Diagnostic role of inflammatory and anti-inflammatory cytokines and effector molecules of cytotoxic T lymphocytes in tuberculous pleural effusion.

BACKGROUND AND OBJECTIVE: Early diagnosis of tuberculous pleural effusion (TPE) remains difficult. While some inflammatory markers in pleural effusion (PE) are helpful in diagnosis, the roles of anti-inflammatory cytokines and effector molecules of cytotoxic T lymphocytes have not been investigated. METHODS: Lymphocyte-predominant exudative PE samples were assayed for inflammatory and anti-inflammatory cytokines and effector molecules of cytotoxic T lymphocytes. Logistic regression analysis was used to predict the probability of TPE and identify independently associated factors. Receiver operating characteristic (ROC) curve analysis was applied to determine the optimal cut-off value for the predicted probability. RESULTS: Of 95 patients enrolled, 35 had TPE, 46 had malignant PE and 14 had PE due to other aetiologies. Interferon-γ (IFN-γ), adenosine deaminase (ADA), decoy receptor (DcR) 3, monocyte chemo-attractant protein (MCP)-1, IFN-induced protein (IP)-10, granzyme A and perforin were higher in TPE than in PE of other aetiologies. By logistic regression analysis, IFN-γ ≥ 75 pg/mL, ADA ≥ 40 IU/mL, DcR3 ≥ 9.3 ng/mL and soluble tumour necrosis factor receptor 1 (TNF-sR1) ≥ 3.2 ng/mL were independent factors associated with TPE. The predicted probability based on the four predictors had an area under the ROC curve of 0.920, with 82.9% sensitivity and 86.7% specificity under the cut-off value of 0.303. In the TPE group, patients with positive PE/pleural culture for Mycobacterium tuberculosis had higher pleural IFN-γ, MCP-1, IP-10 and perforin than those with positive sputum but negative PE culture. CONCLUSIONS: While pleural interferon-γ and ADA are conventional markers for diagnosing TPE, simultaneous measurements of DcR3 and TNF-sR1 can improve the diagnostic efficacy.

Sero-diagnosis of Mycobacterium avium complex lung disease using serum immunoglobulin A antibody against glycopeptidolipid antigen in Taiwan.

BACKGROUND: Lung disease (LD) due to non-tuberculous mycobacteria is an important clinical concern. Mycobacterium avium complex (MAC) is one of the most common causative agents but the diagnosis of MAC-LD remains challenging. Detection of serum IgA antibody against MAC glycopeptidolipid (GPL) has recently been shown to improve the diagnosis of MAC-LD, but has yet to be validated worldwide. METHODS: This prospective study was conducted in a tertiary referral center in northern Taiwan and enrolled patients with MAC-LD, MAC contamination, other lung diseases, and control subjects. Serum immunoglobulin A (IgA) antibody against MAC-GPL was detected in the participants and its specificity and sensitivity was assessed. RESULTS: There were 56 patients with MAC-LD, 11 with MAC contamination, 13 M. kansasii-LD, 26 LD due to rapidly-growing mycobacteria (RGM), 48 pulmonary tuberculosis, and 42 household contacts of patients with TB. Patients with MAC-LD were older and 32% of them had an underlying co-morbidity. By logistic regression, serum MAC-GPL IgA level was an independent predictor of MAC-LD among the study subjects and those with culture-positive specimens for MAC. By the receiver operating characteristic curve, serum MAC-GPL IgA had a good power to discriminate MAC-LD from MAC contamination. Under the optimal cut-off value of 0.73 U/mL, its sensitivity and specificity were 60% and 91%, respectively. Among MAC-LD patients, presence of co-morbidity was associated with MAC-GPL <0.73 U/ml in logistic regression analysis. CONCLUSIONS: Measurement of serum anti-MAC-GPL IgA level is useful for the diagnosis of MAC-LD. However, its implement in clinical practice for immuno-compromised hosts needs careful consideration.

Epidemiologic surveillance to detect false-positive Mycobacterium tuberculosis cultures.

This study was aimed to investigate the ability of potential indices from epidemiologic surveillance to detect false-positive cultures of Mycobacterium tuberculosis (MTB). All clinical specimens for mycobacterial culture from April 1 to August 31, 2010, were reviewed. Single-positive cultures without relevant clinical and pathologic information were categorized as suspected false-positive cultures. Genotyping methods were used to confirm false-positive cultures. The performance of epidemiologic surveillance indices to detect potential false-positive cultures was evaluated. A total of 14,462 specimens were sent to the laboratory and 214 batches were processed in 107 work days (average 67.6 specimens per batch, ranging from 21 to 130 specimens per batch). Seventy-one single-positive cultures were identified, among which 5 cultures of multidrug-resistant MTB in 1 batch were false-positive, confirmed by genotyping methods. Epidemiologic surveillance with statistical process control charts for single-positive cultures per day showed good performance in epidemiologic surveillance. The false-positive rate was 38.5% in the 13 potential false-positive cultures according to the statistical process control chart for single-positive cultures per day. Although the incidence of tuberculous disease is high in Taiwan, clustering of multidrug-resistant MTB in 1 batch or clustering of single-positive cultures still suggested the occurrence of false-positive MTB cultures. Therefore, epidemiologic surveillance for the clustering of single-positive cultures with the statistical process control chart could be used to monitor the occurrence of false-positive results.

Is it appropriate to routinely use a nucleic acid amplification test for the diagnosis of tuberculosis?

The purpose of this study was to compare the usefulness of the nucleic acid amplification (NAA) test against conventional tests under normal laboratory operational conditions. The NAA test was performed on the first sputum specimen of all patients. Liquid media culture, solid media culture, and Ziehl-Neelsen stain for an acid-fast bacilli (AFB) smear were performed on three sputum specimens. The results were calculated using the gold standard of either the culture results or the clinical diagnosis. Of the 593 patients tested, 151 (25.5%) were diagnosed with pulmonary tuberculosis. The sensitivity of the first specimen only was 64% for the NAA test, 54% for the AFB smear, 77% for BACTEC MGIT 960 culture, 40% for Lowestain-Jensen (LJ) culture, and 25% for 7H11 culture. The sensitivity when using all three specimens increased to 63% for AFB smear, 87% for BACTEC MGIT 960 culture, 51% for LJ culture, and 40% for 7H11 culture. The specificity was 100% for all culture tests, 99% for the AFB smear, and 99.5% for NAA test. The mean turnaround time was 1.34 days for NAA, 0.59 days for AFB smear, 11 days for BACTEC MGIT 960 culture, 23 days for LJ culture, and 20 days for 7H11 culture. We conclude that the sensitivity of NAA is still far from ideal, and the test is not cost effective. Thus, the COBAS AMPLICOR PCR system is not suitable for routine use in microbiology laboratories.

Increasing incidence of nontuberculous mycobacteria, Taiwan, 2000-2008.

To assess the species distribution and epidemiologic trends of nontuberculous mycobacteria, we examined isolates from patients in Taiwan. During 2000-2008, the proportion increased significantly from 32.3% to 49.8%. Associated disease incidence increased from 2.7 to 10.2 cases per 100,000 patients. Mycobacterium avium complex and M. abscessus were most frequently isolated.

Comparison of 2 interferon-gamma assays and Roche Cobas Amplicor Mycobacterium tuberculosis assay for rapid diagnosis of tuberculosis among patients with suspected tuberculosis in Taiwan.

BACKGROUND AND PURPOSE: Two commercial interferon-gamma (IFN-gamma) assays, which are commonly used for diagnosing latent tuberculosis (TB), are also useful for diagnosis of active TB. In this study, the IFN-gamma assays and polymerase chain reaction (PCR) for diagnosis of TB were compared. METHODS: A prospective comparison of the performance of 2 commercial IFN-gamma assays - QuantiFERON-TB Gold (QFT-G) and T-SPOT.TB (T SPOT) - and PCR using the Roche Cobas Amplicor Mycobacterium tuberculosis (RCA-TB) assay for the rapid diagnosis of TB was conducted from January 2007 to December 2007 at a university-affiliated hospital in Taiwan. RESULTS: Of 187 patients enrolled in the study, results from both T SPOT and QFT-G were available for 154, including 109 patients with active TB and 45 with no TB. The sensitivity of T SPOT (89.0%) was higher than that of QFT-G (71.4%). RCA-TB had the highest sensitivity (90.2%) and specificity (100%), but was usually performed in patients with positive acid-fast bacilli smear test. In patients with extrapulmonary TB, T SPOT had a high diagnostic value (sensitivity, 81.3%). A significant discordance between the 2 IFN-gamma assays was also noted. IFN-gamma assays provided a more rapid diagnosis for tuberculosis than the conventional culture method (mean +/- standard deviation, 8.23 +/- 12.86 days; p < 0.001). CONCLUSIONS: Use of IFN-gamma may shorten the time to diagnosis of TB, especially for smear-negative patients and those with extrapulmonary disease.

Safety of fluoroquinolone use in patients with hepatotoxicity induced by anti-tuberculosis regimens.

BACKGROUND: Fluoroquinolones are frequently used to replace agents in first-line anti-tuberculosis (anti-TB) regimens in patients with TB who have drug-induced hepatic dysfunction. We investigated the safety of using fluoroquinolone in an area where TB is endemic and where there is a high incidence of drug-induced liver injury. METHODS: From September 2003 through August 2006, patients who had aspartate aminotransferase and/or alanine aminotransferase levels >3 times the upper limit of normal in the presence of hepatitis symptoms or who had aspartate aminotransferase and/or alanine aminotransferase levels >5 times the upper limit of normal after receipt of anti-TB treatment were enrolled. The control group received ethambutol, with or without streptomycin; study groups received either (1) ethambutol plus levofloxacin, with or without streptomycin; or (2) ethambutol plus moxifloxacin, with or without streptomycin. The outcome measurement was the time from onset of hepatitis to normalization of liver functions. RESULTS: One hundred thirty-four (11.3%) of 1191 patients received a diagnosis of hepatotoxicity and needed to stop anti-TB treatment. The risk factor was abnormal baseline transaminase levels. Twenty-two of the 134 patients received the control medication, 40 received levofloxacin, and 45 received moxifloxacin; the remaining patients were excluded from the study. There were no significant prestudy differences between groups. Time to liver function normalization was almost the same for all groups (mean +/- standard deviation, 29.1+/-21.4, 25.5+/-17.6, and 29.7+/-14.3 days, respectively). CONCLUSIONS: Abnormal baseline transaminase levels are the independent risk factors for anti-TB therapy-induced hepatitis. Levofloxacin and moxifloxacin caused no additional hepatotoxicity when they were used by patients with hepatitis induced by first-line anti-TB drugs.

A prospective study of hepatitis during antituberculous treatment in Taiwanese patients and a review of the literature.

BACKGROUND/PURPOSE: The present study prospectively investigated the incidence of and factors associated with hepatitis during antituberculous treatment in patients with tuberculosis and various underlying diseases. The results were compared with those of previously published studies. METHODS: Patients treated with antituberculous agents were enrolled from July 1, 2000 to July 31, 2001, in the divisions of chest and infectious diseases at National Taiwan University Hospital and followed until November 30, 2001. Hepatitis was defined as an aminotransferase level>5 times the upper limit of normal (ULN), or >3 times ULN in the presence of symptoms of hepatitis, or total bilirubin level>3 mg/dL. Studies reporting the incidence of hepatitis during antituberculous treatment were reviewed for comparison. RESULTS: Among 261 patients, median age was 58 years (range, 17-90 years), 17.7% had abnormal baseline liver function tests and 18.4% had concurrent hepatotoxic drug use. Fifteen patients (5.7%) had hepatitis B virus infection, 17 (6.5%) had hepatitis C virus infection, 14 (5.4%) had liver cirrhosis, and 15 (5.7%) had human immunodeficiency virus infection. Hepatitis occurred in 42 patients (16.1%), with 60% of the events in the first 2 months of treatment. Such an incidence was comparable to that in other Asian countries (5.3-18.2%) and slightly higher than that in Western countries (2.4-19%). In multivariate analysis, abnormal liver function tests at baseline and liver cirrhosis were independent factors for development of hepatitis. CONCLUSION: Elevation of liver function tests was not uncommon during antituberculous treatment, especially in the first 2 months. Patients with abnormal liver function tests at baseline or liver cirrhosis should be closely monitored.

Recurrent bilateral pneumothoraces: a rare complication of miliary tuberculosis.

Pneumothorax as a complication of adult cavitary pulmonary tuberculosis is well known and not at all rare, but its occurrence as a complication of miliary tuberculosis is extremely rare. We report a 22-year-old woman who had nonproductive cough and fever for 3 days. Chest radiography showed diffuse, symmetrical miliary nodulation throughout both lung fields. The patient was treated for a presumed diagnosis of miliary tuberculosis with standard antituberculous regimen. Bilateral pneumothorax occurred simultaneously during hospitalization and chest tube thoracostomy was performed. Three days later, recurrent right pneumothorax developed. Video-assisted thoracoscopic surgery (VATS) lung biopsy of the right lung was performed and pathology showed granulomatous interstitial pneumonia with acid-fast positive bacilli. Lung tissue culture was positive for Mycobacterium tuberculosis. In the following 2 months, bilateral pneumothorax recurred twice and chemical pleurodesis with minocycline was performed on both sides, but air leakage persisted. VATS pleurodesis was performed on both sides successfully without recurrence of pneumothorax on either side. Our experience highlights the fact that pneumothorax should be suspected in an adult with miliary tuberculosis who suddenly develops acute respiratory distress. Recurrent pneumothorax can be managed, apart from medical therapy of miliary tuberculosis, with surgical intervention.

Extensively drug-resistant Mycobacterium tuberculosis during a trend of decreasing drug resistance from 2000 through 2006 at a Medical Center in Taiwan.

BACKGROUND: Drug resistance rates are one of the most important aspects in the national tuberculosis (TB) control program, and drug-resistant TB, especially extensively drug-resistant (XDR) TB, is not well understood in Taiwan. The objectives of this study were to investigate the prevalence of drug resistance from 2000 through 2006 and to identify XDR TB isolates to elucidate the clinical characteristics of patients with XDR TB at National Taiwan University Hospital. METHODS: The prevalence of drug resistance among clinical, nonduplicate Mycobacterium tuberculosis isolates was analyzed. Testing of susceptibility to antituberculosis agents, including isoniazid, rifampicin, ethambutol, streptomycin, rifabutin, ofloxacin, ethinamide, and para-aminosalicylic acid, was performed using the proportional method. Minimum inhibitory concentrations of amikacin, capreomycin, isepamycin, linezolid, cycloserine, ciprofloxacin, levofloxacin, moxifloxacin, and gemifloxacin were determined for 40 available multidrug-resistant M. tuberculosis isolates. RESULTS: Significant decreasing trends in rates of resistance to isoniazid, ethambutol, and at least 1 of the 3 first-line agents were observed among 2625 M. tuberculosis isolates from 2000 through 2006. Among these 2625 isolates, 150 (5.7%) were multidrug resistant, and 10 M. tuberculosis isolates (0.4%) fulfilled the definition of XDR M. tuberculosis. Nine (90%) of 10 patients with XDR TB had a previous history of TB and received anti-TB treatment before acquisition of XDR TB. CONCLUSIONS: The remaining high prevalence of multidrug-resistant TB and the presence of XDR TB during a trend of decreasing drug resistance are alarming. Continuous surveillance of clinical isolates of M. tuberculosis is needed to identify XDR TB, especially in patients who have a history of TB and have received prior anti-TB treatment.

Diagnosis of tuberculosis by an enzyme-linked immunospot assay for interferon-gamma.

We evaluated an enzyme-linked immunospot assay for interferon-gamma (T SPOT-TB) for rapid diagnosis of active tuberculosis (TB) in a disease-endemic area. From January to June 2005, patients whose clinical symptoms and radiographic findings were compatible with TB were recruited, and a blood sample was obtained for T SPOT-TB assay within 7 days of microbiologic studies. Sixty-five patients were studied, including 39 (60%) with active TB. Thirty-five (53.8%) patients had underlying medical conditions. Thirty-seven patients had positive cultures for Mycobacterium tuberculosis, and 11 patients had positive cultures for nontuberculous mycobacteria. The sensitivity, specificity, positive predictive value, and negative predictive value of the T SPOT-TB assay were 87.2%, 88.5%, 91.9%, and 82.1%, respectively. The accuracy of this test in diagnosing active TB is >80%, even in an area with a high incidence of nontuberculous mycobacterial disease.

Antibody responses to pneumococcal polysaccharide vaccine in Taiwanese patients with chronic obstructive pulmonary disease.

BACKGROUND/PURPOSE: A study was undertaken to assess the antibody responses to a 23-valent pneumococcal polysaccharide vaccine and clinical outcome in Taiwanese patients with chronic obstructive pulmonary disease (COPD). METHODS: From January to December 1999, 80 Taiwanese patients with COPD were enrolled. Each patient received a 23-valent pneumococcal polysaccharide vaccine (Pneumovax 23). Specific IgG antibodies to pneumococcal capsular antigens of serotypes 4, 6B, 7F, 9V, 14, 18C, 19F, and 23F were measured before vaccination, and 6 weeks and 52 weeks after vaccination. RESULTS: Detectable prevaccination IgG antibody (> 1 microg/mL) was found in the range of 27.5% of patients for serotype 7F to 96.2% for serotype 14. Antibody concentrations in prevaccination sera were not different between middle-aged (< 65 years old) and elderly patients (> or = 65 years old). The percentage of elderly patients with postvaccination antibody concentration > 2 -fold higher than that prior to vaccination ranged from 84% for serotype 18C to 90% for serotypes 7F, 9V, and 19F. The change in antibody level (fold and absolute increases) postvaccination was not significantly different among the different age groups. CONCLUSION: Taiwanese elderly adults with COPD, even in advanced age, can mount a significant antibody response to pneumococcal polysaccharide vaccine. This study may support the existing recommendation that pneumococcal vaccine be offered to persons > or = 65 years old with COPD.

Disseminated tuberculosis: a 10-year experience in a medical center.

Disseminated tuberculosis remains a diagnostic challenge because the presentations are nonspecific. In the current retrospective study we describe the clinical characteristics and outcome of disseminated tuberculosis. From January 1995 to December 2004, patients with culture-confirmed tuberculosis who fulfilled the criteria for disseminated tuberculosis were selected and their medical records reviewed. Their clinical isolates were genotyped. Of the 3058 patients with culture-confirmed tuberculosis, 164 (5.4%) had disseminated disease; 14.0% of patients had acquired immunodeficiency syndrome. The most common radiographic finding was miliary lung lesions (47.0%); 31.1% of patients died at the end of the study. Poor prognostic factors included hypoalbuminemia, hyperbilirubinemia, renal insufficiency, and delayed antituberculosis treatment. Clinical findings suggestive of disseminated tuberculosis were miliary lung lesions, serum ferritin >1000 microg/L, infiltrative liver disease, and adjusted calcium >2.6 mmol/L. Simultaneously performing mycobacterial culture and histopathologic examination of bone marrow biopsy was more sensitive and faster than just performing mycobacterial blood culture in diagnosing disseminated tuberculosis. Of the 64 preserved Mycobacterium tuberculosis isolates, 47 (73.4%) were clustered and 27 (42.2%) were Beijing family. Since prognosis was worse in patients with delayed treatment, a high index of suspicion is required, especially in those with clinical findings suggestive of disseminated tuberculosis.

In vitro activities of various piperacillin and sulbactam combinations against bacterial pathogens isolated from Intensive Care Units in Taiwan: SMART 2004 programme data.

We investigated the in vitro activity of various piperacillin and sulbactam combinations against Gram-negative bacterial isolates from Intensive Care Units (ICUs) in Taiwan. Antimicrobial susceptibility testing of 1030 bacterial isolates recovered from ICUs of nine major teaching hospitals was performed using the agar dilution method. Sulbactam was added to piperacillin either at a fixed sulbactam concentration of 4 mg/L and 8 mg/L or at a piperacillin:sulbactam ratio of 2:1 and 4:1. Piperacillin/sulbactam at a ratio of 2:1 or a fixed 8 mg/L concentration of sulbactam had better activities against Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and Serratia marcescens than other piperacillin/sulbactam formulations. For Pseudomonas aeruginosa, piperacillin/sulbactam (2:1 or 4:1 ratios) had MIC(90) values (minimum inhibitory concentration for 90% of the organisms) of 64 mg/L (>90% susceptibility) compared with 64 mg/L for cefoperazone/sulbactam (68% susceptibility) and 128 mg/L for piperacillin/tazobactam (82% susceptibility). For Acinetobacter baumannii, both piperacillin/sulbactam (either 2:1 ratio or a fixed 8 mg/L sulbactam) and cefoperazone/sulbactam were the most potent agents. Adding sulbactam to piperacillin resulted in increased susceptibility rates among piperacillin-resistant P. aeruginosa (53-57% in either 2:1 or 4:1 ratios) and A. baumannii (38-46% in either 2:1 ratio or a fixed 8 mg/L concentration of sulbactam) isolates. Results of susceptibility tests with piperacillin/sulbactam are dependent on the method used. Piperacillin/sulbactam combinations possessed better in vitro activities than piperacillin alone or piperacillin/tazobactam against P. aeruginosa and A. baumannii.

Identification of alpha-enolase as an autoantigen in lung cancer: its overexpression is associated with clinical outcomes.

PURPOSE: Although existence of humoral immunity has been previously shown in malignant pleural effusions, only a limited number of immunogenic tumor-associated antigens (TAA) have been identified and associated with lung cancer. In this study, we intended to identify more TAAs in pleural effusion-derived tumor cells. EXPERIMENTAL DESIGN: Using morphologically normal lung tissues as a control lysate in Western blotting analyses, 54 tumor samples were screened with autologous effusion antibodies. Biochemical purification and mass spectrometric identification of TAAs were done using established effusion tumor cell lines as antigen sources. We identified a p48 antigen as alpha-enolase (ENO1). Semiquantitative immunohistochemistry was used to evaluate expression status of ENO1 in the tissue samples of 80 patients with non-small cell lung cancer (NSCLC) and then correlated with clinical variables. RESULTS: Using ENO1-specifc antiserum, up-regulation of ENO1 expression in effusion tumor cells from 11 of 17 patients was clearly observed compared with human normal lung primary epithelial and non-cancer-associated effusion cells. Immunohistochemical studies consistently showed high level of ENO1 expression in all the tumors we have examined thus far. Log-rank and Cox's analyses of ENO1 expression status revealed that its expression level in primary tumors was a key factor contributing to overall- and progression-free survivals of patients (P < 0.05). The same result was also obtained in the early stage of NSCLC patients, showing that tumors expressing relatively higher ENO1 level were tightly correlated with poorer survival outcomes. CONCLUSIONS: Our data strongly support a prognostic role of ENO1 in determining tumor malignancy of patients with NSCLC.

Double-blind randomized parallel group study comparing the efficacy and safety of tiotropium and ipratropium in the treatment of COPD patients in Taiwan.

BACKGROUND/PURPOSE: To compare the efficacy and safety of tiotropium and ipratropium in patients with chronic obstructive pulmonary disease (COPD) in Taiwan. METHODS: This double-blind, randomized, placebo-controlled, parallel group study was conducted at six hospitals in Taiwan. COPD patients aged > or = 40 years, with a forced expiratory volume in 1 second (FEV1) < or = 65% of predicted and FEV1/forced vital capacity (FVC) < or = 70% were enrolled. After a 2-week screening/baseline period, 132 patients were randomized to receive 4 weeks of treatment with either tiotropium 18 microg once daily from a dry powder inhaler (HandiHaler) or two puffs of ipratropium 20 microg four times daily from a metered dose inhaler. The primary outcome was the change in trough FEV1 from baseline to week 4. The secondary outcome measures were trough FVC response, FEV1 and FVC responses at 2 hours postinhalation. RESULTS: After 4 weeks, trough FEV1 had increased by 61.7 +/- 25.3 mL for tiotropium but decreased by 16.4 +/- 27.9 mL for ipratropium. The difference between groups was significant (p < 0.05; 95% CI, 10-146.1). The trough FVC also increased by 137.2 +/- 49.3 mL for tiotropium but was decreased by 84.5 +/- 54.5 mL for ipratropium (p < 0.001; 95% CI, 89.0-354.3). No major drug-related adverse events associated with tiotropium and ipratropium were observed. CONCLUSION: Tiotropium 18 microg once daily using HandiHaler was significantly more effective than ipratropium 40 microg four times daily in improving trough FEV1 and FVC over a 4-week period. The safety profiles of both drugs are comparable.

Comparison of in vitro activities of tigecycline with other antimicrobial agents against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in Taiwan.

We compared the in vitro activities of tigecycline to those of other agents against 300 nonduplicate isolates of Streptococcus pneumoniae (194 isolates), Haemophilus influenzae (60 isolates), and Moraxella catarrhalis (46 isolates) recovered from patients treated in three major hospitals in Taiwan from August through December, 2003. All of these isolates were inhibited at 0.5 mg/L of tigecycline. For S. pneumoniae isolates, 72% were not susceptible to penicillin (69% intermediate and 3% resistant) and 96% were not susceptible to azithromycin. Among the 178 isolates resistant to azithromycin, 53 isolates (30%) had the M phenotype and 70% had the cMLSB phenotype. The rate of nonsusceptibility to ertapenem, telithromycin, moxifloxacin, and quinupristindalfopristin in S. pneumoniae was 3%, 2%, 1%, and 57%, respectively. For H. influenzae, 36 (60%) were not susceptible to ampicillin, among which 31 possessed beta-lactamase. A high rate (8.3%) of H. influenzae isolates with beta-lactamase-negative and ampicillin-resistant phenotype was found. All H. influenzae isolates were susceptible to azithromycin, but 40% of them were not susceptible to clarithromycin. Ninety-eight percent (44 isolates) of M. catarrhalis possessed beta-lactamase. All three fluoroquinolones tested were highly active (MIC90 < or =0.12 mg/L) against H. influenzae and M. catarrhalis.

Performance assessment of the DR. MTBC Screen assay and the BD ProbeTec ET system for direct detection of Mycobacterium tuberculosis in respiratory specimens.

The performance of the DR. MTBC PCR-based assay and the BD ProbeTec ET Mycobacterium tuberculosis Complex Direct Detection (DTB) assay for the direct detection of Mycobacterium tuberculosis was evaluated using 1,066 consecutive clinical respiratory samples collected from 494 patients who did not have old cases of pulmonary tuberculosis and were not receiving antituberculosis treatment at National Taiwan University Hospital from January to February 2005. The results of both assays were compared to the "gold standard" of combined culture results and clinical diagnosis. The overall sensitivity and specificity of the DR. MTBC Screen assay were 56.6% and 98.9%, respectively, and of the DTB assay were 63.2% and 98.4%, respectively. The positive and negative predictive values for the DR. MTBC Screen assay were 84.5% and 95.4%, respectively, and for the DTB assay were 81.7% and 96.0%, respectively. The DR. MTBC Screen assay produced 11 false-positive results for 11 patients, including three samples yielding non-M. tuberculosis mycobacteria (one each for M. abscessus, a mixture of M. abscessus and M. chelonae, and unidentified non-tuberculosis mycobacteria). The DTB assay produced 15 false-positive results for 13 patients, including five samples from four patients yielding non-tuberculosis mycobacteria (two for M. abscessus, one for a mixture of M. abscessus and M. chelonae, and two for unidentified non-tuberculosis mycobacteria). This study demonstrated that the DR. MTBC Screen assay has a similar diagnostic value but fewer false-positive results than the DTB assay for respiratory specimens.

Mycobacterium tuberculosis in Taiwan.

OBJECTIVE: The resurgence of tuberculosis (TB) and the emergence of drug resistance of Mycobacterium tuberculosis (MTB) isolates are of great impact on public health. METHODS: Taiwanese data on disease burden of TB and anti-microbial resistance of MTB identified from Annual Reports of Centre for Disease Control, Department of Health, Taiwan and from peer-reviewed publications from MEDLINE (1995-2004). RESULTS: In Taiwan in 2002, the incidence (per 100,000 population) of tuberculosis was 74.6 and it was higher in aborigines (289.8) and in people living in mountainous regions (256.0). The mortality rate of tuberculosis in Taiwan in 2002 was 5.68 per 100,000 population. Susceptibility data summarized from 1990 to 2002 reports showed primary resistance ranged from 4.7 to 12% for isoniazid, 0.7 to 5.9% for rifampin, 1 to 6% for ethambutol, and 4 to 11% for streptomycin. The overall rates of multidrug-resistant tuberculosis (MDRTB) among new cases and previously treated cases were 1 to 3% and 15 to 46%, respectively. The increasing burden of patients with MDRTB infection, the persistent high rate of mortality, the lack of nationwide surveillance system using the standard methodology to determine the trends and current status of resistance, and the inadequate current TB control infrastructure and training to accomplish the tasks required to implement the directly observed treatment short-course (DOTS) strategy are having a great impact on public health in Taiwan. CONCLUSIONS: High disease burden of TB and high resistance rates in MTB as well as inappropriateness of the current control infrastructure for TB services illustrate increasingly serious health problems from TB in Taiwan.