• Title/Summary/Keyword: Drug Susceptibility

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Plasmodium vivax Drug Resistance Genes; Pvmdr1 and Pvcrt-o Polymorphisms in Relation to Chloroquine Sensitivity from a Malaria Endemic Area of Thailand

  • Rungsihirunrat, Kanchana;Muhamad, Poonuch;Chaijaroenkul, Wanna;Kuesap, Jiraporn;Na-Bangchang, Kesara
    • Parasites, Hosts and Diseases
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    • v.53 no.1
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    • pp.43-49
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    • 2015
  • The aim of the study was to explore the possible molecular markers of chloroquine resistance in Plasmodium vivax isolates in Thailand. A total of 30 P. vivax isolates were collected from a malaria endemic area along the Thai-Myanmar border in Mae Sot district of Thailand. Dried blood spot samples were collected for analysis of Pvmdr1 and Pvcrt-o polymorphisms. Blood samples ($100{\mu}l$) were collected by finger-prick for in vitro chloroquine susceptibility testing by schizont maturation inhibition assay. Based on the cut-off $IC_{50}$ of 100 nM, 19 (63.3%) isolates were classified as chloroquine resistant P. vivax isolates. Seven non-synonymous mutations and 2 synonymous were identified in Pvmdr1 gene. Y976F and F1076L mutations were detected in 7 (23.3%) and 16 isolates (53.3%), respectively. Analysis of Pvcrt-o gene revealed that all isolates were wild-type. Our results suggest that chloroquine resistance gene is now spreading in this area. Monitoring of chloroquine resistant molecular markers provide a useful tool for future control of P. vivax malaria.

Conditioning-induced cardioprotection: Aging as a confounding factor

  • Randhawa, Puneet Kaur;Bali, Anjana;Virdi, Jasleen Kaur;Jaggi, Amteshwar Singh
    • The Korean Journal of Physiology and Pharmacology
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    • v.22 no.5
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    • pp.467-479
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    • 2018
  • The aging process induces a plethora of changes in the body including alterations in hormonal regulation and metabolism in various organs including the heart. Aging is associated with marked increase in the vulnerability of the heart to ischemia-reperfusion injury. Furthermore, it significantly hampers the development of adaptive response to various forms of conditioning stimuli (pre/post/remote conditioning). Aging significantly impairs the activation of signaling pathways that mediate preconditioning-induced cardioprotection. It possibly impairs the uptake and release of adenosine, decreases the number of adenosine transporter sites and down-regulates the transcription of adenosine receptors in the myocardium to attenuate adenosine-mediated cardioprotection. Furthermore, aging decreases the expression of peroxisome proliferator-activated receptor gamma co-activator 1-alpha ($PGC-1{\alpha}$) and subsequent transcription of catalase enzyme which subsequently increases the oxidative stress and decreases the responsiveness to preconditioning stimuli in the senescent diabetic hearts. In addition, in the aged rat hearts, the conditioning stimulus fails to phosphorylate Akt kinase that is required for mediating cardioprotective signaling in the heart. Moreover, aging increases the concentration of $Na^+$ and $K^+$, connexin expression and caveolin abundance in the myocardium and increases the susceptibility to ischemia-reperfusion injury. In addition, aging also reduces the responsiveness to conditioning stimuli possibly due to reduced kinase signaling and reduced STAT-3 phosphorylation. However, aging is associated with an increase in MKP-1 phosphorylation, which dephosphorylates (deactivates) mitogen activated protein kinase that is involved in cardioprotective signaling. The present review describes aging as one of the major confounding factors in attenuating remote ischemic preconditioning-induced cardioprotection along with the possible mechanisms.

Prevalence of Drug Resistance-Associated Gene Mutations in Plasmodium vivax in Central China

  • Lu, Feng;Wang, Bo;Cao, Jun;Sattabongkot, Jetsumon;Zhou, Huayun;Zhu, Guoding;Kim, Kwonkee;Gao, Qi;Han, Eun-Taek
    • Parasites, Hosts and Diseases
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    • v.50 no.4
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    • pp.379-384
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    • 2012
  • Resistance of Plasmodium spp. to anti-malarial drugs is the primary obstacle in the fight against malaria, and molecular markers for the drug resistance have been applied as an adjunct in the surveillance of the resistance. In this study, we investigated the prevalence of mutations in pvmdr1, pvcrt-o, pvdhfr, and pvdhps genes in temperate-zone P. vivax parasites from central China. A total of 26 isolates were selected, including 8 which were previously shown to have a lower susceptibility to chloroquine in vitro. For pvmdr1, pvcrt-o, and pvdhps genes, no resistance-conferring mutations were discovered. However, a highly prevalent (69.2%), single-point mutation (S117N) was found in pvdhfr gene. In addition, tandem repeat polymorphisms existed in pvdhfr and pvdhps genes, which warranted further studies in relation to the parasite resistance to antifolate drugs. The study further suggests that P. vivax populations in central China may still be relatively susceptible to chloroquine and sulfadoxine-pyrimethamine.

Genetic Variations of ABCC2 Gene Associated with Adverse Drug Reactions to Valproic Acid in Korean Epileptic Patients

  • Yi, Ji Hyun;Cho, Yang-Je;Kim, Won-Joo;Lee, Min Goo;Lee, Ji Hyun
    • Genomics & Informatics
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    • v.11 no.4
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    • pp.254-262
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    • 2013
  • The multidrug resistance protein 2 (MRP2, ABCC2) gene may determine individual susceptibility to adverse drug reactions (ADRs) in the central nervous system (CNS) by limiting brain access of antiepileptic drugs, especially valproic acid (VPA). Our objective was to investigate the effect of ABCC2 polymorphisms on ADRs caused by VPA in Korean epileptic patients. We examined the association of ABCC2 single-nucleotide polymorphisms and haplotype frequencies with VPA related to adverse reactions. In addition, the association of the polymorphisms with the risk of VPA related to adverse reactions was estimated by logistic regression analysis. A total of 41 (24.4%) patients had shown VPA-related adverse reactions in CNS, and the most frequent symptom was tremor (78.0%). The patients with CNS ADRs were more likely to have the G allele (79.3% vs. 62.7%, p=0.0057) and the GG genotype (61.0% vs. 39.7%, p=0.019) at the g.-1774delG locus. The frequency of the haplotype containing g.-1774Gdel was significantly lower in the patients with CNS ADRs than without CNS ADRs (15.8% vs. 32.3%, p=0.0039). Lastly, in the multivariate logistic regression analysis, the presence of the GG genotype at the g.-1774delG locus was identified as a stronger risk factor for VPA related to ADRs (odds ratio, 8.53; 95% confidence interval, 1.04 to 70.17). We demonstrated that ABCC2 polymorphisms may influence VPA-related ADRs. The results above suggest the possible usefulness of ABCC2 gene polymorphisms as a marker for predicting response to VPA-related ADRs.

Efficacy of Disinfectants against Health-Associated Multi-drug Resistant Clinical Isolates

  • An, Jeong-Lib;Kim, Sang-Ha;Yu, Young-Bin;Kim, Sunghyun;Lee, Moo-Sik;Kim, Young-Kwon
    • Biomedical Science Letters
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    • v.27 no.4
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    • pp.264-269
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    • 2021
  • The purpose of this study was to evaluate the disinfecting efficacy of peracetic acid (PAA), sodium hypochlorite (NaOCl) and phenol, which are representative disinfectants in medical environments using four types of multi-drug resistance (MDR) clinical isolates with healthcare-associated infections (HAI). 26 antibiotic susceptibility tests were conducted for the four types of MDR clinical isolates in the same way as for clinical specimens. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of the disinfectants were determined by using in vitro liquid medium dilution method and inoculation of the plate medium. Both the MIC and MBC of phenol against MRSA and VRE were 3.1%, while those against KPC and MRPA were 6.2%. The MIC and MBC of peracetic acid (PAA) against MRSA, VRE, KPC, and MRPA were 0.18%. The MIC and MBC of sodium hypochlorite (NaOCl) against MRSA were 0.39% and 0.78%, respectively. Both values of MIC and MBC were 0.78% for VRE. In addition, KPC and MRPA showed 0.39% for MIC and 0.78% for MBC. For all MDR strains used in this study, sodium hypochlorite and peracetic acid showed significant sterilizing efficiency, while no clear correlation was identified between antibiotic resistance clinical isolated and ability of disinfection.

Impact of Anti-Tuberculosis Drug Use on Treatment Outcomes in Patients with Pulmonary Fluoroquinolone-Resistant Multidrug-Resistant Tuberculosis: A Nationwide Retrospective Cohort Study with Propensity Score Matching

  • Hongjo Choi;Dawoon Jeong;Young Ae Kang;Doosoo Jeon;Hee-Yeon Kang;Hee Jin Kim;Hee-Sun Kim;Jeongha Mok
    • Tuberculosis and Respiratory Diseases
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    • v.86 no.3
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    • pp.234-244
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    • 2023
  • Background: Effective treatment of fluoroquinolone-resistant multidrug-resistant tuberculosis (FQr-MDR-TB) is difficult because of the limited number of available core anti-TB drugs and high rates of resistance to anti-TB drugs other than FQs. However, few studies have examined anti-TB drugs that are effective in treating patients with FQr-MDR-TB in a real-world setting. Methods: The impact of anti-TB drug use on treatment outcomes in patients with pulmonary FQr-MDR-TB was retrospectively evaluated using a nationwide integrated TB database (Korean Tuberculosis and Post-Tuberculosis). Data from 2011 to 2017 were included. Results: The study population consisted of 1,082 patients with FQr-MDR-TB. The overall treatment outcomes were as follows: treatment success (69.7%), death (13.7%), lost to follow-up or not evaluated (12.8%), and treatment failure (3.9%). On a propensity-score-matched multivariate logistic regression analysis, the use of bedaquiline (BDQ), linezolid (LZD), levofloxacin (LFX), cycloserine (CS), ethambutol (EMB), pyrazinamide, kanamycin (KM), prothionamide (PTO), and para-aminosalicylic acid against susceptible strains increased the treatment success rate (vs. unfavorable outcomes). The use of LFX, CS, EMB, and PTO against susceptible strains decreased the mortality (vs. treatment success). Conclusion: A therapeutic regimen guided by drug-susceptibility testing can improve the treatment of patients with pulmonary FQr-MDR-TB. In addition to core anti-TB drugs, such as BDQ and LZD, treatment of susceptible strains with later-generation FQs and KM may be beneficial for FQr-MDR-TB patients with limited treatment options.

Characterization of Extended Spectrum Beta-Lactamases (ESBL) Producing Escherichia coli Isolates from Surface Water Adjacent to Pharmaceutical Industries in Bangladesh: Antimicrobial Resistance and Virulence Pattern

  • Taslin Jahan Mou;Nasrin Akter Nupur;Farhana Haque;Md Fokhrul Islam;Md. Shahedur Rahman;Md. Amdadul Huq;Anowar Khasru Parvez
    • Microbiology and Biotechnology Letters
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    • v.51 no.3
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    • pp.268-279
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    • 2023
  • The pharmaceutical industry in Bangladesh produces a diverse range of antibiotics for human and animal use, however, waste disposal management is inadequate. This results in substantial quantities of antibiotics being discharged into water bodies, which provide suitable environment for the growth of antibiotic-resistant bacteria, capable of spreading resistance genes. This study intended for exploring the bacterial antibiotic resistance profile in adjoining aquatic environmental sources of pharmaceutical manufacturing facilities in Bangladesh. Seven surface water samples were collected from the vicinity of two pharmaceutical industries located in the Savar area and 51 Escherichia coli isolates were identified using both phenotypic and genotypic methods. Antibiotic susceptibility tests revealed the highest percentage of resistance against ampicillin, azithromycin, and nalidixic acid (100%) and the lowest resistance against meropenem (1.96%) out of sixteen different antibiotics tested. 100% of the study E. coli isolates were observed with Multidrug resistance phenotypes, with the Multiple Antibiotic Resistance (MAR) value ranging from 0.6-1.0. Furthermore, 69% of the isolates were Extended Spectrum Beta-Lactamases (ESBL) positive as per the Double Disk Diffusion Synergy Test (DDST). ESBL resistance genes blaTEM, blaCTX-M-13, blaCTX-M-15, and blaSHV were detected in 70.6% (n = 36), 60.8% (n = 32), 54.9% (n = 28), and 1.96% (n = 1) of the isolates, respectively, by Polymerase Chain Reaction (PCR). Additionally, 15.68% (n = 8) of the isolates were positive for E. coli specific virulence genes in PCR. These findings suggest that pharmaceutical wastewater, if not properly treated, could be a formidable source of antibiotic resistance spread in the surrounding aquatic environment. Therefore, continued surveillance for drug resistance among bacterial populations around drug manufacturing facilities in Bangladesh is necessary, along with proper waste disposal management.

The distribution and antimicrobial susceptibility of pathogenic microorganisms isolated from chicken slaughtering and processing procedure (닭 도계 및 가공공정 중 유해미생물의 분포와 항생제 감수성)

  • Seol, Kuk-Hwan;Kim, Ki Hyun;Jo, Su-Mi;Kim, Young Hwa;Kim, Hyun-Wook;Ham, Jun-Sang
    • Korean Journal of Agricultural Science
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    • v.42 no.1
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    • pp.29-35
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    • 2015
  • This study was performed to analyze the distribution and antimicrobial resistance of pathogenic microorganisms isolated from the carcass and environments of chicken processing plant located in Gyeonggi province from October to November in 2010. Chicken slaughterhouse was visited 3 times and totally 40 samples were collected from chicken carcass before and after washing (n=14), chicken cuts (n=7), cooling water (n=8), brine (n=2), cutting knives (n=7) and working plate (n=2). Whole-chicken rinsing technique (for chicken carcasses) and swab technique (for working plate and knives) were used to analyze the distribution of pathogenic microorganisms. In addition, brine and chilling water from storage tanks were gathered using sterilized tubes and used as samples. The matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) for whole cell fingerprinting in combination with a dedicated bioinformatic software tool was used to identify the isolated microorganisms. The pathogenic microorganisms, such as Bacillus cereus (n=8) and Staphylococcus aureus (n=9), were isolated form the chicken processing process (chicken carcasses of before and after chilling, chicken cuts, and working plate). The antimicrobial susceptibility of those isolated microorganisms was analyzed using 21 antimicrobial agents. In the case of B. cereus, it showed 100% of resistance to subclasses of penicillins and peptides, and it also resistant to cephalothin, a member of critically important antimicrobials (CIA), however there was no resistance (100% susceptible) to vancomycin and chloramphenicol. S. aureus showed 100% resistance to subclasses of peptides and some of penicillins (penicillin and oxacillin), however, it showed 100% susceptibility to cephalosporins (cefazolin and cephalothin). All of the tested pathogens showed multi drug resistance (MDR) more than 4 subclasses and one of B. cereus and S. aureus showed resistance to 9 subclasses. After the ban on using the antimicrobials in animal feed in July 2011, there would be some change in microbial distribution and antimicrobial resistance, and it still has a need to be analyzed.

Trends of Antifungal Agent Susceptibility of Candida Strains Isolated from Blood Cultures in 2009~2018 (2009~2018년 혈액배양으로부터 분리된 Candida 균종의 항진균제 감수성의 경향)

  • Hwang, Yu-Yean;Kang, On-Kyun;Park, Chang-Eun;Lee, Moo-Sik;Kim, Young-Kwon;Huh, Hee-Jae;Lee, Nam-Yong
    • Korean Journal of Clinical Laboratory Science
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    • v.54 no.2
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    • pp.133-141
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    • 2022
  • Candida is one of the most common causes of bloodstream infections and a leading cause of morbidity and mortality among hospitalized patients. The purpose of this study was to provide important information for formulating empirical treatment plans for candidemia by investigating the antifungal resistance rate of Candida. Among the Candida strains (973 cases) isolated from blood culture tests at the S hospital in 2009~2018, 4.7% (N=44) comprising the Candida spp. (932 strains) showed resistance to fluconazole. The resistant strains included C. albicans, C. parapsilosis, C. tropicalis, and C. glabrata. In addition Candida spp. (947 strains) showed resistance to amphotericin B (N=6, 0.6%), flucytosine (N=23, 2.4%) and voriconazole (N=24, 3.1%). C. albicans was resistant to fluconazole (N=23, 6.9%) and voriconazole (N=21, 6.0%), The statistical analysis showed that C. albicans and non-albicans Candida species were resistant to fluconazole (P=0.039) and voriconazole (P<0.001). A monitoring system to understand the rate of candidiasis infections in a hospital setting is required. It is also important to make the right choice of the antifungal agent based on drug susceptibility patterns. Therefore, an infection surveillance policy that tracks Candida resistance through regular antifungal susceptibility tests is necessary.

Evaluation and Improvement of Bioassay for Residual Antibiotics in Foods (식품 내의 잔류 항생제에 대한 미생물학적 간이검사법의 평가 및 개선)

  • Park, Min-Hee;Kim, Tae-Woon;Jo, Nam-Uk;Jeong, Ji-Yoon;Lee, Soon-Ho;Lee, Jong-Ok;Kim, Hae-Yeong
    • Microbiology and Biotechnology Letters
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    • v.36 no.4
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    • pp.360-365
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    • 2008
  • For the screening of residual antibiotics in foods, bioassays and microbiological inhibitor tests are commonly applied. These methods are tested by the various susceptibility of bacteria against different kinds of antibiotics. However, the sensitivity of bioassay is generally insufficient to detect some residual antibiotics at level of interest. This study was performed to investigate the detection limit of variable antibiotics of the bioassay and to improve the sensitivity to some antibiotics. The sensitivity of bioassay using Bacillus megaterium ATCC 9885, B. subtilis ATCC 6633, B. cereus ATCC 11778 and Geobacillus stearothermophilus ATCC 10149 was low in the detection of macrolides, quinolones, chloramphenicol, and monensin. On the contrary, Micrococcus luteus ATCC 9341 showed high sensitivity to macrolides and Escherichia coli ATCC 11303 was highly sensitive to quinolones and aminoglycosides. Consequently, both strains would be useful to improve sensitivity of bioassay with a wide detection range.