• Title/Summary/Keyword: Multidrug Resistance

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Increasing Rates of Community Associated Methicillin-Resistant Staphylococcus aureus in Children with Muscular-Skeletal Infections in Korea: A Single Center Experience from 2000 to 2012 (소아의 근골격계 감염에서 지역사회 관련 메치실린 내성 황색 포도알균의 증가: 2000년 9월-2012년 8월간의 단일기관 연구)

  • Park, Jae-Hong;Lee, Taek-Jin
    • Pediatric Infection and Vaccine
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    • v.20 no.2
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    • pp.63-70
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    • 2013
  • Purpose : This study aimed to explore how prevalent the community-related methicillin-resistant Staphylococcus aureus (CA-MRSA) was in children with muscular-skeletal infections. Methods : We retrospectively reviewed the medical records of patients of 18 years or under who were diagnosed with suppurative arthritis or osteomyelitis and S. aureus from September 2000 through August 2012 at the CHA Bundang Medical center. Results : Thirty-one cases of suppurative arthritis or osteomyelitis were identified. The patients were between 17 days old and 18 years old with an average age of 7. Eleven cases (33.5%) of suppurative arthritis and 16 cases (51.6%) of osteomyelitis were observed. Five cases were accompanied by the two diseases. Methicillin sensitive S. aureus (MSSA) was isolated in 25 cases (80.6%) and methicillin resistant S. aureus (MRSA) was isolated in 6 cases (19.4%). Multidrug resistant strains were not observed. MRSA was not found from 2000 through 2005. All patients were treated with antibiotics and the duration of antibiotics treatment was $26.4{\pm}12.7$ days. Vancomycin was used as the initial antibiotic treatment in 4 cases (12.9%) and vancomycin was used as the definitive antibiotics in the 10 cases (32.3%). Conclusions : The result of this study showed that methicillin resistance rate of S. aureus from muscular-skeletal infections was concentrated in the latter half of the 12 year period.

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Screening of Chemosensitizer Candidates Using Natural Extracts (천연 추출물을 이용한 화학감작제 후보물질 탐색)

  • Ahn, Hee-Jeong;Kim, Ji-Young;Lee, Choong-Hwan;Song, Im-Sook;Liu, Kwang-Hyeon
    • Journal of Life Science
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    • v.18 no.9
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    • pp.1244-1248
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    • 2008
  • P-glycoprotein (P-gp) is a very important drug transporter, which plays an important role in drug disposition and represents an additional mechanism for the development of multidrug resistance. Flavonoids, a major class of natural compounds widely present in foods and herbal products, have been shown to be P-gp inhibitors. The objective of the present study was to identify new chemosensitizer candidates through the screening of various herbal extracts. The inhibitory effects of herbal extracts on P-gp activity were assessed by measuring accumulation of calcein AM using P-gp overexpressed L-MDR1 cells. Curcuma longa showed the most potent inhibition on P-gp function. The inhibitory potential of P-gp was in the order: Curcuma longa > Curcuma aromatica > Ageratum conizoids > Zanthoxylum planispinum > Zedoariae rhizome > Rakta chandan > Dalbergia odorifera > Caesalpinia Sappan > Aloe ferox. To identify individual constituents with inhibitory activity, the herbal extracts were analyzed by LC/MS/MS. Several flavonoids such as curcumin, a well-known P-gp inhibitor, were identified through mass spectral library search. These in vitro data indicate that herbal extracts contain constituents that can potently inhibit the activities of P-gp and suggest that these herbal extracts should be examined for potential chemosensitizer in vivo.

A New Paradigm to Mitigate Osteosarcoma by Regulation of MicroRNAs and Suppression of the NF-${\kappa}B$ Signaling Cascade

  • Mongre, Raj Kumar;Sodhi, Simrinder Singh;Ghosh, Mrinmoy;Kim, Jeong Hyun;Kim, Nameun;Sharma, Neelesh;Jeong, Dong Kee
    • Development and Reproduction
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    • v.18 no.4
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    • pp.197-212
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    • 2014
  • Osteosarcoma (OS) is one of the most common malignant primary bone tumors and NF-${\kappa}B$ appears to play a causative role, but the mechanisms are poorly understood. OS is one of the pleomorphic, highly metastasized and invasive neoplasm which is capable to generate osteoid, osteoclast and osteoblast matrix. Its high incidence has been reported in adolescent and children. Cell signal cascade is the pivotal functional mechanism acquired during the differentiation, proliferation, growth and survival of the cells in neoplasm including OS. The major limitation to the success of chemotherapy in OS is the development of multidrug resistance (MDR). Answers to all such queries might come from the knock-in experiments in which the combined approach of miRNAs with NF-${\kappa}B$ pathway is put into use. Abnormal miRNAs can modulate several epigenetical switching as a hallmark of number of diseases via different cell signaling. Studies on miRNAs have opened up the new avenues for both the diagnosis and treatment of cancers including OS. Collectively, through the present study an attempt has been made to establish a new systematic approach for the investigation of microRNAs, bio-physiological factors and their target pairs with NF-${\kappa}B$ to ameliorate oncogenesis with the "bridge between miRNAs and NF-${\kappa}B$". The application of NF-${\kappa}B$ inhibitors in combination with miRNAs is expected to result in a more efficient killing of the cancer stem cells and a slower or less likely recurrence of cancer.

A Comparative Analysis on The Efficiency of Various Clinical Methods for Diagnosis of Tuberculosis (결핵 진단을 위한 검사 방법간의 효율성에 관한 비교 분석)

  • 최석철;정천환;성희경;김태운;이원재
    • Biomedical Science Letters
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    • v.5 no.2
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    • pp.191-200
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    • 1999
  • In recent years continuously increasing number of tuberculosis (TB) cases due to the emergence of strains with multidrug resistance and AIDS is a significant global health problem. Therefore, more rapid and reliable diagnosis of TB may be one of the most urgent needs in efforts to eradicate the disease. The present study was designed to compare and assess the diagnostic values and efficiencies between the conventional methods (X-ray, AFB stain and culture) and PCR for pulmonary TB on 171 cases. Chest X-ray finding and clinical features revealed that 39 (22.8%) of 171 sputum specimens were pulmonary TB cases. The statistical data were taken on the basis of the definitive diagnosis: In X-ray, overall sensitivity, specificity, efficiency and false positive and false negative incidence was respectively 69.2%, 87.1%, 83.0%, 12.9%, and 30.8%; 79.5%, 95.5%, 91.8%,4.6% and 20.5% in AFB-stain; 56.4%, 99.2%,89.5%, 0.8% and 43.6% in culture; 82.1%, 96.2%, 93.0%, 3.8% and 17.9% in PCR. PCR got a highest sensitivity and efficiency as well as a lowest false negative incidence. Culture had a highest specificity with a lowest false positive incidence. These results imply that PCR assay is fast, sensitive and efficient method for diagnosis of pulmonary TB. However, combined use of the conventional methods with thorough quality control may offer more opportunities for detecting Mycobacterium tuberculosis and diagnosting TB although they have some limits.

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Genetic Relationship between SCCmec Types and Virulence Factors of Methicillin-Resistant Staphylococcus aureus Clinical Isolates in Korea

  • Lim, Kwan-Hun;Lee, Gyu-Sang;Park, Min;Lee, Jin-Hee;Suh, In-Bum;Ryu, Sook-Won;Eom, Yong-Bin;Kim, Jong-Bae
    • Biomedical Science Letters
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    • v.16 no.2
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    • pp.75-82
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    • 2010
  • The molecular epidemiological characteristics of methicillin-resistant Staphylococcus aureus (MRSA) isolates have demonstrated their genetic diversity and evolution. A total of 137 strains of MRSA clinical isolates was collected from Korean healthcare facility in 2007. The MRSA clinical isolates were analyzed by molecular typings (SCCmec element and agr locus typing), virule nce factor gene detections {(Panton-Valentine leukocidin (PVL), enterotoxin, exfoliative toxin and toxic shock syndrome toxin-1), and amplified fragment length polymorphism (AFLP)}. The MRSA clinical isolates were classified as SCCmec type II-agr type 1 (2 strains), type II-agr type 2 (79 strains), type III-agr type 1 (24 strains), type III-agr type 2 (2 strains), type IV-agr type 1 (27 strains), type IV-agr type 2 (2 strains), and non-typable (1 strain, agr type 3). Based on SCCmec types, SCCmec type II (95.1%) and III (88.5%) indicated higher multidrug resistance rate than SCCmec type IV (10.3%) (P<0.001). The most common enterotoxin genes were seg (83.8%), sei (83.1%), and sec (80.2%). The tst gene was present in 86 out of 137 (62.8%) MRSA isolates. All MRSA isolates were negative for PVL and exfoliative toxin genes. The combinations of toxin genes were observed in particular SCCmec types; 97.6% of SCCmec type II strains carried sec, seg, sei and tst genes, 73.0% of SCCmec type III strains carried sea gene, and 89.7% of SCCmec type IV strains carried sec, seg and sei genes. Each of the SCCmec types of MRSA isolates had distinct AFLP profile. In conclusion, SCCmec type II, agr type 1 and 2 have demonstrated to be the most common types in Korea, and the results indicated that the virulence factors are closely associated with their molecular types (SCCmec and agr types).

The National Status of Tuberculosis Using Nationwide Medical Records Survey of Patients with Tuberculosis in Korea

  • Park, Yoon-Sung;Hong, Sung-Jin;Boo, Yoo-Kyung;Hwang, Eun-Suk;Kim, Hyun Jung;Cho, Seung-Hee;Na, Kyung-In;Cho, En-Hi;Shin, Sang-Sook
    • Tuberculosis and Respiratory Diseases
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    • v.73 no.1
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    • pp.48-55
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    • 2012
  • Background: The epidemiology of tuberculosis (TB) has been assessed based on the data of the analysis of TB patients notified to the surveillance system in Korea. However, the national status of TB is not validated through this surveillance system. The objective is to determine the epidemiology of TB and to understand the accurate status of TB patients treated in private institutions. Methods: Medical records of 53,579 patients who had been diagnosed with TB in 2008 were analyzed. Results: Among 53,579 patients, the number of sputum smear positive cases was 15,639(29.2%) and the number of new cases was 39,191 (73.1%). The drug resistance rate of new cases was 5.3%, while the rate stood at 13.3% for TB patients with treatment history. The number of multi-drug resistant TB (MDR-TB) patients was 2,472 (4.6%), which consists of 2.9% of new cases and 9.3% of TB patients with prior treatment history. The number of extensively drug-resistant TB patients was 749 (1.4%), consisting of 1.1% of new cases and 2.2% of TB patients with prior treatment history. In terms of treatment outcomes, 66.4% of all TB patients, 70.5% of new cases, 64.4% of relapse cases, and 46.8% of MDR-TB cases were cured or completed. It was inferred that in 2008, the total number of TB patients reached 70,767, 145.6 per 100,000 people (95% confidence interval, 145.5~145.7). Conclusion: We conclude that the medical records review of the Health Insurance Review and Assessment Service (HIRA) data can be very effective in promoting the understanding of the current status of TB in private institutions.

Diagnostic Evaluation of Non-Interpretable Results Associated with rpoB Gene in Genotype MTBDRplus Ver 2.0

  • Singh, Binit Kumar;Sharma, Rohini;Kodan, Parul;Soneja, Manish;Jorwal, Pankaj;Nischal, Neeraj;Biswas, Ashutosh;Sarin, Sanjay;Ramachandran, Ranjani;Wig, Naveet
    • Tuberculosis and Respiratory Diseases
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    • v.83 no.4
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    • pp.289-294
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    • 2020
  • Background: Line probe assay (LPA) is standard diagnostic tool to detect multidrug resistant tuberculosis. Non-interpretable (NI) results in LPA (complete missing or light wild-type 3 and 8 bands with no mutation band in rpoB gene region) poses a diagnostic challenge. Methods: Sputum samples obtained between October 2016 and July 2017 at the Intermediate Reference Laboratory, All India Institute of Medical Sciences Hospital, New Delhi, India were screened. Smear-positive and smear-negative culture-positive specimens were subjected to LPA Genotype MTBDRplus Ver 2.0. Smear-negative with culture-negative and culture contamination were excluded. LPA NI samples were subjected to phenotypic drug susceptibility testing (pDST) using MGIT-960 and sequencing. Results: A total of 1,614 sputum specimens were screened and 1,340 were included for the study (smear-positive [n=1,188] and smear-negative culture-positive [n=152]). LPA demonstrated 1,306 (97.5%) valid results with TUB (Mycobacterium tuberculosis) band, 24 (1.8%) NI, three (0.2%) valid results without TUB band, and seven (0.5%) invalid results. Among the NI results, 22 isolates (91.7%) were found to be rifampicin (RIF) resistant and two (8.3%) were RIF sensitive in the pDST. Sequencing revealed that rpoB mutations were noted in all 22 cases with RIF resistance, whereas the remaining two cases had wild-type strains. Of the 22 cases with rpoB mutations, the most frequent mutation was S531W (n=10, 45.5%), followed by S531F (n=6, 27.2%), L530P (n=2, 9.1%), A532V (n=2, 9.1%), and L533P (n=2, 9.1%). Conclusion: The present study showed that the results of the Genotype MTBDRplus assay were NI in a small proportion of isolates. pDST and rpoB sequencing were useful in elucidating the cause and clinical meaning of the NI results.

Surgical Management of Multidrug Resistant Pulmonary Tuberculosis (다제내성 폐결핵 환자에서의 수술적 치료)

  • 성숙환;강창현;김영태;김주현
    • Journal of Chest Surgery
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    • v.32 no.3
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    • pp.287-293
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    • 1999
  • Background: Medical treatment of multiple drug resistant(MDR) pulmonary tuberculosis has been quite unsuccessful. We analyzed our experience to identify the benefits and complications of the pulmonary resection in MDR pulmonary tuberculosis. Material and Method: A retrospective review was performed in 27 patients who unerwent pulmonary resection for MDR pulmonary tuberculosis between January 1994 and March 1998. Mean age was 40 years and the average history of diagnosis prior to surgery was 3.1 years. All had resistance to an average of 4.4 drugs, and received second line drugs selected according to the drug sensitivity test. Most patients (93%) had cavitary lesions as the main focus. Bilateral lesions were identified in 19 patients (70%), however, the main focus was recognized in one side of the lung. Eleven patients (41%) were converted to negative sputum smear and/or culture before surgery. Result: Pneumonectomy was performed in 9 patients, lobectomy in 16 and segmentectomy in 2. There was no operative mortality. Morbidity had occurred in 7 patients (26%), prolonged air leak in 3 patients, reoperation due to bleeding in 2, bronchopleural fistula in 1, and reversible neurologic defect in 1. Median follow up period was 15 months (3-45 months). Sputum negative conversion was initially achieved in 22 patients (82%), and with continuous postopertive chemotherapy negative conversion was achieved in other 4 patients (14%). Only one pneumonectized patient (4%) failed due to considerable contralateral cavity. Conclusion: For patients with localized MDR pulmonary tuberculosis and with adequate pulmonary reserve function, surgical pulmonary resection combined with appropriate pre and postoperative anti-tuberculosis chemotherapy can achieve high success rate with acceptable morbidity.

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Impact of NR1I2, adenosine triphosphate-binding cassette transporters genetic polymorphisms on the pharmacokinetics of ginsenoside compound K in healthy Chinese volunteers

  • Zhou, Luping;Chen, Lulu;Wang, Yaqin;Huang, Jie;Yang, Guoping;Tan, Zhirong;Wang, Yicheng;Liao, Jianwei;Zhou, Gan;Hu, Kai;Li, Zhenyu;Ouyang, Dongsheng
    • Journal of Ginseng Research
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    • v.43 no.3
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    • pp.460-474
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    • 2019
  • Background: Ginsenoside compound K (CK) is a promising drug candidate for rheumatoid arthritis. This study examined the impact of polymorphisms in NR1I2, adenosine triphosphate-binding cassette (ABC) transporter genes on the pharmacokinetics of CK in healthy Chinese individuals. Methods: Forty-two targeted variants in seven genes were genotyped in 54 participants using Sequenom MassARRAY system to investigate their association with major pharmacokinetic parameters of CK and its metabolite 20(S)-protopanaxadiol (PPD). Subsequently, molecular docking was simulated using the AutoDock Vina program. Results: ABCC4 rs1751034 TT and rs1189437 TT were associated with increased exposure of CK and decreased exposure of 20(S)-PPD, whereas CFTR rs4148688 heterozygous carriers had the lowest maximum concentration ($C_{max}$) of CK. The area under the curve from zero to the time of the last quantifiable concentration ($AUC_{last}$) of CK was decreased in NR1I2 rs1464602 and rs2472682 homozygous carriers, while $C_{max}$ was significantly reduced only in rs2472682. ABCC4 rs1151471 and CFTR rs2283054 influenced the pharmacokinetics of 20(S)-PPD. In addition, several variations in ABCC2, ABCC4, CFTR, and NR1I2 had minor effects on the pharmacokinetics of CK. Quality of the best homology model of multidrug resistance protein 4 (MRP4) was assessed, and the ligand interaction plot showed the mode of interaction of CK with different MRP4 residues. Conlusion: ABCC4 rs1751034 and rs1189437 affected the pharmacokinetics of both CK and 20(S)-PPD. NR1I2 rs1464602 and rs2472682 were only associated with the pharmacokinetics of CK. Thus, these hereditary variances could partly explain the interindividual differences in the pharmacokinetics of CK.

Bovine mastitis-associated Escherichia coli

  • Hong Qui Le;Se Kye Kim;Jang Won Yoon
    • Journal of Food Hygiene and Safety
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    • v.39 no.3
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    • pp.181-190
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    • 2024
  • Bovine mastitis-associated Escherichia coli (BMEC) is considered the main causative agent of significant financial losses in the dairy industry worldwide, as it alters both the quantity and quality of milk produced and increases the rate of culling. This creates a variety of challenges for researchers, veterinarians, and farmers in understanding and determining the most effective therapies and diagnostic techniques. Subclinical mastitis is particularly concerning, as infected bovines exhibit no obvious symptoms and continue to secrete apparently normal milk over an extended period, allowing the causative pathogen, E. coli, to spread within the herd. For effective prevention, understanding the pathogenesis of mastitis through three stages invasion, infection, and inflammation is essential. To date, no clear correlation has been found between virulence factors and pathogenicity contributing to the clinical severity of BMEC. Multidrug-resistant E. coli and the evolution of novel resistance mechanisms have become concerns owing to the extensive use of antibiotics to treat mastitis. Therefore, it is vital to explore alternative controls to enhance the efficacy of BMEC treatment. Over the past 30 years, various genetic typing techniques have been used to examine the subspecies-level epidemiology of bovine mastitis. These studies have advanced our understanding of the origin, transmission pathway, population structure, and evolutionary relatedness of BMEC strains. In this review we provide an overview of BMEC, including insights into its etiology, genetic relationship, pathogenesis, and management of the disease, as well as new therapy options.