• Title/Summary/Keyword: 다약제내성

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Detection of Multidrug Resistance Using Molecular Nuclear Technique (분자핵의학 기법을 이용한 다약제내성 진단)

  • Lee, Jae-Tae;Ahn, Byeong-Cheol
    • The Korean Journal of Nuclear Medicine
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    • v.38 no.2
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    • pp.180-189
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    • 2004
  • Although the outcome of cancer patients after cytotoxic chemotherapy is related diverse mechanisms, multidrug resistance (MDR) for chemotherapeutic drugs due to cellular P-glycoprotein (Pgp) or multidrug-resistance associated protein (MRP) is most important factor in the chemotherapy failure to cancer. A large number of pharmacologic compounds, including verapamil, quinidine, tamoxifen, cyclosporin A and quinolone derivatives have been reported to overcome MDR. Single photon emission computed tomography (SPECT) and positron emission tomography (PET) are available for the detection of Pgp and MRP-mediated transporter. $^{99m}Tc$-MIBI and other $^{99m}Tc$-radiopharmaceuticals are substrates for Pgp and MRP, and have been used in clinical studies for tumor imaging, and to visualize blockade of PgP-mediated transport after modulation of Pgp pump. Colchicine, verapamil and daunorubicin labeled with $^{11}C$ have been evaluated for the quantification of Pgp-mediated transport with PET in vivo and reported to be feasible substrates with which to image Pgp function in tumors. Leukotrienes are specific substrates for MRP and $N-[^{11}C]acetyl-leukotriene$ E4 provides an opportunity to study MRP function non-invasively in vivo. SPECT and PET pharmaceuticals have successfully used to evaluate pharmacologic effects of MDR modulators. Imaging of MDR and reversal of MDR with bioluminescence in a living animal is also evaluated for future clinical trial. We have described recent advances in molecular imaging of MDR and reviewed recent publications regarding feasibility of SPECT and PET imaging to study the functionality of MDR transporters in vivo.

Causative Agents and Antimicrobial Sensitivity of Neonatal Sepsis : Ten-year Experience in One Neonatal Intensive Care Unit (단일 신생아중환자실에서 경험한 10년간의 신생아 패혈증의 원인균 및 항생제 감수성 변화)

  • Park, Hye-Won;Lim, Gin-A;Koo, So-Eun;Lee, Byong-Sop;Kim, Ki-Soo;Pi, Soo-Young;Kim, Ai-Rhan
    • Neonatal Medicine
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    • v.16 no.2
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    • pp.172-181
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    • 2009
  • Purpose: To identify trends in causative bacterial organisms for neonatal sepsis and antimicrobial susceptibilities over 10 years in one neonatal intensive care unit. Methods: We retrospectively reviewed the cases of culture-proven neonatal sepsis between January 1998 and December 2007. The 10-year period was divided into two phases (phase I, 1998-2002; phase II, 2003-2007) to distinguish the differences during the entire period. Results: Total 350 episodes of neonatal sepsis were identified in 315 neonates. The common pathogens of early-onset sepsis were S. epidermidis, S. aureus, P. aeruginosa, and E. cloacae in phase I, and S. epidermidis and E. cloacae in phase II. In cases of late-onset sepsis, coagulase negative Staphylococcus, S. aureus, and K. pneumoniae were isolated frequently in both phases. The incidence of sepsis caused by multi-drug resistant organisms decreased with strict infection control. Gram positive organisms showed 0-20% susceptibility to penicillin, ampicillin, and cefotaxime in both phases. Sensitivity to amikacin for Enterobacter spp. increased, whereas P. aeruginosa showed decreased sensitivity in phase II. Between 50% and 60% of other gram negative bacteria, except P. aeruginosa, were susceptible to cefotaxime in phase II in contrast to phase I. Greater than 80% of gram negative bacteria were sensitive to imipenem except P. aeruginosa and ciprofloxacin in both phases. Conclusion: The trend in causative microorganisms and antimicrobial susceptibilities can be used as a guideline for selection of appropriate antibiotics. A particular attention should be paid to infection control, especially to reduce sepsis caused by multi-drug resistant organisms.

Current Status of Infection Control of Multidrug Resistant Organisms in Hospitals with more than 200beds in the Republic of Korea (국내 200병상이상 의료기관의 다약제 내성균 감염관리 실태조사)

  • Oh, Hyang-Soon
    • The Korean Journal of Health Service Management
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    • v.8 no.4
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    • pp.163-173
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    • 2014
  • This study was performed to investigate the current status of isolation precautions of multidrug resistant organisms(MDROs) in general hospitals with more than 200bed. The questionnaires were mailed from 3rd, April 2013 to 30th, April 2013. Methicillin resistant Staphylococcus aureus:(MRSA), vancomycin resistant Staphylococcus aureus:(VRSA), vancomycin resistant Enterococcus(VRE), multidrug-resistant Acinetobacter baumannii, carbapenem-resistant Enterobacteriaceae multidrug-resistant Pseudomonas aeruginosa were enrolled. MRSA(100.0%) and VRE(98.7%) were isolated respectively. VRE(97.3%) and MRSA(64.0%) were regulated strictly respectively. VRE(91.5%) and VRSA(50.7%) were isolated in a single room respectively. Hospital being located in Seoul(p<0.001), and beds(${\geq}600$)(p=0.008) were different significantly. The isolation space limitation(71.1%) was the highest difficulty. The development of refunding the costs of the extra supplies and other hygienic materials for infection control was discovered as the most urgent strategy.

Reversal of Multidrug Resistance by Benzotriazepin Analogues in Cancer Cells (Benzotriazepin 유도체의 암세포에 대한 다약제내성 억제효과)

  • Kim Mi Hye;Choi Sang Un;Choi Eun Jung;Kim Sung Soo;Choi Jung Kwon;Ahn Jin Hee;Lee Chong Ock;Kwon Kwang Il
    • YAKHAK HOEJI
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    • v.49 no.1
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    • pp.38-43
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    • 2005
  • The occurrence of resistance to chemotherapeutic drugs is a major problem for successful cancer treatment. This resistant phenotype of cancer cell frequently reveals a broad spectrum to structurally and/or functionally unrelated anticancer drugs, termed multidrug resistance (MDR). Overexpression of P-glycoprotein (P-gp), a transmembrane drug efflux pump, is a major mechanism of MDR. Accordingly, considerable effort has been directed towards to development of compounds that inhibit P-gp, reverse the MDR phenotype and sensitize cancer cells to conventional chemotherapy without undesired toxicological effects. In an effort to search for novel MDR reversal agent, we tested the cytotoxicity of paclitaxel, a well-known substrate of P-gp, against P-gp-expressing HCT15 and HCT15/CL02 human colorectal cancer cells in the presence or absence of benzotriazepin analogues, as well as against P-gp-negative A549 human non-small cell lung and SK-OV-3 human ovarian cancer cells in vitro. Among the compounds tested, the agents that have phenyl amide moiety at 3 position remarkably increased the cytotoxicity of paclitaxel against P-gp-expressing cancer cells, but not against P-gp-negative cancer cells. BTZ-15 and BTZ-16 at $4\;{\mu}M$ revealed similar MDR reversal activity to $10\;{\mu}M$ verapamil, a well-known MDR reversal agent.

Complete genome sequence of multidrug-resistant Moraxella osloensis NP7 with multiple plasmids isolated from human skin (사람의 피부에서 분리한 다약제 내성이며 다수의 플라스미드를 갖는 Moraxella osloensis NP7 균주의 유전체 서열 분석)

  • Ganzorig, Munkhtsatsral;Lim, Jae Yun;Hwang, Ingyu;Lee, Kyoung
    • Korean Journal of Microbiology
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    • v.54 no.3
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    • pp.286-288
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    • 2018
  • Moraxella osloensis NP7 was isolated from human skin of a collage male and showed resistance to ${\beta}-lactam$ and aminoglycoside antibiotics. Herein, we report the complete whole-genome sequence and gene annotations of M. osloensis NP7. It possesses single circular chromosome and seven plasmids. Chromosome is 2,389,582 bp in length with the G + C content of 43.9% and encodes 2,065 protein-coding genes. The combined seven plasmids are 654,202 bp in size with the average G + C content of 40.5% and code for a total of 667 protein-coding genes. The chromosome of NP7 strain contains four ribosomal RNA operon copies, one transfer-messenger RNA gene, forty-seven tRNA genes, three riboswitch genes and three CRISPR arrays. Additional CRISPR array is found in the plasmid pNP7-1. The genes conferring resistance to ${\beta}-lactam$ and aminoglycoside antibiotics were predicted to reside in the plasmid pNP7-1.

Chemical Composition and in vitro Antimicrobial and Antioxidant Activities of Commercially Available Essential Oils against Multidrug Resistant Bacteria (시판 정유의 성분 분석과 다약제 내성균에 대한 항균활성 및 항산화 효능 평가)

  • Yoo, Yeong Wol;Lee, Hyo Jeong;Kim, Seung;Bae, Min Suk;Lee, Mi Ja;Shim, Jung-Hyun;Cho, Seung Sik
    • Journal of Life Science
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    • v.24 no.3
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    • pp.266-273
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    • 2014
  • In the present study, the chemical compositions and antimicrobial and antioxidant activities of commercially available essential oils in Korea were investigated. The essential oils were analyzed by gas chromatography-mass spectrometry (GC-MS). The results demonstrated that they exhibit a broad spectrum of antimicrobial activities against gram positive, gram negative, and multidrug resistant (MDR) strains. The antimicrobial activity of five of the essential oils against 40 organisms was assessed using the minimum inhibitory concentration (MIC). The MIC values were in the ranges of 0.0625-0.5% (v/w) for lemongrass and manuka, 0.03125-1.0% (v/w) for tea tree, 0.0625-1.0% (v/w) for thyme, and 1-4% (v/w) for ravensara, depending on the pathogens studied. This study revealed that, among the essential oils tested, lemongrass and thyme oil showed broad antimicrobial activity against infectious bacteria. The antioxidant activities and the reducing power of the essential oils were determined with a 1, 1-diphenyl-2-picrylhydrazyl (DPPH) assay. Thyme oil exhibited the strongest antioxidant activity comparing with ascorbic acid. This is the first report on the chemical compositions and antimicrobial activities of commercially available essential oils against infectious bacteria and MDR strains acquired from Korean hospitals.

Comparative Uptake of Tc-99m Sestamibi and Tc-99m Tetrofosmin in Cancer Cells and Tissue Expressing P-Glycoprotein or Multidrug Resistance Associated Protein (P-Glycoprotein과 Multidrug Resistance Associated Protein을 발현하는 암세포와 종양에서 Tc-99m Sestamibi와 Tc-99m Tetrofosmin의 섭취율 비교)

  • Cho, Jung-Ah;Lee, Jae-Tae;Yoo, Jung-Ah;Seo, Ji-Hyoung;Bae, Jin-Ho;Jeong, Shin-Young;Ahn, Byeong-Cheol;Sohn, Sang-Gyun;Ha, Jeoung-Hee;Lee, Kyu-Bo
    • The Korean Journal of Nuclear Medicine
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    • v.39 no.1
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    • pp.34-43
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    • 2005
  • Purpose: $^{99m}Tc$-sestamibi(MIBI) and $^{99m}Tc$-tetrofosmin have been used as substrates for P-glycoprotein (Pgp) and multidrug resistance associated protein (MRP), which are closely associated with multidrug resistance of the tumors. To understand different handling of radiotracers in cancer cell lines expressing Pgp and MRP, we compared cellular uptakes of $^{99m}Tc$-MIBI and $^{99m}Tc$-tetrofosmin. The effects of cyclosporin A (CsA), well-known multidrug resistant reversing agent, on the uptake of both tracers were also compared. Materials and Methods: HCT15/CL02 human colorectal cancer cells for Pgp expressing cells, and human non-small cell lung cancer A549 cells for MRP expressing cells, were used for in vitro and in vivo studies. RT-PCR, western blot analysis and immunohistochemistry were used for detection of Pgp and MRP. MDR-reversal effect with CsA was evaluated at different drug concentrations after incubation with MIBI or tetrofosmin. Radioactivities of supernatant and pellet were measured with gamma well counter. Tumoral uptake of the tracers were measured from tumor bearing nude mice treated with or without CsA. Results: RT-PCR, western blot analysis of the cells and irnrnunochemical staining revealed selective expression of Pgp and MRP for HCY15/CL02 and A549 cells, respectively. There were no significant difference in cellular uptakes of both tracers in HCT15/CL02 cells, but MIBI uptake was slightly higher than that of tetrofosmin in A549 cells. Co-incubation with CsA resulted in a increase in cellular uptakes of MIBI and tetrofosmin. Uptake of MIBI or tetrofosmin in HCT15/CL02 cells was increased by 10- and 2.4-fold, and by 7.5 and 6.3-fold in A549 cells, respectively. Percentage increase of MIBI was higher than that of tetrofosmin with CsA for both cells (p<0.05). In vivo biodistribution study showed that MIBI (114% at 10 min, 257% at 60 min, 396% at 240 min) and tetrofosmin uptake (110% at 10 min, 205% at 60 min, 410% at 240 min) were progressively increased by the time, up to 240 min with CsA. But increases in tumoral uptake were not significantly different between MIBI and tetrofosmin for both tumors. Conclusion: MIBI seems to be a better tracer than tetrofosmin for evaluating MDR reversal effect of the modulators in vitro, but these differences were not evident in vivo tumoral uptake. Both MIBI and tetrofosmin seem to be suitable tracers for imaging Pgp- and MRP-mediated drug resistance in tumors.

Coagulase Thping and Antibiotic Resistance of Methicillin Resistant Staphylococcus aureus (MRSA) Isolated form Patients in Pusan (부산지역 환자로부터 분리된 Methicillin Resistant Staphylococcus aureus(MRSA)의 응고효소형 및 항균제 내성에 관한 연구)

  • 류지한;이훈구
    • Korean Journal of Microbiology
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    • v.36 no.3
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    • pp.216-220
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    • 2000
  • Eighty-eight strain3 o~methicillin resistant Stopllylococcus awecis were Isolated from pus (64.7%); spuhm (26.2%), blood, fluid, andurine of 83 patients at Dong-A Hospital in P~~san to invesligate theil-coagulase typ- Ing, and multi-drug resistaut ppattems. The presence of niec A gene confe~~ing melhicillin resistance was tested by polymerase chain reaction (PCR) with uwo mec A gene specific primers using purified clromosonlal DNA as templates. DNA fragments of expected size wel-e detected frorn 86 strains, but not from two strains. !i coagulase typmg, the 86 isolates were assigned to 5 coagulase lypes, I, 11, lll. 1V, VI, VII, VIlI, but there was no isolate helong lo type V. The most abundant coagulase type was type TI(50 %), lollowed by type IV Rest ofthe coagulase types were ininor; ranging fmm 4.5 to 12.5 '% Most of the type I1 ~netlucillin resistant Stapl\ulcorneryiococcus nwem (MRSA) strams were isolated from the generd sulzely ward, but major strains of type IV were Isolated from the otorhinolq~ngology of the hospital's outpatient clinic center. All of the 88 st~nins were sensitive to vancomycin and teicoplanin, but 71 (81%) strains showed multi-drug resitant to penicillin, cephalotl~n, eiythroinycin, gentan~ycin, imipenem, clindamycin, ciprofloxacin and ooxacillin. Yo relationship was found between the antibiotic resistance pattems aud the coagulase typing patterns.

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Characteristics of Coagulase-negative Staphylococci Isolates from Dental Clinic Environments in Busan, Korea (부산지역 치과환경에서 분리된 coagulase-negative staphylococci의 특성)

  • Jung, Hye-In;Jung, So Young;Park, Indal;Bae, Il Kwon
    • Journal of Life Science
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    • v.26 no.2
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    • pp.220-225
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    • 2016
  • Coagulase-negative staphylococci (CNS) have recently become the bacteria most frequently found in clinical infections. The aim of this study was to investigate the prevalence, antimicrobial susceptibilities, and molecular characteristics of CNS isolates from dental clinic environments in Busan, Korea. One hundred and fifty-four samples were collected from 10 dental clinics and dental hospitals in Busan from December 2014 to January 2015. Species were identified by matrix-assisted laser desorption/ionization–time-of-flight. Antimicrobial susceptibility was determined by disk diffusion methods. A polymerase chain reaction was performed to detect mecA, mupA gene, and SCCmec types. Of the 154 samples, 10(6.5%) isolates were identified as CNS (5 Staphylococcus epidermidis, 2 Staphylococcus capitis, 2 Staphylococcus, and 1 Staphylococcus haemolyticus). Among the 10 isolates, 6 were resistant to penicillin, 5 were resistant to gentamicin, 3 were resistant to tetracycline, and 2 were resistant to cefoxitin and erythromycin. However, clindamycin, ciprofloxacin, teicoplanin, and trimethoprim-sulfamethoxazole resistant isolates were not present. Genes encoding mecA were detected in 4 (2 S. warneri and 2 S. haemolyticus) isolates, and mupA in 1 (S. epidermidis) isolate. One methicillin-resistant CNS (S. warneri) isolate was determined as being of the SCCmec type I. It is concluded that CNS resistant to various antimicrobial agents was widely distributed in dental clinic environments in Korea.

Functional Imaging of the Multidrug Resistance In Vivo (기능적 영상술을 이용한 다약제 내성의 체내 진단)

  • Lee, Jea-Tae
    • 대한핵의학회:학술대회논문집
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    • 2001.05a
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    • pp.66-75
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    • 2001
  • Although diverse mechanisms are involved in multidrug resistance for chemotherapeutic drugs, the development of cellular P-glycoprotein(Pgp) and multidrug-resistance associated protein (MRP) are important factors in the chemotherapy failure to cancer. Various detection assays provide information about the presence of drug efflux pumps at the mRNA and protein levels. However these methods do not yield information about dynamic function of Pgp and MRP un vivo. Single photon emission tomography (SPECT) and positron emission tomography (PET) are available for the detection of Pgp and MRP-mediated transport. $^{99m}Tc$-sestaMIBl and other $^{99m}Tc$-radiopharmaceuticals are substrates for Pgp and MRP, and have been used in clinical studies for tumor imaging, and to visualize blockade of Pgp-mediated transport after modulation of Pgp pump. Colchicine, verapamil and daunorubicin labeled with $^{11}C$ have been evaluated for the quantification of Pgp-mediated transport with PET in vivo and reported to be feasible substrates with which to image Pgp function in tumors. Leukotrienes are specific substrates for MRP and N-$[^{11}C]$acetyl-leukotriene E4 provides an opportunity to study MRP function non-invasively in vivo. Results obtained from recent publications are reviewed to confirm the feasibility of using SPECT and PET to study the functionality of MDR transporters in vivo.

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