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Biomedical subjects

Yeon-Joon Park

Publications and source records attributed to Yeon-Joon Park.

18 recordsLinked to original sources

Prevalence and mechanisms of decreased susceptibility to carbapenems in Klebsiella pneumoniae isolates.

In this study, we examined the prevalence of and mechanisms of decreased susceptibility to either imipenem or meropenem in Klebsiella pneumoniae isolates. A total of 230 clinical isolates of K. pneumoniae were collected from 13 clinical laboratories from a nationwide distribution. The MICs of imipenem and meropenem were determined by the agar dilution method. To characterize the isolates with decreased susceptibility to carbapenems (MICs of >2 microg/mL), we performed polymerase chain reaction amplification of a variety of beta-lactamase genes, isoelectric focusing, and outer membrane profile analysis using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and mass spectrometry. Three isolates (BD6, BD8, and KN16) exhibited decreased susceptibility to carbapenems with imipenem MICs of 1, 4, and 8 microg/mL and meropenem MICs of 4, 8, and 4, respectively. Isolate BD6 produced bla(TEM-1), bla(SHV-12), and bla(OXA-17); isolate BD8 produced bla(GES-3), bla(SHV-12), and bla(OXA-17); and isolate KN16 produced bla(TEM-11), bla(SHV-12), and bla(DHA-1). In all the 3 isolates, OmpK35 porin was not expressed, and in 1 isolate (KN16), OmpK36 was not expressed either. The prevalence of decreased susceptibility to carbapenems was low (1.3%), and none of them showed overt resistance to carbapenems. Decreased susceptibility to carbapenems can occur in K. pneumoniae when bla(GES-3), bla(TEM-11), bla(SHV-12), bla(OXA-17), and/or bla(DHA-1) are produced in combination with porin loss. In addition, to our knowledge, this is the 1st report of bla(OXA-17) in Enterobacteriaceae.

Amino Acid Sequence↗

Evaluation of the CombiChip Mycobacteria Drug-Resistance detection DNA chip for identifying mutations associated with resistance to isoniazid and rifampin in Mycobacterium tuberculosis.

The CombiChip Mycobacteriatrade mark Drug-Resistance Detection DNA chip, recently developed by GeneIn (Pusan, South Korea), is an oligonucleotide microchip coupled with polymerase chain reaction for the detection of mutations associated with resistance to isoniazid (INH) and rifampin (RIF). This oligonucleotide chip was compared with DNA sequencing and phenotypic drug susceptibility testing with 69 INH- and/or RIF-resistant and 27 all tested drug-susceptible Mycobacterium tuberculosis isolates. Two selected codons (the katG codon 315 and inhA15) allowed identification of 84.1% of INH-resistant isolates and 100% of RIF resistance were detected by screening for 7 codons: rpoB511, rpoB513, rpoB516, rpoB522, rpoB526, rpoB531, and rpoB533. The overall specificity of this oligonucleotide chip for detecting INH and RIF resistance were 100 and 95.3%, respectively. This level of sensitivity and specificity is concordant with that from the determination of M. tuberculosis drug resistance by DNA sequencing. This oligonucleotide chip is a rapid and reliable genotypic method capable of detecting multiple mutations associated with INH and RIF resistance simultaneously in a single microchip slide.

Antitubercular Agents↗

Vancomycin-tolerant Streptococcus pneumoniae in Korea.

A nationwide surveillance study was undertaken to monitor antimicrobial resistance among clinical isolates of Streptococcus pneumoniae in Korea, with a special focus on vancomycin tolerance. For the 6-month period from March to August 2002, clinical isolates of S. pneumoniae were collected from 11 university hospitals and 1 reference laboratory. One-hundred eighty-eight isolates were measured for lysis rates after exposure to vancomycin for 4 h. Two vancomycin-tolerant S. pneumoniae (VTSP) strains, S3 and H8, were isolated from sputum cultures of two patients, who had stayed in intensive-care units of different hospitals with long-term antibiotic therapy and were not treated for pneumococcal pneumonia. The penicillin, cefotaxime, and vancomycin MICs for S3 were 8 microg/ml, >16 microg/ml, and 0.5 microg/ml, and those for H8 were 2 microg/ml, 2 microg/ml, and 0.5 microg/ml, respectively. While S3 belonged to serotype 23F and was autolysin defective, H8 belonged to serotype 13F and had intact autolysin. These strains were not clonally related as determined by pulsed-field gel electrophoresis of chromosomal DNA. In agreement with previous reports, both isolates showed pairing of TIGR4 vex2 with R6 pep27 and had two identical amino acid substitutions, Q441K in vncS and N25D in vex2. These findings indicate that two VTSP strains have emerged independently in Korea, suggesting a prevalence rate of 1.1%. The emergence of VTSP would be a serious threat in Korea, where there are significant rates of penicillin resistance in S. pneumoniae. Monitoring of the prevalence of VTSP and further investigation of the clinical relevance of VTSP are warranted.

Amino Acid Sequence↗

Plasma eosinophil cationic protein, interleukin-5, and ECP/Eo count ratio in patients with various eosinophilic diseases.

Hypereosinophilia is associated with clonal disorders, reactive conditions, and rarely with idiopathic hypereosinophilic syndrome (IHES). We investigated whether measurement of eosinophilic activity using the plasma eosinophil cationic protein (ECP) level, interleukin-5 (IL-5) level, and the ratio of eosinophilic cationic protein/eosinophil count (ECP/Eo) could improve the early differentiation among various eosinophilic diseases: IHES (n = 9), clonal disorder (n = 35), reactive eosinophilia with malignancy (n = 30), and reactive eosinophilia with inflammation (n = 46). The 120 eosinophilic patients had higher plasma ECP and IL-5 levels than the non-eosinophilic control group (p <0.05). The 9 patients with IHES had significantly higher plasma ECP and IL-5 levels than patients with other eosinophilic diseases (p <0.05). The plasma levels of ECP and the ECP/Eo ratio were higher in patients with non-haematologic malignancy than in those with other reactive eosinophilias (p <0.05). This study shows that levels of plasma ECP, IL-5, and ECP/Eo ratio may assist in the clinical differentiation of various eosinophilic diseases.

Biomarkers↗

Prevalence of Ambler class A and D beta-lactamases among clinical isolates of Pseudomonas aeruginosa in Korea.

OBJECTIVES: Recently, resistance to extended-spectrum cephalosporins due to acquired beta-lactamases has been reported in Pseudomonas aeruginosa. The aim of this study was to investigate the prevalence of Ambler class A and D beta-lactamases and their extended-spectrum derivatives and antimicrobial susceptibilities of P. aeruginosa isolated from various parts of Korea. METHODS: A total of 252 consecutive, non-duplicate isolates of P. aeruginosa were studied for the presence of class A or D beta-lactamase. Antibiotic susceptibility tests and PCR amplification of genes encoding class A (bla(PSE-1), bla(PER-1), bla(VEB-1), bla(TEM), bla(SHV), bla(CTX-M) and bla(GES-1)) and class D beta-lactamases (bla(OXA-groupI), bla(OXA-groupII) and bla(OXA-groupIII)) were performed. For PCR-positive isolates, isoelectric focusing (IEF) analysis, sequencing and pulsed-field gel electrophoresis (PFGE) were performed. RESULTS: In 64 (25.4%) isolates, structural genes for PSE-1 (6.3%), OXA-10 (13.1%), OXA-4 (4.3%), OXA-30 (2.0%), OXA-2 (2.3%) and OXA-17 (0.4%) were found; their distribution varied between provinces. None harboured bla(PER-1), bla(VEB-1), bla(TEM), bla(SHV), bla(CTX-M) and bla(GES-1). The cross-class resistance rates to other antibiotics was significantly higher in class A and D beta-lactamase producers than in non-producers (P < 0.001 for aminoglycosides, ciprofloxacin and meropenem). CONCLUSIONS: OXA-type beta-lactamases are widespread, but their extended-spectrum derivatives are rare among P. aeruginosa in Korea. To our knowledge, this is the first report of OXA-17, an extended-spectrum derivative of OXA-10, outside the Middle East. In addition, combined resistance to ticarcillin and aminoglycosides was a useful indicator for P. aeruginosa producing PSE- or OXA-type beta-lactamases in this study.

Drug Resistance, Bacterial↗

Occurrence of extended-spectrum beta-lactamases among chromosomal AmpC-producing Enterobacter cloacae, Citrobacter freundii, and Serratia marcescens in Korea and investigation of screening criteria.

We assessed the occurrence and screening criterion for extended-spectrum beta-lactamases (ESBLs) among AmpC-producing Enterobacter cloacae, Citrobacter freundii, and Serratia marcescens. The 413 isolates (158 E. cloacae, 126 C. freundii, and 129 S. marcescens) isolated from 11 clinical laboratories in Korea were investigated. ESBL production was confirmed by double-disk synergy test and inhibitor-potentiated diffusion test using ceftazidime (CAZ), cefotaxime (CTX), aztreonam (AZT), and cefepime (FEP) with or without clavulanic acid. One hundred seven isolates (25.9%) were as ESBL producers. Of them, resistance was transferred by conjugation in 82 isolates. In transconjugants, structural genes for CTX-M (53.7%), TEM (46.3%), SHV (29.3%) were found. To evaluate the ESBL screening minimum inhibitory concentration (MIC) criteria, MICs for cefuroxime, CAZ, CTX, AZT, and FEP were determined and cutoff value was selected using receiver operator characteristic curve. The FEP MIC > or = 1 microg/mL had the highest sensitivity (95.3%), specificity (82.7%), and positive (65.8%) and negative predictive values (98.3%).

Anti-Bacterial Agents↗

Prevalence of decreased susceptibility to carbapenems among Serratia marcescens, Enterobacter cloacae, and Citrobacter freundii and investigation of carbapenemases.

Between March and July 2002, total of 612 clinical isolates of Serratia marcescens, Enterobacter cloacae, and Citrobacter freundii (201 S. marcescens, 228 E. cloacae, and 183 C. freundii) were collected from 13 clinical laboratories in a nationwide distribution. Imipenem and meropenem minimum inhibitory concentrations (MICs) were determined using the agar dilution method according to the National Committee for Clinical Laboratory Standards guidelines. For the isolates with a decreased susceptibility to carbapenems (MICs of >or=2 microg/mL), isoelectric focusing, polymerase chain reaction (PCR) amplification of the carbapenemase genes (bla(IMP-1), bla(VIM-2), bla(SME-1), bla(OXA-23), bla(OXA-25), bla(KPC-1)), and sequencing were performed. The prevalence of S. marcescens, E. cloacae, and C. freundii with a decreased susceptibility to imipenem was 17.9% (36/201), 0.4% (1/228), and 0.5% (1/183), respectively, and to meropenem, it was 11.4% (23/201), 0% (0/228), and 0.5% (1/183), respectively. The bla(VIM-2) was the only carbapenemase detected, and was found in 0.5% (1/201) of S. marcescens and 0.5% (1/183) of C. freundii isolate.

Anti-Bacterial Agents↗

Nosocomial transmission of CTX-M-15 and OXA-30 beta-lactamase-producing Escherichia coli in a neurosurgical intensive care unit.

Extended-spectrum beta-lactamase-producing E. coli were recovered from 16 patients in a neurosurgical intensive care unit; surveillance cultures revealed that the organism could be transmitted through the contaminated environment and the hands of health care personnel. All isolates from the patients, environment, and health care personnel showed the same pulsed-field gel electrophoresis pattern. Isoelectric focusing, PCR analysis,and sequencing demonstrated that this E. coli harbored CTX-M-15 and OXA-30 beta-lactamases that were transferred by conjugation. This is the first report of nosocomial transmission caused by E. coli that harbor the combination of CTX-M-15 and OXA-30. This can be a threat because the organisms can hydrolyze cefotaxime, ceftazidime, and cefepime.

Anti-Bacterial Agents↗

Nosocomial outbreak by Proteus mirabilis producing extended-spectrum beta-lactamase VEB-1 in a Korean university hospital.

OBJECTIVES: To examine the molecular mechanisms involved in the beta-lactam resistance of multidrug-resistant Proteus mirabilis isolates that showed an unusual synergy between imipenem and ceftazidime in a Korean hospital. METHODS: Over an 11 month period, a total of 12 P. mirabilis isolates showing resistance to ampicillin, gentamicin, ceftazidime, cefotaxime, cefuroxime, cefalothin, cefepime, piperacillin, trimethoprim/sulfamethoxazole and ciprofloxacin, were recovered from the sputum and urine specimens of nine patients who were hospitalized in the neurosurgery ward. The extended-spectrum beta-lactamases were screened with a double disc synergy test using ceftazidime, cefotaxime, aztreonam, cefepime and clavulanate. The ESBL types were determined by PCR using specific primers for bla(TEM-1), bla(SHV-1), bla(CTX-M-1), bla(CTX-M-2), bla(CTX-M-8), bla(CTX-M-9), bla(PER-1), bla(GES-1), bla(VEB-1), bla(OXA-10) and bla(OXA-13) followed by sequencing. All the isolates underwent molecular typing by PFGE. The transferability was examined by conjugation. RESULTS AND CONCLUSIONS: All the isolates showed a marked synergy between the extended-spectrum cephalosporins and clavulanate together with an unusual synergy between cefoxitin and the cephalosporins (cefalothin, cefuroxime, ceftazidime, cefotaxime) and between imipenem, and ceftazidime and cefotaxime. Isoelectric focusing of the crude bacterial extracts showed a beta-lactamase band with a pI value of 5.4, which was inhibited by clavulanate. PCR and sequencing identified the gene to be bla(VEB-1). In addition, the aadB gene was detected, conferring aminoglycoside resistance. The resistance was not transferred by conjugation. The outbreak was of a clonal origin as shown by PFGE demonstrating an identical banding pattern. This is the first report of VEB-1-producing Enterobacteriaceae in Korea.

Anti-Bacterial Agents↗

Comparison of the BDProbeTec ET system with the roche COBAS AMPLICOR System for detection of Mycobacterium tuberculosis complex in the respiratory and pleural fluid specimens.

The new BDProbeTec ET System (BDET; BD Biosciences, Sparks, MD) was compared with the Roche COBAS AMPLICOR System (CAS) and culture for Mycobacterium tuberculosis (MTB). A total of 253 specimens (152 respiratory and 101 pleural fluid specimens) collected from 240 patients were tested in parallel with the 3 assays. After resolving the discrepancies, the sensitivity, specificity, and positive and negative predictive values of the BDET for detecting MTB was 76.9%, 93.7%, 71.4%, and 95.2% for the respiratory specimens and 88.9%, 92.4%, 53.3%, and 98.8% for the pleural fluid specimens, respectively. The corresponding values of the CAS were 69.2%, 100%, 100%, and 94% for the respiratory specimens and 33.3%, 100%, 100%, and 93.9% for the pleural fluid specimens, respectively. No significant differences in sensitivities were observed between the results of both assays for the respiratory specimens. However, statistically significant differences in sensitivities were found between the BDET and CAS for the pleural fluid specimens (P =.02). Although the BDET was less specific than the CAS (P =.007), the BDET has an excellent sensitivity for detecting MTB in the pleural fluid specimens. Considering the low sensitivity of other available tests, the BDET can be a useful diagnostic tool for excluding MTB, particularly in the pleural fluid specimens.

Bacteriological Techniques↗

Evaluation of Vitek system for susceptibility testing of Enterococcus faecium isolates.

Although imipenem is not a first-line drug for treating enterococcal infection, it could well become a useful drug for treating mixed infections that include enterococci. However, there is no NCCLS guideline for susceptibility testing of imipenem versus enterococci. Moreover, there are no statements to indicate that in vitro susceptibility results for other antimicrobial agents can be used to predict the in vitro activity of imipenem against enterococci. In this study, 52 Enterococcus faecium isolates were collected from patients hospitalized at Kangnam St. Mary's Hospital between March 2002 and December 2002. The sources of the isolates were mainly urine specimens and wounds. For ampicillin, the "major" and "very major" error rates observed with the Vitek system were 0% and 2.0%, respectively. For penicillin, the major and very major error rates observed with the Vitek system were both 0%. For imipenem, the major and very major error rates observed with the Vitek system were 0% and 36.5%, respectively. The MICs of ampicillin and penicillin obtained using the Vitek system were reliable, but that of imipenem was unreliable. In the 52 E. faecium isolates, the in vitro activity of penicillin and ampicillin versus enterococci accurately predicted that of imipenem. Therefore, the MIC of imipenem obtained with the Vitek system must be retested by the agar dilution method, when it disagrees with those of penicillin and ampicillin.

Ampicillin↗

Case report: Bacteremia due to Salmonella enterica Serotype Montevideo producing plasmid-mediated AmpC beta-lactamase (DHA-1).

A Salmonella enterica Serotype Montevideo is described that harbors DHA-1, a plasmid-mediated AmpC beta-lactamase. The organism was isolated from blood and stool specimens of a 3-yr-old girl. The isolate was multi-drug resistant, including cefoxitin, gentamicin, piperacillin, cefuroxime, ceftazidime, and cefotaxime, and an antagonism was observed between cefoxitin and oxyiminocephalosporins. The resistance to ceftazidime and cefotaxime was transferred by conjugation to the recipient E. coli J53. To our knowledge, this is the first description of Salmonella enterica Serotype Montevideo harboring DHA-1.

Bacteremia↗

Prevalence of metallo-beta-lactamase among Pseudomonas aeruginosa and Acinetobacter baumannii in a Korean university hospital and comparison of screening methods for detecting metallo-beta-lactamase.

To identify the metallo-beta-lactamases (MBLs) prevalent in Korea, a total of 130 clinical isolates of Pseudomonas aeruginosa and Acinetobacter baumannii (99 P. aeruginosa and 31 A. baumannii) with a reduced susceptibility to imipenem (IPM) and/or ceftazidime (CAZ) was subjected to PCR analyses with primers specific to bla(IMP-1), bla(VIM-1), and bla(VIM-2). In addition, inhibitor-potentiated disk diffusion methods (IPD) using two kinds of substrate-inhibitor combinations (ceftazidime-2-mercaptopropionic acid (2MPA) and imipenem-EDTA) were investigated. Thirty-three isolates (29 P. aeruginosa and 4 A. baumannii) carried bla(VIM-2) and two P. aeruginosa isolates harbored bla(IMP-1). The enterobacterial repetitive intergenic consensus PCR (ERIC-PCR) pattern revealed that many of the VIM-2-producing P. aeruginosa isolates were clonally related, whereas the A. baumannii isolates were diverse. The inhibitor-potentiated disk diffusion test using imipenem-EDTA was highly sensitive and specific for detecting the VIM-2 producer. These results suggest that VIM-2 is an important MBL in P. aeruginosa and A. baumannii in the Korean hospital of this study and that the IMP-1-producing P. aeruginosa has also emerged. Screening for MBLs and strict infection control for these isolates will contribute to prevent further spread of resistance.

Acinetobacter↗

Molecular analysis of isoniazid resistance in Mycobacterium tuberculosis isolates recovered from South Korea.

The katG, inhA and ahpC genes, in 71 isoniazid (INH)-resistant and 26 INH-susceptible Mycobacterium tuberculosis isolates, from South Korea were examined by sequencing and MspI restriction enzyme analysis. Mutations in the katG 315 alone, katG 315 plus inhA, katG 315 plus ahpC, katG 309 alone, katG 309 plus inhA, inhA alone, and ahpC alone, were detected in 54.9, 2.8, 1.4, 1.4, 1.4, 19.7, and 5.6% of the 71 INH-resistant isolates, respectively. There was no statistically significant difference (p > 0.05) in the frequencies of these mutations for the INH-monoresistant compared with the multidrug-resistant isolates. Mutations in the katG codon 315 were associated with the high-level of INH resistance (MIC, >1 microg/ml), whereas the mutation in the inhA promoter region was associated with the low-level of INH resistance (MIC, >0.2 to 1 microg/ml). The previously undescribed GGT-->GAT (Gly-->Asp) mutation in the katG codon 309 was found in two rifampin, including-multidrug-resistant isolates, but we cannot assess if this is predictive of INH resistance. The sensitivity and specificity of molecular analysis of the katG codon 315 and/or the inhA promoter region were 80.3 and 100%, respectively. Therefore, mutations in these regions are highly predictive of INH resistance in South Korea.

Bacterial Proteins↗