Chih-Cheng Lai

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.

Current challenges in the management of invasive fungal infections

The incidence of invasive fungal infections (IFIs) has increased over the past two decades, as the populations of patients at risk have continued to rise. Early and accurate diagnosis and the subsequent usage of appropriate antifungal therapy are difficult, which leads to a high mortality rate in patients with IFI. Along with the widespread use of antifungal prophylaxis, the epidemiology of invasive fungal pathogens has changed. Non-albicans Candida, Non-fumigatus Aspergillus, and molds other than Aspergillus have become more common pathogens causing invasive diseases, and most of these emerging fungi are resistant to or less susceptible than others to standard antifungal agents. Therefore, invasive infections due to these previously rare fungi are more difficult to treat. Advances in more potent and less toxic antifungal agents, such as second-generation triazoles and echinocandins, may potentially improve the outcomes of these infections. Recent advances in detecting fungal cell-wall components and genomic DNA also allow earlier diagnosis. This article reviews the changing spectrum of invasive fungal infections and the introduction of recent advances in diagnostic tools and antifungal agents.

Clinical and Microbiological Characteristics of Rhizobium radiobacter Infections

Data obtained from 1996 to 2002 on 13 patients with Rhizobium radiobacter infections were analyzed. Ten patients (76%) had underlying hematological malignancy or solid-organ cancer. Six patients (46%) had febrile neutropenia during the course of R. radiobacter infection. The majority (54%) of infections were catheter-related bacteremia, and 92% of infections were hospital acquired. All the patients survived. Eighteen isolates were recovered from the 13 patients, and each isolate was susceptible to cefepime, piperacillin-tazobactam, carbapenems, and ciprofloxacin. The pulsed-field gel electrophoresis profiles differed among the isolates recovered from different patients, indicating the absence of nosocomial spread of the organism.

Correlation between antibiotic consumption and resistance of Gram-negative bacteria causing healthcare-associated infections at a university hospital in Taiwan from 2000 to 2009

OBJECTIVES This study investigated the correlation between antibiotic consumption and antimicrobial resistance in Gram-negative bacteria causing healthcare-associated infections at a university hospital in Taiwan from 2000 to 2009. METHODS Disc susceptibility data of Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens, Proteus spp., Pseudomonas aeruginosa, Acinetobacter spp., Stenotrophomonas maltophilia and other non-fermentative Gram-negative bacilli causing healthcare-associated infections were evaluated. Data on annual patient-days and annual consumption (defined daily doses per 1000 patient-days) of extended-spectrum cephalosporins, β-lactam/β-lactamase inhibitor combinations, carbapenems, aminoglycosides and fluoroquinolones were analysed. RESULTS The trend of total consumption of extended-spectrum cephalosporins, β-lactam/β-lactamase inhibitor combinations, carbapenems, aminoglycosides and fluoroquinolones significantly increased between 2000 and 2003 and remained stable between 2004 and 2009. The decreasing use of gentamicin and amikacin in recent years was associated with increasing susceptibility of E. coli, E. cloacae, S. marcescens and P. aeruginosa to gentamicin, as well as increasing susceptibility of P. aeruginosa to amikacin. The use of piperacillin/tazobactam was positively correlated with the prevalence of piperacillin/tazobactam-resistant E. coli and S. maltophilia. In contrast, the use of cefotaxime and piperacillin/tazobactam was negatively correlated with the prevalence of cefotaxime-resistant E. coli and piperacillin/tazobactam-resistant S. maltophilia, respectively. The consumption of fluoroquinolones was positively correlated with the rates of ciprofloxacin-resistant E. coli, piperacillin/tazobactam-resistant P. aeruginosa and ceftazidime-resistant S. maltophilia. CONCLUSIONS The relationship between antibiotic prescription and the rates of resistance for Gram-negative bacteria is complicated; every type of antimicrobial agent or even individual agent can have distinct associations with different pathogens.

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.

Diagnostic value of procalcitonin for bacterial infection in elderly patients in the emergency department.

OBJECTIVES: To evaluate the diagnostic performance of procalcitonin (PCT) in elderly patients with bacterial infection in the emergency department (ED).

Risk factors for mortality in patients with persistent methicillin-resistant Staphylococcus aureus bacteraemia in a tertiary care hospital in Taiwan

OBJECTIVES To investigate the determinants of outcome in patients with persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia. METHODS All patients >or=18 years old with MRSA bacteraemia for >or=7 days from 2000 to 2008 treated at National Taiwan University Hospital were investigated. The associations of mortality with clinical characteristics, management and vancomycin MICs for serial MRSA isolates were analysed. RESULTS Persistent MRSA bacteraemia occurred in 227 patients. Decreasing trends in the incidence of MRSA bacteraemia (P < 0.001) and persistent MRSA bacteraemia (P = 0.031) were found. Elevated vancomycin MICs for subsequent MRSA isolates were found in 49 (24.6%) of 199 patients, especially those with infective endocarditis (41.9% versus 21.4%; P = 0.027). Metastatic infection [odds ratio (OR) 5.23; 95% confidence interval (CI) 2.17-12.59; P < 0.001], congestive heart failure (OR 4.78; 95% CI 2.19-10.42; P < 0.001) and elevated vancomycin MICs for subsequent MRSA isolates (OR 3.21; 95% CI 1.46-7.07; P = 0.004) were independent predictors of MRSA-related mortality, while metastatic infection (OR 3.01; 95% CI 1.45-6.28, P = 0.003) and congestive heart failure (OR 2.85; 95% CI 1.44-5.56, P = 0.003) were predictors of 30 day mortality. No significant impact of empirical glycopeptide therapy on MRSA-related (P = 0.89) or 30 day mortality (P = 0.26) was found. The 30 day mortality rate was lower in patients who received complete foci eradication (35.6% versus 51.1%; P = 0.03). CONCLUSIONS Congestive heart failure and metastatic infections were predictors of mortality. Isolates with decreased susceptibility to vancomycin that emerged during persistent MRSA bacteraemia were associated with mortality. Aggressive attempts to completely eradicate foci should be encouraged.

CNS infections caused by Mycobacterium abscessus complex: clinical features and antimicrobial susceptibilities of isolates

OBJECTIVES CNS infections caused by non-tuberculous mycobacteria (NTM) are rare and only three cases of CNS infections due to Mycobacterium abscessus complex have been reported. METHODS We searched the Mycobacteriology Database of the National Taiwan University Hospital and identified patients with CNS infections due to NTM. RESULTS A total of 15 patients, namely 4 HIV-seropositive patients and 11 HIV-seronegative patients, with CNS infections caused by NTM were identified during 2000-10. All of the HIV-seropositive patients had disseminated Mycobacterium avium complex infections. Among the 11 HIV-seronegative patients, NTM CNS infections were due to M. abscessus complex in 8 patients, M. avium complex in 2 patients and Mycobacterium kansasii in 1 patient. All the six preserved M. abscessus complex isolates were confirmed to be Mycobacterium massiliense by erm(41) PCR and 23S rRNA gene sequence analysis. Among the eight patients with infections due to M. abscessus complex, three had otolaryngological diseases, four had received neurosurgery and one had disseminated disease. Five patients received surgical debridement or intracranial device removal and three patients died of M. abscessus complex CNS infection. Among the five patients who survived, all received clarithromycin-based combination therapy with a median duration of 12 months and four received surgical intervention. All six isolates available for drug susceptibility testing showed uniform susceptibility to clarithromycin and five were susceptible to amikacin. CONCLUSIONS Our study revealed that M. abscessus complex isolates, particularly M. massiliense, should be considered potential pathogens causing CNS infections. Long-duration clarithromycin-based combination therapy plus surgical intervention may provide the best chance of cure.

Bacteremia caused by non-faecalis and non-faecium enterococcus species at a Medical center in Taiwan, 2000 to 2008

SUMMARY OBJECTIVES Human infections due to non-faecalis and non-faecium Enterococcus species are emerging but data on the characteristics of these infections are limited. METHODS We retrospectively reviewed the computerized database of the bacteriology laboratory at National Taiwan University Hospital from January 2000 through December 2008 to identify patients with non-faecalis and non-faecium enterococcal bacteremia. RESULTS Enterococcal bacteremia was diagnosed in 1887 patients during the study period and was caused by non-faecalis and non-faecium enterococci in 182 (9.6%) of these patients. The causative organisms included Enterococcus casseliflavus (n = 59, 3.1%), Enterococcus gallinarum (n = 58, 3.0%), Enterococcus avium (n = 45, 2.4%), Enterococcus hirae (n = 9, 0.5%), Enterococcus raffinosus (n = 9, 0.5%), Enterococcus durans (n = 2, 0.1%), Enterococcus cecorum (n = 2, 0.1%), and Enterococcus canintestini (n = 1, 0.5%). A commercially-available phenotypic identification system misidentified six isolates based upon sequence analysis of 16S and groESL genes. Among the 182 patients, 74 (40.7%) had catheter-associated bloodstream infection and 69 (37.9%) presented with biliary tract infection. Healthcare-associated enterococcal bacteremia comprised 99 (54.4%) episodes and a polymicrobial etiology was found in 106 (58.2%) episodes. The clinical manifestations varied between the infecting Enterococcus species. Multivariate logistic regression showed that immunocompromised status is the only risk factor for the all cause mortality. CONCLUSIONS Non-faecalis and non-faecium Enterococcus species can cause protean manifestations which vary with the infecting Enterococcus species. Misidentification of unusual enterococcal species might occur by the commercial identification methods and accurate identification with molecular methods is required.