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Biomedical subjects

Yasuhito Higashiyama

Publications and source records attributed to Yasuhito Higashiyama.

At least 19 recordsLinked to original sources

Telithromycin inhibits the number of viable bacteria but not lymphocyte accumulation in a murine model of chronic respiratory infection.

The 14-membered macrolides, such as clarithromycin (CAM) and erythromycin (EM), are effective against diffuse panbronchiolitis. However, there have been no studies on the effects of telithromycin (TEL) on chronic respiratory infection in vivo. In this study, we determined the effect of TEL on an experimental murine model of chronic respiratory infection caused by Pseudomonas aeruginosa with biofilm formation. TEL significantly reduced the number of viable bacteria but had no effect on the proliferation of lymphocytes. In contrast, CAM decreased the number of lymphocytes but had no effect on the number of viable bacteria in the lung. These results suggest that TEL and CAM have different effects on chronic respiratory infection caused by P. aeruginosa.

Animals↗

Severe Japanese spotted fever successfully treated with fluoroquinolone.

A 77 years old woman who had a bite with eschar on her left arm, was admitted to emergency ward in our hospital, because of high fever, severe malaise, skin eruption, and consciousness disturbance beginning 5 days previously. She was diagnosed as Japanese spotted fever by seropositive of Rickettsia japonica (R. japonica) antibody, and successfully treated with fluoroquinolone, after minocycline hydrochloride had been proven ineffective. R. japonica-specific DNA was detected by PCR from the tick: Haemaphysalis hystricis larvae collected from a mountainous location in Fukuoka, Japan where the patient had been bitten.

Aged↗

Clinical comparative study of sulbactam/ampicillin and imipenem/cilastatin in elderly patients with community-acquired pneumonia.

OBJECTIVE: To evaluate the clinical usefulness of sulbactam/ampicillin therapy for community-acquired pneumonia in the elderly. METHODOLOGY: A randomized prospective clinical study was conducted in the elderly patients with moderate-to-severe community-acquired bacterial pneumonia. RESULTS: Overall clinical efficacy of sulbactam/ampicillin therapy (6 g/day) in these patients (efficacy rate: 91.4%) was comparable to that of imipenem/cilastatin therapy (1 g/day; efficacy rate: 87.5%), when each therapy was administered intravenously twice daily for 7-14 days. With regard to clinical efficacy based on disease severity, bacteriological efficacy, improvement of chest X-ray findings and adverse reactions, the two therapies were comparable. CONCLUSION: These results suggest that sulbactam/ampicillin therapy has excellent efficacy and tolerability and that it may be highly effective, even in severe cases of pneumonia. This regimen may thus serve as first-line treatment for the treatment of community-acquired pneumonia in elderly patients.

Age Factors↗

Potency of DX-619, a novel des-F(6)-quinolone, in haematogenous murine bronchopneumonia caused by methicillin-resistant and vancomycin-intermediate Staphylococcus aureus.

In this study, the potency of DX-619, a novel des-fluoro(6)-quinolone agent, was compared with that of vancomycin (VCM) in a murine model of haematogenous bronchopneumonia infection caused by methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-intermediate S. aureus (VISA). The minimum inhibitory concentrations (MICs) of DX-619 and VCM against MRSA were 0.03 microg/mL and 1.0 microg/mL, respectively, whilst the MICs against VISA were 0.125 microg/mL and 8.0 microg/mL, respectively. Treatment with DX-619 resulted in a significant decrease in the number of viable bacteria in the MRSA infection model (mean+/-standard error of the mean for control, VCM and DX-619 groups: 7.97+/-0.32, 7.19+/-0.33 and 2.91+/-0.60 log(10) colony-forming units/lung, respectively). For infection with VISA, mice were pre-treated with cyclophosphamide. The survival rate of mice treated with DX-619 (90% survival) was significantly higher than survival rates in the other two groups (45% both for VCM and control groups; P<0.05). Histopathological examination revealed that inflammatory changes in the DX-619-treated group were less marked than in the other two groups. The parameters in lung tissue for the area under the concentration-time curve/MIC ratio both for MRSA and VISA were higher in the DX-619 group than in the VCM group. Our results emphasise the potency of DX-619 against MRSA and VISA murine haematogenous pulmonary infection.

Animals↗

A case of Mycobacterium nonchromogenicum pulmonary infection showing multiple nodular shadows in an immunocompetent patient.

Mycobacterium nonchromogenicum is generally considered nonpathogenic. However, M. nonchromogenicum rarely causes human disease; particularly, pulmonary disease is extremely rare. The common finding of M. nonchromogenicum pulmonary infection on chest X-ray is a solitary cavity. The present report describes an unusual case of M. nonchromogenicum primary pulmonary infection showing multiple nodular shadows.

Adult↗

Quorum sensing system lactones do not increase invasiveness of a MexAB-OprM efflux mutant but do play a partial role in Pseudomonas aeruginosa invasion.

We studied the quorum sensing (QS) system and the related homoserine lactones (HSLs) observing Pseudomonas aeruginosa invasion using the epithelial cell monolayer penetration assay model. Compared to the PAO1 wild-type, the QS mutants, DeltalasI and DeltarhlI, were compromised in their capacity to invade. The decreased invasiveness of DeltarhlI was restored by adding 100 microM exogenous C(4)-HSL. However, the decreased invasiveness of an efflux mutant, DeltamexAB-oprM, was not restored in the presence of exogenous HSLs. The QS system partially plays a role in P. aeruginosa invasion; however, C(4)-HSL and 3-O-C(12)-HSL are not the essential determinants for invasiveness for P. aeruginosa.

4-Butyrolactone↗

[Case report of disseminated nocardiosis complicated in an elderly person with pneumoconiosis].

Nocardia is typically regarded as an opportunistic infection, with pulmonary nocardiosis frequently disseminated to organs hematogenous by, and nearly half of these cases resulting in complicated nocardia brain abscess. Disseminated nocardia has a dismal prognosis with high mortality, and should be checked for multiple organs including the brain when nocardiosis is diagnosed. We describe the successful treatment of nocardia brain abscesses in an immunocompetent older people with pneumoconiosis by combining trimethoprim-sulfamethoxazole and ciprofloxacin. Patients had no history of fever, headache, or respiratory symptoms such as cough, or sputum until the acute hemiplegia episode. Nocardia infection is not as rare as generally assumed and should be considered as a possibility in the elderly due to its high mortality.

Aged, 80 and over↗

In vivo efficacies and pharmacokinetics of DX-619, a novel des-fluoro(6) quinolone, against Streptococcus pneumoniae in a mouse lung infection model.

DX-619 is a novel des-fluoro(6) quinolone with potent activity against gram-positive pathogens. The in vivo activity of DX-619 against Streptococcus pneumoniae was compared with those of fluoro(6) quinolones, sitafloxacin, and ciprofloxacin in a mouse model. Two strains of S. pneumoniae were used: a penicillin-sensitive S. pneumoniae (PSSP) strain and a penicillin-resistant S. pneumoniae (PRSP) strain. Furthermore, these strains showed intermediate susceptibilities to ciprofloxacin. In murine lung infections caused by PSSP, the 50% effective doses (ED50s) of DX-619, sitafloxacin, and ciprofloxacin were 9.15, 11.1, and 127.6 mg/kg of body weight, respectively. Against PRSP-mediated pneumonia in mice, the ED50s of DX-619, sitafloxacin, and ciprofloxacin were 0.69, 4.84, and 38.75 mg/kg, respectively. The mean +/- standard error of the mean viable bacterial counts in murine lungs infected with PSSP and treated with DX-619, sitafloxacin, ciprofloxacin (10 mg/kg twice daily), and saline (twice daily) were 1.75 +/- 0.06, 1.92 +/- 0.23, 6.48 +/- 0.28, and 7.57 +/- 0.13 log10 CFU/ml, respectively. Furthermore, the numbers of viable bacteria in lungs infected with PRSP and treated with the three agents and not treated (control) were 1.73 +/- 0.04, 2.28 +/- 0.17, 4.61 +/- 0.59, and 5.54 +/- 0.72 log10 CFU/ml, respectively. DX-619 and sitafloxacin significantly decreased the numbers of viable bacteria in the lungs compared to the numbers in the lungs of ciprofloxacin-treated and untreated mice. The pharmacokinetic parameter of the area under the concentration-time curve (AUC)/MIC ratio in the lungs for DX-619, sitafloxacin, and ciprofloxacin were 171.0, 21.92, and 1.22, respectively. The AUC/MIC ratio in the lungs was significantly higher for DX-619 than for sitafloxacin and ciprofloxacin. Our results suggest that DX-619 and sitafloxacin are potent against both PSSP and PRSP in our mouse pneumonia model.

Animals↗

Effects of short interfering RNA against methicillin-resistant Staphylococcus aureus coagulase in vitro and in vivo.

OBJECTIVES: The emergence of antibiotic-resistant bacteria such as Staphylococcus aureus calls for inventive research and development strategies. Inhibition of bacterial pathogenesis may be a promising therapeutic approach in this regard. The gene-silencing effect of short interfering RNA (siRNA) is useful for this strategy. We investigated the efficacy of siRNA on the expression of coagulase because it is the one of the most important enzymes in the pathogenesis of methicillin-resistant S. aureus (MRSA) infection. METHODS: We designed and synthesized 21 bp siRNA duplexes against staphylococcal coagulase. RT-PCR was performed to determine whether the siRNAs inhibit the expression of the coagulase mRNA and radio-labelled siRNA was used to confirm transfection to bacteria in vitro. The efficacy of siRNA was determined in a murine model of haematogenous pulmonary infection. RESULTS: RT-PCR showed that siRNAs significantly inhibited the expression of the coagulase mRNA. The coagulase titres in the siRNA and control groups were 8 and 32, respectively. Measurement of incorporated radioactivity indicated that the siRNAs were delivered into the bacteria. In the murine infection model, in control and siRNA groups, 7.64 +/- 0.42 and 6.29 +/- 0.23 log cfu/mL (mean +/- SEM) MRSA were detected, respectively, showing that there was a significant decrease in the number of viable bacteria in the siRNA group (P < 0.05). CONCLUSIONS: The results show that siRNA inhibited both mRNA expression and the activity of MRSA coagulase in vitro. The in vivo results revealed that the siRNA was effective in reducing the bacterial load in a murine model of haematogenous pulmonary infection. Targeting of coagulase with siRNA appears to be a novel strategy for treating MRSA infections.

Animals↗

Evaluation of the BD Phoenix Automated Microbiology System SMIC/ID panel for identification and antimicrobial susceptibility testing of Streptococcus spp.

The BD Phoenix Automated Microbiology System SMIC/ID panel was evaluated for identification and antimicrobial susceptibility testing (AST) of various streptococci. A group of 97 consecutive clinical isolates of Streptococcus pneumoniae, 23 Streptococcus pyogenes, 24 Streptococcus agalactiae, and 34 viridans streptococci were collected and comparisons made with routine manual methods used in the clinical microbiology laboratory. Overall, in 162 (91%) of 178 isolates, Phoenix identification results demonstrated agreement. For AST results for the 162 isolates that demonstrated identification concordance, the overall essential agreement rate was 98.5%; the category agreement was 94.9%; and the very major error, major error, and minor error rates were 0%, 0.15%, and 5.8%, respectively. Although relatively high minor error rates were observed with S. pneumoniae and beta-lactams, 79.2% of the 77 minor errors were the result of a single log(2) dilution difference. The Phoenix SMIC/ID panel performed favorably and demonstrated the advantages of automation and simple methodology.

Anti-Bacterial Agents↗

Community acquired pneumonia (CAP) caused by Cryptococcus neoformans in a healthy individual.

A 41-y-old male had been diagnosed as having community acquired pneumonia (CAP) with consolidations in the chest radiograph, fever and cough. Since clarithromycin and ss-lactam agents were not effective, bronchoscopic examination was performed. Indian ink staining of bronchial wash smears revealed yeast-like cells with a thick capsule, and Cryptococcus neoformans was isolated several d later. Serum glucuronoxylomannan antigen was > or = x 1024. The patient was treated with itraconazole for 16 weeks.

Adult↗

Role of Pseudomonas aeruginosa quorum-sensing systems in a mouse model of chronic respiratory infection.

The role of quorum-sensing systems in a mouse model of chronic Pseudomonas aeruginosa infection was studied. A chronic P. aeruginosa respiratory infection model was established by placement of a tube pre-coated with strain PAO1 (wild-type) or a quorum-sensing mutant, namely PAO-JP1 (Delta lasI), PDO100 (Delta rhlI) or PAO-JP2 (Delta lasI/Delta rhlI), in the bronchus. At day 14 after infection, the numbers of viable bacteria in the quorum-sensing-mutant groups were lower than in the wild-type group. Histopathological examination showed milder inflammatory changes in the lungs infected with the mutant groups compared with the wild-type group. In the bronchoalveolar lavage fluid from the quorum-sensing-system-mutant groups the proportion of neutrophils was lower than in wild-type group. These findings indicate that the quorum-sensing system plays an important role in chronic P. aeruginosa respiratory infection.

Animals↗

[Clinical studies of sixteen cases with pulmonary cryptococcosis mainly with respect to serum level of cryptococcal antigen].

Clinical studies of sixteen cases with pulmonary cryptococcosis, during the past six years between 1998 and 2004, were peformed mainly with respect to serum cryptococcal antigen titer. Serum cryptococcal antigen was positive in twelve of 16 cases, the other three cases were diagnosed by VATS, the other one by positive culture of cryptococcus in BALF. In these twelve cases, the serum cryptococcal antigen titer was continuously tested after treatment. The serum cryptococcal antigen titer decreased from half to 6 months after treatment. And the cryptococcal Ag changed to negative in six of the 12 cases by antifungal agents from 5 to 19 months. But four cases whose pneumonia was severe tended to have a high titer level of cryptococcal antigen and were positive for a long period. In the Chest CT of four pulmonary cryptococcosis case with negative cryptococcal antigen, all of the maximum nodule size was less than or equal to 15mm in diameter.

Adult↗

Azithromycin exhibits bactericidal effects on Pseudomonas aeruginosa through interaction with the outer membrane.

The aim of the present study was to elucidate the effect of the macrolide antibiotic azithromycin on Pseudomonas aeruginosa. We studied the susceptibility to azithromycin in P. aeruginosa PAO1 using a killing assay. PAO1 cells at the exponential growth phase were resistant to azithromycin. In contrast, PAO1 cells at the stationary growth phase were sensitive to azithromycin. The divalent cations Mg2+ and Ca2+ inhibited this activity, suggesting that the action of azithromycin is mediated by interaction with the outer membranes of the cells, since the divalent cations exist between adjacent lipopolysaccharides (LPSs) and stabilize the outer membrane. The divalent cation chelator EDTA behaved in a manner resembling that of azithromycin; EDTA killed more PAO1 in the stationary growth phase than in the exponential growth phase. A 1-N-phenylnaphthylamine assay showed that azithromycin interacted with the outer membrane of P. aeruginosa PAO1 and increased its permeability while Mg2+ and Ca2+ antagonized this action. Our results indicate that azithromycin directly interacts with the outer membrane of P. aeruginosa PAO1 by displacement of divalent cations from their binding sites on LPS. This action explains, at least in part, the effectiveness of sub-MICs of macrolide antibiotics in pseudomonal chronic airway infection.

Anti-Bacterial Agents↗

A probable case of aspiration pneumonia caused by Candida glabrata in a non-neutropenic patient with candidemia.

Primary Candida pneumonia is rare, and detailed reports of Candida glabrata pneumonia have not been described. A 71-year-old woman had been treated for heart failure and developed aspiration pneumonia, which was refractory to antibacterial treatment. Antifungal treatment against C. glabrata resulted in resolution of pneumonia and candidemia. We report a probable case of C. glabrata pneumonia.

Aged↗

[Case reports of the treatment with tobramycin solution for inhalation in severe bronchiectasis patients continuous infection of Pseudomonas aeruginosa].

Aerosolized tobramycin has been frequently used in cystic fibrosis patients in order to directly deliver the antibiotic to the endobronchial site of infection. Recently, we experienced three cases of severe chronic bronchial infection of Pseudomonas aeruginosa treated by aerosolized tobramycin inhalation (TOBI). For two cases, we succeeded in improving the patient's medical condition, quality of life, and reduced the amount of sputum. We consider that TOBI should be useful for chronic bronchial infection by Pseudomonas aeruginosa in the case of a patient who does not respond to usual antibiotics via other routes. But further investigation is necessary to reveal clinical efficacy and safety in non-CF patients with bronchiectasis.

Administration, Inhalation↗

[A case of brain metastasis discovered after surgery for lung cancer based on changes in CEA, in which long-term survival was obtained by repeated gammaknife irradiation].

A 58-year-old man underwent right lower lobectomy for lung adenocarcinoma in June 1998. Since a high level of tumor marker CEA persisted after surgery, chemotherapy was additionally performed, and the CEA level subsequently normalized. However, the CEA level increased in April 1999, and brain metastasis was found in the left occipital lobe, and the first gammaknife irradiation was performed. Multiple brain metastases were found when CEA increased again in August 1999, and the second gammaknife irradiation was performed. Moreover, brain metastases were found in the left frontal and occipital lobes in February 2000, and the third gammaknife irradiation was performed. CEA normalized thereafter, but increased in February 2001. Brain metastasis was found in the right occipital lobe, and the fourth gammaknife irradiation was performed. CEA has remained within the normal range for about 4 years thereafter. Long-term survival was possible by repeated gammaknife irradiation for brain metastases. Monitoring of CEA played an important role in finding recurrent brain metastasis in this patient.

Adenocarcinoma↗