• Title/Summary/Keyword: Multidrug-Resistant

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Src Family Kinase Inhibitor PP2 Induces LC3 Conversion in a Manner That is Uncoupled from Autophagy and Increases Apoptosis in Multidrug-Resistant Cells

  • Kim, Yun-Ki;Ahn, Jun-Ho;Lee, Mi-Chael
    • Biomolecules & Therapeutics
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    • v.20 no.4
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    • pp.393-398
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    • 2012
  • Recently, we reported that defective autophagy may contribute to the inhibition of the growth in response to PP2 (4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine), a selective SFK inhibitor, in multidrug-resistant v-Ha-ras-transformed NIH 3T3 cells (Ras-NIH 3T3/Mdr). In this study, we demonstrated that PP2 induces LC3 conversion via a mechanism that is uncoupled from autophagy and increases apoptosis in Ras-NIH 3T3/Mdr cells. PP2 preferentially induced autophagy in Ras-NIH 3T3 cells rather than in Ras-NIH 3T3/Mdr cells as determined by LC3-I to LC3-II conversion and GFP-LC3 fluorescence microscopy. Beclin 1 knockdown experiments showed that, regardless of drug resistance, PP2 induces autophagy via a Beclin 1-dependent mechanism. PP2 induced a conformational change in Beclin 1, resulting in the enhancement of the pro-autophagic activity of Beclin 1, in Ras-NIH 3T3 cells. Further, PI3K inhibition induced by wortmannin caused a significant increase in apoptosis in Ras-NIH 3T3 cells, as demonstrated by flow cytometric analysis of Annexin V staining, implying that autophagy inhibition through PI3K increases apoptosis in response to PP2 in Ras-NIH 3T3 cells. However, despite the fact that wortmannin abrogates PP2-induced GFP-LC3 punctae formation, some LC3 conversion remains in Ras-NIH 3T3/Mdr cells, suggesting that LC3 conversion may occur in an autophagy-independent manner. Taken together, these results suggest that PP2 induces LC3 conversion independent of PI3K, concomitant with the uncoupling of LC3 conversion from autophagy, in multidrug-resistant cells.

The Factors Influencing Compliance of Multidrug-resistant Organism Infection Control in Intensive Care Units Nurses (중환자실 간호사의 다제내성균 감염관리 수행에 영향을 미치는 요인)

  • Kim, Ji Hee;Lim, Kyung Hee
    • Korean Journal of Adult Nursing
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    • v.27 no.3
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    • pp.325-336
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    • 2015
  • Purpose: This study was conducted to identify factors influencing compliance of multidrug-resistant organism infection control in intensive care units (ICU) nurses. Methods: Data were collected from 254 ICU nurses who were working at 6 general and advanced general hospitals in D city and G Province. Results: 77.2% and 84.4% of the subjects correctly answered to questions about Methicillin-Resistant Staphylococcus Aureus (MRSA) and Vancomycin-Resistant Enterococcus (VRE), respectively. The scores of MRSA infection control compliance and VRE infection control compliance were 3.41 and 3.43, respectively. The factors influencing MRSA infection control compliance were empowerment, environmental safety recognition, and education satisfaction, which explained 30% of MRSA infection control compliance. The factors significantly related to VRE infection control compliance were empowerment, hospital types, environmental safety recognition, number of education sessions, and neonatal ICU, which explained 37% of VRE infection control compliance. Conclusion: It is necessary to develop efficient educational programs for infection control including educational contents to improve empowerment and environmental safety recognition of nurses. Furthermore, administrative support for those infection control programs is also necessary.

Susceptibility of β-Lactam Antibiotics and Genetic Mutation of Drug-Resistant Mycobacterium tuberculosis Isolates in Korea

  • Park, Sanghee;Jung, Jihee;Kim, Jiyeon;Han, Sang Bong;Ryoo, Sungweon
    • Tuberculosis and Respiratory Diseases
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    • v.85 no.3
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    • pp.256-263
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    • 2022
  • Background: Mycobacterium tuberculosis (Mtb) is resistant to the β-lactam antibiotics due to a non-classical transpeptidase in the cell wall with β-lactamase activity. A recent study showed that meropenem combined with clavulanate, a β-lactamase inhibitor, was effective in multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB). However, in Korea, clavulanate can only be used as drugs containing amoxicillin. In this study, we investigated the susceptibility and genetic mutations of drug-resistant Mtb isolates to amoxicillin-clavulanate and meropenem-clavulanate to improve the diagnosis and treatment of drug-resistant TB patients. Methods: The minimum inhibitory concentration (MIC) of amoxicillin-clavulanate and meropenem-clavulanate was examined by resazurin microtiter assay. We used 82 MDR and 40 XDR strains isolated in Korea and two reference laboratory strains. Mutations of drug targets blaC, blaI, ldtA, ldtB, dacB2, and crfA were analyzed by polymerase chain reaction and DNA sequencing. Results: The MIC90 values of amoxicillin/clavulanate and meropenem/clavulanate in drug-resistant Mtb isolates were 64/2.5 and 16/2.5 mg/L, respectively. Gene mutations related to amoxicillin/clavulanate and meropenem/clavulanate resistance could not be identified, but T448G mutation was found in the blaC gene related to β-lactam antibiotics' high susceptibility. Conclusion: Our results provide clinical consideration of β-lactams in treating drug-resistant TB and potential molecular markers of amoxicillin-clavulanate and meropenem-clavulanate susceptibility.

Multidrug-Resistant Tuberculosis Presenting as Miliary Tuberculosis without Immune Suppression: A Case Diagnosed Rapidly with the Genotypic Line Probe Assay Method

  • Ko, Yousang;Lee, Ho Young;Lee, Young Seok;Song, Junwhi;Kim, Mi-Yeong;Lee, Hyun-Kyung;Shin, Jeong Hwan;Choi, Seok Jin;Lee, Young-Min
    • Tuberculosis and Respiratory Diseases
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    • v.76 no.5
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    • pp.245-248
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    • 2014
  • Miliary tuberculosis (TB) is a rare extrapulmonary form of TB, and there have been only two reports of miliary TB associated with infection with multidrug-resistant (MDR)-TB pathogen in an immunocompetent host. A 32-year-old woman was referred to our hospital because of abnormal findings on chest X-ray. The patient was diagnosed with MDR-TB by a line probe assay and was administered proper antituberculous drugs. After eight weeks, a solid-media drug sensitivity test revealed that the pathogen was resistant to ethambutol and streptomycin in addition to isoniazid and rifampicin. The patient was then treated with effective antituberculous drugs without delay after diagnosis of MDR-TB. To the best of our knowledge, this is the first case of miliary TB caused by MDR-TB pathogen in Korea.

Characterization of Drug-Resistant Salmonella enterica Serotype Typhimurium by Antibiograms, Plasmids, Integrons, Resistance Genes, and PFGE

  • Benacer, Douadi;Thong, Kwai Lin;Watanabe, Haruo;Puthucheary, Savithri Devi
    • Journal of Microbiology and Biotechnology
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    • v.20 no.6
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    • pp.1042-1052
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    • 2010
  • Forty-seven Salmonella Typhimurium (33 zoonotic, 14 clinical) strains were tested for antimicrobial resistance using the standard disk diffusion method. The presence of relevant resistance genes and class 1 integrons were investigated by using PCR. Pulsed-field gel electrophoresis (PFGE) and plasmid profiling were carried out to determine the genomic diversity of Salmonella Typhimurium. Approximately 57.4% of the S. Typhimurium strains were multidrug resistant (MDR) and showed high resistance rates to tetracycline (70.2%), sulfonamides (57.4%), streptomycin (53.1%), ampicillin (29.7%), nalidixic acid (27.6%), kanamycin (23.4%), chloramphenicol (21.2%), and trimethoprim (19.1%). Resistance towards cephalosporins was noted for cephalothin (27.6%), cephradine (21.2%), amoxicillin clavulanic acid (17.0%), and cephalexin (17.0%). Resistance genes, $bla_{TEM}$, strA, aadA, sul1, sul2, tetA, tetB, and tetC, were detected among the drug-resistant strains. Thirtythree strains (70.2%) carried class 1 integrons, which were grouped in 9 different profiles. DNA sequencing identified sat, aadA, pse-1, and dfrA genes in variable regions on class 1 integrons. Thirty-five strains (74.4%) were subtyped to 22 different plasmid profiles, each with 1-6 plasmids (2.0 to 95 kb). PFGE subtyped the 47 strains into 39 profiles. In conclusion, high rates of multidrug resistance were found among the Malaysian Salmonella Typhimurium strains. The emergence of multidrug-resistant Salmonella Typhimurium to cephalosporin antibiotics was also observed. The strains were very diverse and no persistent clone was observed. The emergence of MDR Salmonella Typhimurium is a worldwide problem, and this report provides information for the better understanding of the prevalence and epidemiology of MDR S. Typhimurium in Malaysia.

Development and Application a Multidrug Resistant Organisms Infection Control Simulation Program for Small and Medium-sized Hospital (중소병원 대상 다제내성균 감염관리 시뮬레이션 프로그램 개발 및 적용)

  • Lee, Mi Hyang;Kim, Jae Yeun
    • Journal of Digital Convergence
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    • v.19 no.4
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    • pp.159-166
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    • 2021
  • This study was an attempt to develop a multidrug resistant organisms infection control simulation program for nurses at small and medium sized hospitals and to evaluate the effectiveness of said simulation program. This is a single-group, pre-post experimental design study conducted on 33 nurses working at small and medium sized hospitals. Data obtained were analyzed using the IBM SPSS 21.0 program, along with the use of descriptive statistics and paired t-test. Regarding the results of the study, multdrug resistant organisms infecion control knowledge(t=-10.764, p<.001)and performance levels(t=-4.215, p<.001) of the nurses displayed statistically significant increases following application of the simulation program. There is a need for the development of more diversified simulation programs in the future since the improvement in the infection control knowledge and performance levels of nurses is important to block the spread of multidrug resistant organisms and prevent infection outbreak thereof with medical institutions.

Restoring Ampicillin Sensitivity in Multidrug-Resistant Escherichia coli Following Treatment in Combination with Coffee Pulp Extracts

  • Anchalee Rawangkan;Atchariya Yosboonruang;Anong Kiddee;Achiraya Siriphap;Grissana Pook-In;Ratsada Praphasawat;Surasak Saokaew;Acharaporn Duangjai
    • Journal of Microbiology and Biotechnology
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    • v.33 no.9
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    • pp.1179-1188
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    • 2023
  • Escherichia coli, particularly multidrug-resistant (MDR) strains, is a serious cause of healthcare-associated infections. Development of novel antimicrobial agents or restoration of drug efficiency is required to treat MDR bacteria, and the use of natural products to solve this problem is promising. We investigated the antimicrobial activity of dried green coffee (DGC) beans, coffee pulp (CP), and arabica leaf (AL) crude extracts against 28 isolated MDR E. coli strains and restoration of ampicillin (AMP) efficiency with a combination test. DGC, CP, and AL extracts were effective against all 28 strains, with a minimum inhibitory concentration (MIC) of 12.5-50 mg/ml and minimum bactericidal concentration of 25-100 mg/ml. The CP-AMP combination was more effective than CP or AMP alone, with a fractional inhibitory concentration index value of 0.01. In the combination, the MIC of CP was 0.2 mg/ml (compared to 25 mg/ml of CP alone) and that of AMP was 0.1 mg/ml (compared to 50 mg/ml of AMP alone), or a 125-fold and 500-fold reduction, respectively, against 13-drug resistant MDR E. coli strains. Time-kill kinetics showed that the bactericidal effect of the CP-AMP combination occurred within 3 h through disruption of membrane permeability and biofilm eradication, as verified by scanning electron microscopy. This is the first report indicating that CP-AMP combination therapy could be employed to treat MDR E. coli by repurposing AMP.