• Title/Summary/Keyword: Multidrug-resistant

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Isolation and Properties of Cytotoxic Polyene Antibiotics Produced by Myxococcus stipitatus JW117. (Myxococcus stipitatus JW117이 생산하는 Polyene계 세포독성 물질의 분리 및 특성)

  • 안종웅;최상운;권호정
    • Microbiology and Biotechnology Letters
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    • v.30 no.2
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    • pp.157-161
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    • 2002
  • Drug resistance is one of the most significant impediments to successful chemotherapy of cancer. Multidrug-resistance (MDR) is characterized by decreased cellular sensitivity to anticancer agents due to the overexpression of P-glycoprotein. By employing adriamycin-resistance CL02 cancer cells, we undertook the screening for agents which were effective to multidrug-resistant cancer cells. As a result, a myxobacterial strain JW117 was selected for study since the solvent extract of cell mass of the strain was found to exhibit significant activity against the CL02 cancer cells. Cytotoxicity-guided chromatographic fractionation led to the isolation of phenalamides $A_2$ and $A_3$. The producing organism was identified as Myxococcus stipitatus by taxonomic comparison with type strains of Myxococcus sp. as well as its morphological and physiological characteristics. Phenalamides$ A_1$,$ A_2$ and $A_3$ were as active against drug-resistant cancer cells CL02 and CP70 as against the corresponding sensitive cells with $IC_{50}$ values ranging from 0.23~0.57 $\mu\textrm{g}$/ml.

Effects of C-Terminal Residues of 12-Mer Peptides on Antibacterial Efficacy and Mechanism

  • Son, Kkabi;Kim, Jieun;Jang, Mihee;Chauhan, Anil Kumar;Kim, Yangmee
    • Journal of Microbiology and Biotechnology
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    • v.29 no.11
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    • pp.1707-1716
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    • 2019
  • The development of new antimicrobial agents is essential for the effective treatment of diseases such as sepsis. We previously developed a new short peptide, Pap12-6, using the 12 N-terminal residues of papiliocin, which showed potent and effective antimicrobial activity against multidrug-resistant Gram-negative bacteria. Here, we investigated the antimicrobial mechanism of Pap12-6 and a newly designed peptide, Pap12-7, in which the 12th Trp residue of Pap12-6 was replaced with Val to develop a potent peptide with high bacterial selectivity and a different antibacterial mechanism. Both peptides showed high antimicrobial activity against Gram-negative bacteria, including multidrug-resistant Gram-negative bacteria. In addition, the two peptides showed similar anti-inflammatory activity against lipopolysaccharide-stimulated RAW 264.7 cells, but Pap12-7 showed very low toxicities against sheep red blood cells and mammalian cells compared to that showed by Pap12-6. A calcein dye leakage assay, membrane depolarization, and confocal microscopy observations revealed that the two peptides with one single amino acid change have different mechanisms of antibacterial action: Pap12-6 directly targets the bacterial cell membrane, whereas Pap12-7 appears to penetrate the bacterial cell membrane and exert its activities in the cell. The therapeutic efficacy of Pap12-7 was further examined in a mouse model of sepsis, which increased the survival rate of septic mice. For the first time, we showed that both peptides showed anti-septic activity by reducing the infiltration of neutrophils and the production of inflammatory factors. Overall, these results indicate Pap12-7 as a novel non-toxic peptide with potent antibacterial and anti-septic activities via penetrating the cell membrane.

Hospital Nurses' Knowledge and Compliance on Multidrug-resistant Organism Infection Control Guideline (일 대학병원 간호사의 다약제 내성균 감염관리지침에 대한 지식과 수행정도)

  • Kang, Ji-Yeon;Cho, Jin-Wan;Kim, Yu-Jung;Kim, Dong-Hee;Lee, Ji-Young;Park, Hey-Kyung;Jung, Sung-Hee;Lee, Eun-Nam
    • Journal of Korean Academy of Nursing
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    • v.39 no.2
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    • pp.186-197
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    • 2009
  • Purpose: This study was done to investigate nurses' knowledge of, and compliance with the multidrug-resistant organism (MDRO) infection control guidelines. Methods: A survey questionnaire was developed based on the institutional and national guidelines and was administered to a convenience sample of 306 nurses in a university hospital. Results: The mean score for knowledge was 33.87 (percentage of correct answers: 82.61%). The percentages of correct answers for basic concepts, route of transmission, hand washing/protective devices and environment management were 74.27%, 94.29%, 92.90% and 75.54% respectively. The mean compliance score was 4.15 (range: 1-5). The compliance scores for education, communication, contact precaution, disinfection, surveillance culture, and hand washing were 3.29, 4.05, 4.20, 4.50, 4.40 and 4.48 respectively. Nurses indicated "lack of time (30.06%)", "lack of means (10.78%)" and "lack of knowledge (9.48%)" as reasons for noncompliance. Conclusion: While most educational programs have focused on hand washing or use of protective devices to prevent transmission of MDRO in acute care settings, hospital nurses' knowledge of the basic concepts of MDRO and environmental management has remained insufficient. Nurses are relatively non-compliant to the guidelines in the areas of education (staff, patient, family) and communication. Comprehensive educational programs are needed to decrease hospital infection rates and to improve the health of patients.

Decreased Interaction of Raf-1 with Its Negative Regulator Spry2 as a Mechanism for Acquired Drug Resistance

  • Ahn, Jun-Ho;Kim, Yun-Ki;Lee, Michael
    • Biomolecules & Therapeutics
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    • v.19 no.2
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    • pp.174-180
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    • 2011
  • Experiments were carried out to determine the role of Raf-1 kinase in the development of drug resistance to paclitaxel in v-H-ras transformed NIH 3T3 fibroblasts (Ras-NIH 3T3). We established a multidrug-resistant cell line (Ras-NIH 3T3/Mdr) from Ras-NIH 3T3 cells by stepwise increases in paclitaxel. Drug sensitivity assays indicated that the $IC_{50}$ value for drug-resistant Ras-NIH 3T3/Mdr cells was more than 1 ${\mu}M$ paclitaxel, 10- or more-fold higher than for the parental Ras-NIH 3T3 cells. Western blot and RT-PCR analysis showed that the drug efflux pump a P-glycoprotein were highly expressed in Ras-NIH 3T3/Mdr cells, while not being detectable in Ras-NIH 3T3 cells. Additionally, verapamil, which appears to inhibit drug efflux by acting as a substrate for P-glycoprotein, completely reversed resistance to paclitaxel in Ras-NIH 3T3/Mdr cell line, indicating that resistance to paclitaxel is associated with overexpression of the multidrug resistance gene. Interestingly, Ras-NIH 3T3/Mdr cells have higher basal Raf-1 activity compared to Ras-NIH 3T3 cells. Unexpectedly, however, the colocalization of Raf-1 and its negative regulator Spry2 was less observed in cytoplasm of Ras-NIH 3T3/Mdr cells due to translocation of Spry2 around the nucleus in the perinuclear zone, implying that Raf-1 may be released from negative feedback inhibition by interacting with Spry2. We also showed that shRNA-mediated knockdown of Raf-1 caused a moderate increase in cell susceptibility to paclitaxel. Thus, the results presented here suggest that a Raf-1-dependent pathway plays an important role in the development of acquired drug-resistance.

Screening and Optimal Culture Conditions of Antibiotic-Producing Actinomycetes B-51 for Multidrug Resistant Acinetobacter baumannii (다제내성 Acinetobacter baumannii에 유효한 방선균 B-51의 탐색 및 이 균주가 생산하는 항생물질 발효 최적 배양 조건)

  • Rhee, Moon-Soo;Kim, Gwan-Pil;Bang, Byung-Ho
    • The Korean Journal of Food And Nutrition
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    • v.23 no.1
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    • pp.63-69
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    • 2010
  • With the increase of the use of antibiotics and invasive procedures, infections caused by multidrug-resistant Acinetobacter baumannii(MRAB) are increasing. We screened the antibiotic producing strain B-51 for antibacterial activity against MRAB from the soils and studied the effects of culture medium on the antibiotic production of B-51. The medium conditions for maximum antibiotic productivity of B-51 was 2% glycerol, 0.5% soybean meal, 0.01% $CaCl_2$, 0.01% $MgSO_4{\cdot}7H_2O$ and 0.01% $KH_2PO_4$ at an initial pH of 6.0, at $30^{\circ}C$ for 76 h.

Nursing Students' Knowledge and Compliance with Multidrug-resistant Organism Infection Control Guidelines (다약제 내성균 감염관리지침에 대한 간호학생의 지식과 수행정도)

  • Kang, Ji-Yeon;Lee, Young-Ock;Yun, Seon-Young;Kang, Jeong-Hee;Park, So-Hee
    • Journal of Korean Critical Care Nursing
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    • v.3 no.1
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    • pp.67-78
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    • 2010
  • Purpose: This study was done to investigate knowledge of and compliance with the multidrug-resistant organism (MDRO) infection control guidelines among student nurses on clinical practicum, Methods: survey questionnaire on MORO infection control was administered to a convenience sample of 259 nursing students from 3 different nursing schools Results: The mean knowledge score was 28.01/39 (71.82%). The percentages of correct answers for basic concepts, route of transmission, hand washing/ protective devices and environment management, were 55.40, 81.14, 84.94 and 69.17 respectively. The mean compliance score was 3.83/5. The compliance scores for education, communication, contact precaution, environment management, and hand washing were 3.06, 3.33, 3.86, 4.50, 3.92 and 4.29 respectively. 96.9% of subjects knew that they should wash hands after touching MORO patient while only 22.8% of subjects knew how to collect samples for VRE surveillance culture, The highest compliant item was hand washing after touching MORO patient. The Lo-west compliant item was referring to infection control manual. Conclusion: Comprehensive MDRO infection control education programs for nursing students should be developed to decrease MORO infection.

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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.

Effects of Daily Chlorhexidine Bathing on the Acquisition of Multidrug-resistant Organisms and Healthcare-associated Infection in an Intensive Care Unit (중환자실에서 클로르헥시딘 목욕이 다제내성균 획득과 의료관련감염에 미치는 효과)

  • Lee, Ju Yeon;Jeong, Jae Sim;Kim, Min Young;Park, Sil Hwa;Hwang, Young Hui
    • Journal of Korean Biological Nursing Science
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    • v.20 no.1
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    • pp.38-46
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    • 2018
  • Purpose: The aim of this study was to verify the effects of daily 2% chlorhexidine gluconate (CHG) bathing on the acquisition of multidrug-resistant organisms (MDRO) and healthcare-associated infection (HAI) in a medical intensive care unit (MICU). Methods: The study was a randomized controlled group posttest only design, involving 91 patients in MICU at a tertiary hospital (47 patients in the experimental group and 44 patients in the control group). The 2% CHG bathing was performed daily according to bathing protocol to the patients in the experimental group, and traditional bath was performed every three days to those in the control group. Fisher's exact test and x2 test were used to analyze the data. Results: MDRO were found in 6 patients of the experimental group and in 15 patients of the control group. The difference was statistically significant (p= .016). HAI occurred in 2 patients of the experimental group and in 7 patients of the control group. The difference was not statistically significant (p= .084). Conclusion: The results confirmed that daily bathing with CHG was effective in reducing the incidence of MDRO acquisition. Therefore, it is expected that daily bathing with CHG will be used as an effective nursing intervention to reduce the incidence of MDRO acquisition.

Intensive Care Unit Relocation and Its Effect on Multidrug-Resistant Respiratory Microorganisms

  • Kim, Hyung-Jun;Jeong, EuiSeok;Choe, Pyoeng Gyun;Lee, Sang-Min;Lee, Jinwoo
    • Acute and Critical Care
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    • v.33 no.4
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    • pp.238-245
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    • 2018
  • Background: Infection by multidrug-resistant (MDR) pathogens leads to poor patient outcomes in intensive care units (ICUs). Contact precautions are necessary to reduce the transmission of MDR pathogens. However, the importance of the surrounding environment is not well known. We studied the effects of ICU relocation on MDR respiratory pathogen detection rates and patient outcomes. Methods: Patients admitted to the ICU before and after the relocation were retrospectively analyzed. Baseline patient characteristics, types of respiratory pathogens detected, antibiotics used, and patient outcomes were measured. Results: A total of 463 adult patients admitted to the ICU, 4 months before and after the relocation, were included. Of them, 234 were admitted to the ICU before the relocation and 229 afterward. Baseline characteristics, including age, sex, and underlying comorbidities, did not differ between the two groups. After the relocation, the incidence rate of MDR respiratory pathogen detection decreased from 90.0 to 68.8 cases per 1,000 patient-days, but that difference was statistically insignificant. The use of colistin was significantly reduced from 53.5 days (95% confidence interval [CI], 20.3 to 86.7 days) to 18.7 days (95% CI, 5.6 to 31.7 days). Furthermore, the duration of hospital stay was significantly reduced from a median of 29 days (interquartile range [IQR], 14 to 50 days) to 21 days (IQR, 11 to 39 days). Conclusions: Incidence rates of MDR respiratory pathogen detection were not significantly different before and after ICU relocation. However, ICU relocation could be helpful in reducing the use of antibiotics against MDR pathogens and improving patient outcomes.

Effect of 2% Chlorhexidine Bathing on the Incidence of Hospital-Acquired Infection and Multidrug-Resistant Organisms in Adult Intensive Care Unit Patients: Systematic Review and Meta-Analysis (2% 클로르헥시딘 침상목욕이 중환자실의 의료관련감염과 다제내성균 감염 발생률에 미치는 효과에 대한 체계적 문헌 고찰 및 메타분석)

  • Seo, Jisu;Song, Rhayun
    • Journal of Korean Academy of Nursing
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    • v.51 no.4
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    • pp.414-429
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    • 2021
  • Purpose: This systematic review and meta-analysis analyzed the effects of 2% chlorhexidine bathing on the incidence of hospital-acquired infection (HAI) and multidrug-resistant organisms (MDRO) in adult intensive care units. Methods: PubMed, CINAHL, Cochrane library, and RISS database were systematically searched, and 12 randomized studies were included in the analysis. Comprehensive Meta-Analysis version 3.0 was used to calculate the effect size using the odds ratio (OR) and a 95% confidence interval (CI). Subgroup analysis was performed according to the specific infection and intervention types. Results: In general, 2% chlorhexidine bathing has a significant effect on the incidence of HAI (OR, 0.59; 95% CI, 0.40~0.86) and MDRO (OR, 0.52; 95% CI, 0.34~0.79). Subgroup analyses show 2% chlorhexidine bathing is effective in bloodstream infections (OR, 0.51; 95% CI, 0.39~0.66) but not for urinary tract infections, ventilator-associated pneumonia infections, and Clostridium difficile infections. Moreover, 2% chlorhexidine bathing alone or its combination with other interventions has a significant effect on the incidence of HAI and MDRO (OR, 0.59; 95% CI, 0.38~0.92). Conclusion: This meta-analysis reveals that 2% chlorhexidine bathing significantly reduces the incidence of HAI and MDRO in intensive care units. The effect of 2% chlorhexidine bathing on pediatric patients or patients at general wards should be further assessed as a cost-effective intervention for infection control.