• Title/Summary/Keyword: Multidrug-Resistant

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Concise Clinical Review of Hematologic Toxicity of Linezolid in Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis: Role of Mitochondria

  • Oehadian, Amaylia;Santoso, Prayudi;Menzies, Dick;Ruslami, Rovina
    • 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.

Antimicrobial Activity of Fruit of Crataegus pinnatifida Bunge against Multidrug Resistant Pathogenic Pseudomonas aeruginosa and Candida sp. (항생제 다제내성 Pseudomonas aeruginosa 및 Candida 균주에 대한 산사자의 항균 활성)

  • Ryu, Hee-Young;Ahn, Seon-Mi;Kim, Jong-Sik;Jung, In-Chang;Sohn, Ho-Yong
    • Microbiology and Biotechnology Letters
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    • v.38 no.1
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    • pp.77-83
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    • 2010
  • The fructus of Crataegus pinnatifida Bunge (CBF) has been used as medicinal and food source in worldwide. In this study, antimicrobial activity of the methanol extract and its sequential organic solvent fractions of CBF against different pathogenic bacteria and fungi, including multidrug resistant Pseudomonas aeruginosa and Candida sp., were investigated. The methanol extract of CBF was active against various gram-positive and gram-negative bacteria, and the ethylacetate and butanol fractions of CBF showed strong antibacterial activity against Listeria monocytogenes, Staphylococcus epidermidis, Staphylococcus aureus, Bacillus subtilis, Salmonella typhimurium, Proteus vulgaris, Escherichia coli and various multidrug resistant Pseudomonas aeruginosa with minimal inhibitory concentration of 1.0~7.5 mg/mL. Also the fractions showed anti-Candida activity against C. albicans, C. kruseis and C. geochares. The methanol extract of CBF and its solvent fractions, except n-hexane fraction, did not show any hemolytic activity against human red blood cell up to $500\;{\mu}g/mL$, respectively. The hemolysis in n-hexane fraction at $500\;{\mu}g/mL$ was less than 9.9%. Our results suggest that the CBF could be developed as a potent antibacterial agent, especially for multidrug resistant Pseudomonas aeruginosa.

Multidrug-resistant Staphylococci Found on Book Surfaces in East London Libraries

  • Idris, Adi;Cutler, Ron R
    • Microbiology and Biotechnology Letters
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    • v.45 no.4
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    • pp.354-357
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    • 2017
  • There is an increase in the presence of drug-resistant staphylococci outside of the nosocomial and healthcare setting. Although the presence of staphylococci has been studied in several public spaces, nothing is known on the presence of staphylococci in public libraries. Book surfaces from public libraries in the East London area, United Kingdom were swabbed and cultured and identity of the isolates determined by matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry (MS). Seven different staphylococcal species were identified by MALDI-TOF-MS analysis. This short study provides evidence of the presence of multidrug-resistant staphylococci in public libraries in the East London area.

Isolation and Properties of Cytotoxic Antibiotics Produced by Myxococcus stipitatus JW150 (Myxococcus stipitatus JW150이 생산하는 세포독성 물질의 분리 및 특성)

  • 안종웅;이정옥
    • YAKHAK HOEJI
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    • v.46 no.2
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    • pp.108-112
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    • 2002
  • Drug resistance is one of the most significant impediments to successful chemotherapy of cancer. Multidrug-resistance (MDR) is characterized by decreased cellular sensitivity to anticancer agents due to the overexpression of P-glycoprotein. By employing a resistant subline of HCT15 to adriamycin (CL02), we undertook the screening for agents which were effective to multidrug-resistant cancer cells. As a result, a myxobacterial strain JW150 was selected for study since an activity against CL02 cells was discovered in the strain. Cytotoxicity-guided fractionation of the culture broth led to the isolation of cystothiazole A and melithiazole F. The producing organism was identified as Myxococcus stipitatus by taxonomic comparison with type strains of Myxococcus sp. as well as its morphological and physiological characteristics. Cystothiazole A and melithiazole F demonstrated potent cytotoxicity against certain human cancer cells with $IC_{50}$ values ranging from 0.03~ $0.72{\mu}{\textrm{g}}$/ml. Both compounds were interestingly as active against drug-resistant sublines CL02 and CP70 as against the corresponding parental cells.

WHO Treatment Guidelines for Drug-Resistant Tuberculosis, 2016 Update: Applicability in South Korea

  • Jeon, Doosoo
    • 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.

Characterization of Tetracycline Resistance Plesmid of Multidrug-resistant Staphylococcus aureus (다제내성 황색포도상구균이 가지고 있는 테트라사이클린 내성 플라스미드의 동정)

  • 이대운;문경호
    • YAKHAK HOEJI
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    • v.39 no.1
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    • pp.6-9
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    • 1995
  • The clinical isolate Staphylococcus aureus SA2 had four kinds of plasmids and was resistant to ampicillin, chloramphenicol, clindamycin, erythromycin, gentamicin, kanamycin, methicillin, streptomycin, tetracycline and tobramycin. Transformation experiment demonstrated that 4.44 kb plasmid(pKH6) encoded resistance to tetracycline. The cleavage map of pKH6 was determined by restriction enzyme mapping techniques. The cleavage map is given for EcoRV, HindIII, HpaI, HpaII, KpnI and Xbal. Restriction endonucleases BamHl, BglI, BGIII, BstEII, EcoRI, HaellI, PstI, PvuII, SalI, Smal, and Xhol have no site on this plasmid. The restriction map revealed extensive structural homology between pKH6 and pT181.

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Treatment Outcomes of Patients with Multidrug-Resistant Tuberculosis: Comparison of Pre- and Post-Public-Private Mix Periods

  • Kang, Yewon;Jo, Eun-Jung;Eom, Jung Seop;Kim, Mi-Hyun;Lee, Kwangha;Kim, Ki Uk;Park, Hye-Kyung;Lee, Min Ki;Mok, Jeongha
    • Tuberculosis and Respiratory Diseases
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    • v.84 no.1
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    • pp.74-83
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    • 2021
  • Background: This study compared the treatment outcomes of patients with multidrug-resistant tuberculosis (MDR-TB) before and after the implementation of public-private mix (PPM). Factors affecting treatment success were also investigated. Methods: Data from culture-confirmed pulmonary MDR-TB patients who commenced MDR-TB treatment at Pusan National University Hospital between January 2003 and December 2017 were retrospectively reviewed. Patients were divided into two groups in terms of PPM status: pre-PPM period, patients who commenced MDR-TB treatment between 2003 and 2010; and post-PPM period, patients treated between 2011 and 2017. Results: A total of 176 patients were included (64 and 112 in the pre- and post-PPM periods, respectively). 36.9% of the patients were resistant to a fluoroquinolone or a second-line injectable drug, or both. The overall treatment success rate was 72.7%. The success rate of post-PPM patients was higher than that of pre-PPM patients (79.5% vs. 60.9%, p=0.008). Also, loss to follow-up was lower in the post-PPM period (5.4% vs. 15.6%, p=0.023). In multivariate regression analysis, age ≥65 years, body mass index ≤18.5 kg/m2, previous TB treatment, bilateral lung involvement, and extensively drug-resistant (XDR)- or pre-XDR-TB were associated with poorer treatment outcomes. However, the use of bedaquiline or delamanid for ≥1 month increased the treatment success. Conclusion: The treatment success rate in MDR-TB patients was higher in the post-PPM period than in the pre-PPM period, particularly because of the low rate of loss to follow-up. To ensure comprehensive patient-centered PPM in South Korea, investment and other support must be adequate.

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.

Probiotics with Antimicrobial Activity against Multidrug Resistant Pseudomonas aeruginosa and Acinetobacter baumannii (다제내성 녹농균과 아시네토박터 바우마니에 항균활성을 가지는 프로바이오틱스)

  • Lee, Do Kyung;Kim, Min Ji;Kang, Joo Yeon;Park, Jae Eun;Shin, Hea Soon;Ha, Nam Joo
    • Korean Journal of Microbiology
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    • v.49 no.3
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    • pp.245-252
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    • 2013
  • Pseudomonas aeruginosa and Acinetobacter baumannii are significant opportunistic pathogens in hospitals and are resistant to most antibiotics. Multidrug-resistant P. aeruginosa (MDRPA) and A. baumannii (MDRAB) cause severe human nosocomial infections and are more difficult to treat than methicillin-resistant Staphylococcus aureus (MRSA). Bifidobacteria are among of the most beneficial probiotics and have been widely studied for their antimicrobial activities. The present study explored the antimicrobial activity of Bifidobacterium sp. isolated from healthy Koreans against MDRPA and MDRAB. The antimicrobial activity of the isolates against MDRPA and MDRAB, which are resistant to ciprofloxacin, tobramycin, gentamicin, meropenem, and ceftazidime, was determined by modified broth microdilution methods using absorbance. Among all tested bifidobacteria isolates (nine B. adolescentis, three B. longum, and two B. pseudocatenulatum), the culture supernatant of B. pseudocatenulatum SPM1309 showed a strong growth inhibitory effect against MDRPA and MDRAB. No change in the turbidity of the mixture was observed during incubation, and its inhibitory effect occurred through bacteriostastic action. Moreover, the antibacterial activity was observed in the fraction with molecular weights <10 kDa of bifidobacteria culture supernatant, and the active fraction was heat-stable because it maintained its activity when heated at $70^{\circ}C$ for 10 min. The results suggest that this Bifidobacterium strain could have potential applications for alternative therapy in MDRPA and MDRAB infections.

Genetic Variation in the ABCB1 Gene May Lead to mRNA Level Chabge: Application to Gastric Cancer Cases

  • Mansoori, Maryam;Golalipour, Masoud;Alizadeh, Shahriar;Jahangirerad, Ataollah;Khandozi, Seyed Reza;Fakharai, Habibollah;Shahbazi, Majid
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.18
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    • pp.8467-8471
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    • 2016
  • Background: One of the major mechanisms for drug resistance is associated with altered anticancer drug transport, mediated by the human-adenosine triphosphate binding cassette (ABC) transporter superfamily proteins. The overexpression of adenosine triphosphate binding cassette, sub-family B, member 1 (ABCB1) by multidrug-resistant cancer cells is a serious impediment to chemotherapy. In our study we have studied the possibility that structural single-nucleotide polymorphisms (SNP) are the mechanism of ABCB1 overexpression. Materials and Methods: A total of 101 gastric cancer multidrug resistant cases and 100 controls were genotyped with sequence-specific primed PCR (SSP-PCR). Gene expression was evaluated for 70 multidrug resistant cases and 54 controls by real time PCR. The correlation between the two groups was based on secondary structures of RNA predicted by bioinformatics tool. Results: The results of genotyping showed that among 3 studied SNPs, rs28381943 and rs2032586 had significant differences between patient and control groups but there were no differences in the two groups for C3435T. The results of real time PCR showed over-expression of ABCB1 when we compared our data with each of the genotypes in average mode. Prediction of secondary structures in the existence of 2 related SNPs (rs28381943 and rs2032586) showed that the amount of ${\Delta}G$ for original mRNA is higher than the amount of ${\Delta}G$ for the two mentioned SNPs. Conclusions: We have observed that 2 of our studied SNPs (rs283821943 and rs2032586) may elevate the expression of ABCB1 gene, through increase in mRNA stability, while this was not the case for C3435T.