• Title/Summary/Keyword: Multiple drug-resistant

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Patterns of rpoC Mutations in Drug-Resistant Mycobacterium tuberculosis Isolated from Patients in South Korea

  • Yun, Yeo Jun;Lee, Jong Seok;Yoo, Je Chul;Cho, Eunjin;Park, Dahee;Kook, Yoon-Hoh;Lee, Keun Hwa
    • Tuberculosis and Respiratory Diseases
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    • v.81 no.3
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    • pp.222-227
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    • 2018
  • Background: Rifampicin (RFP) is one of the principal first-line drugs used in combination chemotherapies against Mycobacterium tuberculosis, and its use has greatly shortened the duration of chemotherapy for the successful treatment of drug-susceptible tuberculosis. Compensatory mutations have been identified in rpoC that restore the fitness of RFP-resistant M. tuberculosis strains with mutations in rpoB. To investigate rpoC mutation patterns, we analyzed 93 clinical M. tuberculosis isolates from patients in South Korea. Methods: Drug-resistant mycobacterial isolates were cultured to determine their susceptibility to anti-tubercular agents. Mutations in rpoC were identified by sequencing and compared with the relevant wild-type DNA sequence. Results: In total, 93 M. tuberculosis clinical isolates were successfully cultured and tested for drug susceptibilities. They included 75 drug-resistant tuberculosis species, of which 66 were RFP-resistant strains. rpoC mutations were found in 24 of the 66 RFP-resistant isolates (36.4%). Fifteen different types of mutations, including single mutations (22/24, 91.7%) and multiple mutations (2/24, 8.3%), were identified, and 12 of these mutations are reported for the first time in this study. The most frequent mutation involved a substitution at codon 452 (nt 1356) resulting in amino acid change F452L. Conclusion: Fifteen different types of mutations were identified and were predominantly single-nucleotide substitutions (91.7%). Mutations were found only in dual isoniazid- and RFP-resistant isolates of M. tuberculosis. No mutations were identified in any of the drug-susceptible strains.

Drug Resistance Patterns of the Bacterial Strains Isolated from Rural Areas and an Urban General Hospital (무의촌균주(無醫村菌株) 및 병원균주(病院菌株)의 항균제(抗菌劑) 내성(耐性) 양상(樣相)에 관(關)한 연구(硏究))

  • Rhee, Kwang-Ho;Kim, Ik-Sang;Shin, Hee-Sup;Cha, Chang-Yong;Lee, Seung-Hoon;Chang, Woo-Hyun;Lim, Jung-Kyoo
    • The Journal of the Korean Society for Microbiology
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    • v.15 no.1
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    • pp.19-32
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    • 1980
  • Besides the benefits of antimicrobial agents in the control of various infectious diseases, widespread and prolonged use of particular antimicrobial agents has brought about the increase of drug-resistant strains in a community and the profound changes in the pattern of infectious diseases. In Korea, there are some remote villages where no clinics and drug stores are available and the residents in those areas are assumed to have fewer chances to contact with antimicrobial agents. In the present study, the differences in susceptibilities to 14 antimicrobial agents between the isolates from rural areas(R) and Seoul National University Hospital(SNUH, H) were studied. The isolates and their numbers were Staphylococcus aureus, R;55, H;68), Enterococci(R;28, H;30), Escherichia coli(R;40, H;40), Enterobacter aerogenes(R;25, H;21) and Klebsiella pneunoniae(R;58, H;67). Minimal inhibitory concentrations(MIC's) of penicillin, ampicillin, carbenicillin, cephalexin, tetracycline, oxytetracyline, doxycycline, minocycline, gentamicin, kanamycin, streptomycin, erythromycin, troleandomycin and co-trimoxazole were determined by agar dilution method. I. Comparison of MIC's and resistant strain proportions between isolates from SNUH and rural areas. MIC's and/or resistant strain proportions of the isolates from SNUH were significantly higher than those of the isolates from rural areas in the cases of 1. S. aureus to doxycycline, streptomycin and kanamycin. 2. E. coli to penicillin, ampicillin, carbenicillin, tetracycline, oxytetracycline, doxycycline, minocycline, streptomycin, kanamycin, erythromycin and co-trimoxazole. 3. E. aerogences to carbenicillin, tetracycline, oxytetracycline, doxycycline, minocycline, streptomycin, kanamycin, genaamicin and co-trimoxazole. 4. K pneunoniae to penicillin, ampicillin, tetracycline, oxytetracycline, doxycycline, monocycline, streptomycin, kanamycine, gentamicin and co-trimoxazole. However, the mean MIC and resistant strain proportion of S. aureus to tetracycline were higher in isolates from rural areas than in those from SNUH and Enterococci showed no differences in susceptibilities to the antimicrobial agents between isolates from rural areas and from SNUH. Therefore, in general, differenes in susceptibility to these antimicrobial agents between the isolates from rural areas and SNUH were remarkably greater and broader in gram negative enteric bacteria. II. Multiple drug resistance pattern. Patterns and incidences of multiple drug resistance were studied with penicillin, ampicillin, tetracycline, cephalexin, gentamicin, streptomcin, kanamycin and co-trimoxazole in Enterococci, E. coli, E. aeroges and K. pneumoniae. There appeared significant differences in the incidence of multiply drug-resistant strains and multiple drug resistance patterns between the isolates from SNUH and rural areas in Enterococci, E. coli, E. aerogenes and K. pneumoniae. However, there was no difference in the incidence of multiply drug-resistant strains between isolates of S. aureus from SNUH and rural areas but the pattern of multiple resistance of the SNUH strains of S. aureus was diverse, while that of the rural strains was predominantly confined to penicillin-tetracycline combination. The incidence of multigly drug-resistant strains and diversity of their patterns were the highest in E. coli strains isolated from SNUH and there were no multiply drug resistant strrains in Enterococci and K. pneumoniae strains isolated from rural areas. The number of drug-resistance determinants was also different between the isolates from rural areas and SNUH. Most of the multiply drug-resistant strains of E. coli, E. aerogenes and K. pneumoniae isolated from SNUH were resistant to more than 3 kinds of antimicrobial agents, most frequently to ampicillin, tetracycline and streptomycin, while multiply drug-resistant strains from rural areas were resistant to 2 kinds of antimicrobial agents among ampicillin, tetracycline and streptomycin. With drug-resistant E. coli strains, resistance to tetracycline which was used most widely since 1951 was most frequently involved as a part of mutliple drug-resistance, followed by resistance to ampicillin and streptomycin. This strongly suggests that emergence of drug-restant strains in a community is directly dependent on the selective pressure exerted by the antimicrobial agent used. III. Cross resistance. Cross resistance of bacteria was studied among tetracycline penicillin, aminoglycoside and macrolide derivatives by analyzing correlation coefficients of sucseptibilities using the least square method. In this study, there were high correlations among the susceptibilities to related derivatives. It appears that the relatively low correlations in susceptibilities present in some cases are due to intrinsic resistance of E. aerogenes to penicillin, Enterococci to aminoglycoside and E. coli E. aerogenes and K. pneumoniae to macrolide derivatives.

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Butein Disrupts Hsp90's Molecular Chaperoning Function and Exhibits Anti-proliferative Effects Against Drug-resistant Cancer Cells

  • Seo, Young Ho
    • Bulletin of the Korean Chemical Society
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    • v.34 no.11
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    • pp.3345-3349
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    • 2013
  • Hsp90 shows great promise as a therapeutic target due to its potential to disable multiple signaling pathways simultaneously. In this study, we discovered that a natural product, butein moderately inhibited the growth of drug-resistant cancer cells (A2780cis and H1975), and brought about the degradation of oncogenic Hsp90 client proteins. The study demonstrated that butein would be a therapeutic lead to circumvent drug-resistance in cancer chemotherapy. The structure-based screening, synthesis, and biological evaluation of butein are described herein.

Factors related to the Management of MultiDrug-Resistant Organisms among Intensive Care Unit Nurses: An Application of the Health Belief Model (건강신념모델에 근거한 중환자실 간호사의 다제내성균주 감염관리 수행에 영향을 미치는 요인)

  • Kim, Suyoung;Cha, Chiyoung
    • Journal of Korean Academy of Fundamentals of Nursing
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    • v.22 no.3
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    • pp.268-276
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    • 2015
  • Purpose: The purpose of this study was to identify factors which influence the management of MultiDrug -Resistant Organisms (MDROs) by nurses in Intensive Care Units (ICUs). Methods: Data were collected from December 8 to 20, 2013 and participants were 163 ICU nurses working in one general hospital. The Health Belief Model tool and knowledge and management of MDROs infection tools were used in the study. Descriptive statistics, t-test, analysis of variances, Pearson correlation coefficients and multiple regression were used to analyze the data. Results: Knowledge, perceived susceptibility, and perceived benefits had a significant influence on MRSA (Methicillin Resistant Staphylococcus Aureus,) and MDRAB (Multidrug Resistant Acinetobacter Baumannii) infection management when all the other variables were considered. Significant variable which had influence on VRE (Vancomycin Resistant Eenterococci) infection management were perceived susceptibility and perceived benefits. Conclusion: Perceived susceptibility and perceived benefits had significant influence on MDROs infection management. Emphasis needs to be on the perceived susceptibility and perceived benefits of MDROs infection management when providing an educational program for ICU nurses.

In Vitro Susceptibility of Diarrhea-Causing Escherichia coli to 9 Antibacterial Agents in Clinical Use (최근 분리된 장내 병원성 대장균의 항균제 감수성)

  • Kim, Jai-Ho;Kim, Kyung-Hee;Cho, Yaug-Ja;Suh, Inn-Soo
    • The Journal of the Korean Society for Microbiology
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    • v.22 no.2
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    • pp.155-162
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    • 1987
  • To determine the prevalence of antibiotic resistance in fecal E. coli and to investigate possible associations between antibiotic resistance and other plasmid-mediated virulence properties, antibiotic disk susceptibility tests for nine antibiotics were done on 141 strains of E. coli isolated from diarrheal children and well controls. Eighty two percent of the test strains were resistant to one or more antibiotics. Antibiotics to which the test strains were most resistant in descending order were ampicillin (85%), trimethoprim/sulfamethoxazol (60%), and cephalothin (55%). Seventy nine percent of these resistant strains were resistant to two or more antibiotics. All 141 test strains were sorted into enterotoxigenic E. coli (ETEC), enteropathogenic E. coli (EPEC), enteroadherent E. coli (EAEC) and non-pathogenic E. coli and the percentages of strains resistant to multiple antibiotics were compared. Among ETEC regardless of its source, multiple drug resistance was more frequent in strains producing heatstable enterotoxin (ST) only than in strains producing only heat-labile enterotoxin (LT) or both. In EAEC, multiple resistance was more frequently associated with strains isolated from diarrheal patients than with those from well controls. The major antibiotic resistance patterns possessed by multiple resistant enteropathogenic strains were $SXT^R$ $AM^R$, $CR^R$, and $SXT^R$ $AM^R$ $CR^R$. Of 28 ST- producing $SXT^R$ ETEC, 26(96%) were also resistant to ampicillin and 17 (61%) were resistant to cephalothin. The similar pattern was observed in EAEC and EPEC as well. This study has important implications for the treatment of E. coli diarrhea with antibiotics because it is possible that dissemination of virulence could occur under the force of selective antibiotic pressure. In addition, this study suggests that the in vivo efficacy of SXT in treating diarrheal illness be reevaluated.

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Knockdown of MDR1 Increases the Sensitivity to Adriamycin in Drug Resistant Gastric Cancer Cells

  • Zhu, Chun-Yu;Lv, Yan-Ping;Yan, Deng-Feng;Gao, Fu-Lian
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.11
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    • pp.6757-6760
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    • 2013
  • Gastric cancer is one of the most frequently occurring malignancies in the world. Development of multiple drug resistance (MDR) to chemotherapy is known as the major cause of treatment failure for gastric cancer. Multiple drug resistance 1/P-glycoprotein (MDR1/p-gp) contributes to drug resistance via ATP-dependent drug efflux pumps and is overexpressed in many solid tumors including gastric cancer. To investigate the role of MDR1 knockdown on drug resistance reversal, we knocked down MDR1 expression using shRNA in drug resistant gastric cancer cells and examined the consequences with regard to adriamycin (ADR) accumulation and drug-sensitivity. Two shRNAs efficiently inhibited mRNA and protein expression of MDR1 in SGC7901-MDR1 cells. MDR1 knockdown obviously decreased the ADR accumulation in cells and increased the sensitivity to ADR treatment. Together, our results revealed a crucial role of MDR1 in drug resistance and confirmed that MDR1 knockdown could reverse this phenotype in gastric cancer cells.

Polyamines in Multi-drug Resistant Cancer Cells (다제 내성 암세포에서의 Polyamine 특성)

  • 권혁영;이종호;이동권
    • Biomolecules & Therapeutics
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    • v.5 no.3
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    • pp.265-271
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    • 1997
  • Since the advent of chemotherapy, certain types of cancer have been particularly resistant to chemotherapeutic treatment. One of the most well-studied types of resistance is resistance to multiple struc-turally dissimialr hydrophobic chemotherapeutic agents, or multidrug resistance (MDR). We found that MDR cells (KBV20C, KB7D) being highly resistant to colchicine, etoposide, and vincristine were found to have very low level of putrescine and low level of spermidine than the drug sensitive parental cells (KB) but they had almost same level of spermine as the drug sensitive cells. Although both MDR and drug sensitive cells had almost same rate of polyamine uptake, MDR cells were much more sensitive to an inhibitor of polyamine synthesis, methylglyoxal-bis guanylhydrazone (MGBG), suggesting that MDR cells might be defective in polyamine synthesis. These results also suggest that HGBG can be used for treatment of MDR in vivo.

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Antimicrobial Drug Susceptibility of Bordetella bronchiseptica Isolated from Youngnam Swine Herds (영남지방 돼지에서 분리한 Bordetella bronchiseptica의 약제 감수성)

  • Jang, Hee-kyung;Kim, Bong Hwan
    • Korean Journal of Veterinary Research
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    • v.28 no.1
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    • pp.83-87
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    • 1988
  • The in vitro drug susceptibility of 83 strains of Bordetella bronchiseptica recovered from Korean pigs with atrophic rhinitis was investigated by the use of disk diffusion method. The majority of the organisms were highly resistant in order of prevalence to penicillin(98.7%), ampicillin(91.5%), streptomycin(90.3%), triple sulfa(83.1%), and trimethoprim/sulfamethoxazole(70.7%) while none of them were resistant to gentamicin, only 3.6% to colistin, chloramphenicol and kanamycin and 6.0% to tetracycline. The percentage of the organism resistant to bicozamycin, cephalothin and neomycin were 34.9%, 34.1% and 18.4%, respectively. A high prevalence of multiple drug resistance was observed and the 3 most common resistant patterns among 35 patterns noted were Am Pc Sm Sss Sxt(26.5%), Am Cf Pc Sm Sss Sxt(12.%) and Am Bm Pc Sm Sss Sxt(9.6%) patterns.

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Trend of Antimicrobial Susceptibility and Multiple drug Resistance Patterns of Salmonella entericia Serovar Enteritidis Isolated from Foodborne Patients in Seoul between 2001 and 2005 (최근 5년간 서울시내 식중독 환자에서 분리한 Salmonella enterica serovar Enteritidis의 항생제 감수성 및 다제 내성 특성)

  • Park Seog-Gee;Kim Moo-Sang;Lee Young-Kee
    • Journal of Food Hygiene and Safety
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    • v.21 no.1
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    • pp.23-30
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    • 2006
  • Antimicrobial susceptibility and multiple drug resistance patterns have been carried out on total of 364 isolates of Salmonella enterica serovar Enteritidis isolated from foodborne patients in Seoul from 2001 to 2005. Overall, the highest percentage of resistance was found to the following antimicrobial agents: streptomycin (46.7%), ampicillin (37.3%), ticarcillin (36.7%), tetracycline (36.0%), nalidixic acid (20.7%), chloramphenicol (13.3%), amoxicillin/clavulanic acid (6.7%) and Ampicillin/sulbactam (4.0%). Seventy five percentage of isolates were found to be resistant to one or more of the antimicrobes tested. The resistant rates to nalidixic acid and chloramphenicol in S. Enteritidis tested were annually increased but the resistant rate to tetracycline was decreased and the resistant rates to streptomycin, ampcilin and ticarcillin were remained steadily. The most frequent patterns of multiresistant isolates were only nalidixic acid resistant (18.0%) and streptomycin-tetracycline (18.0%), streptomycin-ampicillin-ticarcillin (10%), and ampicillin-ticarcillin (5.5%). Overall the resistant rates of 1 drug was 19.3%,2 drugs 24.7%, 3 drugs 6.7% and 4 or more drugs 24.0%. The resistant rates of 1 drug and 2 drugs in 2005 were increased dramatically.

Drug Resistance and R-Plasmids of Shigella Strains Isolated from Humans, Korea (Shigella균속의 항균제내성 및 전달성 R-Plasmid에 관한 연구)

  • Kim, Ji-Youn;Lee, Yun-Tai
    • The Journal of the Korean Society for Microbiology
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    • v.19 no.1
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    • pp.11-24
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    • 1984
  • Shigella remains to be an important enteric pathogen in this country for the present. Moreover, most of the isolates have become multiple resistant to various antibiotics which used to be drugs of choice for shigellosis. This study was made as an attempt to assess the present stage of antibiotic resistance and the incidence and transferability of R factors of Shigella. A total of one hundred and seventeen strains of Shigella isolated from patients in Seoul and provincial area between 1982 and 1983 were tested for their resistant to antimicrobial agents and transmission of R-plasmid. Antibiotic susceptibilities were determined by an agar dilution method. Muller hinton agar were used for the assay of drug resistance and tryptic soy broth were used for propagating medium for conjugation. Shigella isolated found to be one or more antibiotics were considered potential donor of R-plasmid. The following results were obtained. 1. Among 117 strains of Shigella isolated, 111 strains(94.9%) were found to be resistant to one or more drugs tested and 97.3% of these resistant strains were multiply resistant, indicating the multiply resistant strains were more than the single resistant strains. Only six strains were susceptible to all drugs tested. 2. Among 117 strains of Shigella isolated, 107 strains(91.5%) were resistant to Tetracyclin(Tc), 106 strains(90.6%) to Chloramphenicol(Cp) and Streptomycin(Sm), 97 strains(82.9%) to Ampicillin(Ap), 68 strains(58.1%) to Cephaloridine(Cr), 10 strains(8.5%) to Nalidixic acid(Na), 5 strains(4.3%) to Kanamycin(Km) and 2 strains(1.7%) to Rifampicin. No strain was resisfant to Amikacin(Ak) and Gentamicin(Gm). 3. All drug-resistant Shigella strains, except three, were multiply resistant to two or more drugs. Fifty eight strains were resistant to five drugs, followed by 26 strains resistant to dour drugs, 12 strains resistant to three drugs and 11 strains resistant to six drugs. 4. The 73% of multiply drug-resistant Shigella transferred their resistance to E. coli by conjugation and the resistance was considered to be mediated by R-plasmid. Resistance to Nalidixic acid and Rifampicin were not transferred by conjugation to recipient. As for the transferability of resistance to each seperate drug, Ap resistance was transferred with 73.2% frequence and Cm and Tc resistance were transferred with approximately 50-60% frequence whereas Sm and Cr resistance were transferred in 19.1-21.4% The other four drugs resistant failed to transfer their resistance to recipient. 5. As for the incidence and transferability of resistance to each seperate drug, the strains resistant to Tc and Cm were encountered most frequently with the rate of 91-92%, whereas transfer of Tc and Cm were low, 51-52%. The incidence of Sm resistance was very high(90.6%) but transferability of drugs resistance was much lower(25.4%). Though the incidence of Km reristance was much lower(4.3%) transferability of Km resistance was considerably higher(60%). 6. The greater the multiplicity of resistance, the greater was the likelihood that part of all of the resistance markers would be transferable.

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