Yu-Tsung Huang

Pyogenic Liver Abscess as Endemic Disease, Taiwan

Increasing incidence and microbiologic shift might have changed the manifestation of this condition.

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.

Increasing trends in antimicrobial resistance among clinically important anaerobes and Bacteroides fragilis isolates causing nosocomial infections: emerging resistance to carbapenems.

ABSTRACT This study reports data on the susceptibilities to five commonly used antianaerobic agents of five clinically frequently encountered anaerobes from 2000 to 2007 and to Bacteroides fragilis isolates causing nosocomial infections from 1990 to 2006. There was a trend of decreasing susceptibilities of these anaerobes to ampicillin-sulbactam, cefmetazole, chloramphenicol, and clindamycin with time during the study period. The rates of susceptibility to clindamycin and cefmetazole for all clinical isolates of Bacteroides fragilis isolates were higher than those of isolates associated with nosocomial infections. The MICs of 207 anaerobic blood isolates collected in 2006 to 14 antimicrobial agents were determined by the agar dilution method. The rates of nonsusceptibility to imipenem and meropenem were 7% and 12% for B. fragilis isolates (n = 60), 7% and 3% for Bacteroides thetaiotamicron isolates (n = 30), 4% and 4% for Fusobacterium species (n = 27), 6% and 0% for Prevotella species (n = 16), 15% and 0% for Clostridium species (n = 28), and 0% and 0% for Peptostreptococcus species (n = 32). The rates of susceptibility to moxifloxacin were 90% for B. fragilis isolates, 87% for B. thetaiotaomicron isolates, 81% for Fusobacterium species, 75% for Prevotella species, 93% for Clostridium species, and 78% for Peptostreptococcus species. Thirty-six percent of Clostridium species and 12% of Peptostreptococcus species were not susceptible to metronidazole. Comparison of the data with the data from a previous survey from the same institute in 2002 revealed higher rates of nonsusceptibility to carbapenems, especially for B. fragilis, Fusobacterium species, and Prevotella species isolates. The high rates of nonsusceptibility to commonly used antianaerobic agents mandate our attention, and periodic monitoring of the trend of the resistance is crucial.

Acinetobacter baumannii and Acinetobacter genospecies 13TU and 3 bacteraemia: comparison of clinical features, prognostic factors and outcomes

OBJECTIVES To investigate the clinical impact of different genospecies of the Acinetobacter calcoaceticus-Acinetobacter baumannii complex (ACB complex; A. baumannii, Acinetobacter gen. sp. 13TU and Acinetobacter gen. sp. 3) on the severity of bacteraemia. METHODS We retrospectively compared the clinical features and outcomes of patients with bacteraemia caused by A. baumannii, Acinetobacter gen. sp. 13TU or Acinetobacter gen. sp. 3. The genospecies were identified using oligonucleotide array sequence analysis (interspacer sequence), and the clonality of Acinetobacter gen. sp. 13TU and 3 isolates was determined by PFGE analysis. RESULTS A total of 215 patients with bacteraemia due to ACB complex were evaluated. Among them, 117 (54.4%) had A. baumannii bacteraemia, 77 (35.8%) had Acinetobacter gen. sp. 13TU bacteraemia and 21 (9.8%) had Acinetobacter gen. sp. 3 bacteraemia. A. baumannii bacteraemia was associated with a higher 14 day mortality rate (P < 0.001), a higher 30 day mortality rate (P < 0.001) and a higher in-hospital mortality rate than bacteraemia due to Acinetobacter gen. sp. 13TU or Acinetobacter gen. sp. 3. Independent prognostic factors for the 30 day mortality included the Charlson co-morbidity index (P < 0.001) and Pitt bacteraemia score (P < 0.001). Bloodstream infection caused by a multidrug-resistant A. baumannii isolate appeared to be associated with a poor outcome (P = 0.069). There was no clonal spread of Acinetobacter gen. sp. 13TU or Acinetobacter gen. sp. 3 during the study period. CONCLUSIONS Bacteraemia due to multidrug-resistant strains but not A. baumannii per se appears to be associated with poor outcome.

Detection of Circulating Galactomannan in Serum Samples for Diagnosis of Penicillium marneffei Infection and Cryptococcosis among Patients Infected with Human Immunodeficiency Virus

ABSTRACT Galactomannan (GM) is a heteropolysaccharide in the cell walls of most Aspergillus and Penicillium species. Cross-reactivity of Cryptococcus neoformans galactoxylomannan in an Aspergillus GM test has also been reported. In this study, we used a Platelia Aspergillus enzyme immunoassay kit (Bio-Rad) to test serum samples obtained from 48 human immunodeficiency virus (HIV)-infected patients (15 with penicilliosis [7 with fungemia alone, 4 with cavitary lung lesions alone, 3 with both fungemia and cavitary lung lesions, and 1 with disseminated disease], 22 with cryptococcosis [11 with fungemia alone, 5 with cavitary lung lesions, 3 with both, and 3 with meningitis alone], and 11 without any invasive fungal infection [control]) for GM levels. None of the patients had aspergillosis or concurrent use of piperacillin-tazobactam or amoxicillin-clavulanate. The median time between diagnosis of fungal infection and collection of serum samples was 0 days for penicilliosis and 1.5 days for cryptococcosis. Of patients with penicilliosis, cryptococcosis, and controls, 73.3%, 13.6%, and 9%, respectively, had GM optical density (OD) indices of >0.5 (P = 0.0001). GM OD indices were higher for penicilliosis (median OD index, 4.419; range, 0.158 to >20) than for cryptococcosis (median, 0.247; range, 0.112 to 3.849) cases (P < 0.001). Patients with fungemic penicilliosis had higher OD indices (median, 10.628; range, 0.401 to >20) than patients with nonfungemic penicilliosis (median, 0.378; range, 0.158 to 4.419) and patients with cryptococcemia (median, 0.231; range, 0.112 to 1.168) (P < 0.001). Of the 15 patients with cavitary lung lesions, those with penicilliosis had higher antigen levels (median OD index, 1.641; range, 0.247 to >20) than those with cryptococcosis (median, 0.227; range, 0.112 to 3.849) (P = 0.011). This study showed that the GM OD index was significantly elevated for HIV patients with penicilliosis. The use of the GM antigen assay may facilitate earlier diagnosis of Penicillium marneffei infection for HIV-infected patients in areas of endemicity.

Antimicrobial susceptibilities of commonly encountered bacterial isolates to fosfomycin determined by agar dilution and disk diffusion methods.

ABSTRACT We studied the antimicrobial activity of fosfomycin against 960 strains of commonly encountered bacteria associated with urinary tract infection using standard agar dilution and disk diffusion methods. Species studied included 3 common species of Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia; methicillin-susceptible and -resistant Staphylococcus aureus; and vancomycin-susceptible and resistant Enterococcus faecalis and E. faecium. MICs and inhibition zone diameters were interpreted in accordance with both the currently recommended Clinical and Laboratory Standards Institute (CLSI) criteria for urinary tract isolates of Escherichia coli and Enterococcus faecalis and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria for Enterobacteriaceae. Tentative zone diameter interpretive criteria were developed for species not currently published by CLSI or EUCAST. Escherichia coli was uniformly susceptible to fosfomycin, as were most strains of Klebsiella pneumoniae and Enterobacter cloacae. A. baumannii was resistant to fosfomycin, while the prevalence of resistance in P. aeruginosa and S. maltophilia was greatly affected by the choice of MIC breakpoint. New tentative zone diameter criteria for K. pneumoniae, E. cloacae, S. aureus, and E. faecium were able to be set, providing some interim laboratory guidance for disk diffusion until further breakpoint evaluations are undertaken by CLSI and EUCAST.

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.