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Background Catheter-related infection (CRI) is one of the serious challenges in clinical practice. This preliminary clinical study aimed to examine whether next-generation sequencing (NGS) targeting 16S rDNA, which was PCR-amplified directly from the tip of a central venous catheter (CVC), can be used to identify causative pathogens in CRI, compared to the culture method. Methods Hospitalized patients, from whom a CVC had just been removed, were prospectively enrolled and divided into the CRI-suspected and routine removal groups. DNA was extracted from the sonication fluid of CVC specimens derived from patients. For analysis of bacterial composition by NGS, the V3–V4 fragments of bacterial 16S rDNA were PCR-amplified, followed by index PCR and paired-end sequencing on an Illumina MiSeq device. Conventional culture methods were also performed in the CRI-suspected group. Results Of CVCs collected from the 156 enrolled patients (114 men; mean age 65.6 years), a total of 14 specimens [nine out of 31 patients suspected with CRI and five out of 125 patients without infection symptoms (routine removal group)] were PCR-positive. In five patients with definite CRI, Staphylococcus was the most frequently detected genus by NGS (4/5 specimens), although no pathogens were detected by NGS in the one remaining specimen. The genera identified by NGS were consistent with those from conventional culture tests. There was high agreement between NGS and the culture method in the CRI-suspected group, with sensitivity and specificity values of 80.0% and 76.9%, respectively; meanwhile, the false-positive rate of NGS was as low as 4.0% in the routine removal group. Moreover, several genera, besides the genus identified by culture test, were detected in each patient with definite CRI and surgical site infection (SSI). Additionally, in one patient with SSI, Enterococcaceae were detected not only by NGS but also by abdominal abscess drainage culture. Conclusions NGS targeting 16S rDNA was able to analyze the bacterial composition of CVC specimens and detect causative pathogens in patients with CRI and was therefore suggested as a promising diagnostic tool for CRI.

Objective The aims of this study were to elucidate the frequency and etiology of community-acquired lobar pneumonia (CALP) and the clinical and radiological differences between CALP and tuberculous lobar pneumonia (TLP). Patients and Methods We retrospectively reviewed medical records of patients with community-acquired pneumonia (CAP) (n = 1032) and tuberculosis (n = 1101) admitted to our hospital. Results Sixty-nine (6.7%) patients with CAP and 23 (2.1%) with pulmonary tuberculosis developed CALP. Legionella species were the most common pathogen (27 patients, 39.1%), followed by Streptococcus pneumoniae (19 patients, 27.5%) and Mycoplasma pneumoniae (18 patients, 26.1%). Symptom duration was longer in the patients with TLP than in those with CALP. On chest radiographs, cavitation in the area of lobar pneumonia and nodular shadows were radiological findings predictive of TLP. High-resolution computed tomography showed cavitation in the area of lobar pneumonia, well-defined centrilobular nodules, and tree-in-bud sign to be the radiological findings predictive of TLP by multivariate logistic regression models. Conclusion Common causes of CALP are Legionella species, S. pneumoniae, and M. pneumoniae. TLP should be considered in patients with lobar pneumonia, particularly in patients with long symptom duration, cavitation, and nodular shadows on chest radiographs, and cavitation, well-defined centrilobular nodules, and tree-in-bud sign on CT.

Background Respiratory tract infection is a major cause of acute exacerbation of bronchial asthma (AEBA). Although recent findings suggest that common bacteria are causally associated with AEBA, a comprehensive epidemiologic analysis of infectious pathogens including common/atypical bacteria and viruses in AEBA has not been performed. Accordingly, we attempted to detect pathogens during AEBA by using real-time polymerase chain reaction (PCR) in comparison to conventional methods. Methods We prospectively enroled adult patients with AEBA from August 2012 to March 2014. Infectious pathogens collected in nasopharyngeal swab and sputum samples were examined in each patient by conventional methods and real-time PCR, which can detect 6 bacterial and 11 viral pathogens. The causal association of these pathogens with AEBA severity and their frequency of monthly distribution were also examined. Results Among the 64 enroled patients, infectious pathogens were detected in 49 patients (76.6%) using real-time PCR and in 14 patients (21.9%) using conventional methods (p

Background Dosages of anti-tuberculosis (TB) drugs are recommended to be adjusted according to renal function for patients complicated with chronic kidney disease (CKD). However, the efficacy and safety outcomes of such renal function-based dosage adjustments are not fully elucidated. Methods We retrospectively reviewed cases of pulmonary TB susceptible to first-line drugs that were treated at Jikei University Daisan Hospital between 2005 and 2014 with standard regimens based on dosage adjustments according to renal function recommended by international guidelines. Patients were divided into four groups, those with no, mild, moderate or severe CKD. In-hospital TB-related mortality, the rate of sputum culture conversion at 2 months, the frequency of adverse events (AEs), for which at least the temporal discontinuation of the suspect drug was required for patient improvement, and the rate of regimen change due to AEs were assessed. Results In the 241 enrolled patients (mean age, 64.1 years; 143 men), fourteen patients (5.8%) died due to TB during their hospitalization. The rate of sputum culture conversion at 2 months was 78.0%. The frequency of in-hospital TB-related death and the conversion rate in the groups did not vary significantly according to CKD severity including those in the non-CKD group (P = 0.310 and P = 0.864). Meanwhile, a total of 70 AEs were observed in 60 patients (24.9%) and the difference between the groups in the overall frequency of AEs was almost significant (P = 0.051). Moreover, for the 154 patients with CKD, severe CKD stage was a significant risk factor for regimen change (OR = 5.92, 95% CI = 1.08–32.5, P = 0.041), as were drug-induced hepatitis and cutaneous reaction (OR = 35.6, 95% CI = 8.70–145, P

Community-acquired pneumonia (CAP) has high morbidity and mortality. Unfortunately, the pathogen detection rate using conventional culture methods is relatively low. We compared comprehensive real-time polymerase chain reaction (real-time PCR) analysis of nasopharyngeal swab specimens (NPS) and sputum samples against conventional methods for ability to detect causative pathogens of CAP.We prospectively enrolled adult CAP patients, including those with prior antibiotic use, from December 2012 to May 2014. For each patient, causative pathogens were investigated conventionally and by real-time PCR that can identify 6 bacterial and 11 viral pathogens.Patients numbered 92 (mean age, 63 years; 59 male), including 30 (33%) with prior antibiotic use. Considering all patients, identification of causative pathogens by real-time PCR was significantly more frequent than by conventional methods in all patients (72% vs. 57%, p = 0.018). In patients with prior antibiotic use, identification rates also differed significantly (PCR, 77%; conventional, 50%; p = 0.027). Mixed infections were more frequent according to real-time PCR than conventional methods (26% vs. 4%, p 0.001). By the real-time PCR, Streptococcus pneumoniae was most frequently identified (38%) as a causative pathogen, followed by Haemophilus influenzae (37%) and Mycoplasma pneumoniae (5%). PCR also identified viral pathogens (21%), with sensitivity enhanced by simultaneous examination of both NPS and sputum samples rather than only NPS samples.Real-time PCR of NPS and sputum samples could better identify bacterial and viral pathogens in CAP than conventional methods, both overall and in patients with prior antibiotic treatment.

Background The effectiveness of hepatoprotective drugs for DIH (drug induced hepatotoxicity) during tuberculosis treatment is not clear. We evaluated the effectiveness of hepatoprotective drugs by comparing the period until the normalization of hepatic enzymes between patients who were prescribed with the hepatoprotective drugs after DIH was occurred and patients who were not prescribed with the hepatoprotective drugs. Methods During 2006–2010, 389 patients with active tuberculosis were included in this study. DIH was defined as elevation of peak serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) of more than twice the upper limit of normal (ULN). We divided the patients into the severe (peak serum AST and/or ALT elevation of >5 times the ULN), moderate (peak serum AST and/or ALT elevation of >3 to ≤5 times the ULN), and mild DIH groups (peak serum AST and/or ALT elevation of >2 to ≤3 times the ULN). We compared the average period until the normalization of hepatic enzymes between patient subgroups with and without hepatoprotective drugs (ursodeoxycholic acid: UDCA, stronger neo-minophagen C: SNMC, and glycyrrhizin). Results In the severe group, there was no significant difference in the average period until the normalization between subgroups with and without hepatoprotective drugs (21.4 ± 10.8 vs 21.5 ± 11.1 days, P = 0.97). In the mild group, the period was longer in the subgroup with hepatoprotective drugs than that without hepatoprotective drugs (15.7 ± 6.2 vs 12.4 ± 7.9 days, P = 0.046). Conclusion Regardless of the severity, hepatoprotective drugs did not shorten the period until the normalization of hepatic enzymes.

Objective In the emergency department, it is sometimes difficult to differentiate heart failure (HF) from other diseases (e.g., respiratory diseases) in patients who develop dyspnea. The plasma B-type natriuretic peptide (BNP) levels increase in patients with HF, and various levels are associated with specific New York Heart Association classes. Although the diagnosis of HF should not be made based only on the plasma BNP levels, the identification of a cut-off value for BNP to diagnose HF would be helpful. Methods Patients admitted to the emergency department of our hospital with dyspnea between January 2010 and December 2011 were retrospectively reviewed. The patients whose estimated glomerular filtration rate was less than 30 mL/min/1.73 m(2) were excluded. Patients were divided into two groups: those with HF (n=131) and those without HF (n=138). The cut-off value for BNP was determined by the receiver-operating characteristic curve. Results The area under the curve of this curve was 0.934. The optimal cut-off point for detection of HF was 234 pg/mL. The sensitivity and specificity were 87.0% and 85.5%, respectively. The fifth and 95th percentiles of the HF group were 132.2 and 2,420.8 pg/mL, respectively. Those of the non-HF group were 9.7 and 430.2 pg/mL, respectively. Conclusion Our study suggests that a plasma BNP level cut-off value of 234 pg/mL can be used to detect HF in the emergency department.

It is difficult to verify the bacteriological diagnosis of Mycobacterium avium complex (MAC) infection. The anti-glycopeptidolipid (GPL)-core IgA antibody test was recently developed as a diagnostic method for MAC pulmonary disease. Only a few studies evaluate its clinical efficacy. We conducted retrospective evaluations of clinical characteristics of patients suspected of MAC infection to explore the usefulness of the anti-GPL-core IgA antibody test.We retrospectively evaluated 296 patients who were suspected to have MAC infection and underwent anti-GPL-core IgA antibody test between March 2013 and July 2014 in Jikei University hospital.A total of 29 patients were diagnosed with 'definite MAC' based on the American Thoracic Society (ATS) criteria with multiple identifications of MAC. On the other hand, 106 patients were diagnosed with other pulmonary diseases than MAC. The sensitivity and specificity of anti-GPL-core IgA antibody test for MAC diagnosis were 58.6% and 98.1%, respectively. The definite MAC group showed no significant differences in strains, treatment history or number of segments involved. The duration of MAC disease in the positive-antibody group was significantly longer than in the negative-antibody group (P = 0.046). A significant increase in the false-negative rate was observed in patients with malignant disease (P = 0.029).The anti-GPL-core IgA antibody test demonstrated high sensitivity and specificity for the diagnosis of MAC infection especially in patients without malignant diseases.

A 32-year-old female with epilepsy presented at our hospital with high-grade fever, seizures, and unconsciousness. She was initially treated for aspiration pneumonia with ampicillin/sulbactam. Despite antibiotic therapy, her chest X-ray findings dramatically worsened, showing extension to the bilateral lung field. Her PaO2/FiO2 ratio decreased to 70.6. Rapid progression of hypoxia, unconsciousness, and hyponatremia led to the suspicion of Legionella pneumonia; however, it was difficult to make a definitive diagnosis because she had denied using a whirlpool spa and the initial urinary Legionella antigen test results were negative. Therefore, we repeated the Legionella urinary antigen test, which was positive. On the basis of these results, sputum polymerase chain reaction findings, and the four-fold elevation of paired antibodies, the patient was diagnosed as having Legionella pneumonia accompanied by acute respiratory distress syndrome. We considered administering fluoroquinolone antibiotics, that are recommended for severe Legionella pneumonia, although quinolones have a potential risk for causing convulsions. In this case, we carefully administered ciprofloxacin. The patient recovered consciousness after treatment without any relapse of epileptic seizures. We also administered a corticosteroid for severe pneumonia with the expectation of clinical improvement and to avoid intubation. We emphasize the importance of aggressive workup and empirical therapy for patients with Legionella pneumonia with rapidly worsening symptoms and clinical features such as unconsciousness, epilepsy, and hyponatremia and in whom fluoroquinolone and corticosteroid therapy are effective despite the presence of epilepsy.

We report a case with an atypical presentation of descending necrotizing mediastinitis (DNM). A 47-year-old woman with a medical history of untreated type 2 diabetes mellitus and influenza type A virus infection 2 weeks prior to admission was referred to our hospital complaining of right cervical pain and right upper limb swelling. A chest enhanced computed tomographic (CT) scan showed a ring-enhanced mass-like shadow extending from the right sternomastoid muscle down to the right upper mediastinum, compressing the right subclavicular vein. We diagnosed the patient as having DNM based on a physical examination and the CT findings. Because the abscess extended from deep in the neck to the upper mediastinum and right upper pleural space, emergent abscess debridement and drainage was required. After hospitalization, antibiotics (Ampicillin/Sulbactam 12 g/day) were also administered based on Gram-stain findings from the drainage fluid, which showed Gram-positive cocci resembling a string of beads. A culture of the drainage fluid identified Streptococcus agalactiae. Aggressive abscess drainage and early antibiotic therapy resulted in a favorable response. She was discharged without complications on the 33rd hospital day. DNM is well known as a rare but lethal disease. In this case, the presence of diabetes mellitus and post-influenza infection might have been risk factors for a serious S. agalactiae infection. Early aggressive therapy and adequate drainage are recommended for patients with DNM.

The aim of the current study was to investigate the lethal complications of Legionella pneumonia. Severe complications and their outcomes in 65 patients with Legionella pneumonia were studied. All patients who eventually had a fatal outcome or who had severe complications received antimicrobial agents active against Legionella on the admission day. Many patients in the severe complication category had multiple severe complications. Six deaths occurred (mortality rate 9.2%), 4 of which were due to septic shock/multiple organ dysfunction syndrome (MODS) (2 patients) or interstitial pneumonia/pulmonary fibrosis after Legionella pneumonia (2 patients), whereas the other 2 deaths were due to causes unrelated to Legionella pneumonia. Mortality rates for each severe complication were as follows: acute respiratory distress syndrome 27.3% (3 of 11); renal failure 33.3% (2 of 6); disseminated intravascular coagulation 33.3% (2 of 6); severe sepsis 0% (0 of 1); septic shock/MODS 66.7% (2 of 3); interstitial pneumonia/pulmonary fibrosis 50% (2 of 4). Despite prompt diagnosis and appropriate treatment with antimicrobial agents active against Legionella, the lethal complications of Legionella pneumonia are septic shock/MODS and interstitial pneumonia/pulmonary fibrosis.

We report the case of a 75-year-old woman with mucoid impaction of the bronchi (MIB) due to Schizophyllum commune who improved with itraconazole (ITCZ) administration and relapsed after discontinuation of the drug. She improved again after readministration of ITCZ, and MIB has not recurred. This patient was not suffering from asthma and has been well without steroid administration. Reports of respiratory disorders due to S. commune have been increasing, and cases of allergic bronchopulmonary mycosis (ABPM), fungus ball, lung abscess, and pneumonia have been reported. Including this report, 12 cases of ABPM and MIB due to S. commune have been reported by Japanese authors. Treatment in these 12 cases included anti-fungal agent in 6, single steroid therapy in 3, combination therapy in 2, and bronchial toilet in 1 case. S. commune is not well recognized; however, one should suspect this fungus to be the causative pathogen when Aspergillus species are not detected or anti-Aspergillus antibody is negative.

We encountered a 59-year-old man, whose chief complaints were sputum and dyspnea on effort. He had suffered from sinusitis since childhood, and chest computed tomography showed bronchiectasis. Electron microscopic examination of bronchial mucosa biopsied by bronchoscopy showed defect of the inner dynein arm in most of his cilia. We diagnosed primary ciliary dyskinesia. Seminal analysis showed no abnormalities, and the etiology of infertility remains unclear. The present case is the fifth case treated at our hospital. In this paper, we compared this case with 4 cases (2 cases of Kartagener's syndrome and 2 cases of primary ciliary dyskinesia without situs invertus) of our hospital, and findings of previous reports. Primary ciliary dyskinesia should be included in the differential diagnosis even in cases of mild bronchiectasis or normal mobility of sperm. Primary ciliary dyskinesia has more variety in radiological and clinical findings than has been recognized.

Kenichiro Shimizu,1 Yutaka Yoshii,1 Miyuki Morozumi,2 Naoko Chiba,2 Kimiko Ubukata,2 Hironori Uruga,3 Shigeo Hanada,3 Nayuta Saito,1 Tsukasa Kadota,1 Saburo Ito,1 Hiroshi Wakui,1 Naoki Takasaka,1 Shunsuke Minagawa,1 Jun Kojima,1 Hiromichi Hara,1 Takanori Numata,1 Makoto Kawaishi,1 Keisuke Saito,4 Jun Araya,1 Yumi Kaneko,1 Katsutoshi Nakayama,1 Kazuma Kishi,3 Kazuyoshi Kuwano1 1Division of Respiratory Diseases, Department of Internal Medicine, TheJikei University School of Medicine, 2Department of Infectious Diseases, Keio University School of Medicine, 3Department of RespiratoryMedicine, Respiratory Center, Toranomon Hospital, 4Department of Respiratory Medicine, The Jikei University Daisan Hospital, Tokyo,Japan Abstract: Respiratory infection is a major cause of exacerbation in chronic obstructive pulmonary disease (COPD). Infectious contributions to exacerbations remain incompletely described. We therefore analyzed respiratory tract samples by comprehensive real-time polymerase chain reaction (PCR) in combination with conventional methods. We evaluated multiple risk factors for prolonged hospitalization to manage COPD exacerbations, including infectious agents. Over 19 months, we prospectively studied 46 patients with 50 COPD exacerbations, collecting nasopharyngeal swab and sputum samples from each. We carried out real-time PCR designed to detect six bacterial species and eleven viruses, together with conventional procedures, including sputum culture. Infectious etiologies of COPD exacerbations were identified in 44 of 50 exacerbations (88%). Infections were viral in 17 of 50 exacerbations (34%). COPD exacerbations caused by Gram-negative bacilli, including enteric and nonfermenting organisms, were significantly associated with prolonged hospitalization for COPD exacerbations. Our results support the use of a combination of real-time PCR and conventional methods for determining both infectious etiologies and risk of extended hospitalization. Keywords: COPD, exacerbation, etiology, real-time PCR, prolonged hospitalization, risk factor