• Korean Journal of Clinical Laboratory Science
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• v.51 no.4
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• pp.444-452
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• 2019

Carbapenem resistance, mediated by the major acquired metallo-β-lactamase (MBL) genes, has been increasingly reported, particularly for clinical isolates of Acinetobacter spp. Of the 191 nonduplicate clinical isolates of the carbapenem-nonsusceptible Acinetobacter spp. evaluated, 125 isolates (65.4%) were positive for the modified imipenem or meropenem-Hodge test, and 49 isolates (25.7%) were positive for the imipenem-EDTA+SMA double disk synergy test (DDS). PCR and sequencing of the bla_VIM-2-allele and bla_IMP-1-allele showed that 29 A. baumannii isolates and 1 A. calcoaceticus isolate had bla_VIM-2, whereas 16 A. baumannii isolates and 2 A. calcoaceticus isolates had bla_IMP-6; 1 isolate of the A. genomospecies 3 had bla_VIM-2 and bla_AIM-1. All the above MBL genes belong to class 1 integron. The size of class 1 integron encompassing bla_VIM-2 or bla_IMP-6 ranges from 2.8 kb to 3.2 kb in clinical isolates of A. baumannii, and 3.2 kb to 3.5 kb in clinical isolates of A. genomospecies 3. bla_VIM-2 was most often located first or second in the class 1 integron, and these integrons often included aacA4. Due to dispersion of the MBL-producing Acinetobacter spp. as well as integron, which may encompass various resistance genes, there is an expectation for the increase of multidrug resistant Gram-negative bacteria, including resistance of carbapenems such as imipenem or meropenem. Hence, the development of new antimicrobial agents for treating severe Acinetobacter spp. infections is needed.

• Journal of the Korean Applied Science and Technology
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• v.39 no.6
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• pp.916-923
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• 2022

Water samples were collected from three spots(Namcheon, Changwoncheon and Cheongwoonji) in Changwon and genomic DNA was isolated from them. Quantitative PCR was performed with the isolated DNA as template and primers targeting five different class A extended-spectrum beta-lactamase(ESBL) genes(bla_OXA-1, bla_SHV, bla_TEM, bla_CTX-M-1, bla_CTX-M-9). The number of total ESBL genes from each sample showed large variations between each sample. Thirty nanograms of DNA from Namcheon contained 1.93×10⁶ copies of ESBL genes whereas the same amount of DNA from Changwoncheon contained 1.47×10⁵ copies of ESBL genes. However, the same amount of DNA from Cheongwoonji pond contained only 9.5×10³ copies of ESBL genes. The ratio of each ESBL genes showed little difference between Namcheon river and Changwoncheon river, but DNA from Cheongwoonji pond showed a large difference from the rest. bla_OXA-1 gene was present at 65.3%, and bla_CTX-M-1 gene 33.6% for Namcheon comprising together almost 99%. bla_OXA-1 gene was present at 64.1%, and bla_CTX-M-1 gene 19.1% for Changwoncheon comprising together over 83%. bla_CTX-M-1 gene was present at 87.5% and bla_CTX-M-9 genes 9.8% for Cheongwoonji, a pond which is a closed and isolated environment.

• Korean Journal of Microbiology
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• v.52 no.4
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• pp.428-436
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• 2016

The emergence of antibiotic-resistant bacteria has been increased and become a public health concern worldwide. Many bacterial infections can be sequentially treated with different types of antibiotics. Thus, this study was designed to evaluate the changes in survival, antibiotic susceptibility, mutant frequency, ${\beta}$-lactamase activity, biofilm formation, and gene expression in Klebsiella pneumoniae after exposure to sequential antibiotic treatments of ciprofloxacin and meropenem. Treatments include control (CON; no addition), 1/2 MIC ciprofloxacin addition (1/2CIP), 2 MIC ciprofloxacin addition (2CIP), initial 1/2 MIC ciprofloxacin addition followed by 1/2 MIC meropenem (8 h-incubation) and 2 MIC ciprofloxacin (16 h-incubation) (1/2CIP-1/2MER-2CIP), initial 1/2 MIC ciprofloxacin addition followed by 1/2 MIC meropenem (8 h-incubation) and 2 MIC meropenem (16 h-incubation) (1/2CIP-1/2MER-2MER), and initial 1/2 MIC ciprofloxacin addition followed by 2 MIC ciprofloxacin(8 h-incubation) and 2 MIC meropenem(16 h-incubation) (1/2CIP-2CIP-2MER). No growth of K. pneumoniae was observed for the 2CIP throughout the incubation period. The numbers of planktonic cells varied with the treatments (7~10 log CFU/ml), while those of biofilm cells were not significantly different among treatments after 24-h incubation, showing approximately 7 log CFU/ml. Among the sequential treatments, the least mutant frequency was observed at the 1/2CIP-1/2MER-2CIP (14%). Compared to the CON, 1/2CIP-2CIP-2MER decreased the sensitivity of K. pneumoniae to piperacillin, cefotaxime, and nalidixic acid. The highest ${\beta}$-lactamase activity was 22 nmol/min/ml for 1/2CIP-1/2MER-2CIP, while the least ${\beta}$-lactamase activity was 6 nmol/min/ml for 1/2CIP-2CIP-2MER. The relative expression levels of multidrug efflux pump-related genes (acrA, acrB, and ramA) were increased more than 2-fold in K. pneumoniae exposed to 1/2CIP-1/2MER-2MER and 1/2CIP-2CIP-2MER. The results suggest that the sequential antibiotic treatments could change the antibiotic resistance profiles in K. pneumoniae.

• Proceedings of the Zoological Society Korea Conference
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• 1994.10a
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• pp.250.2-250
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• 1994

• Bulletin of the Korean Chemical Society
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• v.19 no.10
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• pp.1029-1031
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• 1998

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.162-162
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• 1996

새로 합성된 6-exomethylene penamsulfone derivatives 7종에 대해 In Vitro antibacterial activities를 Broth Microdilution법으로 Sulbactam-Na(SAM), Clavulanic acid-K(CLA)와 Cefotaxime-Na(CFT), Ampicillin Trihydrates(AMP), Amoxicillin-Na(AMX), Cefoperazone(CFZ)을 병용투여하여 $\beta$-lactamase 생성 균주(30 여종)에 실시, MIC를 구하였다. 균주에 따라 SAM, CLA에 비해 CH1145, CH1155 등이 우수한 효과를, CH1140, CH2150등이 유사한 효과를 보였다.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.159-159
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• 1996

6-Substituted exomethylene 기를 갖는 penam계 화합물이 $\beta$-lactamase 억제제로서 강력한 활성을 보여주고 있어서, 6-exomethylene기 도입에 필요한 1-substituted thioalkyl-1,2,3-triazole-4-carboxaldehyde를 합성하였다. Haloalkanol에 NaN$_3$를 반응시켜서 합성한 azidoalkanol과 propargyl alcohol을 산화시킨 propargyl aldehyde를 반응시켜서 1-(2-hydroxyalkyl-1,2,3-triazole-4-carboxaldehyde을 얻었다. 이것을 trifluoromethanesulfonic anhydride와 triethylamine 존재 하에 mercapto 화합물과 반응시켜서 목적물을 합성하였다.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.236-236
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• 1996

DA-1131은 IPM이 D2 channel 특이적인 세포외막투과성을 나타내는 것과는 달리 D2 channel 이외에 azthreonam 투과경로도 이용하는 것으로 확인되었다. IPM 감수성 및 내성인 P aeruginosa 균주들에 대하여 $\beta$-lactamase의 inducible activity, hydrolytic susceptibility, affinity를 측정한 결과, Inducible activity는 DA-1131, PPM 및 MEPM이 거의 동일하였으며, 3가지 약물 모두 가수분해에 대한 안정성을 나타내었다. 그러나 $\beta$-lactamase에 대한 affinity는 IPM이 가장 컸고, MEPM, DA-1131의 순으로 감소하였다. DA-1131은 P8P2와 PBP3를 동시에 저해하며, IPM은 PBP2의 저해 후 순차적으로 PBP3를 저해하였고 이러한 시험결과는 PBPs blinding pattern과 밀접한 관계가 있는 것으로 알려진 균형태변화로도 확인되었다.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.04a
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• pp.70-70
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• 1997

$\beta$-Lactamase 억제제로 6-Substituted exomethylene기를 갖는 penam계 화합물이 강력한 활성을 보여주고 있어서, $\beta$-lactamase억제제의 중간체 합성으로 6-exomethylene기에 도입 할 1-substituted thioalkyl-1,2,3-triazole-4-carboxaldehyde를 합성하였다. 2-Bromoethanol에 NaN$_3$를 반응시켜서 2-Azidoethanol을 합성하였고, 이것을 propargyl aldehyde와 반응시켜서 1-(2-hydroxyethyl)-1,2,3-triazole-4-carboxaldehyde를 합성하였다. 이것을 trifluoromethanesulfonic anhydride와 triethylamine존재 하에 heterocyclic mercapto화합물과 반응시켜서 hetorocyclic ring을 함유한 1-substituted thioalkyl-1,2,3-triazole-4-carboxaldehyde를 합성하였다.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.04a
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• pp.71-71
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• 1997

$\beta$-lactamase를 생성하는 균들이 $\beta$-lactam계 항생제를 분해하여 불활성화 시키므로 이를 해결하기 위하여 그 효소에 대하여 억제활성을 나타내는 새로운 6-exomethylenepenamsulfone화합물들을 합성하였다. Dibromopenamsulfone과 heterocyclic ring을 함유한 thioethyl triazole-4-carboxaldehyde를 반응시키고, acetic anhydride와 Zn으로 처리하여 E-form과 Z-form의 6-exomethylene penmsulfones을 합성하였다. 이것을 AlCl$_3$로 처리하여 deprotection시킨 후, NaHCO$_3$로 처리하여 6-exomethylene penam sulfones의 Na-salt의 형태로 목적물질을 합성하였다.