• Title/Summary/Keyword: Multidrug-resistance

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Diagnosis and treatment of multidrug-resistant tuberculosis

  • Jang, Jong Geol;Chung, Jin Hong
    • Journal of Yeungnam Medical Science
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    • v.37 no.4
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    • pp.277-285
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    • 2020
  • Tuberculosis (TB) is still a major health problem worldwide. Especially, multidrug-resistant TB (MDR-TB), which is defined as TB that shows resistance to both isoniazid and rifampicin, is a barrier in the treatment of TB. Globally, approximately 3.4% of new TB patients and 20% of the patients with a history of previous treatment for TB were diagnosed with MDR-TB. The treatment of MDR-TB requires medications for a long duration (up to 20-24 months) with less effective and toxic second-line drugs and has unfavorable outcomes. However, treatment outcomes are expected to improve due to the introduction of a new agent (bedaquiline), repurposed drugs (linezolid, clofazimine, and cycloserine), and technological advancement in rapid drug sensitivity testing. The World Health Organization (WHO) released a rapid communication in 2018, followed by consolidated guidelines for the treatment of MDR-TB in 2019 based on clinical trials and an individual patient data meta-analysis. In these guidelines, the WHO suggested reclassification of second-line anti-TB drugs and recommended oral treatment regimens that included the new and repurposed agents. The aims of this article are to review the treatment strategies of MDR-TB based on the 2019 WHO guidelines regarding the management of MDR-TB and the diagnostic techniques for detecting resistance, including phenotypic and molecular drug sensitivity tests.

A Drug Efflux Pump for Cationic Drugs including Disinfectants in Bacillus subtilis (양이온약제내성을 유도하는 Bacillus subtilis의 Drug Efflux Pump)

  • Yong Joon Chung
    • Microbiology and Biotechnology Letters
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    • v.31 no.3
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    • pp.230-234
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    • 2003
  • The Bacillus subtilis YvaE protein, the small multidrug resistance (SMR) family (TC #2.A. 7.1), is shown to catalyze efflux of multiple cationic drugs including many disinfectants, when it was cloned and expressed in Escherichia coli. When the yvaD gene was coexpressed with yvaE gene, the yvaD protein, encoded within a single operon with the yvaE gene, is shown to counteract the action ofYvaE. By ethidium efflux analysis, the cells harvoring a vector with yvaE gene showed a rapid ethidium efflux, compared with the control cells. These results clearly suggest that YvaE mediates drug export from the cell cytoplasm.

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.

Virulence gene profiles and antimicrobial susceptibility of Salmonella Brancaster from chicken

  • Evie Khoo ;Roseliza Roslee ;Zunita Zakaria;Nur Indah Ahmad
    • Journal of Veterinary Science
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    • v.24 no.6
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    • pp.82.1-82.12
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    • 2023
  • Background: The current conventional serotyping based on antigen-antisera agglutination could not provide a better understanding of the potential pathogenicity of Salmonella enterica subsp. enterica serovar Brancaster. Surveillance data from Malaysian poultry farms indicated an increase in its presence over the years. Objective: This study aims to investigate the virulence determinants and antimicrobial resistance in S. Brancaster isolated from chickens in Malaysia. Methods: One hundred strains of archived S. Brancaster isolated from chicken cloacal swabs and raw chicken meat from 2017 to 2022 were studied. Two sets of multiplex polymerase chain reaction (PCR) were conducted to identify eight virulence genes associated with pathogenicity in Salmonella (invasion protein gene [invA], Salmonella invasion protein gene [sipB], Salmonella-induced filament gene [sifA], cytolethal-distending toxin B gene [cdtB], Salmonella iron transporter gene [sitC], Salmonella pathogenicity islands gene [spiA], Salmonella plasmid virulence gene [spvB], and inositol phosphate phosphatase gene [sopB]). Antimicrobial susceptibility assessment was conducted by disc diffusion method on nine selected antibiotics for the S. Brancaster isolates. S. Brancaster, with the phenotypic ACSSuT-resistance pattern (ampicillin, chloramphenicol, streptomycin, sulphonamides, and tetracycline), was subjected to PCR to detect the corresponding resistance gene(s). Results: Virulence genes detected in S. Brancaster in this study were invA, sitC, spiA, sipB, sopB, sifA, cdtB, and spvB. A total of 36 antibiogram patterns of S. Brancaster with a high level of multidrug resistance were observed, with ampicillin exhibiting the highest resistance. Over a third of the isolates displayed ACSSuT-resistance, and seven resistance genes (β-lactamase temoneira [blaTEM], florfenicol/chloramphenicol resistance gene [floR], streptomycin resistance gene [strA], aminoglycoside nucleotidyltransferase gene [ant(3")-Ia], sulfonamides resistance gene [sul-1, sul-2], and tetracycline resistance gene [tetA]) were detected. Conclusion: Multidrug-resistant S. Brancaster from chickens harbored an array of virulence-associated genes similar to other clinically significant and invasive non-typhoidal Salmonella serovars, placing it as another significant foodborne zoonosis.

Antimicrobial Resistance Patterns of Salmonella Enteritidis and Salmonella Typhimurium Isolated from Diarrhea Patients in Incheon between 2008 and 2012 (최근 5년간 인천지역 설사환자에서 분리한 Salmonella Enteritidis와 Salmonella Typhimurium의 항생제 내성 양상)

  • Jang, Jae-Seon;Lee, Jea-Man;Gong, Young-Woo;Lee, Mi-Yeon
    • Journal of Environmental Health Sciences
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    • v.39 no.3
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    • pp.239-246
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    • 2013
  • Objectives: Antimicrobial resistance and multidrug resistance patterns have been studied with a total of 189 samples of Salmonella Enteritidis and Salmonella Typhimurium isolated from diarrhea patients in Incheon from 2008 to 2012. Methods: Antimicrobial resistance tests were determined by Disc Diffusion method. Results: The serological distribution of Salmonella spp. showed 108 strains (30.1%) of S. Enteritidis, 81 strains (22.6%) of S. Typhimirium, eight strains (8.0%) of S. Typhi, 11 strains ( 3.1% ) of S. Paratyphi, and the 151 other strains (42.1%). The separation rate of Salmonella spp. by year showed 14.5% (52 strains) in 2008, 13.6% (49 strains) in 2009, 22.8% (82 strains) in 2010, 25.3% (91 strains) in 2011, and 23.7% (85 strains) in 2012. Additionally, the separation rate of S. Enteritidis and S. Typhimirium in 2010 was the highest. The Salmonella spp. isolated from diarrhea patients showed significant differences according to age (p<0.05), gender (p<0.01) and medical institution (p<0.05). The highest resistance was found to the following antimicrobial agents: imipenem 77 strains, ampicillin 47 strains, ciprofloxacin 34 strains, nalidixic acid 29 strains for S. Enteritidis, and ampicillin 45 strains, nalidixic acid 45 strains for S. Typhimurium. Separated S. Enteritidis and S. Typhimurium resistance to the antibiotics by the year showed significant differences (p<0.05). The patterns of multidrug resistance rates were 43.1% (47 strains) for one drug, 8.3% (9 strains) for two drugs, 11.0% (12 strains) for three drugs, 15.62% (17 strains) for four drugs, and 13.7% (15 strains) for five or more drugs for S. Enteritidis. For S. Tyhpimurium, the rates were 15.0% (12 strains) for one drug, 10.0% (8 strains) for two drugs, 6.3% (five strains) for three drugs, 18.7% (15 strains) for four drugs, and 23.8% (19 strains) for five or more drugs. Conclusion: The antibiotic resistance issue is directly related to people's lives. Thus, the usage of antibiotics should be reduced in order to manage antibiotic resistance.

Expression of the Multidrug Resistance Gene and its Product in Osteosarcomas of the Bone - Immunohistochemistry and In Situ Hybridization -

  • Park, Hye-Rim;Park, Yong-Koo
    • The Journal of the Korean bone and joint tumor society
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    • v.3 no.1
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    • pp.9-17
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    • 1997
  • Resistance to combination chemotherapy remains challenge in the treatment of osteosarcoma. One of the mechanisms of multiple drug resistance is an increased expression of the multidrug resistance gene(mdr1). Expression of the P-glycoprotein(mdr-1 gene product) was studied immunohistochemically and the mdr-1 gene by in situ hybridization in 33 osteosarcomas relating to various prognostic factors. Thirty cases out of 33 osteosarcomas(90.9%) showed positive cytoplasmic reactions with P-glycoprotein and nineteen instances(57.6%) were strong positive(2+). The older(>20 years) and female patients revealed more intense immunohistochemical reactions rather than those of the younger and male patients. Osteoblastic and chondroblastic osteosarcomas revealed more strong immunohistochemical reactions compared to fibroblastic types. There were no significant staining differences between the type of bony involvement, Broder's grade and the presence of necrosis. On follow-up, the mean survival rate was decreased in the strong positive group, however, this was not statistically significant. In situ hybridization for mdr-1 gene revealed positive signals in 22 cases out of 29 osteosarcomas(75.9%). Chemotherapy was done in 15 cases out of 28 patients(53.6%). The results of immunohistochemistry and in situ hybridization were not correlated with the protocols for chemotherapy. However, this result should be confirmed by a larger scale study about mdr1 mRNA expression.

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Pediatric tuberculosis and drug resistance (소아 결핵과 약제 내성)

  • Kim, Yae-Jean
    • Clinical and Experimental Pediatrics
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    • v.52 no.5
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    • pp.529-537
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    • 2009
  • Drug-resistant tuberculosis in children has important implications for both the patients and tuberculosis control programs. In Korea, among all new patients, the isoniazid resistance rate was 9.9% and multidrug-resistant tuberculosis rate was 2.7% in 2004 (in patients aged 10-19 yr, the multidrug-resistant tuberculosis rate reached 2.1%). Tuberculosis in pediatric patients is difficult to diagnose because many children have nonspecific clinical signs and the detection rates of acid-fast bacilli smears and cultures are low. Therefore, every effort should be made to identify adult sources and obtain information on drug susceptibility because symptomatic adult patients have a higher chance of culture positivity and drug-susceptibility patterns are the same in most adult-child pair patients. Korean children are at significant risk of drug-resistant tuberculosis. As the isoniazid resistance rate is greater than 4% among the new cases in Korea, a four-drug regimen should be considered for initial treatment of children with active tuberculosis, unless drug-susceptibility test results are available. Treatment of drug-resistant tuberculosis in children is challenging and there are only few available data. Tuberculosis control programs should be continuous with specific focus on pediatric populations because they can serve as reservoirs for future active cases. Further studies are needed regarding treatment of drug-resistant tuberculosis in children.

Serovars distribution and antimicrobial resistance patterns of Salmonella spp. isolated from the swine farms and slaughter houses

  • Jung, Hokyoung;Lee, Sungseok;Kim, Chiyoung;Sunwoo, Sunyoung;Lyoo, Young S.
    • Korean Journal of Veterinary Research
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    • v.51 no.2
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    • pp.123-128
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    • 2011
  • Salmonella spp. is an important pathogen to both public and swine industry. The aim of this study was to investigate the distribution of Salmonella serovar and antibiotics susceptibility of the isolates from Korean swine producing systems. A total of 63 (5.28%) Salmonella spp. was isolated from 1,194 samples (977 fecal materials and 67 organ samples). The predominant Salmonella (S.) enterica serotype and serovar was group B (69.8%) and S. Typhimurium (47.6%), S. Derby (20.6%) and S. Heidelberg (1.6%). But S. Cholerasuis which is characterized host specific by septicemia and enteritis to pigs was not isolated. Antimicrobial susceptibility of the isolates varies as follows: Norfloxacine (75%), Ciprofloxacin (67.5%), Amikacin (60%), Colistin (60%), Enrofloxacin (55%). All of isolates were resistant to Erythromycin, Penicillin, Tetracycline and Lincomycin. The results of this study provided useful information regarding antimicrobial susceptibility and resistance patterns to treat salmonellosis and to prevent emergence of multidrug resistance Salmonella.

Isolation and Characterization of Halophilic Kocuria salsicia Strains from Cheese Brine

  • Youn, Hye-Young;Seo, Kun-Ho
    • Food Science of Animal Resources
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    • v.42 no.2
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    • pp.252-265
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    • 2022
  • Kocuria salsicia can survive in extreme environments and cause infections, including catheter-related bacteremia, in humans. Here, we investigated and evaluated the characteristics of nine K. salsicia strains (KS1-KS9) isolated from cheese brine from a farmstead cheese-manufacturing plant in Korea from June to December, 2020. Staphylococcus aureus American Type Culture Collection (ATCC) 29213 was used as a positive control in the growth curve analysis and biofilm-formation assays. All K. salsicia isolates showed growth at 15% salt concentration and temperatures of 15℃, 25℃, 30℃, 37℃, and 42℃. KS6 and KS8 showed growth at 5℃, suggesting that they are potential psychrotrophs. In the biofilm-formation analysis via crystal violet staining, KS6 exhibited the highest biofilm-forming ability at various temperatures and media [phosphate buffered saline, nutrient broth (NB), and NB containing 15% sodium chloride]. At 25℃ and 30℃, KS3, KS6, and KS8 showed higher biofilm-forming ability than S. aureus ATCC 29213. The antimicrobial resistance of the isolates was evaluated using the VITEK® 2 system; most isolates were resistant to marbofloxacin and nitrofurantoin (both 9/9, 100%), followed by enrofloxacin (7/9, 77.8%). Five of the nine isolates (5/9, 55.6%) showed multidrug resistance. Our study reports the abilities of K. salsicia to grow in the presence of high salt concentrations and at relatively low temperatures, along with its multidrug resistance and tendency to form biofilms.

Antimicrobial resistance and frequency of BlaTEM in Escherichia coli isolated from non-diarrheic and diarrheic piglets (정상돈과 설사돈에서 분리한 대장균의 항균제 내성 및 BlaTEM 분포 조사)

  • Byun, Jae Won;Kim, Ha Young;Jung, Byeong Yeal;Bae, You Chan;Lee, Wan Kyu
    • Korean Journal of Veterinary Research
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    • v.52 no.2
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    • pp.133-139
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    • 2012
  • Antimicrobial resistance is one of the most concerns in pig industry. Escherichia (E.) coli have been used for the indicator to monitor the antimicrobial resistance. In this study, 321 E. coli from diarrheic and non-diarrheic piglets were tested for antimicrobial resistance and frequency of $Bla_{TEM}$. In non-diarrheic piglets, they were resistant to oxytetracycline (93%), streptomycin (92%) and sulfadiazine (90%) but susceptible to ceftiofur (99%), colistin (97%), and enrofloxacin (82%). The isolates from diarrheic piglets were resistant to enrofloxacin (72.9%), ceftiofur (17.6%), and colistin (11.3%), whereas the resistance was 1%, 18% and 3% in case of non-diarrheic piglets, respectively. The resistance for amoxicillin/clavulanic acid (54.1%) and ceftiofur (22%) was high in isolates from post-weaning piglets. The resistance for colistin was 15.2% in nursery piglets. Seventy-three percent of isolates from diarrheic piglets showed high multidrug resistance profile (more than 13 antimicrobials) compared to those from non-diarrheic pigs in which 71% of isolates showed moderate multidrug resistance profile (7 to 12 antimicrobials). The frequency of $Bla_{TEM}$ in E. coli from non-diarrheic and diarrheic piglets was 57% and 69%, respectively. The results might provide the basic knowledge to establish the strategies for treatment and reduce antibiotic resistance of E. coli in piglets.