Predominance of an ST11 extended-spectrum beta-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.

Nonclonal emergence of colistin-resistant Klebsiella pneumoniae isolates from blood samples in South Korea.

In vitro activities of colistin and other drugs were tested against 221 Klebsiella pneumoniae isolates that were collected between 2006 and 2007 in nine tertiary care South Korean hospitals from patients with bacteremia. The clonality of colistin-resistant K. pneumoniae (CRKP) isolates was assessed by multilocus sequence typing (MLST). We found that 15 isolates (6.8%) were resistant to colistin. MLST showed that CRKP isolates were nonclonal, with colistin resistance in K. pneumoniae occurring independently and not by clonal spreading.

Clinical implications of vancomycin-resistant Enterococcus faecium (VRE) with VanD phenotype and vanA genotype.

OBJECTIVES: To investigate the clinical implications of vancomycin-resistant Enterococcus faecium (VRE) with VanD phenotype and vanA genotype (VanD-vanA VRE). METHODS: We tested in vitro and in vivo efficacies of teicoplanin against VanD-vanA VRE strains. Change in teicoplanin MICs was monitored during incubation with teicoplanin. In vitro and in vivo time-kill assay and survival analysis using a mouse peritonitis model were performed. RESULTS: Teicoplanin MICs of VanD-vanA VRE strains increased to 128 mg/L within 48 h when they were cultured with 120 mg/L teicoplanin. In vitro and in vivo time-kill assay showed that VanD-vanA VRE strains were not eliminated by 120 mg/L teicoplanin in contrast to vancomycin-susceptible E. faecium and VanD-vanB strains. The survival rate of mice infected with VanD-vanA VRE strains treated with teicoplanin was comparable with that of untreated mice. CONCLUSION: Data suggest that teicoplanin would fail in the treatment of VanD type VRE infections if the strains contained the vanA gene, which cannot be detected in the clinical microbiology laboratory.

High rates of resistance to colistin and polymyxin B in subgroups of Acinetobacter baumannii isolates from Korea.

OBJECTIVES: To investigate antimicrobial resistance in clinical isolates of Acinetobacter spp. from two Korean hospitals. METHODS: Two hundred and sixty-five isolates of Acinetobacter spp. from two Korean hospitals were collected and were identified to species level using partial rpoB gene sequences. Antimicrobial susceptibility testing was performed using a broth microdilution method. RESULTS: rpoB gene sequences indicated that 214 isolates (80.8%) were Acinetobacter baumannii, and allowed these to be classified into three subgroups (I, II and III); 142 isolates (53.6%) belonged to subgroup I, 54 (20.4%) to subgroup II and 18 (6.8%) to subgroup III. Forty-eight isolates (18.1%) and 74 isolates (27.9%) were resistant to polymyxin B and colistin, respectively. However, antimicrobial resistance rates varied markedly between subgroups. While A. baumannii subgroup I showed low resistance rates to polymyxin B and colistin (2.1% and 7.0%, respectively), subgroups II and III showed high resistance rates to these antibiotics (38.9% and 64.8% in subgroup II and 72.2% and 88.9%, in subgroup III, respectively). Multidrug resistance was also significantly more frequent in subgroup I (45.1%) than in subgroups II and III (13.0% and 16.7%, respectively). CONCLUSIONS: Our data indicate that subgroup identification of A. baumannii may aid selection of appropriate antimicrobial agents for the treatment of Acinetobacter infections.

In vitro activity of fosfomycin against ciprofloxacin-resistant or extended-spectrum beta-lactamase-producing Escherichia coli isolated from urine and blood.

In this study, we evaluated the in vitro activity of fosfomycin and 7 other comparator agents against 307 Escherichia coli isolates including ciprofloxacin-resistant or extended-spectrum beta-lactamase (ESBL)-producing isolates. Bacterial isolates were collected from urine and blood from patients at a Korean tertiary-care hospital. Among 307 E. coli isolates, 30.3% were resistant to ciprofloxacin (MIC(90), >32 mg/L) and 7.8% produced ESBLs. The highest resistance rate was observed in ampicillin (69.7%), followed by trimethoprim-sulfamethoxazole (43.0%), and then amoxicillin-clavulanate (32.2%). All isolates were susceptible to imipenem (MIC(90), 0.125 mg/L). All but 1 isolate was susceptible to fosfomycin (MIC(90), 16 mg/L), regardless of the collected sources, ciprofloxacin resistance, and ESBL production. The data showed excellent activity of fosfomycin against E. coli isolates including fluoroquinolone-resistant strains. The clinical usefulness of fosfomycin, as a 1st-line therapy for urinary tract infection, should be evaluated further, especially in regions where ciprofloxacin resistance rates are high.

In vitro activity of cefditoren: antimicrobial efficacy against major respiratory pathogens from Asian countries.

In this study we evaluated the in vitro activities of cefditoren and 14 other comparator agents against 1025 isolates of major respiratory tract pathogens including Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Klebsiella pneumoniae and Staphylococcus aureus. Bacterial isolates were collected from 11 Asian countries. The majority of S. pneumoniae isolates (98.8%) were susceptible to cefditoren. The MIC(50) and MIC(90) values (minimum inhibitory concentrations for 50% and 90% of the organisms, respectively) of S. pneumoniae were

Comparative analysis of growth-phase-dependent gene expression in virulent and avirulent Streptococcus pneumoniae using a high-density DNA microarray.

The global pattern of growth-dependent gene expres-sion in Streptococcus pneumoniae strains was evalu-ated using a high-density DNA microarray. Total RNAs obtained from an avirulent S. pneumoniae strain R6 and a virulent strain AMC96-6 were used to compare the expression patterns at seven time points (2.5, 3.5, 4.5, 5.5, 6.0, 6.5, and 8.0 h). The expression profile of strain R6 changed between log and station-ary growth (the Log-Stat switch). There were clear differences between the growth-dependent gene ex-pression profiles of the virulent and avirulent pneumo-coccal strains in 367 of 1,112 genes. Transcripts of genes associated with bacterial competence and capsular polysaccharide formation, as well as clpP and cbpA, were higher in the virulent strain. Our data suggest that late log or early stationary phase may be the most virulent phase of S. pneumoniae.

Distribution of major genotypes among methicillin-resistant Staphylococcus aureus clones in Asian countries.

To investigate the evolutionary pattern and genotypic characteristics of methicillin-resistant Staphylococcus aureus (MRSA) strains in the Asian region, 74 MRSA strains isolated from 12 Asian countries were analyzed by multilocus sequence typing (MLST) and SCCmec typing. Overall, a total of 16 genotypes based on sequence type and SCCmec types were identified among MRSA strains from Asian countries. Data revealed two major genotypes of MRSA strains in Asia, with unique geographic distributions. By MLST analysis, all strains from Korea and Japan except one belonged to clonal complex 5 (CC5) while most MRSA isolates from other Asian countries belonged to CC239. SCCmec typing showed that most isolates from Korea and Japan were SSmec type II whereas SCCmec type III (or IIIA) was the most common type in strains from other Asian countries. Our data documented a unique geographic distribution and evolutionary pattern of MRSA clones in Asia.

Emergence in Asian countries of Staphylococcus aureus with reduced susceptibility to vancomycin.

To investigate the prevalence of Staphylococcus aureus with reduced susceptibility to vancomycin among methicillin-resistant S. aureus (MRSA) strains in Asian countries, a total of 1,357 clinical isolates of MRSA collected from 12 Asian countries were screened by using brain heart infusion agar plates containing 4 mg of vancomycin per liter. The presence of strains that were heterointermediately resistant to vancomycin (hVISA) was confirmed by population analysis. Of 347 (25.6%) MRSA isolates that grew on the screening agar plates, 58 isolates (4.3%) were hVISA. hVISA strains were found in India, South Korea, Japan, the Philippines, Singapore, Thailand, and Vietnam. However, neither vancomycin-intermediate S. aureus nor vancomycin-resistant S. aureus isolates were found among MRSA isolates from Asian countries in this survey.

Fluoroquinolone resistance in clinical isolates of Streptococcus pneumoniae from Asian countries: ANSORP study.

Seventeen clinical isolates of Streptococcus pneumoniae showing reduced susceptibility to ciprofloxacin (MIC >/= 4 micro g/ml) collected from eight different Asian countries were analyzed by antimicrobial susceptibility, serotyping, pulsed-field gel electrophoresis (PFGE), and DNA sequencing of the quinolone resistance-determining regions (QRDRs) in gyrA, gyrB, parC, and parE. All isolates but one showed more than one amino acid alteration in QRDRs of four responsible genes. Ile460 --> Val in parE was the most common mutation. Data suggest that Lys137 --> Asn in parC may be a primary step in the development of high-level and multiple FQ resistance. An additional mutation of Ser81 --> Phe in gyrA resulted in high-level resistance to ciprofloxacin, levofloxacin, and gatifloxacin, whereas Ser79 --> Phe in parC may exert an important role in the development of moxifloxacin resistance. Two novel amino acid changes in gyrB, Ala390 --> Val and Asn423 --> Thr, were found. Data from PFGE suggest an introduction and local spread of multiple resistant Spain(23F)-1 clone in Hong Kong, but isolates from other Asian countries were not related to this clone.

High prevalence of antimicrobial resistance among clinical Streptococcus pneumoniae isolates in Asia (an ANSORP study).

A total of 685 clinical Streptococcus pneumoniae isolates from patients with pneumococcal diseases were collected from 14 centers in 11 Asian countries from January 2000 to June 2001. The in vitro susceptibilities of the isolates to 14 antimicrobial agents were determined by the broth microdilution test. Among the isolates tested, 483 (52.4%) were not susceptible to penicillin, 23% were intermediate, and 29.4% were penicillin resistant (MICs >/= 2 mg/liter). Isolates from Vietnam showed the highest prevalence of penicillin resistance (71.4%), followed by those from Korea (54.8%), Hong Kong (43.2%), and Taiwan (38.6%). The penicillin MICs at which 90% of isolates are inhibited (MIC(90)s) were 4 mg/liter among isolates from Vietnam, Hong Kong, Korea, and Taiwan. The prevalence of erythromycin resistance was also very high in Vietnam (92.1%), Taiwan (86%), Korea (80.6%), Hong Kong (76.8%), and China (73.9%). The MIC(90)s of erythromycin were >32 mg/liter among isolates from Korea, Vietnam, China, Taiwan, Singapore, Malaysia, and Hong Kong. Isolates from Hong Kong showed the highest rate of ciprofloxacin resistance (11.8%), followed by isolates from Sri Lanka (9.5%), the Philippines (9.1%), and Korea (6.5%). Multilocus sequence typing showed that the spread of the Taiwan(19F) clone and the Spain(23F) clone could be one of the major reasons for the rapid increases in antimicrobial resistance among S. pneumoniae isolates in Asia. Data from the multinational surveillance study clearly documented distinctive increases in the prevalence rates and the levels of antimicrobial resistance among S. pneumoniae isolates in many Asian countries, which are among the highest in the world published to date.

Macrolide resistance and genotypic characterization of Streptococcus pneumoniae in Asian countries: a study of the Asian Network for Surveillance of Resistant Pathogens (ANSORP).

OBJECTIVES: To characterize mechanisms of macrolide resistance among Streptococcus pneumoniae from 10 Asian countries during 1998-2001. METHODS: Phenotypic and genotypic characterization of the isolates and their resistance mechanisms. RESULTS: Of 555 isolates studied, 216 (38.9%) were susceptible, 10 (1.8%) were intermediate and 329 (59.3%) were resistant to erythromycin. Vietnam had the highest prevalence of erythromycin resistance (88.3%), followed by Taiwan (87.2%), Korea (85.1%), Hong Kong (76.5%) and China (75.6%). Ribosomal methylation encoded by erm(B) was the most common mechanism of erythromycin resistance in China, Taiwan, Sri Lanka and Korea. In Hong Kong, Singapore, Thailand and Malaysia, efflux encoded by mef(A) was the more common in erythromycin-resistant isolates. In most Asian countries except Hong Kong, Malaysia and Singapore, erm(B) was found in >50% of pneumococcal isolates either alone or in combination with mef(A). The level of erythromycin resistance among pneumococcal isolates in most Asian countries except Thailand and India was very high with MIC(90)s of >128 mg/L. Molecular epidemiological studies suggest the horizontal transfer of the erm(B) gene and clonal dissemination of resistant strains in the Asian region. CONCLUSION: Data confirm that macrolide resistance in pneumococci is a serious problem in many Asian countries.