• Asian Pacific Journal of Cancer Prevention
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• 제16권14호
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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.

• Annals of Clinical Microbiology
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• 제21권4호
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• pp.80-85
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• 2018

배경: 본 연구는 국내 병원에서 분리된 methicillin 내성 Staphylococcus aureus (MRSA), vancomycin 내성 Enterococcus faecium (VREFM) 및 다제 내성 multidrug-resistant Pseudomonas aeruginosa (MRPA) 등에 대한 구리, 유기(구리 78%, 주석 22%), stainless steel의 살균력을 비교 실험하여, 국내 병원 환경에 의한 항생제 내성 균주 교차 감염을 예방하는 데 구리와 유기의 활용성을 분석하고자 하였다. 방법: MRSA, VREFM, MRPA 균주는 2017년 의정부성모병원에서 분리 동정된 wild type 3균주씩을 혼합하여 사용하였으며 모두 항생제 다제 내성 균주로 나타났다. MRSA, VREFM, MRPA 균주 각각을 Tryptic soy broth (Oxoid, England)에 접종하여 $35^{\circ}C$에서 24시간 배양한 후, 각각 초기 접종균액의 균수를 $10^5\;log\;CFU/mL$로 조정하였다. 구리, 유기, stainless steel 용기에 준비된 MRSA, VREFM, MRPA 접종균액 100 mL씩을 각각 접종한 후, 습도가 유지되도록 덮개를 덮은 후 $35^{\circ}C$ incubator에서 초기부터 9일까지 생존균수를 측정하였다. 결과: 본 연구결과 국내에서 분리된 항생제 다제 내성 MRSA, VREFM, MRPA 균주에 대한 구리 및 유기의 살균효과를 확인하였다. Stainless steel의 살균력은 구리 및 유기에 비해 매우 미약하였고, MRSA 및 VREFM에 비해 MRPA의 살균효과가 크게 나타났다. 결론: 교차감염을 예방하기 위하여 병원 내 문손잡이, 수도꼭지, 침대레일 등에 구리나 유기를 적용하여, 장기간 실험을 진행하고 있는 국외 사례와 같이, 국내 병원에서도 구리와 유기를 이용한 병원 내 교차 감염 예방 연구가 필요하다고 생각한다.

• Journal of Periodontal and Implant Science
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• 제45권6호
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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.

• Asian Pacific Journal of Cancer Prevention
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• 제16권6호
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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.

• Infection and chemotherapy
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• 제50권4호
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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.

• Journal of Veterinary Science
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• 제21권1호
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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.

• The Korean Journal of Physiology and Pharmacology
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• 제26권2호
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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.

• Clinical and Experimental Pediatrics
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• 제52권1호
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• pp.61-67
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• 2009

목 적 : 소아에서의 항결핵제 내성률은 지역 사회에서의 결핵 관리의 효율성을 파악하는 척도가 되나 국내외의 보고가 많지 않다. 이에 저자들은 소아청소년 결핵에서의 약제 내성률과 변화 경향을 조사하여 결핵 치료 및 예방적 화학요법 처방 선정에 도움을 얻고자 하였다. 방 법 : 1999년 1월부터 2007년 7월까지 대한결핵협회 결핵 연구원 미생물부(세계보건기구 지정 국제자문검사소)에 배양 및 감수성 검사가 의뢰되어 M. tuberculosis가 분리되어 항결핵제에 대한 감수성 검사가 실시된 예 중 19세 이하를 대상으로 항결핵제에 대한 감수성 검사를 실시하였다. 결 과 : 소아청소년에서 한 가지 이상의 약제에 대해 내성을 보인 균주는 607균주(16.6%)였고, IHN에 대해 내성을 보인 균주는 503균주(13.8%), RFP에 대해서는 326균주(8.9%), PZA에 대해서는 155균주(4.2%), SM에 대해서는 134균주(3.7%), EMB에 대해서는 215균주(5.9%), PAS에 대해서는 70균주(1.9%)였다. 다제내성결핵균은 276균주(7.6%)였고 광범위약제내성결핵균은 5균주(0.2%)였다. 15세 이하에서보다(20.5%) 15세 이상에서의 한 가지 이상의 약제에 대한 내성률(16.1%)이 유의하게 낮았고(P=0.016), 다제내성결핵이 차지하는 비율도 낮았으나(각각 8.7 %, 7.4%) 통계적으로 유의하지는 않았다. 본 조사 기간 동안 한 가지 이상의 결핵 약제에 대한 내성률과 다제내성결핵이 차지하는 비율은 유의하게 감소하였다(P<0.001). 이전 1987년부터 1995년까지의 조사와 비교해 보면, 한 가지 이상의 결핵 약제에 대한 내성률은 37.5%에서 20.5%로 유의하게 감소하였고(P=0.007), INH, EMB, PAS에 대한 내성률의 감소는 통계적으로 유의하였으며(P<0.05), 다제내성결핵이 차지하는 비율도 감소하였으나 통계적으로 유의하지는 않았다. 결 론 : 소아청소년 결핵에서의 약제 내성률은 과거에 비해 점차로 감소하는 양상을 보이고 있으나, 아직은 다른 나라보다 높고 다제내성결핵과 광범위약제내성결핵이 새로운 문제로 대두되고 있어 약제 감수성 검사와 내성균 감염 위험 요인 파악을 통한 효율적인 치료 약제 선정으로 치료 성공률을 높이면서 항결핵제 내성균의 증가를 막아야 할 것으로 사료된다.

• Tuberculosis and Respiratory Diseases
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• 제83권1호
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• pp.20-30
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• 2020

Tuberculosis (TB) remains a threat to public health and is the leading cause of death globally. Isoniazid (INH) is an important first-line agent for the treatment of TB considering its early bactericidal activity. Resistance to INH is now the most common type of resistance. Resistance to INH reduces the probability of treatment success and increases the risk of acquiring resistance to other first-line drugs such as rifampicin (RIF), thereby increasing the risk of multidrug-resistant-TB. Studies in the 1970s and 1980s showed high success rates for INH-resistant TB cases receiving regimens comprised of first-line drugs. However, recent data have indicated that INH-resistant TB patients treated with only firs-tline drugs have poor outcomes. Fortunately, based on recent systematic meta-analyses, the World Health Organization published consolidated guidelines on drug-resistant TB in 2019. Their key recommendations are treatment with RIF-ethambutol (EMB)-pyrazinamide (PZA)-levofloxacin (LFX) for 6 months and no addition of injectable agents to the treatment regimen. The guidelines also emphasize the importance of excluding resistance to RIF before starting RIF-EMB-PZA-LFX regimen. Additionally, when the diagnosis of INH-resistant TB is confirmed long after starting the first-line TB treatment, the clinician must decide whether to start a 6-month course of RIF-EMB-PZA-LFX based on the patient's condition. However, these recommendations are based on observational studies, not randomized controlled trials, and are thus conditional and based on low certainty of the effect estimates. Therefore, further work is needed to optimize the treatment of INH-resistant TB.

• 대한수의학회지
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• 제54권2호
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• pp.91-99
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• 2014

An antimicrobial susceptibility test was conducted to compare the resistance rates among Campylobacter spp. isolates from dogs (n = 50) raised under diverse conditions and humans (n = 50). More than 60% of Campylobacter (C.) jejuni from dogs and humans showed resistance to nalidixic acid, enrofloxacin and ciprofloxacin. C. jejuni isolates from humans showed higher resistance to tetracycline (83.3%) and ampicillin (91.3%) than those from dogs. None of the C. jejuni or Campylobacter coli isolates from humans or dogs were resistant to erythromycin. Overall, 85% of Campylobacter spp. isolates showed a multidrug resistant phenotype. Nucleotide sequencing analysis of the gryA gene showed that 100% of $NA^R/CIP^R$ C. jejuni isolates from dogs and humans had the Thr-$86^{th}$-Ile mutation, which is associated with fluoroquinolone resistance. flaA PCR restriction fragment length polymorphism (RFLP) typing to differentiate the isolates below the species level revealed 12 different clusters out of 73 strains. The human isolates belonged to eight different RFLP clusters, while five clusters contained dog and human isolates.