Chien-Hong Chou

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.

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.

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.

Catheter-related bacteraemia and infective endocarditis caused by Kocuria species

We describe five patients with positive blood culture for Kocuria species. Three patients had catheter-related bacteraemia and one had infective endocarditis caused by Kocuria kristinae, and one had a K. marina isolate, which was considered to be a contaminant. Identification of the isolates was further confirmed by 16S rRNA gene sequence analysis. In conclusion, Kocuria species are an unusual cause of infection in immunocompromised patients. Accurate identification with molecular methods is imperative for the diagnosis of these unusual pathogens.

Skin and soft-tissue infection caused by non-tuberculous mycobacteria in Taiwan, 1997-2008.

The aim of this study was to investigate the clinical, microbiological, and pathological characteristics and the outcomes of skin and soft-tissue infection (SSTI) caused by non-tuberculous mycobacteria (NTM). Medical records of 50 patients with SSTI caused by NTM identified from 2005 to 2008 and 63 patients previously reported in a medical centre from 1997 to 2004 were reviewed. The annual incidence (per 100,000 outpatients and in-patients) ranged from 0·57 in 2005, 0·38 in 2007, to 1·1 in 2008, with an average of 0·62/100,000. From 1997 to 2008, the average incidence was 1·39/100,000 patients. The average annual incidence of SSTI caused by NTM was 0·62/100,000 outpatients and in-patients during 2005 and 2008. Of the total of 113 patients identified during the 12-year period, patients infected with Mycobacterium fortuitum and M. marinum were younger than those infected with M. avium-intracellulare complex (MAC) (36 and 44 years vs. 55 years, P=0·004 and P=0·056, respectively), and were more likely to have previous invasive procedures than those infected with MAC and M. abscessus (81·8% and 72·0% vs. 27·8% and 54·8%, P=0·007), and less likely to have associated immunosuppression (9·1% and 24% vs. 66·7% and 45·2%, P=0·006). Granuloma was more often observed in immunocompetent patients (60·1% vs. 40%, P=0·019), and in M. marinum-infected specimens (78·3%). There were significant differences in the demographic and clinical features of patients with NTM SSTI, including immunosuppression, trauma experience, and depth of tissue infections.

Pulmonary infection caused by nontuberculous mycobacteria in a medical center in Taiwan, 2005–2008

The aim of this study was to investigate the epidemiology and clinical characteristics of pulmonary infections caused by nontuberculous mycobacteria (NTM) in a university hospital in Taiwan from 2005 to 2008. During the study period, a total of 312 patients with NTM pulmonary infection were identified. Most patients with NTM pulmonary infection had preexisting pulmonary diseases or malignancies. The incidence (per 100,000 inpatients and outpatients) of patients with NTM isolations (6.67 in 2005 and 9.28 in 2008, P < .0001) from respiratory specimens and the incidence of patients with NTM pulmonary infection (3.54 in 2005 and 4.45 in 2008, P < .0141) increased significantly annually. The most common pathogens in patients with NTM-associated pulmonary infections were Mycobacterium avium complex (n = 110, 35.3%), followed by M. abscessus (n = 66, 21.2%). Incidence (per 100,000 inpatients and outpatients) of patients with pulmonary infections caused by rapidly growing mycobacteria (RGM) also increased significantly (1.06 in 2005 and 2.00 in 2008, P = .008). In conclusion, RGM, especially M. abscessus, had an increasingly important role in NTM pulmonary infections.