• Title/Summary/Keyword: Multidrug Resistance

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Analysis of rpoB Gene in Rifampin-Resistant M. Tuberculosis by Direct Sequencing and Line Probe Assay (염기서열결정과 Line Probe 분석법에 의한 Rifampin내성 결핵균의 rpoB 유전자 분석)

  • Lee, Min-Ki;Kim, Yun-Seong;Lee, Hyo-Jin;Cheon, Du-Su;Yun, Sang-Myung;Park, Sam-Seok;Kim, Cheol-Min;Park, Soon-Kew
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.2
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    • pp.251-263
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    • 1997
  • Background : The emergence of multidrug-resistant strains of Mycobacterium tuberculosis presents a significant challange to the treatment and control of tuberculosis, and there is an urgent need to understand the mechanisms by which strains acquire multidrug resistance. Recent advances in molecular methods for the detection of M. tuberculosis genetic targets have approached the sensitivity of culture. Furthermore the prospect of determining resistance in mycobacteria at the nucleic acid level particulary to first-line drugs like rifampin, isoniazid has provided a glimps of the next generation of sensitivity test for M. tuberculosis. Previous studies in RMP resistant M. tuberculosis have shown that mutation in $\beta$subunit of RNA polymerase is main mechanism of resistance. Method : In this study, rpoB gene for the $\beta$subunit of RNA polymerase from M. tuberculosis of 42 cultured samples (32 were RMP resistant and 10 were sensitive cases) were isolated and characterised the mutations. Direct sequencing data were compared with the results of INNO-LiPA Line Probe Assay (LiPA, Innogenetics, Belgium), commercial RMP resistance detecting kit using reverse hybridization method. Results : All of the RMP resistant samples were revealed the presence of mutation by LiPA. In 22 samples (68.8%) out of 32 RMP resistant cases, the mutation types were confirmed by the positive signal at one of 4 mutation bands in the strip. The most frequent type was R5 (S531L) which were 17 cases (77.3%). Results of direct sequencing were identified the exact characteristics of 8 mutations which were not confirmed by LiPA. S522W type point mutation and 9 base pair deletion at codon 513~515 were new identified mutations for the first time. Conclusion : Mutations in rpoB gene is the main mechanism of RMP resistance in M. tuberculosis and LiPA is a very useful diagnostic tool for the early diagnosis of RMP resistance in M. tuberculosis.

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Listeria Species in Broiler Poultry Farms: Potential Public Health Hazards

  • Dahshan, Hesham;Merwad, Abdallah Mohamed Amin;Mohamed, Taisir Saber
    • Journal of Microbiology and Biotechnology
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    • v.26 no.9
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    • pp.1551-1556
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    • 2016
  • Broiler meat production worldwide has been plagued by lethal food-poisoning bacteria diseases, including listeriosis. A fatality rate of 15.6% was recorded in human beings in the EU in 2015. During 2013, a total of 200 poultry farm samples, including litter, chicken breast, farm feed, and drinking water, were collected to generate baseline data for the characterization of the genus Listeria in broiler poultry farms. Listeria spp. were detected in a total of 95 (47.5%) poultry farm samples. The isolates of Listeria spp. included L. innocua (28.5%), L. ivanovii (12.5%), L. welshimeri (4.5%), and L. monocytogenes and L. seeligeri (1% each). Listeria spp. contamination rates were higher in farm feed (70%), followed by litter (52.5%), chicken breasts (42.2%), and drinking water (10%). Almost all Listeria spp. isolates were resistant to more than three classes of antibiotics (multidrug resistant). Besides this, we observed a significant resistance level to penicillin and fluoroquinolone drugs. However, lower resistance levels were recorded for broad-spectrum cephalosporins. The inlA, inlC, and inlJ virulence genes were detected in almost all of the L. monocytogenes isolates. Thus, food safety management approaches and interventions at all stages of the broiler rearing cycle were needed to control cross-contamination and the zoonotic potential of listeriosis.

Estrogen Receptor α Roles in Breast Cancer Chemoresistance

  • Xu, Chao-Yang;Jiang, Zhi-Nong;Zhou, Ying;Li, Jia-Jia;Huang, Li-Ming
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.7
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    • pp.4049-4052
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    • 2013
  • Resistance to chemotherapy treatment, which may lead to limited efficacy of systemic therapy in breast cancer patients, is multifactorial. Among the mechanisms of resistance to chemotherapy treatment, there are those closely related to estrogen receptor ${\alpha}$, P-glycoprotein, multidrug resistance-related protein, glutathione S-transferase pi and topoisomerase-II. $ER{\alpha}$ is ligand-activated transcription factor that regulates gene expression and plays a critical role in endocrine signaling. In previous preclinical and clinical studies, positive $ER{\alpha}$ expression in breast cancer cells was correlated with decreased sensitivity to chemotherapy. This article reviews current knowledge on the predictive value of $ER{\alpha}$ with regard to response to chemotherapy. Better understanding of its role may facilitate patient selection of therapeutic regimens and lead to optimal clinical outcomes.

Increasing Antimicrobial Resistance Monitored in Surveillance Analysis of Blood Stream Infections in Febrile Neutropenic Pediatric Oncology Patients

  • El-Mahallawy, Hadir A;Hassan, Safaa Shawky;El-Wakil, Mohamed;Moneer, Manar M;Shalaby, Lobna
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.14
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    • pp.5691-5695
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    • 2015
  • Background: Continuous surveillance of pattern of blood stream infection is necessary in febrile neutropenia (FN)especially with the recent escalating trend in the management of pediatric cancer patients towards intensified regimens and with the increase in infections caused by resistant organisms limiting the choice of antibiotics. Aim: To monitor change in pattern of blood stream infections (BSI) in FN pediatric cancer patients. Materials and Methods: Surveillance of FN episodes with positive BSI was prospectively monitored and compared to a previous surveillance in the same pediatric oncology unit. Results: A total of 232 BSI positive episodes were documented in 192 patients during a 6 months period. The results of recent surveillance analysis showed an increase in intensified regimens of chemotherapy, antimicrobial resistance, fungal infections, and prolonged duration of episodes when compared to previous surveillance, with p value sof <0.001, 0.005, 0.021, and <0.001, respectively. There was an apparent decrease in the crude mortality but this was not statistically significant, to 6% in 2011 from 10 % in 2006. Conclusions: The pattern of BSI at our institution is still inclining towards gram positive organisms but is showing a shift towards more antibiotic resistance and fungal infections.

Inhibitory Effect of Metal Surface on the Antimicrobial Resistance Microorganism (금속표면이 항생제 내성균주의 생육억제에 미치는 영향)

  • Kim, Jung-Beom;Kim, Jae-Kwang;Kim, Hyunjung;Cho, Eun Jung;Park, Yeon-Joon;Lee, Hae Kyung
    • Annals of Clinical Microbiology
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    • v.21 no.4
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    • pp.80-85
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    • 2018
  • Background: The aim of this study was to comparatively evaluate the bactericidal effects of copper, brass (copper 78%, tin 22%), and stainless steel against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecium (VREFM), and multidrug-resistant Pseudomonas aeruginosa (MRPA). Methods: The isolates (MRSA, VREFM, MRPA) used in this study were mixed wild type 3 strains isolated from patients treated at Uijeongbu St. Mary's Hospital in 2017. These strains showed patterns of multidrug resistance. The lyophilized strains were inoculated into and incubated for 24 hr in tryptic soy broth at $35^{\circ}C$. The initial bacterial inoculum concentration was adjusted to $10^5CFU/mL$. A 100-mL bacterial suspension was incubated in containers made of brass (copper 78%, tin 22%), copper (above 99% purity), and stainless steel at $35^{\circ}C$. Viable counts of bacteria strains were measured for 9 days. Results: In this study, the bactericidal effects of copper and brass on MRSA, VREFM, and MRPA were verified. The bactericidal effect of stainless steel was much weaker than those of copper and brass. The bactericidal effect was stronger on MRPA than on MRSA or VREFM. Conclusion: To prevent cross infection of multidrug resistant bacteria in hospitals, further studies of longer duration are needed for testing of copper materials on objects such as door knobs, faucets, and bed rails.

Antimicrobial susceptibility and pathogenic genes of Staphylococcus aureus isolated from the oral cavity of patients with periodontitis

  • Kim, Ga-Yeon;Lee, Chong Heon
    • Journal of Periodontal and Implant Science
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    • v.45 no.6
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    • pp.223-228
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    • 2015
  • Purpose: The goal of this study was to characterize the patterns of antimicrobial resistance and virulence genes in samples of Staphylococcus aureus (S. aureus) isolated from periodontitis patients. Methods: From July 2015 to August 2015, oral saliva was collected from a total of 112 patients diagnosed with periodontitis, including 80 outpatients in dental hospitals and 32 patients in dental clinics located in Seoul and Cheonan. The samples were subjected to a susceptibility test to evaluate the prevalence of antimicrobial resistance, and the pathogenic factors and antimicrobial resistance factors in the DNA of S. aureus were analyzed using polymerase chain reaction. Results: A susceptibility test against 15 antimicrobial agents showed that 88% of cultures were resistant to ampicillin, 88% to penicillin, and 2% to oxacillin. Resistance to at least two drugs was observed in 90% of cultures, and the most common pattern of multidrug resistance was to ampicillin and penicillin. Enterotoxins were detected in 65.9% of samples. The cell hemolysin gene hld was detected in 100% of cultures and hla was detected in 97.6% of samples. All strains resistant to penicillin and ampicillin had the blaZ gene. The aph(3')IIIa gene, which encodes an aminoglycoside modifying enzyme, was detected in 46.3% of samples. Conclusions: In the treatment of oral S. aureus infections, it is important to identify the pathogenic genes and the extent of antimicrobial resistance. Furthermore, it is necessary to study patterns of antimicrobial resistance and cross-infection in the context of periodontological specialties in which antimicrobials are frequently used, such as maxillofacial surgery, where the frequency of antimicrobial use for minor procedures such as implant placement is increasing.

siRNA Silencing EZH2 Reverses Cisplatin-resistance of Human Non-small Cell Lung and Gastric Cancer Cells

  • Zhou, Wen;Wang, Jian;Man, Wang-Ying;Zhang, Qing-Wei;Xu, Wen-Gui
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.6
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    • pp.2425-2430
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    • 2015
  • Clinical resistance to chemotherapeutic agents is one of the major hindrances in the treatment of human cancers. EHZ2 is involved in drug resistance and is overexpressed in drug-resistant cancer cell lines. In this study, we investigated the effects of EHZ2 on cisplatin -resistance in A549/DDP and AGS/DDP cells. EHZ2 mRNA and protein were found to be significantly overexpressed in A549/DDP and AGS/DDP cells, compared to parental cells. EHZ2 siRNA successfully silenced EHZ2 mRNA and protein expression. Proliferation was inhibited and drug resistance to cisplatin was improved. Flow cytometry showed that silencing of EHZ2 arrested A549/DDP and AGS/DDP cells in the G0/G1 phase, increasing apoptosis, rh-123 fluorescence intensity and caspase-3/8 activities. Silencing of EHZ2 also significantly reduced the mRNA and protein expression levels of cyclin D1 and MDR1,while up-regulating p15, p21, p27 and miR-218 in A549/DPP cells. Furthermore, silencing of EHZ2 also significantly increased the expression level of tumor suppressor factor miR-218. We also found down-regulating EHZ2 expression increased methylation in A549/DDP and AGS/DDP cells. This study demonstrates that drug resistance can be effectively reversed in human cisplatin-resistant lung and gastric cancer cells through delivery of siRNAs targeting EHZ2.

The Evolving Epidemiology of Serotype Distribution and Antimicrobial Resistance of Streptococcus pneumoniae Strains Isolated from Adults in Crete, Greece, 2009-2016

  • Maraki, Sofia;Mavromanolaki, Viktoria Eirini;Stafylaki, Dimitra;Hamilos, George;Samonis, George
    • Infection and chemotherapy
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    • v.50 no.4
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    • pp.328-339
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    • 2018
  • Background: Pneumococcal disease is a major cause of morbidity and mortality worldwide, especially in patients with comorbidities and advanced age. This study evaluated trends in epidemiology of adult pneumococcal disease in Crete, Greece, by identifying serotype distribution and antimicrobial resistance of consecutive Streptococcus pneumoniae strains isolated from adults during an 8-year time period (2009-2016) and the indirect effect of the infant pneumococcal higher-valent conjugate vaccines 10-valent pneumococcal conjugate vaccine (PCV10) and 13-valent pneumococcal conjugate vaccine (PCV13). Materials and Methods: Antimicrobial susceptibility was performed by E-test and serotyping by Quellung reaction. Multidrug resistance (MDR) was defined as non-susceptibility to penicillin (PNSP) combined with resistance to ${\geq}2$ non-${\beta}$-lactam antimicrobials. Results: A total of 135 S. pneumoniae strains were isolated from adults during the study period. Twenty-one serotypes were identified with 17F, 15A, 3, 19A, and 11A, being the most common. The coverage rates of PCV10, and PCV13 were 17.8% and 37.8%, respectively. PCV13 serotypes decreased significantly from 68.4% in 2009 to 8.3% in 2016 (P = 0.002). The most important emerging non-PCV13 serotypes were 17F, 15A, and 11A, with 15A being strongly associated with antimicrobial resistance and MDR. Among all study isolates, penicillin-resistant and MDR strains represented 7.4% and 14.1%, respectively. Predominant PNSP serotypes were 19A (21.7%), 11A (17.4%), and 15A (17.4%). Erythromycin, clindamycin, tetracycline, trimethoprim-sulfamethoxazole, and levofloxacin resistant rates were 30.4%, 15.6%, 16.3%, 16.3%, and 1.5%, respectively. Conclusion: Although pneumococcal disease continues to be a health burden in adults in Crete, our study reveals a herd protection effect of the infant pneumococcal higher-valent conjugate vaccination. Surveillance of changes in serotype distribution and antimicrobial resistance among pneumococcal isolates are necessary to guide optimal prevention and treatment strategies.

Livestock-associated methicillin-resistant Staphylococcus aureus in Korea: antimicrobial resistance and molecular characteristics of LA-MRSA strains isolated from pigs, pig farmers, and farm environment

  • Back, Seung Hyun;Eom, Hong Sik;Lee, Haeng Ho;Lee, Gi Yong;Park, Kun Taek;Yang, Soo-Jin
    • Journal of Veterinary Science
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    • v.21 no.1
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    • pp.2.1-2.14
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    • 2020
  • The emergence of livestock-associated (LA)-methicillin-resistant Staphylococcus aureus (MRSA) in livestock animal has become a significant zoonotic concern. In the present study, we investigated nationwide prevalence of LA-MRSA across pork production chain including pig farms, slaughterhouses, and retail markets. A total of 40 MRSA strains were isolated during the investigation and the overall prevalence of MRSA was 3.4% (n = 37), 0.6% (n = 2), and 0.4% (n = 1) in pig farms, slaughterhouses, and retail markets, respectively. Multilocus sequence typing analyses revealed that the 2 most significant clonal lineages in pork production chain in Korea were ST398 (n = 25) and ST541 (n = 6). All of the 40 MRSA isolates were further characterized to investigate key genotypic and phenotypic correlates associated with the emergence and spread of clonal complex 398 (CC398; ST398, and ST541) LA-MRSA. Although the prevalence of swine-associated MRSA was still relatively low and mostly restricted to pig farms, multidrug-resistant CC398 LA-MRSA isolates with new spa types (t18102 and t18103) were identified as a major clonal lineage. The CC398 LA-MRSA strains tended to exhibit increased levels of multiple drug resistance (MDR) phenotype compared with non-CC398 MRSA strains. Of note, in comparison with non-CC398 MRSA isolates, CC398 LA-MRSA isolates exhibited significantly enhanced tetracycline (TET) and zinc resistance. These findings suggested that co-selection pressure associated with MDR phenotype, especially TET resistance, and zinc resistance may have played a significant role in the emergence and persistence of CC398 LA-MRSA in pig farms in Korea.

Metformin alleviates chronic obstructive pulmonary disease and cigarette smoke extract-induced glucocorticoid resistance by activating the nuclear factor E2-related factor 2/heme oxygenase-1 signaling pathway

  • Tao, Fulin;Zhou, Yuanyuan;Wang, Mengwen;Wang, Chongyang;Zhu, Wentao;Han, Zhili;Sun, Nianxia;Wang, Dianlei
    • The Korean Journal of Physiology and Pharmacology
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    • v.26 no.2
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    • pp.95-111
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    • 2022
  • Chronic obstructive pulmonary disease (COPD) is an important healthcare problem worldwide. Often, glucocorticoid (GC) resistance develops during COPD treatment. As a classic hypoglycemic drug, metformin (MET) can be used as a treatment strategy for COPD due to its anti-inflammatory and antioxidant effects, but its specific mechanism of action is not known. We aimed to clarify the role of MET on COPD and cigarette smoke extract (CSE)-induced GC resistance. Through establishment of a COPD model in rats, we found that MET could improve lung function, reduce pathological injury, as well as reduce the level of inflammation and oxidative stress in COPD, and upregulate expression of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), multidrug resistance protein 1 (MRP1), and histone deacetylase 2 (HDAC2). By establishing a model of GC resistance in human bronchial epithelial cells stimulated by CSE, we found that MET reduced secretion of interleukin-8, and could upregulate expression of Nrf2, HO-1, MRP1, and HDAC2. MET could also increase the inhibition of MRP1 efflux by MK571 significantly, and increase expression of HDAC2 mRNA and protein. In conclusion, MET may upregulate MRP1 expression by activating the Nrf2/HO-1 signaling pathway, and then regulate expression of HDAC2 protein to reduce GC resistance.