among periods. Detail examinations of rotavirus RNA electropherotypes showed the results as follows; different electropherotypes were found during one winter season and at one hospital, the identical electropherotype was found cross a year and cross a hospital. We could not find the identical electropherotype which belong to two serotypes so far. Seven group C rotaviruses were found since 1987 in three hospitals. It would be important to examine RNA electropherotypes nd serotypes for long period not only for epidemiological studies but also for development of vaccine.
The compromised host has recently increased because of the improvement of medical diagnosis and technology. Infection in the compromised host is somewhat different from that in common patients, since this infection is caused by impairment of the host defense mechanism. And the compromised host easily suffers from opportunistic infections. This situation prompted us to study the effect of biological response modifiers (BRMs), which activate the host defense mechanism agaisnt infections in the compromised host. We used streptozotocin (STZ)-induced diabetic mice, as experimental models of the compromised host. First, we investigated the bactericidial capacity of the perineal exudating neutrophils in diabetic mice, as one of the host defense mechanism. Second, we also studied the effect of Granulocyte-Coloy Stimulating Factor (G-CSF) on diabetic mice with ascending pyelonephritis by P. aeruginosa. At 1 and 2 weeks after inducing the diabetic state, no difference was found in the bactericidal capacity of the perineal exudating neutrophils between normal mice and diabetic mice. At 3 weeks, however, this bactericidal capacity was markedly suppressed in these mice. This result suggested that a depression of host defense mechanisms in diabetics was caused by, in part, a suppression of bactericidal capacity of neutrophils. When G-CSF (2 μg/mouse) was injected subcutaneously once a day into diabetic mice, the suppression of the bactericidal capacity of neutrophils significantly recovered. We thus studied the effect of G-CSF on diabetic mice against infection. Diabetic mice increased their susceptibility to bacterial infection more than normal mice. In diabetic mice, administration of G-CSF (2 μg/mouse) yielded a lower incidence of infection and infection-induced mortality than those of controls. These data show that G-CSF may be of great value for prevention and treatment of opportunistic infections in the compromised host, especially in patients whose bactericidal capacity of neutrophils is depressed, as in diabetics.
We investigated the prophylactic effect of Ubenimex on mice with ascending pyelonephritis induced by Pseudomonas aeruginosa (G-group). This experimental model was established by a two course administration of cyclophosphamide, so that it kept the mice in a neutropenic status (around 2000 white blood cells/mm3) from the time of infection to the time of sacrifice. The cyclophosphamide-treated group increased their susceptibility more than the control group. In the cyclophosphamide-treated group, the prophylactic administration of Ubenimex (100μg/ day/mouse) did not produce significant decreases of infection-induced motality rate, but yielded a lower incidence of infection than of saline alone. Administration of Ubenimex was not able to increase the number of neutrophils during the experiment. An investigation of the bactericidal capacity of peritoneal exudating neutrophils revealed that Ubenimex prophylactic administration accelerated its capacity, although cyclophosphamide alone did not. These results suggest that Ubenimex has a prophylactic effect on bacterial infection in neutropenic mice, and that this effect, in part, depends upon the acceleration of bactericidal capacity of neutrophils produced by Ubenimex.