Toshinori Kawanami

University of Occupational and Environmental Health, Kitakyūshū, Fukuoka, Japan

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Publications (40)44.76 Total impact

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    ABSTRACT: Background Increased expression of nitric oxide synthase (NOS) and an increase in plasma nitrite plus nitrate (NOx) have been reported in patients with pulmonary fibrosis, suggesting that nitric oxide (NO) plays an important role in its development. However, the roles of the entire NO and NOS system in the pathogenesis of pulmonary fibrosis still remain to be fully elucidated.¿The aim of the present study is to clarify the roles of NO and the NOS system in pulmonary fibrosis by using the mice lacking all three NOS isoforms.Methods Wild-type, single NOS knockout and triple NOS knockout (n/i/eNOS¿/¿) mice were administered bleomycin (BLM) intraperitoneally at a dose of 8.0 mg/kg/day for 10 consecutive days. Two weeks after the end of the procedure, the fibrotic and inflammatory changes of the lung were evaluated. In addition, we evaluated the effects of long-term treatment with isosorbide dinitrate, a NO donor, on the n/i/eNOS¿/¿ mice with BLM-induced pulmonary fibrosis.ResultsThe histopathological findings, collagen content and the total cell number in bronchoalveolar lavage fluid were the most severe/highest in the n/i/eNOS¿/¿ mice. Long-term treatment with the supplemental NO donor in n/i/eNOS¿/¿ mice significantly prevented the progression of the histopathological findings and the increase of the collagen content in the lungs.Conclusions These results provide the first direct evidence that a lack of all three NOS isoforms led to a deterioration of pulmonary fibrosis in a BLM-treated murine model. We speculate that the entire endogenous NO and NOS system plays an important protective role in the pathogenesis of pulmonary fibrosis.
    Respiratory research. 08/2014; 15(1):92.
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    ABSTRACT: Azithromycin (AZM) is one of 15-membered rings macrolide antibiotics with wide spectrum of antimicrobial efficacy for Gram-positive and -negative bacteria and also atypical bacteria. So far, there had been no reports of the prospective studies evaluating efficacy and safety of AZM infusion in patients with mild or moderate community-acquired pneumonia (CAP). This study was conducted to evaluate prospectively the efficacy and safety of AZM in patients with mild or moderate CAP. AZM 500 mg was intravenously administered once daily, and the clinical efficacy were evaluated by clinical symptoms, peripheral blood laboratory findings and chest X-rays. Sixty-four patients were firstly registered, and eventually 61 and 62 patients were enrolled for the evaluation of clinical efficacy and safety of AZM, respectively. The efficacy of AZM in 61 patients evaluated was 88.5%. In addition, the efficacies of AZM in each pneumonia severity index by A-DROP system by the Japanese Respiratory Society (JRS) guideline in CAP were 85.2% in mild and 91.2% in moderate. Furthermore, the efficacy of AZM in each differentiation between suspicion of bacterial pneumonia and that of atypical pneumonia by JRS guideline in CAP were 91.7% in suspicion of atypical pneumonia, and its efficacy was high than that of bacterial pneumonia. Nineteen patients (20 cases; 15 with liver dysfunction, 4 with diarrhea, 1 with vascular pain) out of 62 patients were reported to have possible adverse effects of AZM. All of the patients with these adverse effects demonstrated mild dysfunction and continued AZM treatment, and these dysfunctions normalized soon after cessation of AZM. In conclusion, AZM is effective drug for patients with mild or moderate CAP, and we believe that it may be one of effective choice in the treatment of CAP patients who need hospitalization.
    The Japanese journal of antibiotics 06/2014; 67(3):193-203.
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    ABSTRACT: Two cases of acute respiratory distress syndrome related to zinc fume inhalation and zinc powder inhalation are presented. Case 1 demonstrated acute respiratory symptoms during the work of distortion correction of iron boards, coated with a rust preventative including rich zinc using an acetylene gas burner. Case 2 occurred after the work of applying a rust preventative that included zinc powder, mainly using an airless compressor. Since both were working in a boathouse, without using protective equipment, the possible causes of Case 1 and 2 were inhalation exposure to zinc fumes and zinc powder, respectively. The two patients showed similar clinical courses, including favorable treatment outcomes, mimicking acute respiratory failure complicated by a metal fume fever.
    Journal of UOEH 06/2014; 36(2):147-52.
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    ABSTRACT: A 25-year-old Chinese man with no medical history of pulmonary tuberculosis visited to a hospital for an evaluation of chest X-ray abnormal findings of routine health checkup. Chest computed tomography (CT) demonstrated chest wall mass surrounded by calcified walls in the right anterior chest wall. Eighteen months later, he found subcutaneous mass lesion in the right hypochondriac lesion, and this mass became painful in 5 days. Therefore he visited our hospital, and his chest CT showed low density mass with thickened calcified walls in the right anterior thoracic space, small amount of right pleural effusion and subcutaneous localized mass. A needle aspiration of the right subcutaneous mass demonstrated that the specimen were all negative for acid-fast bacilli smear, culture and PCR for M. tuberculosis. On the contrary, right pleural effusion showed positive for PCR for M. tuberculosis, in spite of negative results of acid-fast bacilli smear and culture. Pericostal tuberculosis that was progressed by the rupture of old calcified tuberculous empyema in the chest wall was confirmed. Antituberculous chemotherapy, chest tube drainage for right subcutaneous mass and pleural decortication and empyema were successfully performed. Pericostal tuberculosis should be differentially considered when the calcified mass in the chest wall changes its shape.
    Kekkaku: [Tuberculosis] 06/2014; 89(6):607-11.
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    ABSTRACT: The guideline for the "Clinical Evaluation Methods for New Antimicrobial Agents to Treat Respiratory Infections (Second Version)," published by the Japanese Society of Chemotherapy in January 2012, was proposed to achieve consistency with FDA guidelines based on the concept of clinical evaluation used in Japan. We assessed the clinical efficacy of levofloxacin (LVFX) in patients with bacterial pneumonia according to this new set of guidelines for the first time. The clinical efficacy of LVFX in patients with community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP) at the test of cure (TOC) was 87.5% (56/64) and 85.7% (6/7), respectively, with an overall efficacy of 87.3% (62/71). The clinical efficacy of LVFX at TOC was as follows: intravenous 81.5% (22/27), oral 88.9% (24/27), switchover from intravenous to oral administration 100% (10/10), respectively. The bacterial eradication rate in the patients with CAP and HCAP and overall efficacy at the end of therapy (EOT) was 95.3% (41/43), 100.0% (4/4) and 95.7% (45/47), respectively. The frequent causative bacterial strains included Streptococcus pneumoniae (18), Haemophilus influenzae (14) and Moraxella catarrhalis (6). The incidence of adverse reactions in the patients whose safety was evaluated was 15.7% (14/89), similar to that previously reported. The clinical efficacy of LVFX at the early phase, EOT and TOC of CAP, as assessed according to the new and former guidelines, was 70.4% (38/54) and 27.8% (15/54), 87.0% (60/69) and 79.1% (53/67), 87.5% (56/64) and 88.1% (59/67), respectively, with no significant differences. Therefore, the new efficacy evaluation method can be used in exchange for the former evaluation method.
    Journal of Infection and Chemotherapy 04/2014; · 1.55 Impact Factor
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    ABSTRACT: Abstract Objective: There are several inhaled corticosteroid/long-acting beta-agonist (ICS/LABA) combinations currently used to treat asthmatic patients, but the differences in the clinical effects of these ICS/LABAs are currently unknown. We herein evaluated the effects of two currently available ICS/LABA combinations in a real-world setting. Methods: A fluticasone propionate/salmeterol combined Discus inhaler (FP/SM; 250/50 μg bid) was switched to a budesonide/formoterol Turbuhaler inhaler (BUD/FM; 160/4.5 μg two inhalations bid) and FP/SM (500/50 μg bid) was also switched to BUD/FM (160/4.5 μg four inhalations bid) in symptomatic asthmatic patients treated with FP/SM over 20 years of age. Results: Sixty patients were enrolled in this study, and the scores of the asthma control test (ACT) and asthma control questionnaire-5 item version (ACQ5) were significantly improved four and eight weeks after the switch to ICS/LABA treatments, and well-controlled asthma (ACQ5 score <0.75) and good-control (ACT score >20) was achieved in 54 (90%) and 40 (66.7%) patients, respectively, at eight weeks. The spirometric analysis revealed significant improvements of the values of the peak expiratory flow (PEF) and forced expiratory volume in one second (FEV1) after switching from FP/SM to BUD/FM, and significantly improved small airway impairments (V50 and V25) were observed in patients treated with high-dose ICS/LABA. These subjective and objective improvements were also seen in patients aged over 65 years old. Conclusion: These data demonstrated that changing the combined ICS/LABA inhaler from FP/SM to BUD/FM can lead to more effective management of symptomatic patients with asthma, especially in patients treated with high-dose ICS/LABA.
    Journal of Asthma 03/2014; · 1.85 Impact Factor
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    ABSTRACT: In the present study, we evaluated the antiemetic effect of aprepitant in combination with 5-hydroxytryptophan(5-HT3) receptor antagonist and dexamethasone for chemotherapy-induced emesis and nausea in lung cancer patients treated with carboplatin-based systemic chemotherapy using the Functional Living Index-Emesis, an emesis- and nausea-specific quality of life(QOL)questionnaire. Patients experiencing emesis and/or nausea during and/or after previous courses of carboplatinbased chemotherapy received aprepitant in the following treatment cycle with the same anti-cancer agent. Emesis- and nausea-specific QOL aspects were significantly improved with the addition of aprepitant to the existing regimen containing dexamethasone and 5-HT3 receptor antagonist. Our result suggests that combined antiemetic treatment with aprepitant, dexamethasone, and 5-HT3 receptor antagonist is more effective in lung cancer patients receiving carboplatin-based systemic chemotherapy than dexamethasone and 5-HT3 receptor antagonist alone.
    Gan to kagaku ryoho. Cancer & chemotherapy 03/2014; 41(3):335-9.
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    ABSTRACT: Levofloxacin (LVFX) is one of respiratory quinolones with wide spectrum of antimicrobial efficacy for Gram-positive and -negative bacteria and also atypical bacteria, and 500 mg of intravenous LVFX infusion has recently been able to use once daily based on pharmacokinetics-pharmacodynamics in Japan. So far, there had been no reports of the prospective studies evaluating efficacy and safety of LVFX in patients with nursing and healthcare-associated pneumonia (NHCAP). This study was conducted to evaluate prospectively the efficacy and safety of LVFX in patients with NHCAP categories B and C (other antibacterial agents were allowed to use with LVFX) according to Japanese guideline for NHCAP by the Japanese Respiratory Society (JRS). LVFX 500 mg was intravenously administered once daily, and the clinical efficacy and safety were evaluated by clinical symptoms, peripheral blood laboratory findings and chest X-rays. Sixty-two patients (average age was 81.2 years old, female/male was 22/40) were firstly registered and evaluated for the safety of LVFX, and eventually 54 patients were enrolled for the evaluation of clinical efficacy of LVFX. The percentage of these 54 patients aged over 65 years old was 96.3%, NHCAP category B/C was 33/21. The efficacy of LVFX in all 54 patients evaluated was 85.2% (categories B/C of NHCAP was 81.8/90.5%). In addition, the efficacies of LVFX in each pneumonia severity category by A-DROP system by JRS in NHCAP patients were 100% in mild, 86.7% in moderate, 77.8% in severe/very severe. Nine patients (2 with liver dysfunction, 6 with renal dysfunction and 1 with thrombocytopenia) out of 62 patients were reported to have possible adverse effects of LVFX. All of the patients with liver and renal dysfunctions after starting LVFX administration demonstrated mild dysfunctions and continued LVFX treatment, and these dysfunctions normalized soon after cessation of LVFX. LVFX was changed to other antibacterial agent in one patient with thrombocytopenia, and also thrombocytopenia was normalized thereafter. In conclusion, LVFX is effective and relatively safe for categories B and C in patients with NHCAP.
    The Japanese journal of antibiotics 02/2014; 67(1):23-32.
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    ABSTRACT: The 2011 idiopathic pulmonary fibrosis (IPF) guidelines are based on the diagnosis of IPF using only high-resolution computed tomography (HRCT). However, few studies have thus far reviewed the usefulness of the HRCT scoring system based on the grading scale provided in the guidelines. We retrospectively studied 98 patients with respect to assess the prognostic value of changes in HRCT findings using a new HRCT scoring system based on the grading scale published in the guidelines. Consecutive patients with IPF who were diagnosed using HRCT alone between January 2008 and January 2012 were evaluated. HRCT examinations and pulmonary function tests were performed at six-month intervals for the first year after diagnosis. The HRCT findings were evaluated using the new HRCT scoring system (HRCT fibrosis score) over time. The findings and survival rates were analyzed using a Kaplan-Meier analysis. The HRCT fibrosis scores at six and 12 months after diagnosis were significantly increased compared to those observed at the initial diagnosis (p < 0.001). The patients with an elevated HRCT fibrosis score at six months based on a receiver operating characteristic (ROC) curves analysis had a poor prognosis (log-rank, hazard ratio [HR] 2.435, 95%CI 1.196-4.962; p = 0.0142). Furthermore, among the patients without marked changes in %FVC, those with an elevated score above the cut-off value had a poor prognosis (HR 2.192, 95%CI 1.003-4.791; p = 0.0491). Our data demonstrate that the HRCT scoring system based on the grading scale is useful for predicting the clinical outcomes of IPF and identifying patients with an adverse prognosis when used in combination with spirometry.
    Respiratory research 01/2014; 15(1):10. · 3.64 Impact Factor
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    ABSTRACT: The bacterial species in the Streptococcus anginosus group (S. constellatus, S. anginosus, S. intermedius) are important causative pathogens of bacterial pneumonia, pulmonary abscesses and empyema. However, the bacteria in this group are primarily oral resident bacteria and unable to grow significantly on ordinary aerobic culture media. We experienced a case of pneumonia and empyema caused by Streptococcus intermedius detected using a 16S rRNA gene sequencing analysis of bronchoalveolar lavage fluid and pleural effusion, but not sputum. Even when applying the molecular method, sputum samples are occasionally unsuitable for identifying the causative pathogens of lower respiratory tract infections.
    Internal Medicine 01/2014; 53(1):47-50. · 0.97 Impact Factor
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    ABSTRACT: Introduction Pneumonia is the third leading cause of mortality in Japan. In 2011, the use of meropenem (MEPM) at 3 g daily was approved to treat refractory infections in Japan. However, little has been reported on the clinical efficacy and safety of this regimen in Japanese patients with refractory infections. Objectives This study prospectively assessed the clinical efficacy and safety of MEPM (3 g daily) in Japanese patients with refractory pneumonia and/or intrapleural infections. Methods This study was performed at our university hospital and affiliated hospitals. The plasma concentrations of MEPM before and one and four hours after MEPM administration were also evaluated. Results A total of 48 patients were enrolled for the efficacy and safety evaluations. The response rate to MEPM (3 g daily) treatment was 90.9% (40/44). Adverse drug reactions were observed in 17 of the 48 patients (20.8%), and all improved after the cessation of MEPM. The plasma MEPM concentration one hour after administering 1 g of MEPM was 44.9 ± 12.0 μg/ml. A pharmacokinetic analysis revealed that the percentage of time above the MIC/24 h for an MIC of 4 μg/ml or 8 μg/ml was more than 50% in 12 of 13 (92%) and in nine of the 13 patients (69%), respectively, indicating sufficient efficacy of 3 g daily of MEPM. Conclusion Treatment with MEPM (3 g daily) in Japanese patients with refractory pneumonia and/or intrapleural infections is effective, with sufficient plasma concentrations of MEPM, and the treatment has a relatively good safety profile.
    Journal of Infection and Chemotherapy. 01/2014;
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    ABSTRACT: During the assessments of the correlation of the diseases and the microbiota of various clinical specimens, unique 16S ribosomal RNA (rRNA) gene sequences (less than 80% similarity to known bacterial type strains) were predominantly detected in a bronchoalveolar lavage fluid (BALF) specimen from a patient with chronic lower respiratory tract infection. The origin of this unique sequence is suspected to be the causative agent of the infection. We temporarily named the owner organism of this sequence "IOLA" (Infectious Organism Lurking in Airways). In order to evaluate the significance of IOLA in human lung disorders, we performed several experiments. IOLA-16S rRNA genes were detected in 6 of 386 clone libraries constructed from clinical specimens of patients with respiratory diseases (in our study series). The gene sequences (1,427 bp) are identical, and no significantly similar sequence was found in public databases (using NCBI blastn) except for the 8 shorter sequences detected from patients with respiratory diseases in other studies from 2 other countries. Phylogenetic analyses revealed that the 16S rRNA gene of IOLA is more closely related to eukaryotic mitochondria than bacteria. However, the size and shape of IOLA seen by fluorescent in-situ hybridization are similar to small bacteria (approximately 1 µm with a spherical shape). Furthermore, features of both bacteria and mitochondria were observed in the genomic fragment (about 19 kb) of IOLA, and the GC ratio of the sequence was extremely low (20.5%). Two main conclusions were reached: (1) IOLA is a novel bacteria-like microorganism that, interestingly, possesses features of eukaryotic mitochondria. (2) IOLA is a novel pathogen candidate, and it may be the causative agent of human lung or airway disease. IOLA exists in BALF specimens from patients with remarkable symptoms; this information is an important piece for helping solve the elusive etiology of chronic respiratory disorders.
    PLoS ONE 01/2014; 9(7):e103646. · 3.73 Impact Factor
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    ABSTRACT: Background Evaluating the ratio of CD4/CD8 T-lymphocytes in the bronchoalveolar lavage fluid (BALF) is important for understanding the clinical and pathological conditions of patients with sarcoidosis. However, few studies have thus far demonstrated the usefulness of evaluating the relationship between the ratios of CD4/CD8 T-lymphocytes in the mediastinal lymph nodes and BALF. This study aimed to investigate and identify the relationships between CD4/CD8 T-lymphocyte ratio in the mediastinal lymph nodes and BALF in patients with sarcoidosis. Methods Thirty-three consecutive patients with sarcoidosis with enlarged mediastinal and/or hilar lymphadenopathy were enrolled in the study, and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and bronchoalveolar lavage (BAL) were simultaneously performed. The CD4/CD8 T-lymphocyte ratios in the mediastinal lymph nodes and BALF were evaluated using immunohistochemistry and flow cytometry, respectively. Results The interobserver variability in the CD4/CD8 ratio in the mediastinal lymph nodes as determined by immunostaining was low, and the pathological and cytological profiles of T-lymphocytes in the mediastinal and/or hilar lymph nodes and BALF were correlated in patients with sarcoidosis. Additionally, the CD4/CD8 T-lymphocyte ratios in BALF were significantly higher than those in the mediastinal lymph nodes. Importantly, non-caseating granulomas were detected at a high rate by using EBUS-TBNA. Conclusions Performing EBUS-TBNA in patients with sarcoidosis allows correct diagnosis as well as the estimation of the ratio of CD4/CD8 T-lymphocytes in BALF.
    Respiratory Investigation. 01/2014;
  • Journal of thoracic imaging 11/2013; · 1.42 Impact Factor
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    ABSTRACT: The incidence of bepridil-induced pulmonary toxicity, such as interstitial pneumonia, is still unknown. The aim of the present study was to evaluate the incidence of bepridil-induced pulmonary toxicity. A total of 253 patients treated with bepridil between January 2009 and January 2011 were retrospectively evaluated. Eight out of the 222 evaluable patients (male/female: 5/3, age range: 64-97 years, average age: 80.5 years, median age: 81.0 years) showed bepridil-induced pulmonary toxicity. The incidence of bepridil-induced pulmonary toxicity was 3.60% in our study population.
    Respiratory medicine 10/2013; · 2.33 Impact Factor
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    ABSTRACT: IgG4-related disease (IgG4RD) is a recently recognized disease entity. Differentiating IgG4RD from plasma cell type Castleman's disease (PCD) is important but also difficult using only pathological findings. In addition, little is known about the association between these two diseases with diffuse parenchymal lung involvement. We analyzed the serum IgG4 levels and the ratio of IgG4/IgG-positive plasmacytes in the lung and lymph node specimens of eight patients previously pathologically diagnosed of PCD with diffuse parenchymal lung involvement (DL-PCD). We also compared the clinical and laboratory findings observed in these patients. Six of the eight patients exhibited abundant IgG4-positive plasmacytes in the lung and lymph node tissues and elevated serum IgG4 levels, thereby fulfilling the diagnostic criteria of IgG4RD with DL (DL-IgG4RD) in addition to having obstructive phlebitis and massive lymphoplasmacytic infiltration with fibrosis. However, three of these six patients exhibited higher levels of serum interleukin-6 and were still diagnosed with DL-PCD. Accordingly, three of these eight patients were considered as IgG4RD with DL (DL-IgG4RD), and the other five patients were ultimately given a diagnosis of DL-PCD. These two diseases have different characteristics in terms of age, symptoms, serum levels of C-reactive protein, and IgA, complicating allergic disorders, response to corticosteroids, and prognosis. This is the first report to show a high prevalence of DL-IgG4RD in DL-PCD patients, although additional large investigations are necessary. Clinical and laboratory findings are important for distinguishing between these two diseases in other organs, as previously described.
    Beiträge zur Klinik der Tuberkulose 08/2013; · 2.06 Impact Factor
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    European Respiratory Review 03/2013; 22(127):98-9.
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    ABSTRACT: We report a case of adult T-cell leukemia/lymphoma (ATL) with rapidly progressive pulmonary areas of ground-glass attenuation (GGA) and nodules resulting from acute transformation of chronic ATL. A 48-year-old Japanese man was admitted for progressive dyspnea. Chest computed tomography showed rapidly progressive bilateral pulmonary areas of GGA and nodules. Flow cytometry of bronchoalveolar lavage fluid and immunohistochemical examination of lung biopsy specimens revealed invasion of ATL cells. Systemic chemotherapy improved the pulmonary findings. Rapidly expanding areas of GGA and nodules are a rare manifestation of pulmonary invasion of ATL that clinicians should nevertheless keep in mind.
    Respiratory investigation. 03/2013; 51(1):40-5.
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    ABSTRACT: Molecular biological modalities with better detection rates have been applied to identify the bacteria causing infectious diseases. Approximately 10-48% of bacterial pathogens causing community-acquired pneumonia are not identified using conventional cultivation methods. This study evaluated the bacteriological causes of community-acquired pneumonia using a cultivation-independent clone library analysis of the 16S ribosomal RNA gene of bronchoalveolar lavage specimens, and compared the results with those of conventional cultivation methods. Patients with community-acquired pneumonia were enrolled based on their clinical and radiological findings. Bronchoalveolar lavage specimens were collected from pulmonary pathological lesions using bronchoscopy and evaluated by both a culture-independent molecular method and conventional cultivation methods. For the culture-independent molecular method, approximately 600 base pairs of 16S ribosomal RNA genes were amplified using polymerase chain reaction with universal primers, followed by the construction of clone libraries. The nucleotide sequences of 96 clones randomly chosen for each specimen were determined, and bacterial homology was searched. Conventional cultivation methods, including anaerobic cultures, were also performed using the same specimens. In addition to known common pathogens of community-acquired pneumonia [Streptococcus pneumoniae (18.8%), Haemophilus influenzae (18.8%), Mycoplasma pneumoniae (17.2%)], molecular analysis of specimens from 64 patients with community-acquired pneumonia showed relatively higher rates of anaerobes (15.6%) and oral bacteria (15.6%) than previous reports. Our findings suggest that anaerobes and oral bacteria are more frequently detected in patients with community-acquired pneumonia than previously believed. It is possible that these bacteria may play more important roles in community-acquired pneumonia.
    PLoS ONE 01/2013; 8(5):e63103. · 3.73 Impact Factor