[Show abstract][Hide abstract] ABSTRACT: Background and objectiveEarly 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.ResultsOf 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.
[Show abstract][Hide abstract] ABSTRACT: Conclusions
During the 9-year period, NTM accounted for 39.2% of positive mycobacterial cultures and increased significantly. In concordance with the increased incidence of NTM isolations, incidence of NTM diseases also increased significantly. The increase of NTM isolations since 2002 might have resulted from use of the BACTEC system. This apparent increase in NTM disease could also be attributed to increasing vigilance and awareness of these bacteria as human pathogens, improved methods of detection, or more immunocompromised hosts (e.g., as a result of tumor necrosis factor inhibitors, human interleukin 1 receptor antagonists, and anti-CD20 antibodies) (1,8).Prevalence of mycobacteria species responsible for different diseases varies markedly by geographic region. In the United States and Japan, MAC and M. kansasii are the most common species (4), whereas in England and Scotland, M. kansasii and M. malmoense, respectively, are the most common (9). Our study showed that MAC was the most common NTM species in Taiwan, followed by M. abscessus. The most common organism in localized pulmonary infection and disseminated infection was MAC, and M. abscessus predominated in skin and soft tissue infection and lymphadenitis, consistent with findings of a previous study in Taiwan (2). Thus, M. abscessus deserves as much attention as MAC, especially for extrapulmonary NTM disease, in Taiwan.Identification of clinical isolates beyond the genus level is crucial because NTM species differ in the clinical spectrum of the diseases they cause and in their susceptibility to antimicrobial drugs. Previous studies have demonstrated that the rare strains identified in this study are pathogenic and cause human infections, e.g., 1 case of catheter-related bloodstream infection caused by M. neoaurum, 1 case of pulmonary infection caused by M. celatum, and 2 cases of soft tissue infection caused by M. conceptionene and M. arupense (10–13). In addition, in this study M. mageritense and M. immunogenum were the causative agents for pulmonary infection in an adult and submandibular abscess in a child from Taiwan, respectively.One study limitation was lack of a quantifiable denominator, which is critical for understanding the epidemiology of an illness. True population-based inferences about NTM epidemiology are usually impossible to conclude from a study of only hospital inpatients and outpatients. Although the hospital has a reference mycobacteriology laboratory and is a major referral center in Taiwan, how the study sample may have affected the results or the approximate size of its catchment of patients remains unknown. During the study period, an increasing percentage of patients (≈20% in 2008) was referred from other hospitals in different parts of Taiwan. However, because this study was conducted in a tertiary-care center in northern Taiwan, these findings might not reflect the overall situation in Taiwan.As prevalence and incidence of NTM increases, clinicians in Taiwan should consider NTM as a possible cause of TB-like disease. Accurate species identification is imperative before proper treatment can be determined for diseases caused by the diversity of NTM species. Further studies of clinical isolates are also needed to understand the spectrum of disease caused by these rare pathogens.
[Show abstract][Hide abstract] ABSTRACT: It has been well documented that smoking increases the risk of tuberculosis (TB). However, few studies have evaluated the impact of smoking on TB. We conducted this retrospective study to evaluate the influences of smoking on the manifestation and outcome of TB.
All culture-confirmed TB patients from July 2002 to December 2003 were identified and their medical records reviewed.
A total of 523 TB patients, including 207 (39.6%) who had ever smoked, were studied. The ever-smokers were significantly older, more likely to have underlying diseases and a duration of symptoms > 60 days, and less likely to have extra-pulmonary involvement and have completed treatment (64.7% vs. 78.5%). Radiographically, more ever-smokers with pulmonary tuberculosis (PTB) presented with miliary lesions, multiple nodules or masses, upper lung predominance and cavitation than never-smokers. Although smoking was associated with poor prognosis on univariate survival analysis, multivariate analysis revealed that independent poor prognostic factors included age, underlying disease, symptom duration < or = 60 days, extra-pulmonary involvement, serum albumin level < 3.5 g/dl and delayed treatment.
Our results demonstrate that smoking is significantly associated with radiographic manifestations of PTB, but not with death among PTB patients.
The International Journal of Tuberculosis and Lung Disease 02/2007; 11(2):143-9. · 2.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The annual incidence of meningococcal disease (meningitis and septicaemia) in Taiwan was 0.94/10(5) population in 1953. It then declined to below 0.001 from 1980 to 1987, and re-emerged in 2000 with a rate of 0.07/10(5) population. In 2001 there was a further increase in incidence (43 cases, 0.19/10(5)). Of 43 isolates of Neisseria meningitidis available for this study, including 41 from patients treated in 2001, three (7.0%) were penicillin insensitive (MIC > or = 0.12 microg/ml), though all were beta-lactamase negative: 16 (37.2%) were resistant to trimethoprim-sulphamethoxazole (MIC > or = 4/76 microg/ml). Serogrouping and genotype analysis revealed nine domestic clones. None of the 43 patients had any relationship (travel or contact history) with the 2000 or 2001 Hajj pilgrimage. Epidemiological information and typing results suggested wide dissemination of a limited number of domestic clones of N. meningitidis, manifesting as serogroups W-135, B and Y. Two clones of serogroup W-135 involved in the outbreak were genetically distinct from the 2000 or 2001 Hajj-related W-135 clone.
Epidemiology and Infection 09/2004; 132(4):637-45. DOI:10.1017/S0950268804002316 · 2.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Mortality remains high among patients with pulmonary tuberculosis requiring mechanical ventilation (TBMV). This study was carried out to establish the mortality rates of TBMV and to identify factors that contribute to in-hospital mortality. From January 1996-April 2001, there were 825 patients with active pulmonary tuberculosis at the National Taiwan University Hospital, Taipei, Taiwan. Of these, 41 suffered acute respiratory failure and required mechanical ventilation in the intensive care unit (ICU). Of these 41 patients, 38 were followed up for 180 days. In-hospital deaths were documented in the medical records and all possible parameters contributing to mortality were collected. Of the 41 patients, 27 died in the hospital and 14 were discharged alive (in-hospital mortality rate 65.9%), with (mean +/- SD) 40.7 +/- 35.4 admission days before death. Of the 27 that died, 25 died during ICU admission and two died after being transferred to the ward. The mortality rate for the 180-day monitoring period was 79%. Factors contributing to in-hospital mortality included consolidations on chest radiographs and multiple organ failure. The mortality rate in the patients with pulmonary tuberculosis requiring mechanical ventilation is very high, with two factors affecting in-hospital mortality. These factors were multiple organ failure and consolidation on chest radiographs.
European Respiratory Journal 08/2003; 22(1):141-7. DOI:10.1183/09031936.03.00038703 · 7.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the clinical characteristics of patients with tuberculous myositis.
From January 1996 to March 2001, patients with positive cultures of Mycobacterium tuberculosis or histology-proven caseous granulomatous inflammation from muscular specimens were identified and their medical records were reviewed.
Thirty-five patients were identified. Infection-related myositis was initially suspected in 20 patients (57.1%). The routes of infection were contiguous spread in 22 patients (62.8%), haematogenous spread in 10 (28.6%) and traumatic inoculation in three (8.6%). Five patients (14.3%), including the three who had received corticosteroids, died of uncontrolled sepsis. The computed tomography or the magnetic resonance imaging of the involved muscles showed findings suggestive of tuberculous myositis in 15 patients (42.9%).
Tuberculosis should be considered as one of the possible aetiologies of myositis, especially among patients with suggestive radiographic findings or in endemic areas of tuberculosis. Patients who develop tuberculous myositis after using corticosteroids have poor prognoses.
[Show abstract][Hide abstract] ABSTRACT: National Taiwan University Hospital, Taipei, Taiwan.
To study the variations in the NRAMP1 gene using five genotypes (274C/T, 577-18G/A, A318V, D543N and 3' untranslated region [UTR]), and the susceptibility of tuberculosis and HIV infection in Taiwanese.
The study sample included 49 patients with tuberculosis, 48 healthy control subjects and 60 HIV-infected patients. The polymerase chain reaction (PCR) products amplified from their genomic DNA were subjected to restriction enzyme digestion and were analysed using agarose gel electrophoresis.
A318V was not polymorphic in the studied population. Only D543N and 3'UTR were more heterozygous. In 274 C/T and 577-18G/A, the allele frequencies showed the predominant type to be the homozygous patterns C/C (94%) and G/G (94%), respectively. There were no statistically significant differences between the tuberculosis patients and the healthy control subjects. Despite the high susceptibility to Mycobacterium tuberculosis in HIV-infected patients, genotypic frequencies in the HIV-positive patients were not significantly different between tuberculous (n = 29) and non-tuberculous patients (n = 31). In comparison with previous studies, there were significant differences between different ethnic groups in allele frequencies for 274C/T, D543N and 3'UTR.
The allele and genotype of NRAMPI polymorphism among Taiwanese differed from those of Caucasians, Africans and Hispanics. No allelic associations were identified between the NRAMP1 alleles and tuberculosis susceptibility.
The International Journal of Tuberculosis and Lung Disease 06/2002; 6(5):454-60. · 2.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Susceptibilities to 13 antimicrobial agents were determined by measurement of MICs for 60 isolates of Streptococcus bovis from blood cultures. Thirty-eight isolates (63.3%) had high-level resistance to erythromycin (MICs, >or=128 microg/ml). Among the 38 erythromycin-resistant strains, 21 isolates (55%) had inducible resistance to macrolides-lincosamides-streptogramin B (iMLS isolates) and 17 (45%) had constitutive resistance to macrolides-lincosamides-streptogramin B (cMLS isolates). Tetracycline resistance was also found among all of the erythromycin-resistant strains. None of the strains displayed resistance to penicillin, chloramphenicol, or vancomycin. Detection of erythromycin resistance genes by PCR and sequencing indicated that all 17 cMLS isolates were positive for the ermB gene and that 7 of 21 iMLS isolates carried the ermB gene and the remaining 14 iMLS isolates carried the ermT gene. Sequence analysis of amplified partial ermB fragments (594 bp) from S. bovis isolates revealed a 99.8% nucleotide identity and a 100% amino acid homology compared with the sequences from gene banks. The sequences of amplified fragments with primers targeted for ermC were shown to be very similar to that of ermGT (ermT) from Lactobacillus reuteri (98.5% nucleotide identity). This is the first report to describe the detection of the ermT class of erythromycin resistance determinants in S. bovis. The high rate of inducible erythromycin resistance among S. bovis isolates in Taiwan was not reported before. The iMLS S. bovis isolates were shown to be heterogeneous by randomly amplified polymorphic DNA analysis. These results indicate that the prevalence of inducible erythromycin resistance in S. bovis in Taiwan is very high and that most of the resistant strains carry the ermT or the ermB gene.
[Show abstract][Hide abstract] ABSTRACT: p-Nitrophenylglycerol (PNPG) inhibits the co-ordinately regulated activities of swarming behaviour and virulence factor expression in Proteus mirabilis. The inhibitory action of PNPG was investigated by the isolation of Tn5 insertion mutants that could swarm, albeit with much reduced ability, in the presence of PNPG. The mutants exhibited a super-swarming phenotype in the absence of PNPG; i.e., they migrated further in a given time than did the wild-type cells. Cloning and sequence analysis of the mutants indicated that Tn5 was inserted into the rsbA gene, which may encode a membrane sensor histidine kinase of the bacterial two-component signalling system. In the absence of PNPG, the mutants exhibited several swarming-related phenotypes that were different from those of the wild type; they initiated swarming earlier and had a less conspicuous consolidation phase, they differentiated earlier and maintained a differentiated state for longer, they started to express virulence factors earlier and maintained high expression levels of these factors for longer, and they had higher cell invasion ability than the wild type. These mutant phenotypes could be complemented by a plasmid-borne copy of rsbA. Together, these data suggest that RsbA may act as a repressor of swarming and virulence factor expression. In the presence of PNPG, these rsbA-mutated mutants could still swarm, differentiate and express virulence factors, whereas the wild type could not, suggesting that PNPG may target RsbA or RsbA-regulated pathways to exert its inhibitory effect. Together, these data reveal a novel mechanism through which bacteria may negatively regulate swarming differentiation and virulence factor expression and identify a potential target of PNPG action.
Journal of Medical Microbiology 01/2002; 50(12):1039-48. DOI:10.1099/0022-1317-50-12-1039 · 2.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Since 1990, vancomycin-resistant enterococci have emerged as important nosocomial pathogens. Invasive infections caused by these organisms have challenged most physicians because they are resistant to multiple antibiotics. We analyzed the clinical characteristics of adult patients with invasive vancomycin-resistant enterococci infections in the National Taiwan University Hospital from January 1993 through December 2000. A total of 11 adult patients were identified, 9 of whom had bacteremia (7 caused by vancomycin-resistant Enterococcus faecalis and 2 by vancomycin-resistant Enterococcus faecium) and one each had thoracic empyema (vancomycin-resistant E. faecium) and peritonitis (vancomycin-resistant E. faecium). Five patients had rectal swab cultures positive for vancomycin-resistant enterococci; 4 of them had underlying malignancies. The majority (91%) of these patients had prolonged hospitalization and prior long-term use of broad-spectrum cephalosporins (ceftriaxone, ceftazidime, or cefepime) or anti-anaerobic agents (clindamycin or metronidazole). The crude mortality rate was 64%. In conclusion, invasive infection caused by vancomycin-resistant enterococci is an emerging problem among hospitalized patients in Taiwan, particularly those with severe underlying diseases and exposure to multiple antibiotics.
Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi 01/2002; 34(4):281-6. · 2.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Nosocomial Candida infections are an important cause of morbidity and mortality in critically ill patients. Although there is growing evidence that candidemia develops primarily as a consequence of endogenous colonization, hospital outbreaks of Candida infection are not uncommon. To examine the prevalence and consequence of Candida colonization in critically ill patients and to elucidate the contribution of cross-transmission to the high frequency of nosocomial fungal infection in intensive care units (ICUs), a 6-month prospective surveillance study was conducted.
A total of 342 adult patients with an expected ICU stay of 48 hours or more were enrolled in the study. Surveillance cultures were taken from the rectal region, oropharynx, and urine on ICU entry and weekly thereafter. The electrophoretic karyotypes (EKs) of all isolates were characterized using pulsed-field gel electrophoresis.
A total of 873 Candida strains were isolated from 208 of the 342 patients (60.8%) during ICU stay. A comparison of the EK patterns generated from Candida strains isolated from different patients demonstrated a variability of karyotypes, and failed to identify predominant clones colonizing or infecting ICU patients. For 62 of 102 patients colonized with multiple isolates of the same Candida spp., the EK patterns of the Candida strains isolated from individual patients were identical or similar, even when isolated from different anatomical sites, and the patterns remained the same for up to 62 days. A total of 57 episodes of Candida infection occurred in 53 (25.5%) of these 208 patients. Thirty-six episodes (63.1%) of Candida infection were preceded by colonization with the same Candida spp. All infecting strains had identical or similar EK patterns to prior colonizing strains.
While Candida colonization was common in ICU patients, karyotyping did not identify cross-transmission among these patients. Further, only 25.5% of patients with Candida colonization subsequently developed Candida infection. These findings suggest that universal prophylaxis is not warranted in critically ill patients with Candida colonization.
Journal of the Formosan Medical Association 01/2002; 100(12):791-7. · 1.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The in vitro susceptibilities of 266 isolates ofStreptococcus agalactiae determined by the agar dilution method showed that 6% of isolates were nonsusceptible to penicillin and 46% was resistant
to erythromycin. Of the erythromycin-resistant isolates, 86.3% had the macrolide-lincosamide-streptogramin (MLS) resistance
phenotype (constitutive MLS, 85.5%; inducible MLS, 0.8%) and 13.7% had the M phenotype.
[Show abstract][Hide abstract] ABSTRACT: Aberrant expression of mucin genes occurs frequently in advanced cancer. Using quantitative competitive reverse transcriptase/polymerase chain reaction (QC RT-PCR), the expression of three mucin genes--MUC1 (widely expressed in epithelial cells), MUC2 (mainly expressed in intestinal epithelial cells), and MUC5AC (mainly from airway and gastric epithelial cells)--was evaluated in 112 patients with pleural effusions (including 54 cytologically positive malignant pleural effusions, 35 benign exudative pleural fluids, and 23 cytologically negative pleural effusions from cancer patients). The expression ratios of MUC1 and MUC5AC, but not MUC2 gene, were significantly higher in malignant than benign pleural fluids (p < 0.000). The cutoff value, sensitivity, and specificity of MUC1 expression ratio were: 0.126, 64.6%, and 95.7%; and were 0.028, 72.3%, and 95.7%, respectively, for MUC5AC. In combined evaluation with both MUC1 and MUC5AC, the sensitivity was 86.1% and specificity was 91.5%. The positive and negative predictive values were 93.3%, and 82.7%, respectively. We considered mucin QC RT-PCR to be a useful tool in assisting the diagnosis of malignant pleural effusion.
American Journal of Respiratory and Critical Care Medicine 11/2001; 164(7):1312-8. DOI:10.1164/ajrccm.164.7.2102067 · 13.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the clinical, epidemiologic, and microbiological characteristics of community-acquired pneumonia (CAP) due to Acinetobacter baumannii.
Retrospective chart and radiographic reviews of all patients who were admitted to National Taiwan University Hospital from January 1993 to August 1999, fulfilled the criteria for CAP, and had an isolate of A. baumannii from blood or pleural fluid at hospital admission.
Thirteen patients (9 men and 4 women; age range, 37 to 85 years) met the criteria. Conditions associated with the infection included male gender, old age, alcoholism, malignancy, cerebrovascular disease, diabetes mellitus, renal disease, and liver cirrhosis. Eleven patients (85%) acquired the infection during the warmer months of April to October. Twelve patients (92%) had a fulminant course presenting with septic shock and respiratory failure, and 11 patients (85%) needed ventilator support and were treated in an ICU. Six patients (46%) had leukopenia. Lobar consolidations were found in 12 patients (92%), and pleural effusions were present in 4 patients (31%). All patients had positive blood culture results, two patients (15%) had positive pleural effusion culture findings, and nine patients (69%) positive sputum culture results. All the isolates were susceptible to imipenem, and most were susceptible to aminoglycosides, ceftazidime, ciprofloxacin, and extended-spectrum penicillins. Eight patients (62%) died. Four of the five survivors were initially treated with combination of a third-generation cephalosporin and an aminoglycoside.
A. baumannii should be considered as a possible etiologic agent in community-acquired lobar pneumonia when (1) patients with a fulminant course present during the warmer and more humid months of the year, and (2) patients are younger alcoholics. A good sputum smear, defined as a Gram stain smear of an adequate sputum specimen that comes from the lower respiratory tract and contains > 25 leukocytes per high-power (100x) field on microscopic examination, can help early diagnosis and treatment. A combination of a third-generation cephalosporin and an aminoglycoside may be appropriate empirical therapy.
[Show abstract][Hide abstract] ABSTRACT: During the period from August 1994 to October 1998, a total of 19 isolates of Exophiala jeanselmei were recovered from 17 patients with various underlying thoracic diseases treated at National Taiwan University Hospital. The purpose of this study was to describe the clinical characteristics of these patients and to determine the microbiologic relatedness of the E. jeanselmei.
Of the 19 isolates, 11 from nine patients were preserved and were identified based on their biotypes as determined by the API ID32C System, their cellular fatty acid profiles by gas-liquid chromatography, their antibiotypes to five antifungal agents by the E-test, and their random amplified polymorphic DNA (RAPD) patterns by arbitrarily primed PCR. Extensive environmental surveillance cultures and cultures from the skin of eight patients and hands of one physician were also performed.
One of the 17 patients had E. jeanselmei isolated from cutaneous phaeohyphomycosis (3 isolates), and the other 16 patients had isolations from pleural effusion specimens (15 isolates) or lung mass (1 isolate) following sonography-guided aspiration. The latter 16 patients had no clinical or pathologic evidence of fungal infection. Isolates (clone 1) from aspirated specimens had identical biotypes, antibiotypes, and RAPD patterns, which were different from those of the three isolates (clone 2) from the patient with a cutaneous lesion. All specimens from environmental sources, patients' skin, and the hands of the physician were negative for E. jeanselmei.
This series of patients demonstrates the difficulty in identifying the sources of a nosocomial pseudoinfection due to this slow-growing microorganism when isolated from pleural effusion specimens.
Journal of the Formosan Medical Association 10/2001; 100(9):613-9. · 1.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Amplification of the partial Cpn60 (or GroEL) gene segment has been used for identification of many bacteria, includingEnterococcus species. To obtain more sequence data fromgroESL genes of Enterococcus faecalis, the full-length sequence of the E. faecalis groESL genes containing groES (285 bp), spacer (57 bp), andgroEL (1,626 bp) was determined. A database search of GenBank revealed that the deduced E. faecalis GroES and GroEL proteins show significant homology to the GroES and GroEL proteins of other bacteria. The GroEL (groEL) ofE. faecalis had the highest identity withStreptococcus pneumoniae (81.8% amino acid sequence identity and 73.0% nucleotide sequence identity), followed byLactococcus zeae, while GroES (groES) had 60.2% (64.6%) identity with Lactobacillus zeae and 58.5% (66.2%) identity with Lactococcus lactis, followed by 57.0% (65.5%) identity with Bacillus subtilis. Based on the groES sequence, anE. faecalis-specific PCR assay was developed, and this PCR assay was positive for all the E. faecalis strains tested. Dot blot hybridization using either groES orgroEL as the probe distinguished E. faecalis clearly from other species, indicating that both genes can be used as suitable targets for E. faecalisidentification. Moreover, broad-range PCR-restriction fragment length polymorphism of groESL was designed to differentiate eight commonly encountered Enterococcus species. TheEnterococcus species of reference strains could be easily differentiated on the basis of restriction patterns produced byHaeIII and RsaI. The DNA-based assays developed in this study provide an alternative to currently used methods of identification for clinically
important enterococcal species.