• Archives of Pharmacal Research
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• v.21 no.3
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• pp.344-347
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• 1998

To overcome multidrug resistance (MDR) in cancer chemotherapy, we prepared various plant extracts and searched for a component which is effective for inhibition of MDR. MDR inhibition activity was determined by measuring cytotoxicity to MDR cells using multidrug resistant human fibrocarcinoma KB V20C, which is resistant to 20 nM vincristine and expresses high level of mdr1 gene. Of various plant extracts, the MeOH extract of the root of Aconitum pseudo-laeve var. erectum was found to have potent inhibitory activity on MDR. The bioassayguided fractionation of the MeOH extract of the plant led to the isolation of an alkaloid, lycaconitine, as an active principle. And the $IC_{50}$ of lycaconitne for KB V20C cells was $74\mu{g}$/ml.

• Archives of Pharmacal Research
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• v.19 no.3
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• pp.213-218
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• 1996

Multidrug resistance (MDR) has been a major problem in cancer chemotherapy. To overcome this problem, we prepared minor ginsenosides stereoselectively from ginseng saponins and searched for a ginseng component which is effective for inhibition of MDR. MDR inhibition activity was determined by measuring cytotoxicity to MDR cells using multidrug resistant human fibrocarcinoma KB V20C, which is resistant to 20 nM vincristine and expresses high level of mdr1 gene. Of several ginseng components, 20(S)-ginsenoside Rg_3$, a red ginseng saponin, was found to have the most potent inhibitory activity on MDR and it's concentration capable of inhibiting 50% growth was $82\muM$.

• Korean Journal of Clinical Pharmacy
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• v.22 no.2
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• pp.181-186
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• 2012

Objective: To report a fatal case of Multidrug-resistant Acinetobacter baumannii (MDR-AB) in a patient with interstitial lung disease (ILD) on high-dose glucocorticoids. Case Summary: A 66-year-old man with a history of coniosis was transferred to the hospital with progressive cough and sputum production. This patient has been diagnosed with pneumonia and ILD on admission, requires antimicrobial therapy and systemic immunosuppressants. He received high dose of methylprednisolone and cyclophosphamide for ILD as well as ceftriaxone and azithromycin for pneumonia. On day 7 in the intensive care units (ICUs), patient had fever and leukocytosis, thus antimicrobials were switched to piperacillin. After 13 days in the ICU, Acinetobacter baumannii and methicillin-resistant Staphylococcus aureus (MRSA) were isolated on transtracheal aspirate (TTA) and meropenem was initiated. However, it was revealed a multidrug-resistant Acinetobacter baumannii (MDR-AB) species, resistant to carbapenem. Patient was administered colistin but expired due to septic shock on day 84. Discussion: Systemic immunosuppressive therapy can result in infections that may compromise patient's survival. MDR-AB has emerged as a serious cause of nosocomial infections in immunocompromised patients. MDR-AB is resistant to most standard antimicrobials and therapeutic options are limited. Conclusion: We report our recent experience with a fatal MDR-AB pneumonia in a patient with ILD, who had to be treated with high dose glucocorticoids and immunosuppressnts.

• Journal of Yeungnam Medical Science
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• v.37 no.4
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• pp.277-285
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• 2020

Tuberculosis (TB) is still a major health problem worldwide. Especially, multidrug-resistant TB (MDR-TB), which is defined as TB that shows resistance to both isoniazid and rifampicin, is a barrier in the treatment of TB. Globally, approximately 3.4% of new TB patients and 20% of the patients with a history of previous treatment for TB were diagnosed with MDR-TB. The treatment of MDR-TB requires medications for a long duration (up to 20-24 months) with less effective and toxic second-line drugs and has unfavorable outcomes. However, treatment outcomes are expected to improve due to the introduction of a new agent (bedaquiline), repurposed drugs (linezolid, clofazimine, and cycloserine), and technological advancement in rapid drug sensitivity testing. The World Health Organization (WHO) released a rapid communication in 2018, followed by consolidated guidelines for the treatment of MDR-TB in 2019 based on clinical trials and an individual patient data meta-analysis. In these guidelines, the WHO suggested reclassification of second-line anti-TB drugs and recommended oral treatment regimens that included the new and repurposed agents. The aims of this article are to review the treatment strategies of MDR-TB based on the 2019 WHO guidelines regarding the management of MDR-TB and the diagnostic techniques for detecting resistance, including phenotypic and molecular drug sensitivity tests.

• Tuberculosis and Respiratory Diseases
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• v.80 no.4
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• pp.336-343
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• 2017

Despite progress made in tuberculosis control worldwide, the disease burden and treatment outcome of multidrug-resistant tuberculosis (MDR-TB) patients have remained virtually unchanged. In 2016, the World Health Organization released new guidelines for the management of MDR-TB. The guidelines are intended to improve detection rate and treatment outcome for MDR-TB through novel, rapid molecular testing and shorter treatment regimens. Key changes include the introduction of a new, shorter MDR-TB treatment regimen, a new classification of medicines and updated recommendations for the conventional MDR-TB regimen. This paper will review these key changes and discuss the potential issues with regard to the implementation of these guidelines in South Korea.

• Journal of Yeungnam Medical Science
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• v.14 no.1
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• pp.67-76
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• 1997

The occurrence of multidrug resistance (MDR) is one of the main obstacles in the successful chemotherapeutic treatment of cancer. In this study The gene expressions of multidrug resistance-associated protein (MRP), c-myc and c-fos were investigated in L1210 cells. Adriamycin- or vincristine-resistant L1210 cells, L1210AdR or L1210VcR, respectively, has been identified to overexpression of mdr1 gene. The expression leve of MRP gene in L1210AdR and L1210Cis was more decreased than that in L1210 cells. The c-myc and c-fos genes were expressed both in L1210 and resistant sublines. In L1210AdR, the expressions level of c-myc and c-fos genes were decreased than in L1210. However, in L1210VcR and L1210Cis, c-myc and c-fosgene expressionwere rather increased than L1210. These results suggested that MRP does not contribute in resistance of drug-resistant L1210 cells and there is no relations between MRP and mdr1 gene expression. The expression of c-myc and c-fos gene may be changed during transformation of L1210 to drug-resistant sublines.

• Journal of Microbiology and Biotechnology
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• v.29 no.9
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• pp.1460-1469
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• 2019

The extensive distribution of multidrug-resistant (MDR) methicillin-resistant Staphylococcus aureus (MRSA) poses a threat to healthcare worldwide. This study aimed to investigate the MDR and molecular patterns of MRSA isolates in children admitted to the two biggest tertiary care pediatric hospitals in northern and southern Vietnam. A total of 168 MRSA strains were collected to determine antibiotic susceptibility by minimum inhibitory concentration tests. Antibiotic-resistant genes, pulsed-field gel electrophoresis, staphylococcal cassette chromosome mec (SCCmec) typing, and multilocus sequence typing were used for the molecular characterization of MRSA. Among the total strains, the MDR rate (51.8%) was significantly higher in the northern hospital than in the southern hospital (73% vs. 39%, p < 0.0001). The MDR-MRSA with the highest rates were "ciprofloxacin-erythromycin-gentamicintetracyclines" (35.6%), followed by "erythromycin-tetracycline-chloramphenicol" (24.1%), and "ciprofloxacin-erythromycin-gentamicin" (19.5%), showing an accumulative total of 79.3%. The most susceptible antibiotics were rifampicin (100%) and vancomycin (100%), followed by doxycycline (94.0%), meropenem (78.0%), and cefotaxime (75.0%). The SCCmecII strains showed greater resistance to gentamicin, ciprofloxacin, tetracycline, meropenem and cephalosporins compared with the other strains. The SCCmecII strains exhibited the highest rate in the tested genes (aacA/aphD: 55.2%, ermA/B/C: 89.7%, and tetK/M: 82.8%). ST5-SCCmecII was the predominant clone in the northern hospital, whereas SCCmecIVa was more pronounced in the southern hospital. In conclusion, our results raised concerns about the predominant MDR-MRSA strains in the pediatric hospitals in Vietnam. The north-south difference in the antibiotic resistance patterns and genetic structure of MRSA suggests different MRSA origins and various uses of antimicrobial agents between the two regions.

• 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.

• Biomedical Science Letters
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• v.13 no.1
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• pp.47-53
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• 2007

Due to wide abuse of antibiotics both in human and livestock use, the advent and spread of multidrug resistant (MDR) pathogens becomes a serious health problem all over the world. Since the development of new antibiotics is at a standstill in pharmaceutical industry, the choice of therapeutic antibiotics is getting narrower. In this study, in an effort to search new antibiotics, the antimicrobial activity of Paenibacillus DY1 isolated from Korean soil was characterized on its growth inhibition spectrum against various health threatening MDR strains, with its stability and chemical structure. Extracellular culture filtrate of Paenibacillus DY1 effectively inhibits the growth of all the tested MDR enteropathogenic Eshcherichia coli, enterohemolytic E. coli, and enterotoxigenic E. coli strains, at a similar level to that on the nonresistant control E. coli strains. It showed significant growth inhibition effect against the causative agents of class one legal communicable disease, MDR Salmonella typhi, MDR Salmonella paratyphi A, food poisoning bacteria, MDR Salmonella typhimurium, and other MDR Salmonella spp. The growth of all of 10 different MDR Shigella spp. strains and 6 different Vibrio spp. strains tested was also inhibited. The antimicrobial activity of Paenibacillus DY1 was well preserved after heat treatment, and was also stable in both alkaline and acidic environment. The antimicrobial activity was partially purified with Diaion HP20 column and TLC. By NMR study, the putative structure of the activity was postulated as an alkane having hydroxyl groups.

• Tuberculosis and Respiratory Diseases
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• v.85 no.2
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• pp.111-121
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• 2022

Multidrug-resistant tuberculosis (MDR-TB) is caused by an organism that is resistant to both rifampicin and isoniazid. Extensively drug-resistant TB, a rare type of MDR-TB, is caused by an organism that is resistant to quinolone and one of group A TB drugs (i.e., linezolid and bedaquiline). In 2018, the World Health Organization revised the groupings of TB medicines and reclassified linezolid as a group A drug for the treatment of MDR-TB. Linezolid is a synthetic antimicrobial agent in the oxazolidinone class. Although linezolid has a good efficacy, it can cause substantial adverse events, especially hematologic toxicity. In both TB infection and linezolid mechanism of action, mitochondrial dysfunction plays an important role. In this concise review, characteristics of linezolid as an anti-TB drug are summarized, including its efficacy, pathogenesis of hematologic toxicity highlighting mitochondrial dysfunction, and the monitoring and management of hematologic toxicity.