Kouichiro Yoshida

Clinical Reevaluation of the QuantiFERON TB-2G Test as a Diagnostic Method for Differentiating Active Tuberculosis from Nontuberculous Mycobacteriosis

INTRODUCTION We reevaluated the usefulness of a whole-blood interferon-gamma enzyme-linked immunosorbent assay (QuantiFERON TB-2G [QFT-TB]; Cellestis) in obtaining a differential diagnosis between active tuberculosis (TB) and nontuberculous mycobacteriosis (NTM). METHODS The subjects were 50 healthy volunteers, 50 patients with active TB, and 100 patients with NTM who satisfied the diagnostic guidelines of the American Thoracic Society from April 2005 through June 2006. The tuberculin skin test (TST) and the QFT-TB test were performed for all subjects. The QFT-TB test was performed every 2 months. RESULTS Of the healthy volunteers, 64% had a negative TST result and 94% had a negative QFT-TB test result. Of the patients with active TB, 64% had a positive TST result and 4% had a negative QFT-TB test result. Of the patients with pulmonary Mycobacterium avium complex disease, 60% had a positive TST result and 7% had a positive QFT-TB test result. The QFT-TB test had a mean sensitivity of 86% and a mean specificity of 94%. The QFT-TB test results for patients with active TB transiently decreased during treatment involving antituberculous drugs. The rate of positive QFT-TB test results was 86% at the initiation of treatment, 48% 6 months later, and 33% 12 months later. CONCLUSIONS We confirmed that the QFT-TB test is a useful diagnostic method for differentiating active pulmonary TB from NTM, compared with the TST. However, because it is possible that the effect of the QFT-TB test may be long lasting after treatment and may not be resolved over time, even with treatment, as in this study, it may not provide any level of certainty regarding cure of infection.

Chronic necrotizing pulmonary aspergillosis as a complication of pulmonary Mycobacterium avium complex disease.

Objective and background:  To investigate the characteristic clinical features of chronic necrotizing pulmonary aspergillosis (CNPA) as a complication of pulmonary Mycobacterium avium complex (MAC) disease.

The perforin mediated apoptotic pathway in lung injury and fibrosis

Aims: The perforin mediated pathway is the major pathway of cytotoxicity induced by activated T cells and natural killer cells, and may be involved in the development of pulmonary fibrosis. Methods: Perforin and granzyme B expression were examined in idiopathic pulmonary fibrosis by means of immunohistochemistry, and perforin knockout mice were used to examine whether or not perforin mediated cytotoxicity participates in the pathophysiology of bleomycin induced pneumopathy. Results: Perforin and granzyme B expression were upregulated in infiltrating lymphocytes in lung tissue from patients with idiopathic pulmonary fibrosis compared with normal lung parenchyma. Perforin and granzyme B expression were upregulated predominantly in infiltrating mononuclear cells after bleomycin instillation in wild-type mice. Although the development of bleomycin induced pneumopathy was not completely prevented, the pathological grade of inflammation and fibrosis, and the number of apoptotic cells in lung tissue, were significantly decreased in perforin knockout mice compared with wild-type mice. Conclusions: These results suggest that perforin mediated apoptosis may be associated with the pathophysiology of lung injury and fibrosis.

Evaluating the Use of a Streptococcus pneumoniae Urinary Antigen Detection Kit for the Management of Community-Acquired Pneumonia in Japan

Background: The urinary antigen detection kit for Streptococcus pneumoniae was tested. Objectives: It was our aim to evaluate the usefulness of the immunochromatographic membrane test by doing a large prospective study of community-acquired pneumonia (CAP) in Japan. Methods: We prospectively evaluated the use of the S. pneumoniae urinary antigen detection kit and analyzed the treatment and clinical effect seen in patients with positive test kit results. One hundred and fifty-six patients with CAP admitted to our hospital between October 2001 and September 2003 were evaluated. Results: In 49% of these CAP patients, the causative microorganisms were isolated. S. pneumoniae was suspected to be the causative microorganism in 15%, but positive results of the urinary antigen detection kit indicated S. pneumoniae to be a probable microorganism in 28%, even though antibiotics had previously been administered to half of the patients. The kit was particularly useful for diagnosing patients with poor quality sputum in whom antibiotics treatment nevertheless had to be selected. Antibiotics appropriate for S. pneumoniae (mainly penicillin) were given. The treatment was found to have excellent clinical results in 89% of the CAP patients. Conclusions: The S. pneumoniae urinary antigen detection kit was considered to be useful in selecting treatment since there was a high level of clinical effectiveness when the most suitable antibiotics were immediately administered to positive patients. The use of the S. pneumoniae urinary antigen kit is rapid and simple compared with conventional microbiological procedures.

The first nationwide surveillance of bacterial respiratory pathogens conducted by the Japanese Society of Chemotherapy. Part 1: a general view of antibacterial susceptibility

The Japanese Society of Chemotherapy (JSC) conducted the first nationwide surveillance of bacterial respiratory pathogens during the period from January to August 2006. With the cooperation of 32 medical institutions throughout Japan, a total of 924 strains belonging to seven clinically relevant bacterial species were collected from adult patients with well-diagnosed respiratory tract infections (RTIs). Antimicrobial susceptibility testing of the 887 evaluable strains (205 Staphylococcus aureus, 200 Streptococcus pneumoniae, 9 Streptococcus pyogenes, 165 Haemophilus influenzae, 91 Moraxella catarrhalis, 74 Klebsiella pneumoniae, and 143 Pseudomonas aeruginosa) to 42 antibacterial agents was conducted at the Central Laboratory of the Research Center for Anti-infective Drugs of the Kitasato Institute, according to recommendations issued by the Clinical and Laboratory Standards Institute (CLSI). The antibacterial agents employed were 25 β-lactams, three aminoglycosides, four macrolides (including one azalide and one ketolide), one lincosamide, one tetracycline, two glycopeptides, five fluoroquinolones, and one oxazolidinone. The incidence of methicillin-resistant S. aureus (MRSA) was 63.4%, and the incidences of penicillin-intermediately resistant S. pneumoniae (PISP) and penicillin-resistant S. pneumoniae (PRSP) were 35.0% and 4.0%, respectively. Among H. influenzae, 21.2% of the strains were found to be β-lactamase-nonproducing ampicillin (ABPC)-intermediately resistant (BLNAI), 29.1% to be β-lactamase-nonproducing ABPC-resistant (BLNAR), and 4.8% to be β-lactamaseproducing ABPC-resistant (BLPAR) strains. The incidence of extended-spectrum β-lactamase-producing K. pneumoniae was 2.7% (2 of 74 strains). Three (2.1%) of the 143 P. aeruginosa strains were found to be metallo-β-lactamaseproducing, including 1 (0.7%) multidrug-resistant strain. Through the nationwide surveillance, we obtained fundamental antimicrobial susceptibility data of clinically relevant bacterial pathogens in adult RTI to various antibacterial agents. These data will be a useful reference for future periodic surveillance studies, as well as for investigations to control antimicrobial-resistant pathogens.

Four cases of pulmonary Mycobacterium avium intracellulare complex presenting as a solitary pulmonary nodule and a review of other cases in Japan

Objective:  To evaluate clinical findings of patients with a solitary pulmonary nodule in Japan caused by pulmonary Mycobacterium avium complex (MAC) disease.

Transitional Change in the Clinical Features of Pulmonary Tuberculosis

Background: An aging population, increased use of immunosuppressive therapy and an increase in patients with risk factors for tuberculosis have induced changes in the clinical features of pulmonary tuberculosis in Japan. Objective: To investigate transitional changes in the clinical features of recent patients with pulmonary tuberculosis. Methods: This study analyzed 820 patients with pulmonary tuberculosis who were culture positive for Mycobacterium tuberculosis in the Kawasaki Medical School Hospital and ten associated community hospitals between January 1986 and December 2005 (406 patients between January 1986 and December 1995 and 414 patients between January 1996 and December 2005). Results: The characteristic clinical features of the latter period were as follows: (1) an increase in the percentages of patients with both malignant diseases and collagen vascular diseases, (2) a decrease in the proportion of patients with obvious clinical symptoms, (3) an increase in the number of microbiologically smear-positive patients, (4) an increase in the percentages of patients with atypical radiological findings, (5) no change in the incidence of multidrug-resistant M. tuberculosis and (6) no change in the rate of the effect of treatment or prognosis. Conclusions: The findings of an increase in atypical features may be related to the increase in immunocompromised patients and should therefore be investigated further. Performance of acid-fast bacillus examination is extremely important because a good prognosis can be achieved if an accurate diagnosis is established as soon as possible and the resistance of M. tuberculosis to antituberculous drugs has not progressed.