Po-Ren Hsueh

Molecular Evidence for Strain Dissemination of Penicillium marneffei: An Emerging Pathogen in Taiwan

From January 1987 through December 1998, Penicillium marneffei infection (23 patients) or colonization (1 patient) was diagnosed in a total of 24 patients in Taiwan. Of these 24 patients, 16 (67%) had AIDS and 20 (83%) had disseminated P. marneffei infection. The majority (63%) of the infections were considered indigenous. The number of cases has increased markedly in recent years, with 17 of the 24 cases diagnosed from 1996 through 1998. Twenty preserved isolates of P. marneffei, recovered from 11 patients treated at National Taiwan University Hospital during the period of January 1996 through December 1998, were studied to determine the epidemiology of P. marneffei infections. Among the 20 isolates, a total of 8 strains (highly related isolates) were identified on the basis of tests for susceptibility to 5 antifungal agents, for chromosomal DNA restriction fragment-length polymorphism types, and for randomly amplified polymorphic DNA patterns. One of the strains (6 isolates) was isolated from 4 patients treated in 1997 and 1998. Strain spreading of P. marneffei may partially contribute to the increased number of infections caused by this organism in immunosuppressed patients in Taiwan.

Klebsiella pneumoniae Genotype K1: An Emerging Pathogen That Causes Septic Ocular or Central Nervous System Complications from Pyogenic Liver Abscess

BACKGROUND Since 1986, researchers have noted a syndrome of Klebsiella pneumoniae pyogenic liver abscess that is complicated by endophthalmitis or central nervous system infections. There are limited data regarding the role of bacterial genotype in the pathogenesis of this syndrome. METHODS We conducted a retrospective cohort study involving 177 cases of K. pneumoniae pyogenic liver abscess treated during 1997-2005 at a tertiary university hospital in Taiwan. We performed bacterial cps genotyping by polymerase chain reaction detection of serotype-specific alleles at wzy and wzx loci and used an in vitro serum assay to evaluate the virulence of bacterial strains. RESULTS Septic ocular or central nervous system complications developed in 23 patients (13%). Logistic regression analysis showed that genotype K1 was the only significant risk factor (adjusted odds ratio, 4.8; 95% confidence interval, 1.5-15.7, P=.009). The serum resistance assay indicated that, on average, K1 strains (n=100) were significantly more virulent than were strains of K2 (n=36), K20/K5/K54 (n=21), or other genotypes (n=20) (P<.001 for each comparison). In addition to the serotype-specific cps region, the genomic background of K1 strains also differed significantly from that of non-K1 strains (20-kb kfu/PTS region, 97/100 vs. 13/77; P<.001). Of the 19 cases in which genotype K1 strains caused complications, 8 patients (42%) did not have identifiable underlying medical diseases. CONCLUSIONS K. pneumoniae genotype K1 is an emerging pathogen capable of causing catastrophic septic ocular or central nervous system complications from pyogenic liver abscess independent of underlying diseases in the host.

The geographic diversity of nontuberculous mycobacteria isolated from pulmonary samples: an NTM-NET collaborative study

A significant knowledge gap exists concerning the geographical distribution of nontuberculous mycobacteria (NTM) isolation worldwide. To provide a snapshot of NTM species distribution, global partners in the NTM-Network European Trials Group (NET) framework (www.ntm-net.org), a branch of the Tuberculosis Network European Trials Group (TB-NET), provided identification results of the total number of patients in 2008 in whom NTM were isolated from pulmonary samples. From these data, we visualised the relative distribution of the different NTM found per continent and per country. We received species identification data for 20 182 patients, from 62 laboratories in 30 countries across six continents. 91 different NTM species were isolated. Mycobacterium avium complex (MAC) bacteria predominated in most countries, followed by M. gordonae and M. xenopi. Important differences in geographical distribution of MAC species as well as M. xenopi, M. kansasii and rapid-growing mycobacteria were observed. This snapshot demonstrates that the species distribution among NTM isolates from pulmonary specimens in the year 2008 differed by continent and differed by country within these continents. These differences in species distribution may partly determine the frequency and manifestations of pulmonary NTM disease in each geographical location. Species distribution among nontuberculous mycobacteria isolates from pulmonary specimens is geographically diverse http://ow.ly/npu6r

Adult-onset immunodeficiency in Thailand and Taiwan

BACKGROUND Autoantibodies against interferon-γ are associated with severe disseminated opportunistic infection, but their importance and prevalence are unknown. METHODS We enrolled 203 persons from sites in Thailand and Taiwan in five groups: 52 patients with disseminated, rapidly or slowly growing, nontuberculous mycobacterial infection (group 1); 45 patients with another opportunistic infection, with or without nontuberculous mycobacterial infection (group 2); 9 patients with disseminated tuberculosis (group 3); 49 patients with pulmonary tuberculosis (group 4); and 48 healthy controls (group 5). Clinical histories were recorded, and blood specimens were obtained. RESULTS Patients in groups 1 and 2 had CD4+ T-lymphocyte counts that were similar to those in patients in groups 4 and 5, and they were not infected with the human immunodeficiency virus (HIV). Washed cells obtained from patients in groups 1 and 2 had intact cytokine production and a response to cytokine stimulation. In contrast, plasma obtained from these patients inhibited the activity of interferon-γ in normal cells. High-titer anti-interferon-γ autoantibodies were detected in 81% of patients in group 1, 96% of patients in group 2, 11% of patients in group 3, 2% of patients in group 4, and 2% of controls (group 5). Forty other anticytokine autoantibodies were assayed. One patient with cryptococcal meningitis had autoantibodies only against granulocyte-macrophage colony-stimulating factor. No other anticytokine autoantibodies or genetic defects correlated with infections. There was no familial clustering. CONCLUSIONS Neutralizing anti-interferon-γ autoantibodies were detected in 88% of Asian adults with multiple opportunistic infections and were associated with an adult-onset immunodeficiency akin to that of advanced HIV infection. (Funded by the National Institute of Allergy and Infectious Diseases and the National Institute of Dental and Craniofacial Research; ClinicalTrials.gov number, NCT00814827.).

Spread of methicillin-resistant Staphylococcus aureus between the community and the hospitals in Asian countries: an ANSORP study

OBJECTIVES Methicillin-resistant Staphylococcus aureus (MRSA) is highly prevalent in hospitals in many Asian countries. Recent emergence of community-associated (CA) MRSA worldwide has added another serious concern to the epidemiology of S. aureus infections. To understand the changing epidemiology of S. aureus infections in Asian countries, we performed a prospective, multinational surveillance study with molecular typing analysis. METHODS We evaluated the prevalence of methicillin resistance in S. aureus isolates in CA and healthcare-associated (HA) infections, and performed molecular characterization and antimicrobial susceptibility tests of MRSA isolates. RESULTS MRSA accounted for 25.5% of CA S. aureus infections and 67.4% of HA infections. Predominant clones of CA-MRSA isolates were ST59-MRSA-SCCmec type IV-spa type t437, ST30-MRSA-SCCmec type IV-spa type t019 and ST72-MRSA-SCCmec type IV-spa type t324. Previously established nosocomial MRSA strains including sequence type (ST) 239 and ST5 clones were found among CA-MRSA isolates from patients without any risk factors for HA-MRSA infection. CA-MRSA clones such as ST59, ST30 and ST72 were also isolated from patients with HA infections. CONCLUSIONS Our findings confirmed that MRSA infections in the community have been increasing in Asian countries. Data also suggest that various MRSA clones have spread between the community and hospitals as well as between countries.

Emergence of High Levels of Extended-Spectrum-β-Lactamase-Producing Gram-Negative Bacilli in the Asia-Pacific Region: Data from the Study for Monitoring Antimicrobial Resistance Trends (SMART) Program, 2007

ABSTRACT Of 3,004 gram-negative bacilli collected from intra-abdominal infections in the Asia-Pacific region during 2007, 42.2% and 35.8% of Escherichia coli and Klebsiella spp., respectively, were extended-spectrum β-lactamase (ESBL) positive. Moreover ESBL rates in India for E. coli, Klebsiella pneumoniae, and Klebsiella oxytoca were 79.0%, 69.4%, and 100%, respectively. ESBL-positive E. coli rates were also relatively high in China (55.0%) and Thailand (50.8%). Ertapenem and imipenem were the most active drugs tested, inhibiting over 90% of all species, including ESBL-positive isolates with the exception of Pseudomonas aeruginosa isolates (<90% susceptible to all study drugs) and ESBL-positive Klebsiella pneumoniae isolates (<90% susceptible to all study drugs except imipenem). Quinolones achieved 90% inhibition levels only against ESBL-negative K. pneumoniae and ESBL-negative K. oxytoca. A decline in ampicillin-sulbactam activity was noted, with only 34.5% of all Enterobacteriaceae inhibited in this study.

Pandrug-Resistant Acinetobacter baumannii Causing Nosocomial Infections in a University Hospital, Taiwan

The rapid emergence (from 0% before 1998 to 6.5% in 2000) of pandrug-resistant Acinetobacter baumannii (PDRAB) was noted in a university hospital in Taiwan. To understand the epidemiology of these isolates, we studied 203 PDRAB isolates, taken from January 1999 to April 2000: 199 from 73 hospitalized patients treated at different clinical settings in the hospital and 4 from environmental sites in an intensive-care unit. Pulsed-field gel electrophoresis analysis and random amplified polymorphic DNA (RAPD) generated by arbitrarily primed polymerase chain reaction of these 203 isolates showed 10 closely related genotypes (10 clones). One (clone 5), belonging to pulsotype E and RAPD pattern 5, predominated (64 isolates, mostly from patients in intensive care). Increasing use of carbapenems and ciprofloxacin (selective pressure) as well as clonal dissemination might have contributed to the wide spread of PDRAB in this hospital.

Relationships between antimicrobial use and antimicrobial resistance in Gram-negative bacteria causing nosocomial infections from 1991–2003 at a university hospital in Taiwan

Abstract This study was conducted to evaluate the relationship between antimicrobial resistance and antimicrobial use in a university hospital in Taiwan. Disk 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 nosocomial infections were evaluated. Data on annual patient-days and annual consumption (defined daily dose (DDD) per 1000 patient-days) of extended-spectrum cephalosporins (cefotaxime, ceftriaxone, ceftazidime, flumoxef, cefepime and cefpirome), β-lactam–β-lactamase inhibitor combinations (ticarcillin/clavulanic acid and piperacillin/tazobactam), carbapenems (imipenem and meropenem), aminoglycosides (amikacin, gentamicin and tobramycin), fluoroquinolones (ciprofloxacin (oral and injectable) and oral levofloxacin and moxifloxacin) from 1991 to 2003 were analysed. Increasing trends of incidences of several of these bacteria causing all nosocomial infections or nosocomial bloodstream infections were noted from 1991 to 2003. The annual patient-days of the hospital significantly increased, from 360210 in 1991 to 672676 in 2002 (linear regression analysis, P <0.05), but slightly decreased in 2003 (629168) owing to the severe acute respiratory syndrome epidemic in Taiwan. The rise in cefotaxime-resistant or ciprofloxacin-resistant E. coli and meropenem-resistant P. aeruginosa was significantly correlated with increased consumption of extended-spectrum cephalosporins, β-lactam–β-lactamase inhibitor combinations, carbapenems, fluoroquinolones and aminoglycosides (for ciprofloxacin-resistant E. coli and meropenem-resistant P. aeruginosa only) in the hospital (Pearsons correlation coefficient, r >0.72 (or <−0.72) and P-value<0.05). Increased ciprofloxacin-resistant K. pneumoniae and meropenem-resistant Acinetobacter spp. was significantly associated with the increased usage of extended-spectrum cephalosporins but not with the other four classes of antibiotics. This 13-year study in a hospital demonstrated significant changes in antimicrobial use, which may have affected antimicrobial resistance in certain Gram-negative bacteria at the hospital.

Changing Trends in Antimicrobial Resistance and Serotypes of Streptococcus pneumoniae Isolates in Asian Countries: an Asian Network for Surveillance of Resistant Pathogens (ANSORP) Study

ABSTRACT Antimicrobial resistance in Streptococcus pneumoniae remains a serious concern worldwide, particularly in Asian countries, despite the introduction of heptavalent pneumococcal conjugate vaccine (PCV7). The Asian Network for Surveillance of Resistant Pathogens (ANSORP) performed a prospective surveillance study of 2,184 S. pneumoniae isolates collected from patients with pneumococcal infections from 60 hospitals in 11 Asian countries from 2008 to 2009. Among nonmeningeal isolates, the prevalence rate of penicillin-nonsusceptible pneumococci (MIC, ≥4 μg/ml) was 4.6% and penicillin resistance (MIC, ≥8 μg/ml) was extremely rare (0.7%). Resistance to erythromycin was very prevalent in the region (72.7%); the highest rates were in China (96.4%), Taiwan (84.9%), and Vietnam (80.7%). Multidrug resistance (MDR) was observed in 59.3% of isolates from Asian countries. Major serotypes were 19F (23.5%), 23F (10.0%), 19A (8.2%), 14 (7.3%), and 6B (7.3%). Overall, 52.5% of isolates showed PCV7 serotypes, ranging from 16.1% in Philippines to 75.1% in Vietnam. Serotypes 19A (8.2%), 3 (6.2%), and 6A (4.2%) were the most prominent non-PCV7 serotypes in the Asian region. Among isolates with serotype 19A, 86.0% and 79.8% showed erythromycin resistance and MDR, respectively. The most remarkable findings about the epidemiology of S. pneumoniae in Asian countries after the introduction of PCV7 were the high prevalence of macrolide resistance and MDR and distinctive increases in serotype 19A.

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.