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Biomedical subjects

Yoshitsugu Miyazaki

Publications and source records attributed to Yoshitsugu Miyazaki.

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↗

[A case of toxocariasis with eosinophilic pleural effusion].

A 76-year-old man admitted for general malaise with fever was found in clinical examination on admission to have eosinophilic pleural effusion, peripheral eosinophilia, and a slightly elevated inflammatory reaction. Immunological examination, including microplate ELISA, showed a high titer of specific antibody against Toxocara canis in both the serum and pleural effusion. We started treatment using albendazole, and found inflammatory findings and serum IgE were ameliorated. Parasitic disease is an important consideration in the differential diagnosis of eosinophilic pleural effusion, and serology is useful in screening for this.

Aged↗

[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↗

Fluconazole treatment is effective against a Candida albicans erg3/erg3 mutant in vivo despite in vitro resistance.

Candida albicans ERG3 encodes a sterol C5,6-desaturase which is essential for synthesis of ergosterol. Defective sterol C5,6 desaturation has been considered to be one of the azole resistance mechanisms in this species. However, the clinical relevance of this resistance mechanism is still unclear. In this study, we created a C. albicans erg3/erg3 mutant by the "Ura-blaster" method and confirmed the expected azole resistance using standard in vitro testing and the presence of ergosta-7,22-dien-3beta-ol instead of ergosterol. For in vivo studies, a wild-type URA3 was placed back into its native locus in the erg3 homozygote to avoid positional effects on URA3 expression. Defective hyphal formation of the erg3 homozygote was observed not only in vitro but in kidney tissues. A marked attenuation of virulence was shown by the longer survival and the lower kidney burdens of mice inoculated with the reconstituted Ura+ erg3 homozygote relative to the control. To assess fluconazole efficacy in a murine model of disseminated candidiasis, inoculum sizes of the control and the erg3 homozygote were chosen which provided a similar organ burden. Under these conditions, fluconazole was highly effective in reducing the organ burden in both groups. This study demonstrates that an ERG3 mutation causing inactivation of sterol C5,6-desaturase cannot confer fluconazole resistance in vivo by itself regardless of resistance measured by standard in vitro testing. The finding questions the clinical significance of this resistance mechanism.

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↗

Antimicrobial susceptibilities of potential bacterial pathogens in adults with acute respiratory tract infections Prospective Epidemiological Network Investigating Community-acquired Infection SurveiLLance In Nagasaki (PENICILLIN) Study.

The prevalence and the antimicrobial susceptibilities of bacterial pathogens in acute upper respiratory tract infections (AURTIs) is not clear. We conducted a prospective community-based multicenter study in 45 centers across Nagasaki, Japan, between December 2001 and April 2002. We examined the nasopharyngeal or throat isolates in 930 adult outpatients with AURTIs. Potential bacterial pathogens, including Streptococcus pyogenes (from 6.8% patients), S. pneumoniae (5.3%), S. milleri group (2.0%), Staphylococcus aureus (26.0%), Moraxella catarrhalis (7.4%), Haemophilus influenzae (17.6%), and Klebsiella pneumoniae (1.2%), were isolated from 51.8% of the patients. Penicillin nonsusceptible phenotype accounted for 44.9% of S. pneumoniae isolates. Among Staphylococcus aureus isolates, 9.1% were methicillin-resistant. In H. influenzae isolates, 6.7% produced beta-lactamase and 23.2% were beta-lactamase-negative ampicillin-resistant. The results indicated that the potential bacterial pathogens were detected in the remarkable population of the adults with AURTIs and the current antimicrobial susceptibilities of such pathogens.

Acute Disease↗

Regional variation in the prevalence of extended-spectrum beta-lactamase-producing clinical isolates in the Asia-Pacific region (SENTRY 1998-2002).

We examined the prevalence of extended-spectrum beta-lactamase (ESBL)-producing strains of Klebsiella pneumoniae, Klebsiella oxytoca, Escherichia coli, Proteus mirabilis, Citrobacter koseri, and Salmonella spp. that were isolated as part of the SENTRY Asia-Pacific Surveillance Program between 1998 and 2002. During the study period, a total of 6,388 strains were gathered from 17 medical centers in 7 countries and examined for ESBL production and hyperproduction of K. oxytoca chromosomal K1 beta-lactamase enzyme. High rates of confirmed ESBL-producing isolates were found in K. pneumoniae strains from Singapore (35.6%), followed by those from mainland China (30.7%), South Africa (28.1%), and the Philippines (21.9%), whereas the rates were less than 10% in Japan and Australia. ESBL-producing E. coli strains were also prominent in mainland China (24.5%), Hong Kong (14.3%), and Singapore (11.3%). ESBL-producing K. oxytoca were common in the Philippines (38.5%), Singapore (33.3%), and China (30.0%). Hyperproduction of K. oxytoca chromosomal K1 beta-lactamase enzyme was common in Australia and Japan. P. mirabilis strains from Singapore produced ESBL (17.9%) despite the low prevalence (0-8.1%) in other countries. Few ESBL-producing C. koseri and Salmonella spp. strains were found in Japan, Singapore, Taiwan, and South Africa. Although there was variation among countries in substrate preference, ceftazidime was more likely to detect presumptive ESBL phenotype in K. pneumoniae and aztreonam more likely in E. coli, whereas ceftriaxone was the best substrate for the confirmation of ESBL production. ESBL-producing strains showed high levels of co-resistance to aminoglycosides, tetracycline, trimethoprim-sulfamethoxazole, and ciprofloxacin. Imipenem retained activity against all ESBL-producing strains. Organisms expressing ESBLs are widely distributed in the Asia-Pacific region, although prevalence rates vary significantly.

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↗

Chronic necrotizing pulmonary aspergillosis following cryptococcal infection of the lung.

A 64-y-old male with steroid-induced diabetes mellitus was admitted to our hospital because of a nodular shadow found by chest radiography. Pathological examination revealed pulmonary cryptococcosis, and he was positive for serum Cryptococcus antigen. After oral treatment with fluconazole, he experienced clinical and radiographic improvement, but during ensuing observation without antifungal treatment his respiratory symptoms gradually worsened. Chest radiography showed progressive infiltration around the cavity, and Aspergillus mold was isolated by transbronchial lung biopsy from the lesion where previous cryptococcal infection was present. In addition, serum antibodies to Aspergillus antigens were demonstrated by immunodiffusion. Thus, pulmonary aspergillosis was found to complicate a case of pulmonary cryptococcal infection.

Aspergillosis↗

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↗

[A survival case of tetanus complicated with disseminated intravascular coagulation syndrome in the elderly, rescued by mechanical ventilation and administration of thiamylal].

A 78-year-old Japanese female was admitted to our hospital because of headache. Trismus, opisthotonus and convulsion appeared in the early morning on the second hospital day. She was diagnosed as tetanus based on these symptoms and the history of trauma on her left hand 6 days ago. A piece of bamboo was extracted from her left hand. However, Clostridium tetani was not identified. Thiamylal and mechanical ventilation were initiated combined with Pancronium, Diazepam and tetanus immune globulin. Gabexate Mesilate was also added for disseminated intravascular coagulation syndrome probably associated with rhabdomyolysis. By these treatments, she was healed leaving only a disuse syndrome of her limbs.

Aged↗