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Biomedical subjects

Toshiyuki Yamaguchi

Publications and source records attributed to Toshiyuki Yamaguchi.

6 recordsLinked to original sources

Clinical and bacteriological characteristics of IMP-type metallo-beta-lactamase-producing Pseudomonas aeruginosa.

IMP-type metallo-beta-lactamase-producing bacteria have recently emerged worldwide. We conducted a case-control study in which 69 inpatients harboring bla(IMP)-positive Pseudomonas aeruginosa and 247 control subjects with bla(IMP)-negative pathogens were investigated. Prolonged hospitalization, antineoplastic chemotherapy, corticosteroid therapy (P=.001), and indwelling urinary catheters (P=.04) were risk factors for isolation of bla(IMP)-positive pathogens. The predominant source was urine (P=.001). The duration of antibiotic treatment and the total dose (including of carbapenems) were significantly greater among case patients than among control subjects (P<.01). bla(IMP)-positive P. aeruginosa isolates were more frequently resistant to multiple drugs (P=.001) and caused more infections (P=.001) than bla(IMP)-negative pathogens. There were no significant differences in bacteriological outcome (P=.94); however, infection-related death was more frequent among case patients than among control subjects (P=.023). These results suggest that precautionary measures against the spread of bla(IMP)-positive isolates are needed, because, for most of such pathogens, no antibiotic is potent enough to be used as a single agent in treatment of infection.

Anti-Bacterial Agents↗

[Candidiasis].

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Antifungal Agents↗

An elderly patient with hemophagocytic syndrome due to severe mycoplasma pneumonia with marked hypercytokinemia.

We present an extremely rare case of hemophagocytic syndrome (HPS) induced by fulminant Mycoplasma pneumoniae (Mp) pneumonia in an elderly adult. Erythrocytopenia and thrombocytopenia were observed in a patient with acute respiratory failure, liver dysfunction and renal failure. Mp-associated HPS was diagnosed in this case by clinical and laboratory findings, including a bone marrow aspiration specimen and serum Mp antibody titer. High serum levels of soluble interleukin-2 receptor, interleukin-6, human interleukin-10 and macrophage-colony stimulating factor were observed. Hypercytokinemia is a useful marker of disease activity and prognosis. Combined treatment with methylprednisolone and erythromycin was successful and led to a favorable outcome. Physicians should be aware of HPS as a complication in Mp infection.

Aged↗

Prolonged survival of mice with Pseudomonas aeruginosa-induced sepsis by rIL-12 modulation of IL-10 and interferon-gamma.

Interleukin-12 (IL-12) is thought to play an important role as a modulator of levels of IL-10 and interferon-gamma (IFN-gamma). To address the therapeutic effects of rIL-12 in an endogenous sepsis model in mice, which closely mimics the pathophysiology of septicaemia in man, the effects of rIL-12 on the levels of cytokines such as IL-10 and IFN-gamma, and on the survival of septic mice infected with Pseudomonas aeruginosa PAO1 were examined. First, in the endogenous sepsis model, the serum levels of IFN-gamma and IL-10 remained normal until days 8 and 10, respectively, when significant rises were seen. On day 11, levels of IFN-gamma returned to normal, but levels of IL-10 remained high. Interestingly, the IL-10 serum level reached a maximum 2 days later than the IFN-gamma serum level. In the light of these results, septic mice were given 0.01 microg of rIL-12 by intraperitoneal injection and the serum levels of endogenous cytokines and the survival times were examined. Mice treated with rIL-12 on days 5, 6 and 7 after infection survived significantly longer than control septic mice treated with saline only. Treatment with rIL-12 also led to a significant increase of the serum IFN-gamma level and a decrease of the serum IL-10 level on day 11. These results suggest that rIL-12 exerts therapeutic activity against endogenous sepsis caused by P. aeruginosa by stimulating proinflammatory responses and attenuating anti-inflammatory responses.

Animals↗

Two sporadic cases of infections due to Klebsiella pneumoniae resistant to expanded-spectrum cephalosporins in Japan.

TEM- or SHV-type extended-spectrum beta-lactamases (ESBLs) are of clinical concern in Europe and the United States, whereas bacterial strains producing such types of ESBLs have not been reported in Japan. We report here two cases of infection due to Klebsiella pneumoniae resistant to extended-spectrum cephalosporins in Japan. A ceftadizime-resistant K. pneumoniae strain (minimum inhibitory concentration; 32 &mgr;g/ml) was isolated transiently from the sputum of an 87-year-old woman with acute myocardial infarction and pneumonia (patient 1). Ceftadizime-susceptible and -resistant (minimum inhibitory concentration; >/=8 &mgr;g/ml) K. pneumoniae strains were isolated over a month from the blood, ascites, and feces of a 44-year-old man after bone marrow transplantation for acute lymphoblastic leukemia (patient 2); this patient died of K. pneumoniae sepsis and peritonitis followed by multiple organ failure. These isolates produced penicillinase, which was inhibited by clavulanic acid. A polymerase chain reaction (PCR) study showed that both isolates carried the SHV or LEN genes, but not the TEM, Toho-1, and IMP-1 genes. The pulsed-field gel electrophoresis profile of the strain isolated from patient 1 was genetically distinguishable from the profiles of the strains isolated from patient 2. It appeared that mutation of the beta-lactamase gene may have occurred in the body of patient 2, since the genotypes of the ceftadizime-susceptible and -resistant isolates from this patient were identical. Another 12 strains of K. pneumoniae, isolated from other patients in the same wards during the period in which the K. pneumoniae strains were isolated from patients 1 and 2, did not produce ESBLs and showed different genotypes. The results suggest that these isolates of resistant K. pneumoniae did not spread by cross transmission in the hospital and that the two cases were sporadic. Surveillance of these types of resistant bacteria is necessary, since they may well be present in other hospitals in Japan. Although the organisms are suspected to produce SHV-type ESBLs or LEN-1 variant beta-lactamases, further studies are necessary to specify the resistance genes.

Journal Article↗

Effect of Pseudomonas aeruginosa exotoxin A on endotoxin-induced tumour necrosis factor production in murine lung.

The ability of several Pseudomonas aeruginosa exo-enzymes, including exotoxin A (ETA), to induce inflammation and their influence on endotoxin-induced tumour necrosis factor (TNF) production in murine lung were evaluated. Intratracheal administration of lipopolysaccharide (LPS; 0.1-10 microg/mouse), 2(-1) LD50 of P. aeruginosa alkaline protease (7.5 microg/mouse) and elastase (1.2 microg/mouse) elevated total cell number and the percentage of neutrophils in broncho-alveolar lavage fluid (BALF), whereas ETA (0.1 microg/mouse) did not. LPS induced TNF production in BALF in a dose-dependent manner, whereas the P. aeruginosa exo-enzymes did not. When ETA was inoculated into the respiratory tract before LPS, production of TNF in BALF was significantly suppressed in a dose-dependent manner. ETA also suppressed TNF production by alveolar macrophages (AMs) stimulated with LPS in vitro. Flow cytometric analysis showed that ETA markedly reduced the expression of CD14 and CD11c/CD18 on the surface of AMs. ETA also depressed partially the expression of TNF-alpha mRNA in AMs. These findings suggest that ETA regulates TNF production in murine lung by suppressing LPS receptor expression, mRNA expression and protein synthesis and/or secretion of TNF.

ADP Ribose Transferases↗