• Title/Summary/Keyword: Multidrug-resistance

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Curcumin-loaded PLGA Nanoparticles Conjugated with Anti-P-glycoprotein Antibody to Overcome Multidrug Resistance

  • Punfa, Wanisa;Suzuki, Shugo;Pitchakarn, Pornsiri;Yodkeeree, Supachai;Naiki, Taku;Takahashi, Satoru;Limtrakul, Pornngarm
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.21
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    • pp.9249-9258
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    • 2014
  • Background: The encapsulation of curcumin (Cur) in polylactic-co-glycolic acid (PLGA) nanoparticles (Cur-NPs) was designed to improve its solubility and stability. Conjugation of the Cur-NPs with anti-P-glycoprotein (P-gp) antibody (Cur-NPs-APgp) may increase their targeting to P-gp, which is highly expressed in multidrugresistance (MDR) cancer cells. This study determined whether Cur-NPs-APgp could overcome MDR in a human cervical cancer model (KB-V1 cells) in vitro and in vivo. Materials and Methods: First, we determined the MDR-reversing property of Cur in P-gp-overexpressing KB-V1 cells in vitro and in vivo. Cur-NPs and Cur-NPs-APgp, in the range 150-180 nm, were constructed and subjected to an in vivo pharmacokinetic study compared with Cur. The in vitro and in vivo MDR-reversing properties of Cur-NPs and Cur-NPs-APgp were then investigated. Moreover, the stability of the NPs was determined in various solutions. Results: The combined treatment of paclitaxel (PTX) with Cur dramatically decreased cell viability and tumor growth compared to PTX treatment alone. After intravenous injection, Cur-NPs-APgp and Cur-NPs could be detected in the serum up to 60 and 120 min later, respectively, whereas Cur was not detected after 30 min. Pretreatment with Cur-NPs-APgp, but not with NPs or Cur-NPs, could enhance PTX sensitivity both in vitro and in vivo. The constructed NPs remained a consistent size, proving their stability in various solutions. Conclusions: Our functional Cur-NPs-APgp may be a suitable candidate for application in a drug delivery system for overcoming drug resistance. The further development of Cur-NPs-APgp may be beneficial to cancer patients by leading to its use as either as a MDR modulator or as an anticancer drug.

Prevalence and Characteristics of Antimicrobial-Resistant Staphylococcus aureus and Methicillin-Resistant Staphylococcus aureus from Retail Meat in Korea

  • Kim, Yong Hoon;Kim, Han Sol;Kim, Seokhwan;Kim, Migyeong;Kwak, Hyo Sun
    • Food Science of Animal Resources
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    • v.40 no.5
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    • pp.758-771
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    • 2020
  • This study was to investigate the prevalence and characteristics of antimicrobial-resistant Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) from 4,264 retail meat samples including beef, pork, and chicken in Korea between 2013 and 2018. A broth microdilution antimicrobial susceptibility testing was performed for S. aureus. Molecular typing by multilocus sequence typing (MLST), spa typing, and pulsed-field gel electrophoresis (PFGE), was performed on mecA-positive S. aureus strain. S. aureus was isolated at a rate of 18.2% (777/4,264), of which MRSA comprised 0.7% (29 strains). MLST analysis showed that 11 out of the 29 MRSA isolates were predominantly sequence type (ST) 398 (37.9%). In addition, ST72, ST692, ST188, ST9, and ST630 were identified in the MRSA isolates. The spa typing results were classified into 11 types and showed a high correlation with MLST. The antimicrobial resistance assays revealed that MRSA showed 100% resistance to cefoxitin and penicillin. In addition, resistance to tetracycline (62.1%), clindamycin (55.2%), and erythromycin (55.2%) was relatively high; 27 of the 29 MRSA isolates exhibited multidrug resistance. PFGE analysis of the 18 strains excluding the 11 ST398 strains exhibited a maximum of 100% homology and a minimum of 64.0% homology. Among these, three pairs of isolates showed 100% homology in PFGE; these results were consistent with the MLST and spa typing results. Identification of MRSA at the final consumption stage has potential risks, suggesting that continuous monitoring of retail meat products is required.

Antimicrobial Resistance and the Presence of Virulence Genes in Escherichia coli Strains Isolated from Ruditapes philippinarum in Gomso Bay, Korea (곰소만 해역의 바지락(Ruditapes philippinarum)에서 분리한 대장균 (Escherichia coli)의 항균제 내성 및 병원성 유전자의 보유성)

  • Kim, Tae-Ok;Eom, In-Seon;Park, Kwang-Ho;Park, Kwon-Sam
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.49 no.6
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    • pp.800-806
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    • 2016
  • In total, 151 Escherichia coli isolates from Ruditapes philippinarum in Gomso Bay were analyzed for their susceptibility to 18 different antimicrobial agents and for genes associated with virulence. For virulence genes, each strain of the isolates was positive for the enterotoxigenic E. coli (ETEC)-specific heat-stable toxin (estA), enteroinvasive E. coli (EIEC)-specific invasion-associated locus (iaa) gene and enteropathogenic E. coli (EPEC)-specific attaching and effacing (eae) gene. According to a disk diffusion susceptibility test, resistance to ampicillin was most prevalent (23.2%), followed by resistance to amoxicillin (22.5%), ticarcillin (20.5%), tetracycline (18.5%), nalidixic acid (12.6%), ciprofloxacin (10.6%), streptomycin (9.9%), and chloramphenicol (6.6%). More than 35.8% of the isolates were resistant to at least one antimicrobial agent, and 19.9% were resistant to four or more classes of antimicrobials; these were consequently defined as multidrug resistant. Minimum inhibitory concentration (MIC) ranges for the antimicrobial resistance of the 15 different antimicrobial agents of 54 E. coli strains were confirmed by varying the concentrations from $32-2,048{\mu}g/mL$. Overall, these results not only provide novel insights into the necessity for seawater and R. philippinarum sanitation in Gomso Bay but they also help to reduce the risk of contamination by antimicrobial-resistant bacteria.

Prevalence and antimicrobial resistance of Salmonella spp. isolated from duck farms in Jeollanam-do Province, South Korea

  • Sin-Wook Park;Keon Kim;Chang-Yun Je;Chang-Hyeon Choi;Sang-Gyue Choi;Jong-Soo Lim;Ok-Mi Jeong;Guk-Hyun Suh;Chang-Min Lee
    • Korean Journal of Veterinary Service
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    • v.46 no.3
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    • pp.211-218
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    • 2023
  • This study was carried out to investigate the prevalence and antimicrobial resistance of Salmonella serotypes in duck farms of Jeollanam-do Province, South Korea. A total of 1112 samples (breeder ducks, 286; broiler ducks, 826) were collected from 196 duck farms (breeder duck farms, 25; broiler duck farms, 171) between January 2018 and November 2019. The total prevalence of Salmonella serotypes was 45.4% (89/196) in the duck farms, with no significant difference between prevalence in breeder and broiler duck farms (48% and 45%, respectively; P>0.05). The most prevalent serotype among the 127 Salmonella isolates was Salmonella Typhimurium (20.5%) followed by Salmonella Albany (17.3%), Salmonella Hadar (15.7%), and Salmonella Enteritidis (11.8%). Maximum resistance was observed against penicillin (78.74%), followed by tetracycline (68.50%), and kanamycin (65.35%). Of the 127 isolates, 117 (92.13%) were resistant to ≥3 antimicrobials and 2 to all 18 antimicrobials. Our results demonstrate the presence of Salmonella strains and their resistance to multiple antimicrobials, thus indicating a public health concern in South Korea. The emergence of Salmonella stains that are resistant to multiple drugs highlight the need for careful use of antimicrobials in duck farms.

Distribution and Antibiotic Resistance of Vibrio spp. Isolated from Fishery Products and Coastal Areas in Gyeongsangnam-do (경상남도 유통 어패류와 해양환경에서 분리된 비브리오균속 (Vibrio spp.) 분포 및 항생제 내성 특성)

  • Jin Yeong Tak;Jeong Gil Park;Ji-Young Um;Su Wan Choi;Na Lam Hwang;Mi Suk Kim;Jae Dong Kim
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.56 no.5
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    • pp.626-633
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    • 2023
  • Vibrio spp. are aquatic bacteria that are ubiquitous in warm estuarine and marine environments. Especially, V. vulnificus and V. cholerae are currently known to cause potentially fatal infections in humans. This study investigated the distribution and antibiotic resistance of V. vulnificus and V. cholerae isolated from coastal areas of Gyeongsangnam-do in 2022. A total of 252 samples of water, shellfish and coastal sediment were collected from 7 locations along the coast, and 124 samples of fishery products were collected from markets. Among the 252 samples, forty-four V. vulnificus (11.7%) and fourteen V. cholerae non-O1/non-O139 (3.7%), none of which carried the ctx gene, were isolated. Out of the 124 samples, 6 (4.8%) tested positive for V. vulnificus and V. cholerae was not detected. The isolation rates of V. vulnificus and V. cholerae showed a significant correlation with environmental factors such as seawater temperature and salinity. In an antibiotic resistance test, V. vulnificus was susceptible to amikacin, gentamicin, imipenem trimethoprim/sulfamethoxazole, and ciprofloxacin, but resistant to cefoxitin (100.0%), followed by tetracycline (9.1%). Multidrug resistance was also observed. Continuous monitoring of Vibrio pathogens with water temperature and salinity is expected to help reduce the outbreaks, and rational use of antibiotic agents is needed to prevent the accession of antibiotic-resistant microorganisms in aquatic ecosystems.

H2O2 Generating Ability and Multi-Drug Resistance of Lactic Acid Bacteria Required for Long-Term Inpatient Treatment with Antibiotic Resistance

  • Yuk, Young Sam
    • International journal of advanced smart convergence
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    • v.11 no.4
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    • pp.227-239
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    • 2022
  • Purpose: In our study, in order to find lactic acid bacteria (LAB) with multi-drug resistance to antibiotics, we isolated 140 strains from 15 types of kimchi commercially available in Korea and 20 types of Kimchi made at home from January to December in 2016, and investigated their H2O2 generating ability and multi-drug resistance to antibiotics. Methods: In order to observe the H2O2 generation ability of LAB, we performed the experiment with methods such as Rabe, Hillier, and Kang. To test the antibacterial susceptibility of LAB, we used the disc agar diffusion method using MRS agar (Difco, USA) according to the CLSI and WHO test methods. There are 18 types of antibiotic discs used. Results: Out of the total numbers of 140 strains, 6 strains of Ent. Faecium, 25 strains of L. plantarum, 1 strain of L. rhamnosus, 3 strains of L. sakei, 1 strain of L. acidophilus, 1 strains St. thermophilus, and 7 of unidentified strains generated H2O2. The antibiotic susceptibility of Ent. Faecium indicated SXT, OX, NA, and E; and the antibiotic susceptibility of L. plantarum indicated NA; and the antibiotic susceptibility of St. thermophilus indicated NA, CC, RA, CTT, CM, and P ; and the antibiotic susceptibility of L. rhamnosus indicated SXT, VA, NA and CTT; and the antibiotic susceptibility of 6 strains of L. sakei indicated SXT, OX, NOR, NA, CTT and CIP, all indicating antibiotic resistance. In the case of multi-drug resistance to antibiotics for 53 strains of L. antarum, 8-drug resistance was the most common with 25 strains, followed by 7-drug-resistant strains with 18 strains, 9-drug-resistant strains with 4 strains, 6-drug-resistant strains with 3 strains, 5-drug-resistant strains with 2 strains, and 17-drug-resistant strains with 1 strain. In the case of multi-drug resistance to antibiotics for Ent. Faecium 27 strains, 9-drug resistance was most commonly identified as 9 strains, 8-drug resistance was identified as 6 strains, 7- and 11 drug resistances were identified as 4 strains each, and 4- and 6-drug resistances were identified as 1 strain each. Conclusion: Ent. Faecium, L. plantarum, L. rhamnosus, L. sakei, and St. thermophilus, shown to have anantibacterial activity in previous studies on LAB and shown to have and H2O2 generating ability, antibiotic resistance and multi-drug resistance in this study, are expected to be able to play an excellent role for long-term inpatients to use as an alternative to antibiotics and to cope with emerging antibiotic resistance.

Respiratory Review of 2014: Tuberculosis and Nontuberculous Mycobacterial Pulmonary Disease

  • Park, Cheol Kyu;Kwon, Yong Soo
    • Tuberculosis and Respiratory Diseases
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    • v.77 no.4
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    • pp.161-166
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    • 2014
  • Since tuberculosis (TB) remains a major global health concern and the incidence of multi-drug resistant (MDR)-TB is increasing globally, new modalities for the detection of TB and drug resistant TB are needed to improve TB control. The Xpert MTB/RIF test can be a valuable new tool for early detection of TB and rifampicin resistance, with a high sensitivity and specificity. Late-generation fluoroquinolones, levofloxacin, and moxifloxacin, which are the principal drugs for the treatment of MDR-TB, show equally high efficacy and safety. Systemic steroids may reduce the overall TB mortality attributable to all forms of TB across all organ systems, although inhaled corticosteroids can increase the risk of TB development. Although fixed dose combinations were expected to reduce the risk of drug resistance and increase drug compliance, a recent meta-analysis found that they might actually increase the risk of relapse and treatment failure. Regarding treatment duration, patients with cavitation and culture positivity at 2 months of TB treatment may require more than 6 months of standard treatment. New anti-TB drugs, such as linezolid, bedaquiline, and delamanid, could improve the outcomes in drug-resistant TB. Nontuberculous mycobacterial lung disease has typical clinical and immunological phenotypes. Mycobacterial genotyping may predict disease progression, and whole genome sequencing may reveal the transmission of Mycobacterium abscessus. In refractory Mycobacterium avium complex lung disease, a moxifloxacin-containing regimen was expected to improve the treatment outcome.

Study on Oxytetracycline Resistant Bacteria in the Surface Water Environment (하천에서의 Oxytetracycline 내성주에 관한 연구)

  • Kim, Young Jin;Kim, Jong Oh
    • Journal of Environmental Health Sciences
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    • v.41 no.1
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    • pp.40-48
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    • 2015
  • Objectives: This study aims to understand the concentration, diversity, and antibiotic characteristics of oxytetracycline resistant bacteria present in a surface water environment. Methods: Water sampling was performed in Cheongmi Stream in Gyeonggi-do, Korea in February and August 2014. Water samples collected from two sites were plated in triplicate on tryptic soy agar plates with 30 mg/L of oxytetracycline. Oxytetracycline resistant bacteria were selected from surface water in Cheongmi Stream and were subjected to 16S rDNA analysis for oxytetracycline resistant species determination. Identified resistant strains were tested for resistance to various antibiotics. Results: Results from this study indicate that the dominant resistant organisms in this aquatic environment are from family Acinetobacter and family Aeromonas. As to culturable heterotrophic bacteria, Oxytetracycline resistant bacteria were present 0.45-0.93% during winter and 0.08-0.38% during summer. Most oxytetracycline resistant bacteria exhibited resistance to more than ten of the antibiotics studied. The diversity of oxytetracycline resistant bacteria in winter was higher than in summer. Conclusion: Most of these resistant bacteria are Gram negative and are closely related to pathogenic species. These results suggest that increasing multi-antibiotic resistant bacteria in the surface water environment has a close relation to the reckless use of antibiotics in livestock.

Combination of Curcumin and Paclitaxel-loaded Solid Lipid Nanoparticles to Overcome Multidrug Resistance

  • Li, Rihua;Xu, Wenting;Eun, Jae-Soon;Lee, Mi-Kyung
    • Journal of Pharmaceutical Investigation
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    • v.41 no.6
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    • pp.381-386
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    • 2011
  • Multi-drug resistance (MDR) has been known as a major hurdle in cancer chemotherapy. One of the most clinically significant causes of MDR was the efflux of anticancer agents mediated by p-glycoprotein (p-gp) over-expressed in MDR cancer cells. To overcome MDR, there have been several strategies such as co-administration with p-gp inhibitors and encapsulation of anticancer drugs into drug delivery systems. In the present study, curcumin was evaluated for its potential as p-gp inhibitor and MDR reversal activity when combined with paclitaxel incorporated into lipid nanoparticles (PTX/LN). Western blot assay showed curcumin did not modulate the level of p-gp expression in MCF-7/ADR which is a MDR variant of human breast cancer cell line, MCF-7, and over-expresses p-gp. However, curcumin inhibited p-gp-mediated efflux of calcein in a dose-dependent manner even though it showed lower activity compared to verapamil, a well-known p-gp inhibitor. Incorporation of paclitaxel into lipid nanoparticles partially recovered the anticancer activity of paclitaxel in MCF-7/ADR. The combined use of curcumin and PTX/LN exhibited further full reversal of MDR, suggesting susceptibility of PTX/LN to the efflux system. In conclusion, combined approach of using p-gp inhibitors and incorporation of the anticancer agents into nano-delivery systems would be an efficient strategy to overcome MDR.

in vitro Modulation of P-glycoprotein, MRP-1 and BCRP Expression by Mangiferin in Doxorubicin-Treated MCF-7 Cells

  • Louisa, Melva;Soediro, Tjahjani Mirawati;Suyatna, Frans Dhyanagiri
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.4
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    • pp.1639-1642
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    • 2014
  • The multidrug resistance phenotype is one of the major problems in development of cancer cell resistance to chemotherapy. Some natural compounds from medicinal plants have demonstrated promising capacity in enhancing anticancer effects in drug resistant cancer cells. We aimed to investigate whether mangiferin might have an ability to re-sensitize MCF-7 breast cancer cells previously treated with short-term doxorubicin in vitro, through the modulation of efflux transporters, P-glycoprotein (P-gp), MRP1 and BCRP. We exposed MCF-7 breast cancer cells pretreated with doxorubicin for 10 days to mangiferin (10, 25 or 50 ${\mu}M$) for 96 hours. Afterwards, we evaluated influence on cell viability and level of mRNA expression of P-gp, MRP1 and BCRP. Doxorubicin given in combination with mangiferin at low concentrations (10 and 25 ${\mu}M$) failed to give significant reduction in cell viability, while at the highest concentrations, the combination significantly reduced cell viability. The mRNA expression analysis of P-gp, MRP1 and BCRP showed that mangiferin had inhibitory effects on P-gp but no effects on MRP1 and BCRP. In conclusion, we suggest that mangiferin at high concentrations can be used as chemosensitizer for doxorubicin therapy. This effect might be attributed by inhibitory effects of mangiferin on P-glycoprotein expression.