Shin Woo Kim

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.

Epidemiology and clinical outcomes of community-acquired pneumonia in adult patients in Asian countries: a prospective study by the Asian network for surveillance of resistant pathogens.

Abstract Appropriate antimicrobial treatment of community-acquired pneumonia (CAP) should be based on the distribution of aetiological pathogens, antimicrobial resistance of major pathogens, clinical characteristics and outcomes. We performed a prospective observational study of 955 cases of adult CAP in 14 hospitals in eight Asian countries. Microbiological evaluation to determine etiological pathogens as well as clinical evaluation was performed. Bronchopulmonary disease (29.9%) was the most frequent underlying disease, followed by cardiovascular diseases (19.9%), malignancy (11.7%) and neurological disorder (8.2%). Streptococcus pneumoniae (29.2%) was the most common isolate, followed by Klebsiella pneumoniae (15.4%) and Haemophilus influenzae (15.1%). Serological tests were positive for Mycoplasma pneumoniae (11.0%) and Chlamydia pneumoniae (13.4%). Only 1.1% was positive for Legionella pneumophila by urinary antigen test. Of the pneumococcal isolates, 56.1% were resistant to erythromycin and 52.6% were not susceptible to penicillin. Seventeen percent of CAP had mixed infection, especially S. pneumoniae with C. pneumoniae. The overall mortality rate was 7.3%, and nursing home residence, mechanical ventilation, malignancy, cardiovascular diseases, respiratory rate>30/min and hyponatraemia were significant independent risk factors for mortality by multivariate analysis (P <0.05). The current data provide relevant information about pathogen distribution and antimicrobial resistance of major pathogens of CAP as well as clinical outcomes of illness in Asian countries.

Clinical Outcomes of Pneumococcal Pneumonia Caused by Antibiotic-Resistant Strains in Asian Countries: A Study by the Asian Network for Surveillance of Resistant Pathogens

To evaluate the clinical outcomes of pneumococcal pneumonia caused by antibiotic-resistant strains in Asian countries, we performed a prospective observational study of 233 cases of adult pneumococcal pneumonia in 9 Asian countries from January 2000 to June 2001. Among 233 isolates, 128 (55%) were not susceptible to penicillin (25.3% were intermediately susceptible, and 29.6% were resistant). Clinical severity of pneumococcal pneumonia was not significantly different between antibiotic-resistant and antibiotic-susceptible groups. Mortality rates among patients with pneumococcal pneumonia caused by penicillin-, cephalosporin-, or macrolide-resistant strains were not higher than those with antibiotic-susceptible pneumococcal pneumonia. Bacteremia and mechanical ventilation were significant risk factors for death, but any kind of antibiotic resistance was not associated with increased mortality due to pneumococcal pneumonia. Outcome of pneumococcal pneumonia was not significantly affected by drug resistance, and current antimicrobial regimens are mostly effective in the treatment of pneumococcal pneumonia, despite the widespread emergence of in vitro resistance.

Protective role of interleukin-10 promoter gene polymorphism in the pathogenesis of invasive pulmonary aspergillosis after allogeneic stem cell transplantation

Summary:The current study attempted to evaluate the association between the IL-10 promoter gene single nucleotide polymorphism (SNP) and invasive pulmonary aspergillosis (IPA) after allogeneic stem cell transplantation (SCT) in 105 patients. Three single-nucleotide polymorphisms were investigated in the proximal region of the IL-10 promoter gene (−1082/−819/−592). Two haplotypes (1082*A/819*T/592*A [ATA] and 1082*A/819*C/592*C [ACC]) were found in the current study. The overall incidence of IPA was estimated as 14.1±4.5% with a median onset at 186 days post-transplant (62∼405 days). An increased occurrence of IPA was noted dependent on the IL-10 haplotype (0% vs 11.5±6.4% vs 19.7±7.7% for ACC/ACC vs ATA/ACC vs ATA/ATA haplotype, P=0.0307 when comparing ACC with non-ACC haplotype). In a multivariate survival analysis using Coxs proportional hazard model, the IL-10 promoter gene SNPs were identified as an independent predictive factor for the development of IPA (P=0.012, hazard ratio (HR) 9.3), along with an histocompatibility leukocyte antigen (HLA)-identical donor (P=0.005, HR 16.3), the CD34+ cell dose transplanted (P=0.004, HR 26.5), and time-dependent chronic graft-versus-host disease (GVHD; P=0.049, HR 16.0). The IL-10 ACC haplotype was found to have an apparent protective role in the development of IPA after allogeneic transplantation, regardless of HLA-disparity or chronic GVHD.

Transforming Growth Factor β–induced Protein Promotes Severe Vascular Inflammatory Responses

RATIONALE Sepsis is a systemic inflammatory condition resulting from bacterial infections; it has a high mortality rate and limited therapeutic options. Despite extensive research into the mechanisms driving bacterial sepsis, the target molecules controlling vascular leakage are still largely unknown. Transforming growth factor β-induced protein (TGFBIp) is an extracellular matrix protein expressed in several cell types, which is known to interact with integrins. OBJECTIVES The aim of this study was to determine the roles of TGFBIp in vascular proinflammatory responses, and the mechanisms of action driving these responses. METHODS Circulating levels of TGFBIp were measured in patients admitted to the hospital with sepsis, severe sepsis, and septic shock and in cecal ligation and puncture (CLP)-induced septic mice. Effects of TGFBIp knockout on CLP-induced septic mortality and effects of TGFBIp on multiple vascular proinflammatory responses were determined. MEASUREMENTS AND MAIN RESULTS Circulating levels of TGFBIp were significantly elevated compared with healthy controls, and were strongly correlated with disease severity. High blood TGFBIp levels were also observed in CLP-induced septic mice. The absence of the TGFBIp gene in mice attenuated CLP-induced sepsis. TGFBIp enhanced vascular proinflammatory responses including vascular permeability, adhesion and migration of leukocytes, and disruption of adherence junctions through interacting with integrin αvβ5. CONCLUSIONS Collectively, our findings demonstrate that the TGFBIp-αvβ5 axis can elicit severe inflammatory responses, suggesting it to be a potential target for development of diagnostics and therapeutics for sepsis.

High Rate of Reduced Susceptibility to Ciprofloxacin and Ceftriaxone among Nontyphoid Salmonella Clinical Isolates in Asia

ABSTRACT This multinational study from Asia revealed that reduced susceptibility to ciprofloxacin (MIC, 0.125 to 1 μg/ml) in nontyphoid Salmonella isolates was common in Taiwan (48.1%) and Thailand (46.2%) and in S. enterica serotype Choleraesuis (68.8%) and S. Virchow (75.0%) from all countries. Reduced susceptibility to ceftriaxone (MIC, 2 to 8 μg/ml) remained uncommon in Asia, except in Taiwan (38.0%) or in S. Typhimurium (25.0%) from all countries.

Prevalence and characterization of extended-spectrum β-lactamase-producing Enterobacteriaceae isolated in Korean hospitals

Prevalence and characteristics of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae in Korean hospitals were assessed. A total of 1484 clinical Enterobacteriaceae isolates were collected from 8 tertiary-care hospitals in various regions of Korea over a 3-month period (June to August) in 2005. Among 546 Klebsiella pneumoniae isolates, 123 isolates (22.4%) showed ESBL-producing activity, and 47 (10.2%) of 460 isolates of Escherichia coli were ESBL producers. Of the Enterobacter cloacae isolates, 16.2% (17/105) evidenced ESBL-producing activity. The most prevalent ESBLs were SHV-12 and CTX-M-14 in K. pneumoniae and E. coli, respectively. In E. cloacae, SHV-12 was also the most prevalent. Prevalence of ESBL production differed among the specimens. Although the K. pneumoniae isolates from urine and aspirates evidenced high ESBL production rates (35.4% and 57.1%, respectively), those from sputum, blood, and pus showed relatively low ESBL production rates (17.0%, 14.8%, and 5.3%, respectively). However, E. coli isolates obtained from sputum showed significantly higher ESBL production rates (37.5%) than were seen in samples obtained from other sources, but those obtained from urine showed lower ESBL production rates (8.3%). These significant differences in ESBL-producing K. pneumoniae and E. coli isolates among the isolated specimens should be examined further, with an eye toward the implications of this research in clinical settings.

Prevalence of the ST239 Clone of Methicillin-Resistant Staphylococcus aureus and Differences in Antimicrobial Susceptibilities of ST239 and ST5 Clones Identified in a Korean Hospital

ABSTRACT A total of 188 nonduplicate methicillin-resistant Staphylococcus aureus (MRSA) isolates obtained between 2001 and 2004 in a university hospital in Daegu, Korea, were analyzed for their clonal types by molecular typing techniques, including multilocus sequence typing, spaA typing, staphylococcal chromosomal cassette mec (SCCmec) typing, and pulsed-field gel electrophoresis (PFGE). They were examined for their antimicrobial susceptibilities. The majority (87%) of MRSA isolates belonged to sequence type 239 (ST239; n = 100; 53%) and ST5 (n = 63, 34%) on the basis of sequence typing. MRSA isolates belonging to ST239 were genotypically homogeneous, while those belonging to ST5 showed variations in spaA type, SCCmec type, and PFGE patterns. The rates of resistance of the MRSA isolates belonging to ST239 to trimethoprim, sulfamethoxazole, tobramycin, gentamicin, erythromycin, and tetracycline were significantly higher than those of the isolates belonging to ST5 (P < 0.05). This study demonstrated that the ST239 clone, while rarely detected in Korea, was prevalent and that the antimicrobial susceptibility of the ST239 clone was significantly different from that of the ST5 clone.

Risk factors and treatment outcomes of community-onset bacteraemia caused by extended-spectrum β-lactamase-producing Escherichia coli

The purpose of this study was to identify risk factors for extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli amongst community-onset bacteraemia and to evaluate treatment outcomes. From the database of a nationwide surveillance programme for bacteraemia, data from patients with community-onset E. coli bacteraemia were analysed. Patients with ESBL-producing E. coli bacteraemia were compared with those with non-ESBL-producing bacteraemia. The overall proportion of ESBL-producers was 9.5% (82/865) amongst community-onset E. coli bacteraemia cases. Healthcare-associated infection, underlying liver disease and primary bacteraemia were significant independent factors associated with ESBL-producing E. coli bacteraemia (P<0.05). There was a trend toward mortality being higher in the ESBL group compared with the non-ESBL group (15.0% vs. 7.6%; P=0.096). ESBL production was found to be an independent factor associated with mortality after adjusting for confounding variables (odds ratio=2.99, 95% confidence interval 1.01-8.84; P=0.048), along with severe sepsis, higher Pitt bacteraemia score, primary bacteraemia, pneumonia and underlying liver disease (P<0.05). ESBL-producing E. coli is a significant cause of bacteraemia, even in patients with community-onset infections, predicting higher mortality, particularly in patients with primary bacteraemia, underlying liver disease or healthcare-associated infection.

Predominance of an ST11 extended-spectrum β-lactamase-producing Klebsiella pneumoniae clone causing bacteraemia and urinary tract infections in Korea.

To investigate the antimicrobial resistance, extended-spectrum beta-lactamases (ESBLs) and clones of Klebsiella pneumoniae isolates causing bacteraemia or urinary tract infection (UTI) in Korea, a total of 406 K. pneumoniae isolates from patients with bacteraemia (221 isolates) and UTI (185 isolates) were collected from 10 tertiary-care Korean hospitals from July 2006 to October 2007. In vitro antimicrobial susceptibility testing was performed for all isolates and ESBL production was tested. Multilocus sequence typing (MLST) analyses were performed to characterize genotypes of ESBL-producing K. pneumoniae isolates. PFGE was performed for sequence type 11 (ST11) isolates. Forty-seven UTI isolates (25.4 %) produced ESBLs, while 30 bacteraemia isolates (13.6 %) produced ESBLs (P=0.002). Among 77 ESBL-producing isolates, thirty-two (41.6 %) produced SHV-type ESBLs. bla(CTX-M) genes such as bla(CTX-M-14) and bla(CTX-M-15) were detected in 36.4 %. MLST and PFGE analyses showed that ST11 was dominant in ESBL-producing K. pneumoniae isolates causing UTI (57.4 %) and in those causing bacteraemia (70.0 %) and has been prevalent in Korean hospitals. ST11 isolates harbour a combination of different ESBL genes. The ST11 clone of ESBL-producing K. pneumoniae isolates prevails in Korea, but most isolates might acquire ESBL genes independently or several different clones might be distributed in Korea.