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Biomedical subjects

Takashi Shinzato

Publications and source records attributed to Takashi Shinzato.

At least 19 recordsLinked to original sources

In vitro activity of sitafloxacin compared with several fluoroquinolones against Streptococcus anginosus and Streptococcus constellatus.

The in vitro activities of sitafloxacin and seven other fluoroquinolones a (ciprofloxacin, tosufloxacin, sparfloxacin, levofloxacin, T-3811ME, moxifloxacin and trovafloxacin) were examined by the microdilution method against 79 clinically isolated 'Streptococcus milleri' group (SMG) microorganisms. No statistically significant differences were found between the minimum inhibitory concentrations (MIC(50) and MIC(90)) against Streptococcus anginosus and Streptococcus constellatus. Sitafloxacin was the most active agent of the eight fluoroquinolones tested against SMG, with a MIC(90) of 0.06 microg/mL, which was 8 times more active than ciprofloxacin and 16 times more active than levofloxacin. Although none of the SMG strains showed high resistance to any of the fluoroquinolones tested, three agents (trovafloxacin, sitafloxacin and T-3811ME) had low MICs against 23 SMG strains against which levofloxacin had a MIC> 1 microg/mL. In conclusion, several fluoroquinolones have low MICs against SMG, but sitafloxacin has the lowest.

Anti-Bacterial Agents↗

In vitro activity of pazufloxacin, tosufloxacin and other quinolones against Legionella species.

OBJECTIVES: The activities of pazufloxacin and tosufloxacin against Legionella spp. were evaluated in vitro and compared with those of other quinolones, macrolides and azithromycin. METHODS: The conventional MICs were determined by the microbroth dilution method. Intracellular activities of drugs were evaluated by a cfu count. The minimal extracellular concentration inhibiting intracellular growth of bacteria (MIEC) was determined by a colorimetric cytopathic assay. RESULTS: MICs of pazuloxacin and tosufloxacin at which 90% (MIC90) of isolates are inhibited in 76 different Legionella spp. strains (38 ATCC strains and 38 clinical isolates) were 0.032 and 0.016 mg/L, whereas the MIC90s of levofloxacin, ciprofloxacin, garenoxacin, erythromycin, clarithromycin and azithromycin were 0.032, 0.032, 0.032, 2.0, 0.125 and 2.0 mg/L, respectively. Pazufloxacin and tosufloxacin at 4x MIC inhibited intracellular growth of Legionella pneumophila SG1 (80-045 strain), as did other quinolones, clarithromycin and azithromycin, whereas erythromycin at 4x MIC did not. MIECs of pazufloxacin, tosufloxacin, levofloxacin, ciprofloxacin and garenoxacin for the strain were 0.063, 0.004, 0.016, 0.032 and 0.008 mg/L respectively, which were superior to those of macrolides and azithromycin. Pazufloxacin showed potent activity against three additional clinical isolates of L. pneumophila SG1, one clinical isolate each of L. pneumophila SG3 and SG5, as well as Legionella micdadei, Legionella dumoffii and Legionella longbeachae SG1. CONCLUSIONS: Pazufloxacin and tosufloxacin, as well as other quinolones, were more potent than macrolides and an azalide. Present data warrant further study on the efficacy of these drugs in the treatment of Legionella infections.

Animals↗

Efficacy of pazufloxacin mesilate in Legionnaires' disease: a case report and in vitro study of the isolate.

We report here a case of culture-proven Legionnaires' disease successfully treated with intravenous injection of pazufloxacin mesilate (PZFX), a fluoroquinolone newly approved in Japan. The patient was a 51-year-old man hospitalized after a diagnosis of community-acquired pneumonia. Legionella pneumophila SG1 was isolated from the patient's bronchoalveolar lavage (BAL) fluid, and the soluble antigen of the bacterium was detected in the fluid as well. Subsequently, intravenous PZFX was administered for a week and proved markedly effective. An in vitro study confirmed that PZFX had excellent extracellular and intracellular activity against the isolate from the patient. This case suggests that PZFX is an option for treating Legionnaires' disease.

Anti-Bacterial Agents↗

[Two cases of pulmonary aspergillosis successfully treated with combinated micafungin and itraconazole therapy].

We report 2 cases of pulmonary aspergillosis treated successfully by combining micafungin and traconazole. Case 1: A 51-year-old man with hemoptysis and dyspnea on effort treated for pulmonary tuberculosis and aspergillosis was found on chest CT on admission to have a fungus ball in the left upper lobe and increasing consolidation around the cavity of both lung fields. Bronchoscopy proved positive for aspergillus PCR in bronchial lavage. He was diagnosed with chronic necrotizing pulmonary aspergillosis, based on clinical and radiological findings and the positive reaction for aspergillus PCR. He was treated with micafungin alone at first, this proved ineffective, so itraconazole was added, resulting in improvement. Case 2: A 24-year-old woman with stabilized Hodgkin's disease (mixed). She had suffered from a cough and back pain, and chest CT showed increasing consolidation inside and around a giant bulla. She was diagnosed with chronic necrotizing pulmonary aspergillosis, based on isolation for Aspergillus sp. in sputum culture and a positive reaction for Aspergillus antigen in bronchial lavage and Aspergillus antibody in serum. She was treated with the combined micafungin and itraconazole, which rapidly improved symptoms and radiological findings. Pulmonary aspergillosis therapy is often difficult, because delivery of the drug to the infection site is limited and drug tolerance is poor. We found that combination micafungin and itraconazole therapy is tolerable and effective in these cases.

Adult↗

Legionella pneumophila NudA Is a Nudix hydrolase and virulence factor.

We studied the identity and function of the 528-bp gene immediately upstream of Legionella pneumophila F2310 ptsP (enzyme I(Ntr)). This gene, nudA, encoded for a Nudix hydrolase based on the inferred protein sequence. NudA had hydrolytic activity typical of other Nudix hydrolases, such as Escherichia coli YgdP, in that Ap(n)A's, in particular diadenosine pentaphosphate (Ap(5)A), were the preferred substrates. NudA hydrolyzed Ap(5)A to ATP plus ADP. Both ptsP and nudA were cotranscribed. Bacterial two-hybrid analysis showed no PtsP-NudA interactions. Gene nudA was present in 19 of 20 different L. pneumophila strains tested and in 5 of 10 different Legionella spp. other than L. pneumophila. An in-frame nudA mutation was made in L. pneumophila F2310 to determine the phenotype. The nudA mutant was an auxotroph that grew slowly in liquid and on solid media and had a smaller colony size than its parent. In addition, the mutant was more salt resistant than its parent and grew very poorly at 25 degrees C; all of these characteristics, as well as auxotrophy and slow-growth rate, were reversed by transcomplementation with nudA. The nudA mutant was outcompeted by about fourfold by the parent in competition studies in macrophages; transcomplementation almost completely restored this defect. Competition studies in guinea pigs with L. pneumophila pneumonia showed that the nudA mutant was outcompeted by its parent in both lung and spleen. NudA is of major importance for resisting stress in L. pneumophila and is a virulence factor.

Amino Acid Sequence↗

[Smallpox].

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Animals↗

The role of the capsule of the Streptococcus milleri group in its pathogenicity.

Study of the pathogenicity of encapsulated strains of the Streptococcus milleri group (SMG) was performed by examination of the ability to cause subcutaneous abscesses in mice and by phagocytosis and phagocytic killing of human polymorphonuclear neutrophils (PMNs) against the organisms. All 3 encapsulated isolates from patients with pneumonia or lung abscess induced abscesses in the mice; however, only 2 of 20 unencapsulated isolates from patients with lung abscess or thoracic empyema did so. The 3 encapsulated strains inhibited more phagocytosis and phagocytic killing of PMNs than the unencapsulated strains. In addition, encapsular material separated from Streptococcus constellatus RZYK001 also inhibited phagocytosis and phagocytic killing in proportion to increasing concentrations of the capsular material. These results suggest that capsular material produced by SMG might be a pathogenic factor.

Abscess↗

Pulmonary strongyloidiasis in a patient receiving prednisolone therapy.

Strongyloidiasis is widely distributed in tropical and subtropical areas. Disseminated strongyloidiasis may develop in patients with immunodeficiencies. In the absence of early diagnosis and treatment, the prognosis of disseminated strongyloidiasis is extremely poor. We report a case of pulmonary strongyloidiasis that was successfully treated. The patient was an 83-year-old woman who had been receiving long-term oral prednisolone therapy for uveitis. The patient visited our emergency department complaining of breathing difficulties and diarrhea. A chest X-ray revealed a diffuse enhancement of interstitial shadows. A bronchoalveolar lavage (BAL) was performed, and both Gram staining and Grocott's staining revealed the presence of multiple filariform larvae of Strongyloides stercoralis in the bronchoalveolar lavage fluid (BALF). A stool examination performed at the same time also yielded S. stercoralis. The patient was diagnosed as having pulmonary strongyloidiasis and was treated with thiabendazole and ivermectin, in addition to antimicrobial agents; her respiratory symptoms and diarrhea improved, and S. stercoralis was not detected in subsequent follow-up examinations thereafter. In endemic areas of S. stercoralis, pulmonary strongyloidiasis should be considered as part of a differential diagnosis if chest imaging findings like alveolar and interstitial shadow patterns or lobar pneumonia are seen in patients with immunodeficiencies.

Adrenal Cortex Hormones↗

In vitro and in vivo activity of olamufloxacin (HSR-903) against Legionella spp.

The activity of the fluoroquinolone olamufloxacin (HSR-903) against Legionella spp. was studied in vitro and in vivo. The olamufloxacin MIC at which 50% of isolates are inhibited (MIC50) for 81 different Legionella spp. strains (59 type strains and 22 clinical isolates) was 0.008 mg/L, which was identical to sparfloxacin, whereas the MIC50s for erythromycin, levofloxacin and ciprofloxacin were 0.25, 0.032 and 0.032 mg/L, respectively. Olamufloxacin and sparfloxacin (at 0.008 mg/L) inhibited intracellular growth and subsequent cytotoxicity of L. pneumophila 80-045 in J774.1 macrophages, whereas levofloxacin and ciprofloxacin did not, at the same concentration. When olamufloxacin was given to the infected guinea pigs orally (5 mg/kg of body weight), peak levels in the lung were 3.02 mg/kg at 2 h post-administration, with a half-life of 3.41 h and an AUC0-12 of 12.31 mg.h/kg. The 2 day post-infection bacterial burden of the lung in the animals treated with olamufloxacin (5 and 1.25 mg/kg given orally twice a day) was much lower than in those treated with levofloxacin (same dose as olamufloxacin) or erythromycin (10 mg/kg given orally twice a day). When treated with olamufloxacin (5 mg/kg given orally twice a day) for 7 days, 11 of 12 L. pneumophila-infected guinea pigs survived for 14 days post-infection, as did all 12 guinea pigs treated with levofloxacin (5 mg/kg given orally twice a day) for 7 days. In contrast, only two of 12 animals treated with erythromycin survived and 10 of 11 died in the physiological saline group. Olamufloxacin was as effective as levofloxacin in a guinea pig model of Legionnaires' disease. These data warrant further study of whether olamufloxacin is an option for the treatment of Legionella infections.

Animals↗

High plasma osteopontin level and its relationship with interleukin-12-mediated type 1 T helper cell response in tuberculosis.

Osteopontin (OPN, also known as Eta-1), a noncollagenous matrix protein produced by macrophages and T lymphocytes, is expressed in granulomatous lesions caused by Mycobacterium tuberculosis infection. In the present study, we compared plasma concentrations of OPN in patients with active pulmonary tuberculosis with those of healthy control subjects and patients with sarcoidosis, another disease associated with granuloma formation. Plasma OPN levels were significantly higher in patients with tuberculosis (n = 48) than in control subjects (n = 34) and patients with sarcoidosis (n = 20). OPN levels correlated well with severity of pulmonary tuberculosis, as indicated by the size of lung lesions on chest X-ray films. Furthermore, chemotherapy resulted in a significant fall in plasma OPN levels. In patients with tuberculosis, plasma OPN concentrations correlated significantly with those of interleukin (IL)-12. In vitro experiments showed that OPN production by peripheral blood mononuclear cells infected with Mycobacterium bovis bacillus Calmette-Guérin preceded the synthesis of IL-12 and interferon-gamma and that the neutralizing anti-OPN monoclonal antibody significantly reduced the production of IL-12 and interferon-gamma. Our results suggest that OPN may be involved in the pathologic process associated with active pulmonary tuberculosis by inducing IL-12-mediated type 1 T helper cell responses.

Adolescent↗

Isolation of Legionella anisa from multiple sites of a hospital water system: the eradication of Legionellacontamination.

For the prevention of nosocomial cases of legionellosis in the Ryukyu University Hospital neonatal wards, we examined nine shower units and a sink tap water unit for the presence of Legionella, over a 6-year period. We isolated Legionella-like organisms (LLO) from showerheads by culturing sediments from the water samples on buffered charcoal yeast extracts (BCYE). We used DNA-DNA hybridization to determine that the organisms were L. anisa. A fingerprinting technique called random amplified polymorphism DNA (RAPD) also showed that all the organisms were identical at the genome level. Replacement of the shower heads harboring colonies of L. anisa prevented further contamination. Nosocomial cases of legionellosis have not been reported from the wards during the period of this survey. This is the first description of the isolation of L. anisa from multiple sites within a hospital, and RAPD analysis suggests that these may be the spread of a single clone.

Cross Infection↗

Trends in antimicrobial susceptibility of the Streptococcus milleri group.

A collection of 114 clinical Streptococcus milleri group (SMG) strains at the Ryukyu University Hospital obtained in 1999 and 2000, was identified and tested for susceptibility to 12 antibiotics. The percentage of strains with intermediate susceptibility to penicillin G was relatively high (14%). Cefaclor and cefotiam, with a MIC 90 of 2 microg/ml, were less active than cefotaxime. Strains nonsusceptible to erythromycin, clindamycin, and azithromycin were found with a frequency of 8%, 5%, and 4%, respectively. Almost all of the SMG strains were susceptible to fluoroquinolones (except for 1% of the strains nonsusceptible to levofloxacin), and sitafloxacin (DU-6859a) was the most active agent among the 12 tested antibiotics.

Anti-Bacterial Agents↗

[A case of cat scratch disease with encephalopathy].

We report an atypical case of cat scratch disease (CSD), accompanied with encephalopathy that is a rare complication of CSD. A 17-year old man consulted a doctor for his right axillary lymphadenopathy. The history of his contact with cats and the sign of lymphnode swelling and fever suggested a suspect of cat scratch disease. Administration of ampicillin improved his clinical symptoms, but a few days later he suddenly fell into coma after an episode of convulsion. The CT scan of the brain and laboratory tests showed no significant findings except the slightly elevated cell counts and concentration of protein in his cerebrospinal fluid. He was referred to our hospital on the next day for further examinations and treatments for his coma of unknown cause. The physical examination on admission revealed slight neck stiffening and hypertonicity of his right lower limb, but radiological and laboratory tests showed no significant findings. He gradually recovered from his coma without apparent sequelae in three weeks. Indirect fluorescence antibody titers for CSD in his serum showed a significant elevation to 1:160 of IgM and 1:512 of IgG, and his clinical features were compatible to these of CSD with complications of the central nervous system.

Adolescent↗

[Two cases of mixed infection of malaria diagnosed by PCR method].

We here reported two Japanese cases of mixed infections of plasmodium species, whose DNAs were detected using the PCR test. One case was a 31 year-old male, who presented fever and fatigue, and had a travel history to Kenya, Cameroon and Indonesia. Smear test of his peripheral blood found the presence of Plasmodium vivax, while nested-PCR diagnosis detected the DNAs both P. vivax and Plasmodium malariae. The other was a 54 year-old female suffering from general fatigue. She had been treated with chloroquine for falciparum malaria in Indonesia two weeks before. Malaria antigen test showed positive although no Plasmodium organisms were found in the smear test. The nested PCR detected the DNA of Plasmodium ovale in addition to that of Plasmodium falciparum. In conclusion, the PCR test is helpful and useful for detection of mixed infections of Plasmodium species.

Adult↗

Legionella pneumophila pneumonia successfully treated with intravenous ciprofloxacin.

A 69-year-old man developed a cough and fever during treatment with corticosteroid (p.o. and external use) for erythroderma. Chest X-ray films revealed a consolidation shadow in the right upper lung field. Initial treatment with sulbactam sodium/ampicillin followed by imipenem/cilastatin was not effective. A urinary antigen test for Legionella was positive, making for a diagnosis of Legionella pneumonia. Intravenous treatment with ciprofloxacin (CPFX) was remarkably effective. His symptoms, chest X-ray and laboratory data rapidly improved after its initiation. Our findings strongly suggest that intravenous treatment with fluoroquinolones including CPFX should also be a first choice for Legionella pneumonia in Japan.

Aged↗