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Biomedical subjects

Kazuhiro Tateda

Publications and source records attributed to Kazuhiro Tateda.

49 records · Page 3Linked to original sources

The in vitro and in vivo antibacterial characterization of vancomycin and linezolid against vancomycin-susceptible and -resistant enterococci.

The present study was designed to compare in vitro antibacterial activities of linezolid and vancomycin against vancomycin-susceptible Enterococcus faecalis (VSEF) and vancomycin-resistant enterococci (VRE) isolated in Japan with those of quinupristin-dalfopristin, teicoplanin and minocycline, and the in vitro short time bactericidal activity and the in vivo activities of linezolid and vancomycin against vancomycin-susceptible and -resistant E. faecalis. The MIC90s of linezolid, quinupristin-dalfopristin, vancomycin, teicoplanin and minocycline for VSEF and VRE were both 2 mg/L, both 2 mg/L, 2 and >128 mg/L, 0.25 and >128 mg/L, and both 32 mg/L, respectively. The efficacy of linezolid for mice with bacteraemia caused by VSEF was similar to that of vancomycin, but the elimination ratio of viable organisms from the blood of mice treated with vancomycin was significantly higher than in linezolid-treated and untreated mice at 2 h post-administration, and those of the two groups at 4 and 6 h were significantly higher than in untreated mice. Moreover, linezolid was highly active in mice with bacteraemia caused by vancomycin-resistant E. faecalis because this drug had potent in vitro activity against the organisms. Our results indicate that linezolid is suitable for the treatment of VRE and VSEF bacteraemia, and vancomycin is suitable for VSEF bacteraemia.

Acetamides↗

[A case of falciparum malaria successfully treated with intravenous artesunate].

The case was a 28-year-old Japanese female who was considered to be infected with malaria in India. She manifested fever in Tokyo, Japan, and was brought to Toho University Hospital due to continuous high fever and severe thrombocytopenia. Ring forms at 11% of her RBCs and ICT Malaria P.f/P.v test was also positive for Plasmodium falciparum diagnosis. Not only the high parasitemia and delay of the diagnosis (6 days after the onset of fever), but also her DIC status required prompt and proper treatment. The diagnosis of severe malaria was strongly considered, and intravenous Artesunate (a qinghaosu derivative) was decided to be administered to the patient. After the four series of administration, mefloquine was subsequently given to prevent recrudescence. Parasite clearance time and fever clearance time were 24 hours and 108 hours, respectively. Thrombocytopenia was improved shortly after the treatment, but then anemia was once worsened with following gradual improvement. No other significant side effects were observed and no recrudescence occurred up to 8 months after her discharge. In Japan, very few cases treated with intravenous Artesunate were reported and our results showed its safe and excellent effect for a Japanese malaria patient.

Adult↗

[Evaluation of Streptococcus pneumoniae-urinary antigen detection kit in patients with community acquired pneumonia].

We evaluated a new rapid urinary antigen detection kit. NOW Streptococcus pneumoniae (Binax Inc., USA) that detected S. pneumoniae antigen by immunochromatographic membrane assay, with 66 Japanese adult patients of community acquired pneumonia. Twenty-two (33.3%) patients were found to be positive with the kit and S. pneumoniae was isolated from six patients (27.3%) of these 22 patients. S. pneumoniae was not isolated from eight of the 22 patients by blood or sputum culture. Analysis of clinical laboratory data showed that the levels of C-reactive protein (CRP) in the serum were significantly higher in the urine-antigen positive group than those in the urine-antigen negative group. There were no significant difference between the two groups including renal function, urinalysis, clinical symptom, and severity of pneumonia. Our study suggests that more cases of community acquired pneumonia are caused by S. pneumoniae than conventional tests can currently confirm. Since it is not technically complex, does not require equipment, and detects within as quickly as in 15 minutes, the S. pneumoniae urinary antigen kit is useful for rapid diagnosis of community acquired pneumonia in adults.

Adult↗

[Clinical characteristics in 8 sporadic cases of community-acquired Legionella pneumonia].

To study the clinical characteristics of community-acquired Legionella pneumonia, we carried out a study of 8 patients (7 men and a woman; mean age, 68.4 years) with Legionella pneumonia at Yaizu Municipal General Hospital between 1996 and 1999. We surmised that the sources of infection were travel or a hot spring, or both, in 4 cases, occupation (plumbing and fish market work) in 2 cases and gardening in one. All patients had fever above 38 degrees C, hypoxemia and a high inflammation reaction of. The initial findings of chest radiography were air-space consolidation in all cases, lobar pneumonia in 7, and unilateral shadows in 6, similar to those seen in acute Streptococcus pneumoniae pneumonia. Diagnostic methods were urinary antigen in 4 of 7 cases, bacterial culture in 4 of 6 cases (L. pneumophila, 3 cases; L. longbeachae, 1 case), polymerase chain reaction on the serum in 2 of 5 cases, and serum antibody in 1 of 7 cases. Urinary antigen was most useful for early diagnosis. The clinical presentation and the initial chest radiography findings were non-specific, despite the high fever, severe hypoxemia, and radical progression within a few days.

Aged↗

[From the perspective of clinical laboratory physicians].

In this symposium, how clinical laboratory doctors can contribute to diagnosis and management of infectious diseases will be discussed. A case of community-acquired pneumonia that was finally diagnosed as Legionella infection is presented, and the etiology and pathogenesis of pneumonia is discussed from the perspective of a clinical laboratory doctor. Community-acquired pneumonia (CAP) remains an important infectious disease, not only in developing countries but also in developed countries including Japan. Accumulating epidemiological data demonstrated that Streptococcus pneumonia remains a leading cause of CAP, followed by atypical pathogens, such as Legionella, Mycoplasma and Chlamydia. Recent progress in diagnostic methods has facilitated the rapid diagnosis of these infections by PCR and antigen detection. Especially, urinary antigen detection kits for S. pneumonia and L. pneumophila became available recently and these have proven to be convenient and reliable. Clinical laboratory doctors may contribute to the clinical side by providing these kinds of new information, such as epidemiology, diagnosis and antimicrobial chemotherapy. In addition, construction of reliable relationships between clinical doctors and clinical laboratory doctors may be prerequisite for efficient contribution of the laboratory side.

Clinical Laboratory Techniques↗

Protection against pulmonary infection with Klebsiella pneumoniae in mice by interferon-gamma through activation of phagocytic cells and stimulation of production of other cytokines.

The study was designed to determine the role of interferon (IFN)-gamma in inflammatory responses against experimentally induced pneumonia caused by Klebsiella pneumoniae. The host immunological responses in IFN-gamma gene knockout (IFN-gamma(-/-)) mice and immunocompetent control mice were compared. K. pneumoniae strain T-113 was inoculated intranasally into anaesthetised mice to induce pneumonia. Infected control mice survived significantly longer than infected IFN-gamma(-/-) mice. Viable bacterial counts in lungs and blood abruptly increased in IFN-gamma(-/-) mice; in contrast, a gradual decrease in the number of bacteria was noted in control mice. During the early stages of infection, the concentrations of interleukin (IL)-1beta and IL-6 in broncho-alveolar lavage fluid and IL-1beta in serum of IFN-gamma(-/-) mice were significantly lower than in control mice. During the late stage of infection, serum IL-6 level in IFN-gamma(-/-) mice was significantly higher than in control mice. These results suggest that the defective immunological host response, including inflammatory cytokine production caused by deficiency of IFN-gamma, is one of the mechanisms that allow the progression of pulmonary infection to systemic septicaemia.

Animals↗

Induction of interleukin-10 and down-regulation of cytokine production by Klebsiella pneumoniae capsule in mice with pulmonary infection.

The role of the capsule of Klebsiella pneumoniae in inducing cytokine production was investigated by comparing the responses of mice with experimentally induced pneumonia caused by capsulate (strain DT-S) or non-capsulate (mutant strain DT-X) K. pneumoniae. Anaesthetised ICR mice were inoculated intranasally. Whereas all DT-S-infected mice died within 3 days, no deaths were observed in DT-X-infected mice by 14 days after infection. During the early stage of infection, interferon-gamma (IFN-gamma) levels in bronchoalveolar lavage fluid (BALF) of DT-X-infected mice were significantly higher than those in DT-S-infected mice. In contrast, in the late stage of infection, serum levels of granulocyte macrophage-colony stimulating factor (GM-CSF) and IFN-gamma in DT-S-infected mice were significantly higher than those in DT-X-infected mice. Levels of interleukin10 (IL-10) in BALF and serum of DT-S-infected mice were significantly and persistently higher than those of DT-X-infected mice. The IL-10/TNF-alpha (tumour necrosis factor-a) ratios in BALF and serum indicated that higher levels of IL-10 production were induced in mice infected with strain DT-S than in those infected with strain DT-X. The results suggest that the capsule of K. pneumoniae may induce IL-10 production at the site of infection and, thereafter, these high IL-10 levels may serve to down-regulate the expression of pro-inflammatory cytokines.

Animals↗

Development of systemic bacteraemia after oral inoculation of vancomycin-resistant enterococci in mice.

Bacteraemia caused by vancomycin-resistant enterococci (VRE) is an important clinical problem because there are only a few potent antimicrobial agents against such bacteria. Therefore, understanding the pathogenic mechanisms of VRE bacteraemia is important for prophylaxis. This study shows that treatment of mice with cyclophosphamide and a combination of metronidazole, kanamycin and vancomycin reduced normal intestinal flora and induced systemic VRE bacteraemia. Translocation of VRE and the normal intestinal flora to the mesenteric lymph nodes, liver, spleen and blood, and mortality rate were dependent on treatment with cyclophosphamide and each of the three antimicrobial drugs. Among the different strains studied, C57BL/6 mice were the most susceptible to VRE. The virulence of vancomycin-resistant Enterococcus faecalis was greater than that of vancomycin-resistant Ent. faecium. On the day after inoculation of VRE, Escherichia coli was also detected in many VRE-positive specimens including blood, liver and the mesenteric lymph nodes. Moreover, both VRE and E. coli were detected simultaneously in almost all blood samples obtained from dead and dying mice, and VRE organisms outnumbered E. coli in those samples by 100:1 or more. These results indicate that changes in normal intestinal flora by administration of antimicrobial drugs and severity of neutropenia induced by cyclophosphamide are important factors that contribute to the development of systemic VRE bacteraemia. E. coli may be intimately associated with the establishment of VRE translocation.

Administration, Oral↗

Effects of interaction between Escherichia coli verotoxin and lipopolysaccharide on cytokine induction and lethality in mice.

In Escherichia coli 0157 infections, verotoxins (VT) play a critical role in causing the disease, although other factors such as lipopolysaccharide (LPS) and inflammatory cytokines may affect the progression and course of the disease. The present study examined the roles of VT and LPS in induction of serum cytokines and lethality in mice. LD50 of VT2 (13 ng) was c. 10(4)-fold smaller than that of LPS (400 microg). Although the lethal toxicity of these toxins was examined in several experimental conditions, such as VT2 (5, 10, 20, 40 ng/mouse) alone or in combination with LPS (100 microg/mouse) at various times (-2 days to +2 days), no evidence of synergy was observed. VT2 did not augment LPS-induced tumour necrosis factor-alpha (TNF-alpha) or interleukin-6 production, and conversely suppressed TNF-alpha production when it was injected 2 days before LPS challenge. The data failed to indicate either synergic or additive effects of VT and LPS on cytokine production or lethality in mice. In contrast, antagonistic interactions were clearly observed in cytokine production in certain conditions. The results suggested that these toxins may be co-operatively involvedin the pathology of VT-related diseases, but not through synergic interactions.

Animals↗

Role of bacterial capsule in local and systemic inflammatory responses of mice during pulmonary infection with Klebsiella pneumoniae.

The role of bacterial capsule in inflammatory responses in experimentally induced pneumonia caused by Klebsiella pneumoniae was evaluated by comparing the host immunological responses in mice infected with capsulate strain DT-S and non-capsulate mutant strain DT-X. Anaesthetised ICR mice were infected intranasally with inocula of strain DT-S or DT-X. Mice infected with strain DT-X survived significantly longer than those inoculated with strain DT-S. Viable bacterial counts in lungs and blood increased rapidly in mice infected with strain DT-S, in contrast to the gradual decrease in their density in lungs and intermittent bacteraemia in mice infected with strain DT-X. The number of broncho-alveolar lavage (BAL) cells in mice infected with strain DT-X at 24 h after inoculation was significantly higher than in those infected with strain DT-S. In the early stages of infection, the levels of tumour necrosis factor-a and interleukin-6 in BAL fluid of mice infected with strain DT-X were significantly higher than those of mice infected with strain DT-S. In contrast, in the late stage of infection, the levels of these cytokines in serum of mice infected with strain DT-S were significantly higher than in mice infected with strain DT-X. These results suggest that K. pneumoniae capsule may suppress the host immunological responses,thus allowing the bacteria to grow, causing pneumonia, septicaemia and death.

Animals↗

Factors affecting the course and severity of transnasally induced Staphylococcus aureus pneumonia in mice.

In order to examine several factors that may affect the course and severity of transnasally induced Staphylococcus aureus pneumonia in mice, bacteria were prepared in a free suspension or bound to fetal mouse cells. Immunosuppression was induced in five strains of mice (ICR, C57BL/6, BALB/c, C3H/He and CBA/J) by injection of cyclophosphamide (200 mg/kg body weight), 2 days before infection. Impairment of mucociliary clearance was induced by intranasal instillation of formalin. Mice were then infected with various doses and strains of the organism. Although no significant differences were observed between either form of inoculum, pretreatment with formalin plus cyclophosphamide was associated with a significant increase in lung bacterial counts. In particular, cyclophosphamide treatment was associated with a high mortality in mice infected with several strains of S. aureus irrespective of their toxin production profiles. Histopathological examination demonstrated that in mice treated with formalin plus cyclophosphamide, clusters of bacteria were observed in lung parenchyma, associated with a mild accumulation of inflammatory cells at day 2 and extensive cell infiltration at day 7. CBA/J mice represented the most susceptible strain among those examined, with 10(4)- and 10(2)-fold higher bacterial counts in the lungs at days 3 and 5, respectively. These results indicate that neutropenia and impaired mucociliary clearance are major factors that influence the severity of S. aureus pneumonia in mice. Analysis of the role of genetic background in enhancement of vulnerability to infection is warranted in future studies.

Animals↗

The pathogenic role of fimbriae of Haemophilus influenzae type b in murine bacteraemia and meningitis.

Complement activation and development of murine bacteraemia and meningitis following intranasal instillation of cell-bound fimbriated or non-fimbriated organisms were compared to clarify the role of fimbriae in the pathogenesis of illnesses caused by Haemophilus influenza type b (Hib). In-vitro resistance of non-fimbriate bacteria to the bactericidal effects of normal human serum was at least 400 times greater than that of fimbriate bacteria. The amount of C3 bound to fimbriate Hib was more than that to non-fimbriate Hib. When mice were infected with fimbriate bacteria, 11.5% died. When mice were infected with non-fimbriate bacteria, the mean number of viable organisms gradually increased or was constant up to day 7; 38.5% of these mice died. These in-vivo results were coincident with the in-vitro data. However, the content of polyribosyl ribitol phosphate (PRP) in fimbriate organisms was the same as in non-fimbriate organisms. These results indicate that fimbriate Hib may be less likely to produce bacteraemia and meningitis, correlating with the greater susceptibility to complement-mediated bacteriolysis and the lower mortality seen with this type of organism, although fimbriae increase adherence to epithelial cells (mucosal surface).

Animals↗

Effect of passive immunotherapy on murine gut-derived sepsis caused by Pseudomonas aeruginosa.

The effect of passive immunotherapy with antisera against heat-killed Pseudomonas aeruginosa and three of its exo-enzymes (elastase, alkaline protease and exotoxin A) in gut-derived P. aeruginosa sepsis was evaluated. Mice were given a suspension of P. aeruginosa strain D4 in their drinking water, together with ampicillin (200 mg/kg) to disrupt the normal bacterial flora. Cyclophosphamide was then administered to induce translocation of P. aeruginosa that had colonised the gastrointestinal tract so that gut-derived septicaemia was produced. In this model, intraperitoneal administration of antiserum against heat-killed bacteria, 100 microl/mouse, twice a day for 3 consecutive days significantly increased the survival rate over that of mice treated with normal rabbit serum. Antiserum against elastase, alkaline protease, or a combination of these two antisera, failed to provide significant protection. In contrast, antiserum against exotoxin A significantly increased the survival rate over that of mice treated with normal rabbit serum. These results indicate that passive immunisation with antiserum against heat-killed bacteria and exotoxin A, but not with antiserum against either elastase or alkaline protease, protects mice against gut-derived sepsis caused by P. aeruginosa.

ADP Ribose Transferases↗