Hsiao-Leng Hsu

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.

Diagnosis of Tuberculosis by an Enzyme-Linked Immunospot Assay for Interferon-γ

*National Taiwan University Hospital, Taipei, Taiwan, This assay for interferon-γ can rapidly and accurately diagnose active tuberculosis in a disease-endemic area.

Enzyme-linked immunospot assay for interferon-gamma in the diagnosis of tuberculous pleurisy

Patients presenting with pleural effusion of undetermined aetiology were prospectively enrolled, and an enzyme-linked immunospot (ELISPOT) assay on pleural fluid and peripheral blood was performed. Forty patients were studied, including 19 with culture- or biopsy-confirmed (n = 15) or clinically compatible (n = 4) tuberculous pleurisy, and 21 with pleural effusions due to non-tuberculous causes. The sensitivity, specificity and positive and negative predictive values of the assay were 94.7%, 85.7%, 85.7% and 94.7%, respectively, on pleural fluid, and 77.8%, 90.5%, 87.5% and 82.6%, respectively, on blood. Antigen-specific, interferon-gamma-secreting T-cells were concentrated eight to ten times in pleural fluid as compared with blood. Among the seven patients not suitable for pleural biopsy and three patients whose biopsy results were non-diagnostic, nine had positive ELISPOT result with pleural fluid. The ELISPOT assay for interferon-gamma can accurately diagnose tuberculous pleurisy and is helpful for patients not suitable for pleural biopsy and those whose biopsy results are non-diagnostic.

Clinical and microbiological characteristics of Nocardiosis including those caused by emerging Nocardia species in Taiwan, 1998–2008

The genus of Nocardia is rapidly expanding and the species distribution varies with different geographical locations. We retrospectively reviewed the laboratory records of the bacteriology laboratory at National Taiwan University Hospital from January 1998 to June 2008 to identify patients with nocardiosis. During the study period, 164 isolates of Nocardia spp. were identified from 134 patients but only 113 patients had Nocardia infection. Nocardia brasiliensis (n = 54) was the most common pathogen, followed by N. asteroides (n = 36), N. farcinica (n = 7), N. flavorosea (n = 4), N. otitidiscaviarum (n = 3), N. nova (n = 3), N. beijingensis (n = 2) and one each of N. puris, N. jinanensis and N. takedensis. The major types of infection were cutaneous infection (56.6%), pulmonary infection (33.6%) and disseminated infection (7.1%). Eighty-eight patients received sulfonamide-containing antibiotic and eight of 100 patients with available data on outcomes died during the episode of nocardiosis. In conclusion, the clinical and microbiological manifestations of Nocardiosis vary with the different Nocardia species. Accurate identification of the species is crucial to make the diagnosis.

Diagnostic performance of an enzyme-linked immunospot assay for interferon-γ in extrapulmonary tuberculosis varies between different sites of disease.

OBJECTIVES To evaluate diagnostic performance of an enzyme-linked immunospot assay for interferon-gamma (T SPOT-TB) in patients with suspected extrapulmonary tuberculosis (TB). METHODS From January 2007 to December 2008, patients with suspected extrapulmonary TB were prospectively enrolled from 2 tertiary care hospitals. RESULTS A total of 138 patients with suspected extrapulmonary TB were enrolled; 50 patients had positive culture for Mycobacterium tuberculosis and 39 patients had probable TB. The sites of infection were lymph node (n = 20), pleura (n = 19), bone/joint (n = 15), urinary tract (n = 7), peritoneum (n = 7), meninges (n = 6), disseminated (n = 5), intestine (n = 3), pericardium (n = 2), skin (n = 2), throat (n = 1), neck (n = 1), and genitalia (n = 1). The overall sensitivity and specificity were 79.8% (71/89) and 81.6% (40/49). The sensitivity ranged from 100% for tuberculous meningitis, tuberculous pericarditis, and intestinal TB, 95% for lymphadenitis, to 42.9% for tuberculous peritonitis. The sensitivity of the T SPOT-TB assay was 70.6% in immunocompromised patients and 85.5% in immunocompetent patients (p = 0.09). CONCLUSIONS The T SPOT-TB assay can be a useful tool for diagnosing extra-pulmonary TB in immunocompetent and immunocompromised patients, particularly for tuberculous meningitis, pericarditis, lymphadenitis, and intestinal TB.

Prediction of the Tuberculosis Reinfection Proportion from the Local Incidence

BACKGROUND Reinfection is a major contributor to tuberculosis (TB). It seems that the higher the local incidence, the higher the proportion of reinfection. METHODS Based on a systematic review of the literature, we established a regression model to predict the reinfection proportion from the local incidence. We then used our local data to verify the algorithm. RESULTS Of the 23 studies addressing reinfection in recurrent TB, 6 were population based. The reinfection proportion was correlated with the local incidence (reinfection proportion=-29.7+36.8 x log Incidence) (95% confidence interval [CI] for coefficient, 15.3-58.3; R2=0.849). The reinfection proportion in Taiwan (incidence, 62.4/100,000 people) was estimated to be 36% (95% CI, 3%-69%). Of our 49 recurrent patients, 51% had reinfection. Patients with reactivation seemed more likely to have underlying diseases and less likely to be smear positive. The relapse isolates seemed more resistant than the initial isolates. CONCLUSIONS The regression model could possibly predict the TB reinfection proportion from the local incidence. This algorithm is probably helpful in policy making for TB control programs. In areas where TB is endemic, reinfection might be responsible for >50% of TB cases, and aggressive surveillance to detect asymptomatic carriers could be an important strategy for controlling the disease.

Comparative in vitro activities of nemonoxacin, doripenem, tigecycline and 16 other antimicrobials against Nocardia brasiliensis, Nocardia asteroides and unusual Nocardia species

OBJECTIVES The aim of this study was to assess the in vitro activities of nemonoxacin (a novel non-fluorinated quinolone), doripenem, tigecycline and 16 other antimicrobial agents against the Nocardia species. METHODS MICs of 19 antimicrobial agents for 125 clinical isolates of the Nocardia species were determined by the broth microdilution method. RESULTS Nocardia brasiliensis (n = 61), Nocardia asteroides (n = 45), Nocardia flavorosea (n = 5), Nocardia otitidiscaviarum (n = 4), Nocardia farcinica (n = 3), Nocardia beijingensis (n = 2), Nocardia puris (n = 2) and one each of Nocardia nova, Nocardia jinanensis and Nocardia takedensis were identified based on a 16S rRNA gene sequencing analysis. For N. brasiliensis isolates, the MIC(90)s of the tested quinolones were in the order nemonoxacin < gemifloxacin = moxifloxacin < levofloxacin = ciprofloxacin, and the MIC(90)s of the tested carbapenems were in the order doripenem = meropenem < ertapenem < imipenem. Tigecycline had a lower MIC(90) (1 mg/L) than linezolid (8 mg/L). For N. asteroides isolates, the MIC(90)s of the tested quinolones were in the order nemonoxacin < gemifloxacin = moxifloxacin < levofloxacin < ciprofloxacin, and the MIC(90)s of the tested carbapenems were in the order doripenem = meropenem = imipenem < ertapenem. For the other 19 Nocardia species isolates, nemonoxacin showed good activity with the lowest MIC(90) of the tested quinolones. Among the four tested carbapenems, doripenem and meropenem had comparatively lower MIC(90)s. CONCLUSIONS The results of this in vitro study suggest that nemonoxacin, linezolid and tigecycline show promise as treatment options for nocardiosis. Further investigation of their clinical role is warranted.

Comparative in vitro activities of the new quinolone nemonoxacin (TG-873870), gemifloxacin and other quinolones against clinical isolates of Mycobacterium tuberculosis

Department of Intensive Care Medicine, Chi-Mei Medical Center, Tainan, Taiwan; Department of Internal Medicine, Yi-Min Hospital, Taipei, Taiwan; Department of Internal Medicine, Far Eastern Memorial Hospital, Taipei County, Taiwan; Department of Internal Medicine, National Taiwan University Hospital Yun-Lin Branch, Yun-Lin, Taiwan; Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan

Performance Assessment of the DR. MTBC Screen Assay and the BD ProbeTec ET System for Direct Detection of Mycobacterium tuberculosis in Respiratory Specimens

ABSTRACT 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.

Clinical and Genotypic Characteristics of Extensively Drug-Resistant and Multidrug-Resistant Tuberculosis

The aims of this study were to compare the clinical features of patients with extensively drug-resistant tuberculosis (XDRTB) and multidrug-resistant tuberculosis (MDRTB) and the genotypic characteristics of these Mycobacterium tuberculosis isolates. A total of 90 non-HIV-infected patients having MDRTB (n = 80, not including XDRTB, 88.9%) and XDRTB (n = 10, 11.1%) were identified from 2000 to 2007. Genotypes of the 39 available isolates were evaluated by spoligotyping and the 24-locus mycobacterial interspersed repetitive units–variable number of tandem repeats (MIRU-VNTR) scheme. Patients with XDRTB were more likely to have previous history of TB and cavitary lung lesions than patients with MDRTB (P < 0.05). Among the 39 isolates for spoligotyping analysis, the Beijing genotype was the most common (n = 21, 53.8%). Four (44.4%) isolates of XDRTB and 17 (56.7%) isolates of MDRTB belonged to Beijing family genotypes. There was no significant difference in the anti-tuberculosis drug resistance rates between Beijing and non-Beijing genotype isolates or in the clinical features of infected patients. In conclusion, significant differences in clinical manifestations existed among patients with XDRTB and MDRTB. The clinical features of patients infected with the Beijing genotype and the drug resistance profile of the Beijing genotype isolates were similar to those for the non-Beijing family genotype.