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Jachez, B., and F. Loor. "Atypical multi-drug resistance (MDR)." Anti-Cancer Drugs 4, no. 6 (December 1993): 605–16. http://dx.doi.org/10.1097/00001813-199312000-00002.
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Putra, Pradana Maulana. "Effect of Anti-Tuberculosis Multi Drug Resistance Regimen on Hematological Lung Tuberculosis Patients Profile with Multi Drug Resistance." Berkala Kedokteran 14, no. 1 (March 1, 2018): 59. http://dx.doi.org/10.20527/jbk.v14i1.4550.
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Abstract: ATD administration of tuberculosis in combination and duration often causes multi drug resistance (MDR) ATD due to discontinuation of treatment. Reported hematologic abnormal changes due to ATD. This study investigated hematological changes before and during MDR therapy of MDR TB patients in Tuberculosis MDR RSUD Ulin Banjarmasin from September to December 2017. The study population was patients treated in TB MDR Poly and selected samples with a time-limiting method. Inclusion and exclusion criteria were MDR-TB patients detected by Gene Xpert® examination, treated <30 days, between 18 and 65 years of age, HIV negative, as well as identification and laboratory data recorded in the complete medical record. 17 samples collected by hematological parameters were collected. There were significant changes in hemoglobin, hematocrit, platelets, RDW-CV, MCV, eosinophils, lymphocytes, granulocytes, and monocytes after treatment. It was concluded that MDR regimen ATD did not cause anemia and thrombocytopenia. There was also no significant change in WBC even though the count of the species changed significantly Keywords: Tubeculosis, Multi Drug Resistency (MDR), Anti Tuberculosis Drugs (ATD), profil hematologis
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Suparno, Suparno, Suhartono Suhartono, Muchlis Achsan Udji Sofro, Mohammad Sulchan, and Kusmiyati Tjahjono. "Kadar seng dan kadar malondialdehyde pada penderita multi drug resistant tuberculosis dan tuberkulosis sensitif." Jurnal Gizi Indonesia (The Indonesian Journal of Nutrition) 7, no. 1 (December 30, 2018): 8–14. http://dx.doi.org/10.14710/jgi.7.1.8-14.
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Background: Zinc is the main constituent element of Superoxide Dismutase (SOD) which acts to protect cells from inflammation and the toxic effects of Reactive Oxygen Species (ROS). High ROS production induces fat peroxidation, and forms malondialdehyde (MDA) which causes oxidative stress.Objectives: This study aimed to analyze the difference of zinc and malondialdehyde levels among Multi Drug Resistant Tuberculosis and sensitive Tuberculosis.Methods: Crossectional study with 55 subjects consisted of 32 MDR-TB subjects and 23 subjects TB sensitive. Selection of subjects using consecutive sampling. Zinc and MDA serum was obtained from venous blood. Zinc and MDA concentration were assessed by quantitative colometric and Thiobarbituric Acid Reactive Substances (TBARS) respectively. Data were analized statistic by independent t-test and Mann Whitney test.Results: Zinc level of MDR-TB and TB sensitive were 74.85 (64 - 97) μg/dl and 73.03 (63 - 97) μg/dl respectively, while MDA of MDR-TB and sensitive TB were 2.262±1.055 nmol/mL and 2.66±0.992 nmol/mL. There was no significantly different in zinc level between MDR-TB and sensitive TB (p=1.000). Furthermore, there was not significantly different of MDA level between MDR-TB and sensitive Tuberculosis (p=0,147).Conclusion: There are no differences in zinc and MDA levels in patient between MDR-TB and sensitive TB.
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Tuladhar, Pranita, Dhruba Kumar Khadka, Megha Raj Banjara, and Reshma Tuladhar. "Second Line Drugs Resistant Mycobacterium Tuberculosis in Multi-Drug Resistant Tuberculosis Patients." Journal of Institute of Science and Technology 22, no. 2 (April 9, 2018): 168–74. http://dx.doi.org/10.3126/jist.v22i2.19609.
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With an increase in Multi-drug resistant tuberculosis (MDR-TB), there is a need of second line drug susceptibility test that helps in early diagnosis and minimize the risk of other powerful drug resistant Mycobacterium tuberculosis. The aim of this study was to determine second line drugs (ofloxacin, kanamycin, capreomycin) resistance pattern in MDR-TB isolates and to determine the prevalence of pre-Extensively drug resistant tuberculosis (pre-XDR-TB) and XDR-TB in MDR-TB patients. The study was conducted from February to September 2015 at National Tuberculosis Centre, Thimi, Bhaktapur. MDR-TB (resistant to isoniazid and rifampicin) patients’ sputum samples were processed by Modified Petroff’s method. Out of 92 samples, 57 were found culture positive. Following the species identification of culture positive MDR-TB isolates, second line drug susceptibility test was performed by conventional proportion method. Of 57 MDR-TB isolates, 22 (38.59%) showed resistance to ofloxacin (Ofx), 9 (15.79%) to capreomycin (Cm) and 9 (15.79%) to kanamycin (Km). One XDR-TB (1.8%) resistant to all drugs was detected. Of the remaining, 21(36.8%) were resistant to ofloxacin only and 8(15.4%) were resistant to two drugs i.e.29 (50.9%) were pre-XDR-TB. The prevalence of pre-XDR-TB and XDR-TB was found to be 50.88% and 1.75% respectively. The resistance pattern of second line anti-tuberculosis drugs showed higher ofloxacin resistance in MDR-TB patients. In a nutshell, MDR-TB cases need urgent and timely susceptibility report for second line anti-tuberculosis drugs to help the clinicians start proper drug combinations to treat MDR-TB patients. Journal of Institute of Science and Technology Volume 22, Issue 2, January 2018, page: 168-174
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Cho, Cheong-Weon. "Formulation strategy to overcome multi-drug resistance (MDR)." Archives of Pharmacal Research 34, no. 4 (April 2011): 511–13. http://dx.doi.org/10.1007/s12272-011-0400-0.
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Saini, Sanjeev, Manoj Kumar Dubey, Uma Bhardwaj, M. Hanif, Chopra Kk, Ashwani Khanna ., Kaushal Kumar Dwivedi, et al. "RAPID DETECTION OF MULTI DRUG RESISTANCE AMONG MULTI DRUG RESISTANT TUBERCULOSIS SUSPECTS USING LINE PROBE ASSAY." Asian Journal of Pharmaceutical and Clinical Research 10, no. 1 (January 1, 2016): 131. http://dx.doi.org/10.22159/ajpcr.2017.v10i1.14341.
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ABSTRACTObjective: GenoType MTBDRplus line probe assay (LPA) is developed for performing drug susceptibility testing (DST) for Rifampicin (RIF) andisoniazid in sputum specimens from smear-positive pulmonary tuberculosis (TB) patients and revised national TB control Programme (RNTCP)has endorsed LPA for the diagnosis of multi drug resistant TB (MDR-TB). This study was conducted to assess the potential utility of LPA for MDR-TBpatient management.Methods: MDR-TB suspects under RNTCP PMDT criteria C referred from different districts in Delhi state were included in the study January 2013 toDecember 2014. Sputum specimens found acid-fast bacilli positive by fluorescent microscopy were processed for LPA.Results: Out of 3062 specimens, 2055 (67.1%) MDR-TB suspects were read as positive and specimens from 1007 (32.9%) suspects were read asnegative in sputum smear microscopy. Out of 2019 specimens valid LPA results, 1427 were found to be pan-sensitive, 280 were MDR-TB, 40 were RIFmonoresistant, 183 were Isoniazid (INH) monoresistant, and 89 specimens were found negative for Mycobacterium tuberculosis.Conclusion: Routine use of LPA can substantially reduce the time to diagnosis of RIF and/or INH-resistant TB and can hence potentially enable earliercommencement of appropriate drug therapy and thereby facilitate prevention of further transmission of drug resistant strains.Keywords: Multi drug resistant tuberculosis, Line probe assay, Rifampicin, Isoniazid.
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Ghazaei, Ciamak. "Upcoming Multi-drug-Resistant and Extensively Drug-Resistant Bacteria." Research in Molecular medicine 10, no. 2 (May 1, 2022): 0. http://dx.doi.org/10.32598/rmm.10.2.820.7.
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Multi-drug-resistant (MDR) and extensively drug-resistant (XDR) bacteria are becoming a serious global health issue, which may soon become untreatable by clinicians. Since the invention of antibiotics, inappropriate consumption, non-prescribed drugs, overuse, and hoarding have caused the rapid emergence of MDR and XDR bacteria. The ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, and Enterobacter spp.) cause many nosocomial infections and thus escape the biocidal action of the antibiotic. Gram-positive and Gram-negative bacteria have acquired self-defense tools like ESBL (extended spectrum beta-lactamase), a mutation in porin genes, biofilm production, and many more to develop multi-drug resistance. Antimicrobial resistance (AMR) endangers patients' treatment as it causes high mortality and morbidity rates, economic loss of both patient and country, and prolonged hospital stay. To combat upcoming MDR and XDR bacteria, it is essential to design novel therapeutic techniques to eradicate such resistant bacteria via burgeoning technologies like nanoparticles, CRISPER-Cas9, genetic engineering, and synthetic biology.
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Yadav, Pramod. "Challenges & Solutions for Recent Advancements in Multi-Drugs Resistance Tuberculosis: A Review." Microbiology Insights 16 (January 2023): 117863612311524. http://dx.doi.org/10.1177/11786361231152438.
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In MDR-TB, mycobacterium is resistant to battlefront drugs like rifampicin and isoniazid. Now it’s an urgent global challenge for treatment & diagnosis because more than 50% of drugs are resistant. Till today's information, 5 reasons are liable for MDR: (1) Errors of physicians/patients in therapy management, (2) Complexity and poor vascularization of granulomatous lesions, which obstruct drug distribution to some sites, leading to resistance development, (3) Intrinsic drug resistance of tubercle bacilli, (4) Formation of non-replicating, drug-tolerant bacilli inside the granulomas, (5) Development of mutations in Mtb genes, which are the foremost important molecular mechanisms of resistance. the most contribution of this work is a brief & clear explanation of things chargeable for resistant development, and recent diagnostic & treatment methods for MDR-TB. This study shall help researchers & scientists to develop replacement rapid diagnostic tools, drugs, and treatment protocols.
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Neophytou, Christiana M., Ioannis P. Trougakos, Nuray Erin, and Panagiotis Papageorgis. "Apoptosis Deregulation and the Development of Cancer Multi-Drug Resistance." Cancers 13, no. 17 (August 28, 2021): 4363. http://dx.doi.org/10.3390/cancers13174363.
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The ability of tumor cells to evade apoptosis is established as one of the hallmarks of cancer. The deregulation of apoptotic pathways conveys a survival advantage enabling cancer cells to develop multi-drug resistance (MDR), a complex tumor phenotype referring to concurrent resistance toward agents with different function and/or structure. Proteins implicated in the intrinsic pathway of apoptosis, including the Bcl-2 superfamily and Inhibitors of Apoptosis (IAP) family members, as well as their regulator, tumor suppressor p53, have been implicated in the development of MDR in many cancer types. The PI3K/AKT pathway is pivotal in promoting survival and proliferation and is often overactive in MDR tumors. In addition, the tumor microenvironment, particularly factors secreted by cancer-associated fibroblasts, can inhibit apoptosis in cancer cells and reduce the effectiveness of different anti-cancer drugs. In this review, we describe the main alterations that occur in apoptosis-and related pathways to promote MDR. We also summarize the main therapeutic approaches against resistant tumors, including agents targeting Bcl-2 family members, small molecule inhibitors against IAPs or AKT and agents of natural origin that may be used as monotherapy or in combination with conventional therapeutics. Finally, we highlight the potential of therapeutic exploitation of epigenetic modifications to reverse the MDR phenotype.
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Gu, Liu-Qing, Peng-Fei Cui, Lei Xing, Yu-Jing He, Xin Chang, Tian-Jiao Zhou, Yu Liu, Ling Li, and Hu-Lin Jiang. "An energy-blocking nanoparticle decorated with anti-VEGF antibody to reverse chemotherapeutic drug resistance." RSC Advances 9, no. 21 (2019): 12110–23. http://dx.doi.org/10.1039/c9ra01356c.
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Multi-drug resistance (MDR) of tumor has greatly hindered the therapeutic effect of chemotherapeutic drugs, resulting in chemotherapy failure, and overexpression of ATP-binding cassette (ABC) transporters in cell membrane is the main cause of MDR.
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Rambi, Elne Vieke, Dyan R. Sukandar, Linda Augustien Makalew, Yohanis Tomastola, and Ketrina Konoralma. "Multi drugs resistance to Diabetes Mellitus patients with tuberculosis in Manado City." Jurnal Teknologi Laboratorium 10, no. 1 (August 5, 2021): 40–45. http://dx.doi.org/10.29238/teknolabjournal.v10i1.286.
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Diabetes mellitus (DM) with pulmonary tuberculosis (TB) is an infectious disease if not educated regularly, there will be a high risk of drug resistance and even some anti-tuberculosis drugs. This study aims to identify anti-tuberculosis drug resistance in DM patients with TB in Manado City. The population in the study types 2 DM patients as amount 80 patients. Based on TCM/GenExpert examination from 47 respondents, there were 17 respondents positive multi drugs resistance rifampicin (RR). Sampling taking based on inclusion criteria, i.e., have had type DM for five years, had suffered TB MDR RR based on GenXpert examination as much as 17 respondents followed in the resistance test with Sputum TB culture and MGIT method. The result of the study showed that MDR DM-TB with MGIT method as followed is obtained from 17 samples, six samples (35.30%) resistance INH 0.4 mg and 1 sample (5.88%) MDR canamycin, and still sensitive INH 0.4 mg and camaycin is ten samples (58.82%). This study results could be used to program planning of prevention and controlling efforts TB-DM in this treatment obedience and regimen anti-tuberculosis medicine for MDR-TB patients.
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Aristiana, Cynthia Devi, and Magdalena Wartono. "Faktor-faktor yang mempengaruhi kejadian Multi Drug Resistance Tuberkulosis (MDR-TB)." Jurnal Biomedika dan Kesehatan 1, no. 1 (June 29, 2018): 65–74. http://dx.doi.org/10.18051/jbiomedkes.2018.v1.65-74.
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LATAR BELAKANGBerdasarkan data WHO Global Report 2016, Indonesia berada diperingkat ke-8 dari 27 negara dengan beban MDR-TB terbanyak di dunia. Terdapat 5.100 kasus MDR-TB yang terjadi di Indonesia yaitu 2,8 % dari kasus baru dan 16 % dari kasus TB yang mendapatkan pengobatan ulang. Banyaknya jumlah kasus MDR-TB yang terjadi melibatkan berbagai faktor yang terkait. Penelitian ini bertujuan untuk menganalisis faktor resiko yang berpengaruh dengan MDR-TB.
METODEPenelitian ini menggunakan metode observasional analitik dengan disain potong lintang yang dilakukan bulan November 2017-Januari 2018. Subjek penelitian adalah 88 pasien TB yang berobat di Puskesmas Kecamatan Kramat Jati, Kecamatan Makassar, Kecamatan Pasar Rebo, dan Kecamatan Ciracas. Pengambilan data menggunakan kuisioner dan status pasien TB. Analisis data dengan menggunakan uji chi-square dan uji fisher dengan nilai kemaknaan p<0,05 serta odd ratio untuk menentukan besar risiko antara variabel bebas dan variabel terikat.
HASILMotivasi penderita (p=0,000; OR=47,500), kepatuhan minum obat (p=0,000; OR=10,733), konsumsi alkohol (p=0,000; OR=9,059), Kebiasaan merokok (p=0,000; OR=7,632), dan status gizi (p=0,005; OR=3,791) mempunyai hubungan yang bermakna dengan MDR-TB.
KESIMPULANFaktor-faktor yang berhubungan dengan timbulnya MDR-TB antara lain kepatuhan minum obat, konsumsi alkohol, kebiasaan merokok dan status gizi.
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Samanta, Ankita. "A Literature Curated Profile of miRNA IN Modulating Multi-Drug Resistance for Cancer Therapy." International Journal for Research in Applied Science and Engineering Technology 9, no. 8 (August 31, 2021): 2830–39. http://dx.doi.org/10.22214/ijraset.2021.37884.
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Abstract: At present, cancer is one of the major causes of death, affecting millions of people each year. Multi Drug Resistance (MDR) remains the major clinical obstacle in cancer treatment. Till date various mechanisms of MDR has been elucidated which includes- over expression of drug transporter, defect in cell cycle and apoptotic machinery, induction of autophagy, alteration in drug metabolism and drug target. microRNAs (miRNAs) are an extensive class of 22 nucleotide long non coding RNAs which are involved in gene regulation. Recent work has underlined the involvement of miRNA in cancer development with several studies regarding their involvement in drug resistance, thereby holding much promise for developing novel and more effective therapy for cancer treatment. This review presents the mechanisms of MDR and focuses on the profile of miRNA in regulating MDR in cancer treatment. Keywords: miRNA, Cancer, Multi-drug resistance, Drug target, Drug transporter, Apoptotic machinery.
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Thiruvalluvan, E., B. Thomas, C. Suresh, S. Sellappan, M. Muniyandi, and B. Watson. "THE PSYCHOSOCIAL CHALLENGES FACING MULTI DRUG RESISTANCE TUBERCULOSIS PATIENTS: A QUALITATIVE STUDY." SAARC Journal of Tuberculosis, Lung Diseases and HIV/AIDS 14, no. 1 (July 12, 2017): 14–21. http://dx.doi.org/10.3126/saarctb.v14i1.17724.
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Background: The treatment for MDR-TB characterized by rigorous treatment regimen for long duration, higher incidence of adverse side effects, lower cure rate, and high treatment costs. This could lead to number of psychosocial problems that influence treatment adherence. MDR-TB patients registered under DOTS Plus programme during the period of 2013-2014 in Chennai and Madurai districts, of Tamilnadu were included for this study.Objective: To understand the psychosocial issues facing MDR-TB patients, who are diagnosed and registered for treatment under DOTS plus programme.Methodology: This study used Focus Group Discussions with people with MDR-TB. Focus Group Discussions were focused on physical, psychological, social and economical challenges which MDR-TB patients faced during their treatment.Results: Most of the study participants did not disclose their TB status, even to their family members. The majority of patients were not aware of the diagnosis of MDR-TB and long duration of treatment. Stigma from family, community and health providers has been experienced by the majority of patients. Patients and their families were afraid of losing economic stability which was already precarious owing to the disease. This fear has often generated a great deal of stress.Conclusion: Study finding indicates that there is a significant psychological, social, and financial impact of MDR-TB that has a direct impact on quality of life of MDR-TB patients and their families. There is a need for psychosocial intervention model (strategies) for MDR-TB patients and their caregivers to mitigate the negative effects.SAARC J TUBER LUNG DIS HIV/AIDS, 2017; XIV(1), page: 14-21
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Orakzai, Nasir, Liaqat Ali, Majid Khan Kakakhel, Arshad ., Faiza Hayat, and Ihsanullah Khan. "Multi Drug Resistance (MDR) Urinary Tract Infection: An Evidence Based Study." Pakistan Journal of Medical and Health Sciences 15, no. 6 (June 30, 2021): 1910–13. http://dx.doi.org/10.53350/pjmhs211561910.
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Background: Urinary tract infections are the most frequently reported infections that drive the use of antibiotics around the world. UTI is the 4th most common healthcare-associated infection. Multidrug-resistant (MDR) organisms are predominantly bacteria that are resistant to one or more classes of antimicrobials. The increasing rise in the incidence of MDR-UTI has resulted in increased morbidity, mortality, and treatment cost of the patients. Thus, it is important to highlight the magnitude of the problem, identify the risk factors that result in MDR-UTI, and to take appropriate measures to control its occurrence. Objective: To determine the magnitude of the multidrug-resistant bacteria, their antibiotic-resistant profile, andtheir effect on the treatment cost of the patients Methods: It is a descriptive study conducted in the Department of Urology at the Institute of Kidney Diseases (IKD) from Jan 2019 till 30th March 2020. A total of 54 patients with multi-drug resistant UTI were included in the study irrespective of age and gender. All the data was recorded on a structured pro-forma and was analyzed on SPSS. Results: A total of 3190 patients were operated on from Jan 2019 till 30th March 2020. Out of which 54 patients (1.6 %) developed MDR-UTI. Among them,38 were male and 16 females. The mean age of the patients was 41 ± 18.4. Urolithiasis with infections was found most frequent, in 32 (59.3%) patients. All patients were on broad-spectrum oral antibiotics and had a history of urethral catheterization before the development of MDR-UTI. The most common procedure was Emergency cystoscopy and DJ stent 15 (27.8%). Followed by Percutaneous nephrostomy in 8 (14.8%). Regarding co-morbidities, 38(68.5%) patients had none, 3 patients had diabetes and 6 patients were having Diabetes and Hypertension. Pseudomonas aeruginosa was found most frequent microorganisms in 34 (63%) patients while E.coli in 10 (18.5%) and Klebsiella in 5 (9.3%) patients. Colistin was found sensitive in 36 patients (66.7%). The mean hospital stay in MDR-UTI is 9.28± 5.17 days as compared to 2.1 days in routine cases. Approximately a 4-fold increase was observed in medicines alone in the management of MDR UTI. We recorded 1 mortality (1.9%), case of MDR urosepsis. Linear regression revealed previous use of antibiotics; catheterization, old age, and endo-urological procedures in an emergency as independent risk factors for MDR-UTI. Conclusion: MDR-uti is an emerging local problem. pseudomonas aeruginosa is the most frequently found microorganism in the present setup. it is associated with significant morbidity and very high treatment cost. Keywords: Urinary Tract Infection, Multidrug Resistance, Micro-Organism, Urology, Antimicrobials
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Zorkaltseva, E. Yu, O. A. Vorobyeva, E. D. Savilov, and O. B. Ogarkov. "Multi-Drug Resistance of Mycobacterium Tuberculosis – the Problem of Modern Phthisiology." Acta Biomedica Scientifica 4, no. 2 (May 25, 2019): 55–59. http://dx.doi.org/10.29413/abs.2019-4.2.8.
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The 21st century is characterized by the exacerbation of the problem formation and spreading of drug-resistant strains throughout the world. Genetic mutations of Mycobacterium tuberculosis lead to the formation of drug-resistant forms because of long-term use of anti-tuberculosis drugs. The Russian Federation is among the top three countries with a high burden of tuberculosis with multidrug resistance (MDR). The estimated number of cases of tuberculosis with MDR in the Russian Federation was 60,000, which corresponds to half the burden of the European Region in 2015. In the Irkutsk region from 2014 till 2018 the proportion of TB cases with MDR cases increased from 15.2 % to 18.3 %. According to the reference laboratory of the Irkutsk Regional Clinical Tuberculosis Hospital, a significantly higher level of MDR among primary diagnosed was registered in the cities (27.7 %) and the lowest in rural areas of the region (16.5 %). Among the cohorts of patients with tuberculosis, the highest proportion of MDR was in the northern territories of the region (43.1 %), in Irkutsk district (41.2 %) and in large cities, including Irkutsk (38.5 %). Positive correlations were established between cohort of primary diagnosed TB with MDR and among populations in areas with high morbidity along the railway (r = 0.91; p = 0.00001), in the Irkutsk region (r = 0.89; p = 0,00008), and also in the Irkutsk city (r = 0.91; p = 0.00002). This is probably due to the influence of reservoir of tuberculosis infection formed in these localities. The regulatory documents of the Ministry of Health of the Irkutsk Region was developed on the basis of the data obtained, and they include recommendations for improving the diagnosis of tuberculosis in the region using fast and accelerated microbiological diagnostic methods.
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Lendrum, Elizabeth, David Haslam, and Lilliam Ambroggio. "1170. Applying Machine Learning Algorithms to Predict Multi-Drug-Resistant Bacterial Infections From Prior Drug Exposure." Open Forum Infectious Diseases 5, suppl_1 (November 2018): S353. http://dx.doi.org/10.1093/ofid/ofy210.1003.
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Abstract Background Multi-drug-resistant (MDR) infection in the acute care setting prolongs hospital stay and causes high mortality, especially in the pediatric population. Being able to predict MDR infection risk upon or during admission could help prevent and reduce morbidity and mortality in children requiring acute care in the future. This study aimed to develop and validate a predictive model for MDR infection in the pediatric population using machine learning (ML) analysis. Methods The study population included hospitalized pediatric patients diagnosed with MDR infection between January 1, 2010 and March 8, 2018. All positive cultures during that period were coded as growing either an MDR or non-MDR organism. ML was performed with random forest (RF) analysis to determine whether hospital drug exposure in the 90 days prior to culture was able to accurately classify cultures as positive for an MDR or non-MDR organism. Results During the study period, 7,551 positive cultures were defined as MDR out of a total of 26,913 cultures (28% of all positive cultures). When all cultures were included in the analysis, RF was modestly successful at classifying MDR vs. non-MDR organisms. Significant improvements in classification accuracy were obtained by subdividing cultures based on growth of individual species. RF was able to classify MDR Enterococcus with accuracy = 0.87, positive predictive value of 0.81, and negative predictive value of 0.88. Surprisingly, exposure to many nonantibiotic drugs were important in predicting antibiotic resistance, indicating either that these drugs altered risk directly, or were correlated with MDR risk indirectly. Conclusion Drugs without known antimicrobial activity were important predictors of MDR status. Nonantimicrobial drug exposure may be a marker for disease types or therapeutic interventions that place patients at higher risk of MDR infection. Monitoring antimicrobial and nonantimicrobial drug exposure may accurately identify patients at highest risk of MDR infection. Disclosures All authors: No reported disclosures.
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Ford, Mary, Kathryn Lago, Quratulain Kizilbash, and Adriana Vasquez. "801. Emergence of Multi-Drug Resistance Tuberculosis During the Treatment Course of Pan-Susceptible TB: A Case Series." Open Forum Infectious Diseases 5, suppl_1 (November 2018): S287. http://dx.doi.org/10.1093/ofid/ofy210.808.
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Abstract Background Successful treatment of tuberculosis (TB) requires monitoring for clinical, radiographic, and microbiologic improvement. Even after negative cultures are obtained, there should be continued monitoring of sputa. If cultures become positive during treatment of drug susceptible TB (DS-TB), there should be concern for multi-drug-resistant tuberculosis (MDR-TB). We present two cases diagnosed with DS-TB who developed MDR-TB during treatment. Case Report: Case 1 is a 33-year-old male who was incarcerated in Peru. During incarceration in 2008, three of his cellmates had MDR-TB and he was diagnosed with DS-TB and treated with directly observed therapy (DOT) for 7 months. In Texas in 2015 he was diagnosed with DS-TB and was initiated on rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE). Five months into DOT, his sputa became culture positive with molecular detection of drug resistance (MDDR) and drug susceptibility testing (DST) revealing resistance to all of RIPE. Repeat MDDR and DST of the 2015 isolate showed no resistance. Genotyping of the two isolates were identical by mycobacterial interspersed repetitive units (MIRU) and spoligotyping. However, whole genome sequencing showed two different isolates. Case 2 is a 63-year-old female diagnosed with DS-TB in Saipan and started on RIPE in April 2017. She was on DOT until July when she moved to Texas and was lost to follow-up until September. She claims adherence with rifampin and isoniazid during this time. All sputa collected between diagnosis and September were smear and culture negative. Six months into therapy, she had sputa that was culture positive with MDDR and DST showing MDR-TB. Her isolates from Saipan and Texas were sent for genotyping. The MIRU and spoligotyping showed two different isolates. Conclusion These cases show the importance of following cultures throughout treatment. Traditionally, MDR-TB is thought to be due to poor adherence. However, in high prevalence areas, heterogeneous infection with two different strains is an important consideration for the cause of MDR-TB. Concomitant infection of DS and MDR-TB can occur with MDR-TB not being detected until far into therapy. These cases represent heterogeneous exogenous infection of DS and MDR-TB—only discovered after meticulous culture monitoring. Disclosures All authors: No reported disclosures.
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Meroni, Gabriele, Joel F. Soares Filipe, Lorenzo Drago, and Piera A. Martino. "Investigation on Antibiotic-Resistance, Biofilm Formation and Virulence Factors in Multi Drug Resistant and Non Multi Drug Resistant Staphylococcus pseudintermedius." Microorganisms 7, no. 12 (December 16, 2019): 702. http://dx.doi.org/10.3390/microorganisms7120702.
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Staphylococcus pseudintermedius is a commensal bacterium frequently isolated from canine skin and recognized as a zoonotic agent especially for dog-owners. This study focused on (a) the antibiotic-resistance phenotypes; (b) the ability to produce biofilm (slime); and (c) the dissemination of virulence factors in S. pseudintermedius strains. Seventy-three S. pseudintermedius strains were screened for antibiotic-resistance against 22 different molecules by means of Kirby-Bauer assay. The ability to produce biofilm was investigated using the microtiter plate assay (MtP) and the amplification of icaA and icaD genes. Virulence factors such as cytotoxins (lukI), enterotoxins (seC), and exfoliative toxins (siet, expA, and expB) were evaluated. The antibiotic-resistance profiles revealed 42/73 (57%) multi-drug resistant (MDR) strains and 31/73 (43%) not-MDR. All the MDR strains and 8/31 (27%) of not-MDR resulted in biofilm producers. Leukotoxin LukI was found in 70/73 (96%) of the isolates. Moreover, the enterotoxin gene seC was detected in 47/73 (64%) of the strains. All the isolates carried the siet gene, whereas expA and expB were found in 3/73 (4%) and 5/73 (7%), respectively. In conclusion, S. pseudintermedius should be considered a potential zoonotic and human agent able to carry different virulence determinants and capable of producing biofilm which facilitates horizontal gene transfer.
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Oloche, Jeremiah John, Bolaji Bosede Oluremi, and Temiloluwa Oyindamola Koya. "In vitro inhibition of multi-drug resistant Pseudomonas efflux pump by Xylopia aethiopica (Dunal) A. Rich." AROC in Pharmaceutical and Biotechnology 1, no. 2 (September 14, 2021): 20–27. http://dx.doi.org/10.53858/arocpb01022027.
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Global health is under constant threat due to antimicrobial drug resistance. Bacterial Infections caused by Pseudomonas aeruginosa are of importance because of their antibiotics resistance. This study aimed at evaluating the effects of extracts of Xylopia aethiopica (XA) on multidrug-resistant (MDR) Pseudomonas isolates. Fresh samples of XA leaf, stem bark and roots were collected from the botanical garden, University of Ibadan, Nigeria. Dried and pulverized samples were extracted with methanol and partitioned into n-hexane, dichloromethane and ethyl acetate. Phytochemical screening of the extracts was performed by standard methods. Antimicrobial activity and synergistic interaction were determined using microdilution and checkerboard broth dilution methods, respectively. The results revealed that crude methanol extracts of XA leaf, stem bark and root significantly (p<0.05) inhibited the growth of all tested MDR Pseudomonas isolates at 10 mg/mL. At 1 mg/mL, the ethyl acetate fraction of the leaf, and dichloromethane fraction of the roots produced clear zones of inhibition of 12 – 20 mm, and minimum inhibitory concentrations (MICs) of 1 µg/mL and 0.5 mg/mL, respectively. The modulation factor (MF) of ciprofloxacin, dichloromethane fraction of XA roots and ethyl acetate fraction of XA leaf were 4, 8, and 4 on MDR isolates E01006, OAU058 and P. aeruginosa ATCC 27853, respectively. In all tested isolates, but not E01006 and E01024, the fractional MICs of ciprofloxacin/ethylacetate fraction of XA leaf extract combination was not significantly different (p>0.05) compared with ciprofloxacin/verapamil combination. In conclusion, the root and leaf fractions Xylopia aethiopica that demonstrated antimicrobial activity against MDR P. aeruginosa and synergised with ciprofloxacin have the potential to rejuvenate the antimicrobial activity of ciprofloxacin in MDR P. aeruginosa.
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ALI, SAJID, MUHAMMAD TAHIR KHAN, ANWAR SHEED KHAN, NOOR MOHAMMAD, MUHAMMAD MUMTAZ KHAN, SAJJAD AHMAD, SADIQ NOOR, ABDUL JABBAR, CANTILLON DAIRE, and FARIHA HASSAN. "Prevalence of Multi-Drug Resistant Mycobacterium Tuberculosis in Khyber Pakhtunkhwa – A High Tuberculosis Endemic Area of Pakistan." Polish Journal of Microbiology 69, no. 2 (April 6, 2020): 133–37. http://dx.doi.org/10.33073/pjm-2020-005.
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Anti-tuberculosis therapy involves the combination of drugs to hamper the growth of Mycobacterium tuberculosis (MTB). The emergence of multidrug-resistant tuberculosis (MDR-TB) is a global concern. Pakistan has been ranked 5th position in terms of a high burden of MDR-TB in the world. The aim of the current study was to investigate the prevalence of drug resistance in MTB in Khyber Pakhtunkhwa. Random samples were collected from 25 districts using the simple random sampling formula. All samples were processed in a biosafety level 3 laboratory for culture and drug susceptibility testing. Among 5759 presumptive tuberculosis (TB) cases, 1969 (34%) were positive. The proportion of TB was higher in females (39%) than males (29%), thus it represents a significant association between gender and tuberculosis (p < 0.05). People ages between 25 to 34 years were more likely to be infected with MTB (40%). Drug-resistant profile showed 97 (4.9%) patients were infected with MDR-TB. Streptomycin resistance was the highest and was observed in 173 (9%) isolates followed by isoniazid in 119 (6%) isolates. The lowest resistance was observed to pyrazinamide (3%). The prevalence of MDR-TB (10.4%) among patients that previously received anti-tuberculosis treatment is seemingly high. A large-scale drug resistance survey is required to evaluate the drug resistance for better management of tuberculosis.
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SAIER, MILTON H., IAN T. PAULSEN, and A. MATIN. "A Bacterial Model System for Understanding Multi-Drug Resistance." Microbial Drug Resistance 3, no. 4 (January 1997): 289–95. http://dx.doi.org/10.1089/mdr.1997.3.289.
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Tulpule, Anil, Andy Sherrod, Maria Norilyn Sanchez, Byron M. Espina, Dharshika Dharmapala, Lasika C. Seneviratne, and Alexandra M. Levine. "Multi-Drug Resistance (MDR-1) in Newly Diagnosed AIDS-Lymphoma." JAIDS: Journal of Acquired Immune Deficiency Syndromes 21, no. 1 (May 1999): A32. http://dx.doi.org/10.1097/00126334-199905010-00110.
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Perron, Gabriel G., Alexander E. G. Lee, Yun Wang, Wei E. Huang, and Timothy G. Barraclough. "Bacterial recombination promotes the evolution of multi-drug-resistance in functionally diverse populations." Proceedings of the Royal Society B: Biological Sciences 279, no. 1733 (November 2, 2011): 1477–84. http://dx.doi.org/10.1098/rspb.2011.1933.
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Bacterial recombination is believed to be a major factor explaining the prevalence of multi-drug-resistance (MDR) among pathogenic bacteria. Despite extensive evidence for exchange of resistance genes from retrospective sequence analyses, experimental evidence for the evolutionary benefits of bacterial recombination is scarce. We compared the evolution of MDR between populations of Acinetobacter baylyi in which we manipulated both the recombination rate and the initial diversity of strains with resistance to single drugs. In populations lacking recombination, the initial presence of multiple strains resistant to different antibiotics inhibits the evolution of MDR. However, in populations with recombination, the inhibitory effect of standing diversity is alleviated and MDR evolves rapidly. Moreover, only the presence of DNA harbouring resistance genes promotes the evolution of resistance, ruling out other proposed benefits for recombination. Together, these results provide direct evidence for the fitness benefits of bacterial recombination and show that this occurs by mitigation of functional interference between genotypes resistant to single antibiotics. Although analogous to previously described mechanisms of clonal interference among alternative beneficial mutations, our results actually highlight a different mechanism by which interactions among co-occurring strains determine the benefits of recombination for bacterial evolution.
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Sharma, Namita, Anil K. Chhillar, Sweety Dahiya, Pooja Choudhary, Aruna Punia, and Prity Gulia. "Antibiotic Adjuvants: A Promising Approach to Combat Multidrug Resistant Bacteria." Current Drug Targets 22, no. 12 (August 6, 2021): 1334–45. http://dx.doi.org/10.2174/1389450122666210120084406.
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The escalating emergence and prevalence of infections caused by multi-drug resistant (MDR) pathogenic bacteria accentuate the crucial need to develop novel and effectual therapeutic strategies to control this threat. The recent past surprisingly indicates a staggering decline in effective strategies against MDR. Different approaches have been employed to minimize the effect of resistance, but the question still lingers over the astounding number of drugs already tried and tested. Furthermore, the detection of new drug targets and the action of new antibacterial agents against already existing drug targets also complicate the condition. Antibiotic adjuvants are considered as one such promising approach for overcoming bacterial resistance. Adjuvants can potentiate the action of generally adopted antibacterial drugs against MDR bacterial pathogens either by minimizing the impact and emergence of resistance or improving the action of antibacterial drugs. This review provides an overview of the mechanism of antibiotic resistance, the main types of adjuvants and their mode of action, achievements and progression.
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Hoffmann, Else K., and Ian H. Lambert. "Ion channels and transporters in the development of drug resistance in cancer cells." Philosophical Transactions of the Royal Society B: Biological Sciences 369, no. 1638 (March 19, 2014): 20130109. http://dx.doi.org/10.1098/rstb.2013.0109.
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Multi-drug resistance (MDR) to chemotherapy is the major challenge in the treatment of cancer. MDR can develop by numerous mechanisms including decreased drug uptake, increased drug efflux and the failure to undergo drug-induced apoptosis. Evasion of drug-induced apoptosis through modulation of ion transporters is the main focus of this paper and we demonstrate how pro-apoptotic ion channels are downregulated, while anti-apoptotic ion transporters are upregulated in MDR. We also discuss whether upregulation of ion transport proteins that are important for proliferation contribute to MDR. Finally, we discuss the possibility that the development of MDR involves sequential and localized upregulation of ion channels involved in proliferation and migration and a concomitant global and persistent downregulation of ion channels involved in apoptosis.
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Chua, Mary Francine P., Syeda Sara Nida, Jerry Lawhorn, and Janak Koirala. "1597. Ceftolozane-Tazobactam and Meropenem Synergy Testing Against Multi-Drug and Extensively-Drug Resistant Pseudomonas aeruginosa." Open Forum Infectious Diseases 7, Supplement_1 (October 1, 2020): S794—S795. http://dx.doi.org/10.1093/ofid/ofaa439.1777.
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Abstract Background Multidrug-resistant (MDR) and extensively drug-resistant (XDR) Pseudomonas aeruginosa (PA) have limited therapeutic options for treatment. Ceftolozane/tazobactam is a newer anti-pseudomonal drug effective against resistant PA infections, however resistance against this drug has now also developed and is increasing. In this study, we explored the combination of ceftolozane/tazobactam (CT) and meropenem (MP) as a possible effective regimen against MDR and XDR PA. Methods We obtained 33 non-duplicate isolates of MDR and XDR PA grown from blood, urine and respiratory samples collected from patients admitted between 2015 and 2019 at our two affiliate teaching hospitals. MDR PA was defined as resistance to 3 or more classes of anti-pseudomonal antibiotics, and XDR PA as resistance to all but two or less classes of anti-pseudomonal antibiotics. Antimicrobial preparations of both MP and CT were made according to manufacturer instructions. Susceptibility testing was performed using the checkerboard method in accordance to CLSI guidelines (CLSI M100, 2017). The ATCC 27853 strain of PA used as control. Synergy, additive effect, indifference and antagonism were defined as FIC (fractional inhibitory concentration) indices of ≤0.5, >0.5 to <1, >1 to <4, and >4, respectively. Results Thirteen (39%) of 33 PA isolates were classified as XDR, while 20 (61%) PA isolates were MDR. All isolates were resistant to MP (MIC50 >32 ug/mL), while only 2 (6%) isolates were susceptible to CT (MIC50 64 ug/mL). A synergistic effect was seen in 9 (27.3%) of PA isolates (FIC index range 0.28 to 0.5)— 2 of which were XDR PA, and 7 were MDR PA. An additive effect was seen in 12 (36.4%), with indifference seen in 12 (36.4%) of isolates. In this study, no antagonism was seen when CT and MP were combined. Conclusion When used in combination, CT and MP can exert a synergistic effect against MDR and XDR PA. Additive effect and indifference can also be seen when both antibiotics were used. Moreover, there was no antagonism seen when both antibiotics were combined. This study shows that the use of CT and MP in combination may be an option against XDR and MDR PA infections. Disclosures All Authors: No reported disclosures
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Farida, Farida. "Faktor keberhasilan pengobatan Multi Drug Resistance Tuberculosa (MDR-TB) di Indonesia : Tinjauan Sistematik." Journal of Health Epidemiology and Communicable Diseases 6, no. 1 (November 12, 2020): 33–39. http://dx.doi.org/10.22435/jhecds.v6i1.3206.
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Tingginya angka kejadian MDR-TB adalah salah satu masalah kesehatan yang dihadapi saat ini. Pengelolaan pengobatan TB yang salah, penggunaan obat antimikroba dan formulasi yang tidak tepat, tidak patuh terhadap pengobatan dan penghentian pengobatan dini dapat menyebabkan resistensi obat. Tujuan penulisan artikel review ini adalah untuk mengetahui faktor–faktor yang mempengaruhi keberhasilan pengobatan MDR-TB di Indonesia. Metode yang digunakan dalam penulisan ini adalah telaah literatur. Kata kunci yang digunakan yaitu Faktor keberhasilan, MDR-TB, dan Pengobatan. Literatur review dilakukan melalui mesin pencari jurnal internasional yaitu Journal of Epidemiology and Public Health (JEPH) dari tahun 2016 sampai dengan tahun 2019. Kriteria inklusinya adalah penelitian dengan studi case control, Full text, open access, TB Paru dengan Multi Drug Resistance di Indonesia dan kriteria ekslusi adalah TB Paru dan ekstra paru yang mendapat pengobatan anti TB yang teratur, kasus MDR-TB di luar negeri, artikel yang terdiri atas abstrak saja, artikel jurnal dibawah tahun 2016, penelitian kualitatif, cross sectional, cohort, dan ekperimen. Berdasarkan analisis terhadap literatur diketahui bahwa faktor–faktor yang mempengaruhi keberhasilan dalam pengobatan MDR-TB adalah pengawasan dalam minum obat, kepatuhan minum obat, efek samping obat, status gizi serta faktor lainnya yaitu penyakit diabetes mellitus tipe 2, depresi, perawatan rutin, usia, kemitraan antara pasien dan tenaga kesehatan, tingkat pendidikan, pengetahuan dan perilaku seperti kebiasaan merokok. Faktor-faktor ini memiliki pengaruh langsung dan tidak langsung pada keberhasilan pengobatan TB-MDR di Indonesia.
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Pławińska-Czarnak, Joanna, Karolina Wódz, Magdalena Kizerwetter-Świda, Janusz Bogdan, Piotr Kwieciński, Tomasz Nowak, Zuzanna Strzałkowska, and Krzysztof Anusz. "Multi-Drug Resistance to Salmonella spp. When Isolated from Raw Meat Products." Antibiotics 11, no. 7 (June 29, 2022): 876. http://dx.doi.org/10.3390/antibiotics11070876.
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Salmonella spp. is the most frequent cause of foodborne diseases, and the increasing occurrence of MDR strains is an additional and increasing problem. We collected Salmonella spp. strains isolated from meat (poultry and pork) and analysed their antibiotic susceptibility profiles and the occurrence of resistance genes. To determine the susceptibility profiles and identify MDR strains, we used two MIC methods (MICRONAUT and VITEC2 Compact) and 25 antibiotics. Phenotypic tests showed that 53.84% strains were MDR. Finally, molecular analysis strains revealed the presence of blaSHV, blaPSE-1, blaTEM, but not blaCTX-M genes. Moreover, several genes were associated with resistance to aminoglycosides, cephalosporins, fluorochinolones, sulfonamides, and tetracyclines. This suggests that further research on the prevalence of antibiotic resistance genes (ARGs) in foodborne strains is needed, especially from a One Health perspective.
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Weldon, Emily, Naveen Patil, Jan Voyles, Sandra Chai, Marsha Majors, and Leonard Mukasa. "770. Multi-Drug-Resistant Tuberculosis Cases in Arkansas in 2017: A Tale of Two Threats." Open Forum Infectious Diseases 5, suppl_1 (November 2018): S276. http://dx.doi.org/10.1093/ofid/ofy210.777.
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Abstract Background Multi-drug-resistant tuberculosis (MDR-TB) is a threat to TB elimination strategies worldwide. From 1998 to 2016, six cases of MDR-TB were reported in Arkansas. In 2017 alone, three cases were detected. We sought to describe the characteristics of these cases to inform our MDR-TB prevention strategy in AR. Methods The surveillance database identified three MDR-TB cases in 2017. A detailed review was done to define the demographics, clinical presentation, and laboratory reports relating to drug susceptibility testing (DST), including molecular detection of drug resistance (MDDR). A search was done in the Genotyping database for genotype patterns of the patient isolates. Results All three cases were born outside the United States and developed active disease after arrival in AR. Case 1, age 52, was born in the Marshall Islands, arrived in 2016, and had a history of Type 2 diabetes. He developed MDR-TB in February 2017. Case 2, age 42, was born in Mexico, arrived over 20 years ago, and was HIV positive. He developed TB in July 2016 with a pan-sensitive organism and completed an intermittent treatment regimen. A second TB episode with matching genotype but different drug sensitivities occurred in April 2017, less than 4 months after treatment completion, and was considered treatment failure. Case 3, age 56, was born in the Philippines, arrived in 1990, and was reportedly treated for latent TB infection in 1993 with 6 months of isoniazid. She visited the Philippines April–May 2017 and developed MDR-TB in October 2017. Her isolate was in cluster with a case in Oklahoma who came from Mexico in 2006 and was admitted in an AR hospital with a pan-sensitive organism. There are no epidemiological links between the two cases; only one isolate in each case. Because both isolates were identified in AR State TB laboratory, a complex contamination has been considered with no definite resolution at this time. Conclusion MDR-TB, due to both primary and secondary drug resistance, remains a threat in AR. Cooperation and communication between all levels of healthcare are crucial to avoid delayed diagnosis of MDR-TB. Timely DST via technologies like GeneXpert and MDDR service at CDC is critical. Consultation from Centers of Excellence is vital in the treatment of MDR-TB complicated by diabetes and HIV. Whole-genome sequencing could provide clarity in the cluster with discordant DST patterns. Disclosures All authors: No reported disclosures.
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Wahyudin, William, Dyah Indrasworo, and Ahmad Dian Wahyudiono. "Hubungan Pemberian Kanamisin dengan Kejadian Ototoksik pada Penderita Tuberkulosis Multi Drug Resistance." Oto Rhino Laryngologica Indonesiana 48, no. 2 (January 30, 2019): 121. http://dx.doi.org/10.32637/orli.v48i2.266.
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Latar Belakang: Ototoksik merupakan salah satu efek samping kanamisin yang sulit dihindari. Ototoksisitas kanamisin ditandai dengan gangguan pendengaran sensorineural yang progresif dan sering irreversible dimulai dari frekuensi lebih dari 8000 Hz yang akhirnya akan mengenai frekuensi yang lebih rendah jika terapi dilanjutkan. Tujuan: Penelitian ini bertujuan untuk mengetahui pengaruh pemberian kanamisin pada pasien tuberkulosis multi drug resistance (TB MDR) terhadap munculnya ototoksik dengan pemeriksaan audiometri. Metode: Penelitian observasional longitudinal dengan pendekatan cohort ini mengevaluasi fungsi pendengaran sebelum dan setelah pemberian kanamisin pada pasien TB MDR. Pemeriksaan fungsi pendengaran menggunakan audiometri nada murni. Kanamisin adalah aminoglikosida pilihan pada pasien dengan TB MDR yang akan diberikan secara injeksi intramuskular. Hasil: Uji Friedman’s menunjukkan ditemukan perubahan yang bermakna pada hasil pengukuran audiometri pada frekuensi tinggi antara pasca injeksi kanamisin bulan pertama, kedua, hingga kelima dengan hasil pengukuran sebelum terapi (p>0,05). Diagnosis ototoksisitas menggunakan kriteria American-Speech-Language-Hearing-Association (ASHA) dapat dideteksi sejak bulan pertama pemberian kanamisin (25%). Kesimpulan: Ada hubungan antara kejadian ototoksik dengan pemberian kanamisin pada penderita TB MDR. Telah terjadi ototoksisitas sejak injeksi kanamisin bulan pertama yang dideteksi dengan menggunakan pemeriksaan audiometri, dan bermakna secara statistik. Introduction: Ototoxicity is one of common side effects of kanamycin which is hard to avoid. Ototoxicity can be detected by a progressive and irreversible high frequency sensorineural hearing loss that can further affect low frequency if the therapy is continued. Kanamycin is the drug-of-choice for TB MDR through intramuscular (IM) injection. Purpose: This study aims to determine whether kanamycin can cause ototoxicity in patient with MDR TB by using audiometry examination. Method: An observational longitudinal study with cohort design, evaluating patient’s hearing threshold before and after kanamycin IM injection once per month using pure tone audiometry. Result: A significant alteration in high pitch before and after injection of kanamycin was revealed with Friedman’s test (p<0.05) for hearing threshold using pure tone audiometry. Furthermore, using American Speech-Language-Hearing Association (ASHA) the diagnosis of ototoxicity can be established since the first month of kanamycin injection in 25% of the subjects, and also 25% in the second month of injection. Conclusion: There is a significant connection between ototoxicity with kanamycin injection in MDR TB patients, statistically proven. The ototoxicity can happen since the first month of injection, which can be detected using pure tone audiometry.
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Chizimu, Joseph Yamweka, Eddie Samuneti Solo, Precious Bwalya, Thoko Flav Kapalamula, Kaemba Kunkuta Mwale, David Squarre, Misheck Shawa, et al. "Genomic Analysis of Mycobacterium tuberculosis Strains Resistant to Second-Line Anti-Tuberculosis Drugs in Lusaka, Zambia." Antibiotics 12, no. 7 (June 29, 2023): 1126. http://dx.doi.org/10.3390/antibiotics12071126.
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The emergence of pre-extensively drug-resistant tuberculosis (pre-XDR-TB) is a threat to TB control programs in developing countries such as Zambia. Studies in Zambia have applied molecular techniques to understand drug-resistance-associated mutations, circulating lineages and transmission patterns of multi-drug-resistant (MDR) Mycobacterium tuberculosis. However, none has reported genotypes and mutations associated with pre-XDR TB. This study characterized 63 drug-resistant M. tuberculosis strains from the University Teaching Hospital between 2018 and 2019 using targeted gene sequencing and conveniently selected 50 strains for whole genome sequencing. Sixty strains had resistance mutations associated to MDR, one polyresistant, and two rifampicin resistant. Among MDR strains, seven percent (4/60) had mutations associated with pre-XDR-TB. While four, one and nine strains had mutations associated with ethionamide, para-amino-salicylic acid and streptomycin resistances, respectively. All 50 strains belonged to lineage 4 with the predominant sub-lineage 4.3.4.2.1 (38%). Three of four pre-XDR strains belonged to sub-lineage 4.3.4.2.1. Sub-lineage 4.3.4.2.1 strains were less clustered when compared to sub-lineages L4.9.1 and L4.3.4.1 based on single nucleotide polymorphism differences. The finding that resistances to second-line drugs have emerged among MDR-TB is a threat to TB control. Hence, the study recommends a strengthened routine drug susceptibility testing for second-line TB drugs to stop the progression of pre-XDR to XDR-TB and improve patient treatment outcomes.
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Yadav, K., S. Prakash, NP Yadav, and RS Sah. "Multi-Drug Resistance of Bacterial Isolates among Dental Caries Patients." Janaki Medical College Journal of Medical Science 3, no. 1 (July 27, 2016): 37–44. http://dx.doi.org/10.3126/jmcjms.v3i1.15374.
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Background and Objectives: Dental caries is a well known major oral health problem in most developing countries which has multifactorial etiology caused by many facultatively anaerobes. S. mutans is the main pathogen associated with this disease. Recently Multi-Drug Resistant (MDR) species of S. mutans were identified from the dental caries patients against many commercial antibiotics. MDR is a natural phenomenon, posing a serious worldwide threat to public health. Several therapeutic agents are available to treat or prevent tooth decay, but still global burden of the disease with MDR are emerging. Therefore, the present study was designed for assessing the antibiotic sensitivity pattern of commercially available antibiotics.Material and Methods: This cross-sectional study was carried out by following Standard protocols of Bergey’s Manual of Systematic Bacteriology to isolate and identify the organism and further followed by antibiotic susceptibility test of bacterial isolates by disc diffusion method.Results: Streptococcus mutans (40%) was the most predominant to cause dental caries followed by S. aureus with 28.92. Gram positive isolates were found to be frequently resistant towards penicillin and tetracycline whereas Gram negative isolates were found to be Cotrimoxazole resistant.Conclusion: A high frequency of penicillin resistance in oral isolates and its co-resistance to erythromycin, tetracycline, gentamycin and amipicillin among the pateints was observed. The various awareness programmes should be facilitating the appropriate use of antibiotic to re-establish dominance over diseases must be implemented.Janaki Medical College Journal of Medical Sciences (2015) Vol. 3 (1):37-44
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Pringgenies, Delianis, and Mijil Ciptaning Dananjoyo. "Penapisan Bakteri Simbion Gastropoda Stramonita armigera Penghasil Senyawa Antibakteri Multi Drug Resistant dari Perairan Ternate." Jurnal Natur Indonesia 13, no. 3 (October 21, 2012): 200. http://dx.doi.org/10.31258/jnat.13.3.200-206.
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Antibiotic resistance is an ability of bacteria to hold the antibiotic effect. It was reported that there is a human-patogen bacteria that resistance to one or more classes of antibiotic. It become a problem on medical world. Tosolve those problems, it is necessary to search the new antibiotic compounds that more effective and efficient tosolve the problem of Multi Drug Resistance (MDR). The secondary metabolite-producing marine invertebrates andsymbiont microorganisms, have prospect as an antibiotic. The symbiont microorganisms may produce thesecondary metabolite similar to their host. The aims of the reseach were to determinate of gastropods symbiontbacteria that capable of producing Antibacterial MDR (Multi Drugs Resistant) Compound. Sample of Molusc werecollected from Ternate (Molucas) islands. Isolation of symbiotic bacteria, screening for bacteria which producingsecondary metabolites as anti-MDR bacteria, antibacterial test, isolation of clinical pathogenic bacteria (MDR),conducting anti-bacterial sensitivity test, sensitivity test for antibacterial, DNA exctraction, DNA amplificationbased on PCR method, DNA sequencing. Result of 16S r-DNA sequence was then analyzed and edited usingGENETYX program and followed by 16S rDNA sequence analysis. The result showed that 17 strains were isolatedfrom gastropods Stramonita armigera. Antibacterial assays showed that TSA 8.7 isolate have ability to inhibitPseudomonas sp., Escherichia coli dan Enterobacter sp. the molecular analyses showed that isolate TSA 8.7closed by related to Vibrio sp. Strain JZDN1, with 98% of homology. Based on this experimental result, it could beconcluded that gastropods-symbiont bacterium Stramonita armigera capable of producing antibacterial compoundagainst strain Multi Drug Resistant (MDR). There is 11 isolates of gastropods-symbiont bacteria Stramonita armigerathat have an antibacterial MDR activity.
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Xiong, Hui, Jiang Ni, Zhijie Jiang, Fengchun Tian, Jianping Zhou, and Jing Yao. "Intracellular self-disassemble polysaccharide nanoassembly for multi-factors tumor drug resistance modulation of doxorubicin." Biomaterials Science 6, no. 9 (2018): 2527–40. http://dx.doi.org/10.1039/c8bm00570b.
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Drug efflux induced by multidrug resistance (MDR) overexpression, as well as secondary drug resistance caused by subtoxic drug microenvironments as a result of inefficient drug release of nanoscopic drug carriers in tumor cells, are major bottlenecks for chemotherapy.
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Raja Iqbal Mulya Harahap, Juandika Juandika, and Dety Mulyanti. "PERBANDINGAN BIAYA PEMERIKSAAN LABORATORIUM PADA PASIEN TUBERKULOSIS MULTIDRUG RESISTANCE (TB-MDR) DENGAN TUBERKULOSIS EXTENSIVE DRUG RESISTANCE (TB-XDR): STUDI PADA RUMAH SAKIT TERSIER DI BANDUNG." DIAGNOSA: Jurnal Ilmu Kesehatan dan Keperawatan 1, no. 1 (April 29, 2023): 01–09. http://dx.doi.org/10.59581/diagnosa-widyakarya.v1i1.156.
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Introduction. Tuberculosis (TB) is one of the oldest diseases known to attack humans, caused by the bacterium Mycobacterium tuberculosis. Multi-drug-resistant TB (MDR-TB) is a stage or condition in which Mycobacterium tuberculosis becomes minimally resistant to rifampicin administration and also insonicotinylhydrazine (INH). Extensive-drug-resistant TB (XDR-TB) is an MDR-TB with Mycobacterium tuberculosis immune characteristics against one of the fluoroquinolone class drugs and one of the second-line injection OAT (capreomycin, kanamycin, and amikacin). The aim of this study was to find out the description of variation in laboratory costs of MDR-TB/XDR patients on one treatment cycle.
Method. The inclusion criteria were patients who had been diagnosed with MDR-TB/XDR and performed laboratory tests. The design of this study was a cross-sectional retrospective analytics using medical records of MDR-TB/XDR patients in MDR division.
Results. There were 30 MDR-TB research subjects and 2 XDR-TB research subjects examined for laboratory examination. Comparison of laboratory mean of MDR-TB/XDR (p = 0,018).
Discussion. There was a significant difference in the total cost of MDR-TB/XDR laboratory examinations in one treatment cycle.
Conclusion. Laboratory examination of MDR-TB/XDR patients requires considerable cost, this is due to the side effects of OAT that require patient clinical monitoring.
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Singh, Richa, Itika Varshney, D. S. Chauhan, and Tulika Prasad. "Cell Envelope Thickening: A Mechanism of Drug Resistance in Mycobacterium Tuberculosis." ECS Transactions 107, no. 1 (April 24, 2022): 19671–80. http://dx.doi.org/10.1149/10701.19671ecst.
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Emergence of multi-drug-resistant (MDR) strains of Mycobacterium tuberculosis (Mtb) is recognized as an alarming threat to public health and it limits the number of compounds available for treatment of global tuberculosis (TB) epidemic. MDR is defined as resistance to at least two first line drugs, e.g. Rifampicin and Isoniazid, used commonly for the treatment of this disease. Multi-drug resistance may be due to presence of a thick, hydrophobic, impermeable, and waxy cell envelope (cell wall and cell membrane combined together). The present study investigated the cell envelope thickness in Rifampicin and Isoniazid resistant and sensitive Mtb isolates by transmission electron microscopy (TEM). Electron microscopic examination exhibited evident differences in cell envelope thickness between the sensitive (approx. 24 - 27 nm) and resistant (approx. 34 - 42 nm) Mtb isolates. Thus, this study demonstrated that thickening of cell envelope in resistant isolates might be one of the primary defense mechanisms adopted by Mtb against antibacterial drugs and the observed resistance towards Rifampicin and Isoniazid, the major first line drugs used against TB, might be attributed to this enhanced cell envelope thickness in drug resistant strains.
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Abdul-Aziz, Ahmed A., Mogahid M. Elhassan, Salma A. Abdulsalam, Eman O. Mohammed, and Mohamed E. Hamid. "Multi-drug resistance tuberculosis (MDR-TB) in Kassala State, Eastern Sudan." Tropical Doctor 43, no. 2 (April 2013): 66–70. http://dx.doi.org/10.1177/0049475513490421.
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Oyedeji, Gbadebo J., Charles Adeyemo, Affolabi Dissou, Tope Abiodun, Oyebode A. T. Alli, Olakunle J. Onaolapo, Adejoke Y. Onaolapo, Yemisi Adesiji, and Olugbenga A. Olowe. "Prevalence of Multi-Drug Resistant Tuberculosis among Tuberculosis Patients Attending Chest Clinics in Osun-State, Nigeria." Current Pharmaceutical Biotechnology 21, no. 10 (September 7, 2020): 939–47. http://dx.doi.org/10.2174/1389201021666200226100242.
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Background: The development of multidrug-resistant tuberculosis (MDR-TB) poses a considerable threat to tuberculosis control programmes in Nigeria. There is an increase in the prevalence of MDR-TB worldwide both among new tuberculosis cases as well as previously-treated ones. There is also a rise in transmission of resistant strains due to an increase in MDR-TB patients largely due to the poor drug compliance and the impact of Human immunodeficiency virus infection. Therefore, we intend to determine the extent of MDR-TB among attendees of chest clinics in Osun-State, Nigeria. Objectives: The objective of this study was to determine the prevalence of MDR-TB among confirmed tuberculosis patients attending chest clinics in Osun-State, Nigeria. Methods: This study was conducted among 207 attendees of chest clinics in Osun-State between June, 2015 and October 15, 2016. Sputum and blood samples of the participants were collected. GeneXpert test was carried out first on the samples for simultaneous identification of MTB and rifampicin resistance. Sputum samples were cultured on Lowenstein-Jensen (L-J) medium using N-acetyl-Lcysteine- sodium hydroxide (NALC-NaOH) decontamination method. Drug susceptibility testing (DST) to three first-line drugs was carried out using the proportion DST method. Results: The prevalence of MTB was found to be 27.5% while the prevalence of MDR-TB from the fifty-seven isolates was 10.5%. Previously treated and new cases had a prevalence of 7.0% and 3.5% MDR-TB, respectively. Seventy (33.8%) participants were positive for HIV infection, out of which twenty-six (12.6%) had co-infection of tuberculosis and HIV. The mono-resistance rates of the three first-line drugs used were: 5.3% and 8.7% for ethambutol (EMB) and isoniazid (INH), respectively. No isolate had mono-resistance (0%) to rifampicin (RIF). Conclusion: This study observed the prevalence of 27.5% MTB and a prevalence of 10.5% MDR-TB among the MTB isolates. The prevalence of TB is high in Osun State. MDR-TB prevalence is higher compared with the national estimate of MDR-TB (5.1%) of 2017. Resistant TB is a threat to national tuberculosis control and it is recommended that all the facilities be equipped to cater to its diagnosis.
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Perween, Nusrat, Asfia Sultan, Anees Akhtar, Fatima Khan, Meher Rizvi, Haris M. Khan, and Manzoor Ahmad. "Nitrofurantoin and fosfomycin for the carbapenem resistant Enterobacteriales and multi drug resistant uropathogens: are the choices still same?" International Journal Of Community Medicine And Public Health 7, no. 10 (September 25, 2020): 3980. http://dx.doi.org/10.18203/2394-6040.ijcmph20204364.
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Background: Urinary tract infection (UTI) is one of the most common bacterial infections, affecting 150 million people each year worldwide with substantial clinical and financial burden. With upcoming multi drug resistance (MDR) and carbepenem resistance among uropathogens there is urgent need to explore other new or old treatment options like nitrofurantoin and fosfomycin trometamol.Methods: This is a cross-sectional (descriptive study) conducted over 6 month’s period from October 2019 to March 2020. Out of 9045 urine samples, 1788 (19.8%) were positive (1721 samples with single organism and 67 samples with 2 organisms). Total 1855 isolates were identified and antimicrobial susceptibility was performed by Kirby-Bauer method and VITEK 2 system. Methicillin‑resistant Staphylococcus aureus (MRSA), vancomycin resistant enterococci (VRE), multi drug resistance (MDR) and metallo‑beta‑lactamases (MBL) production was detected.Results: E. coli 41.8% was found commonest followed by enterococcus species (21.6%). Methicillin resistance was 66% while 1.8% were VRE. 429 (34.5%) were CRE (carbapenem resistant enterobacteriales) out of which, 154 (36%) were MBL while 188 (44%) were detected as serine carbapenemase producers via modified carbapenem inactivation method (mCIM) and EDTA-modified carbapenem inactivation method (eCIM) testing. Among 742 (40%) MDR, fosfomycin was effective in 611 (82.3%) while 331 (77.1%) of the CRE isolates were susceptible to fosfomycin.Conclusions: Fosfomycin should be reserved for MDR and nitrofurantoin should be used cautiously otherwise resistance will increase to these drugs in the coming days.
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Mohiuddin, Md, and J. Ashraful Haq. "First Line Anti-Tubercular Drug Resistance Pattern of Mycobacterium Tuberculosis Isolated From Specialized Hospitals of Dhaka City." Ibrahim Medical College Journal 8, no. 2 (February 4, 2016): 41–46. http://dx.doi.org/10.3329/imcj.v8i2.26677.
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The present study was undertaken to determine the drug resistance pattern of M. tuberculosis isolated from 225 pulmonary and 45 extrapulmonary tuberculosis cases. The samples were cultured on Lowenstein Jensen (L-J) media for isolation of M. tuberculosis. Drug resistance to first line anti tubercular drugsnamely isoniazid (INH), rifampicin (RIF), Ethambutol (ETH) and streptomycin (SM) were determined by indirect proportion method. The overall drug resistance of M. tuberculosis was 53.6% to any of the first line anti tubercular drugs. Rate of multi drug resistant tuberculosis (MDR-TB) among the untreated cases was 4.2%, while it was 36.0% in previously treated cases. It was found that 83.3% rifampicin resistant M. tuberculosis was cross resistant to one or more of other first line anti-tubercular drugs, while cross resistance of INH, ETH and SM resistant isolates was much low. The present study revealed that high level of drug resistance exists to individual anti tubercular drugs and MDR-TB is an emerging problem, particularly in treated cases. Rifampicin resistance could be used as a surrogate marker for drug resistance to other first line anti tubercular drugs.Ibrahim Med. Coll. J. 2014; 8(2): 41-46
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Brar, Amarpreet, Satwik Majumder, Maria Zardon Navarro, Marie-Odile Benoit-Biancamano, Jennifer Ronholm, and Saji George. "Nanoparticle-Enabled Combination Therapy Showed Superior Activity against Multi-Drug Resistant Bacterial Pathogens in Comparison to Free Drugs." Nanomaterials 12, no. 13 (June 24, 2022): 2179. http://dx.doi.org/10.3390/nano12132179.
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The emergence of multidrug-resistant (MDR) bacterial pathogens in farm animals and their zoonotic spread is a concern to both animal agriculture and public health. Apart from antimicrobial resistance (AMR), bacterial pathogens from the genera of Salmonella and Staphylococcus take refuge inside host cells, thereby demanding intervention strategies that can eliminate intracellular MDR pathogens. In this study, seven clinical isolates of Salmonella and Staphylococcus from swine farms were characterized for antibiotic (n = 24) resistance, resistance mechanisms, and virulence characteristics. All isolates showed resistance to one or more antibiotics and S. enterica ser. Typhimurium isolate had the highest resistance to the panel of antibiotics tested. Major resistance mechanisms identified were efflux pump and beta-lactamase enzyme activities. Staphylococcus isolates showed complete hemolysis and strong biofilm formation, while Salmonella isolates caused partial hemolysis, but showed no or weak biofilm formation. MDR isolates of S. aureus M12 and S. enterica ser. Typhimurium bacteria were subsequently tested against combinations of antibiotics and potentiating adjuvants for improved antibacterial efficacy using a checkerboard assay, and their fractional inhibitory concentration index (FICI) was calculated. A combination of chitosan and silica nanoparticles containing tetracycline (TET) and efflux pump inhibitor chlorpromazine (CPZ), respectively, was characterized for physicochemical properties and effectiveness against MDR Salmonella enterica ser. Typhimurium isolate. This combination of nano-encapsulated drugs improved the antibacterial efficacy by inhibiting AMR mechanisms (efflux activity, beta-lactamase enzyme activity, and hydrogen sulfide (H2S) production) and reducing intracellular pathogen load by 83.02 ± 14.35%. In conclusion, this study sheds light on the promising applicability of nanoparticle-enabled combination therapy to combat multidrug-resistant pathogens encountered in animal agriculture.
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Chumovatov, N. V., O. G. Komissarova, and N. A. Chernykh. "MODERN APPROACHES TO TREATMENT OF PATIENTS WITH MULTI-DRUG RESISTANT TB USING NOVEL TB DRUGS." Вестник ЦНИИТ 7, no. 1 (2023): 5–12. http://dx.doi.org/10.57014/2587-6678-2023-7-1-5-12.
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According to the World Health Organization (WHO), in 2021 the number of TB patients increased worldwide and reached 10.6 million people, while in 2020 this rate was 9.9. million people. We also observed proliferation of drug-resistant TB. According to the WHO, 450,000 TB patients with multiple drug resistance (MDR) were registered worldwide in 2021, which exceeded the similar rate in 2020 by 3%. In the recent years we observed decrease in TB incidence in the Russian Federation.TB incidence was 53.3 people per 100,000 population in 2016, and 32.4 people per 100,000 population in 2020. MDR-TB prevalence was 16.4 per 100,000 population in the Russian Federation in 2021. The share of extensively drug resistant (XDR) TB patients was 22.3% in the end of 2021. Many scientists have emphasized the need for active development of novel drugs for drug-resistant (DR) TB treatment. Delamanid is one of the novel TB drugs, included in the list of DR-TB drugs by the WHO in 2015. Wide use of delamanid in MDR-TB treatment regimens may improve effectiveness of chemotherapy, also by increasing patients’ adherence to treatment, and decrease adverse events. However, use of delamanid and other novel TB drugs in MDR/XDR-TB treatment regimens requires further research.
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St. Cyr, Sancta, Ellen Kersh, Hillard Weinstock, and Elizabeth Torrone. "1167. Trends in Multi-Drug-Resistant Gonorrhea, Gonococcal Isolate Surveillance Project, United States, 1987–2016." Open Forum Infectious Diseases 5, suppl_1 (November 2018): S352. http://dx.doi.org/10.1093/ofid/ofy210.1000.
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Abstract Background Neisseria gonorrhoeae’s ability to develop resistance to antibiotics used for treatment and a limited development of new therapies have made this organism one of three urgent threat pathogens in the United States. We provide the first report of US trends in multi-drug-resistant (MDR) and extensively-drug-resistant (XDR) gonorrhea. Methods The Gonococcal Isolate Surveillance Project (GISP) monitors trends in antimicrobial susceptibility in N. gonorrhoeae in the United States. Antimicrobial susceptibility testing by agar dilution is performed on urethral isolates from male patients at participating STD clinics. Minimum inhibitory concentration (MIC) are used to identify isolates with resistance or reduced susceptibility using the following criteria: fluoroquinolones (ciprofloxacin [MIC ≥1.0 μg/mL]) and elevated MICs to cephalosporins (cefixime [MIC ≥0.25 μg/mL], ceftriaxone [MIC ≥0.25 μg/mL]) and macrolides (azithromycin [MIC ≥1.0 μg/mL before 2005 and ≥2.0 μg/mL 2005–2016]). In this analysis, MDR is defined as resistance or elevated MICs to ≥2 classes of antimicrobials; XDR as resistance or elevated MICs to ≥3 classes. This classification excludes penicillin and tetracycline due to their long history and high prevalence of gonococcal resistance. Results During 1987–2016, 159,445 isolates were collected through GISP. In 1998, the first MDR strains were identified. Although only 0.04% of isolates that year, these isolates showed elevated MICs to both cephalosporins and macrolides. By 2010, 1.0% of GISP isolates were MDR with elevated MICs or resistance to two of the cephalosporins, macrolides, or fluoroquinolones. In 2011, the proportion of isolates that were MDR peaked at 1.3%. In 2016, after minor fluctuations, 1.1% of GISP isolates were considered MDR. Only one occurrence of XDR, in 2011, has been seen in GISP. The strain was resistant to fluoroquinolones with elevated MICs to both cephalosporins and macrolides. Conclusion MDR and XDR gonorrhea have remained low over the past three decades; however, dual treatment with cephalosporins and macrolides is the last remaining recommended therapy for N. gonorrhoeae. Until new treatment options become available, a combination of surveillance and ensuring appropriate treatment are needed to delay further resistance. Disclosures All authors: No reported disclosures.
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Ohene Larbi, Rita, Wisdom Adeapena, Matilda Ayim-Akonor, Ebenezer D. O. Ansa, Hannock Tweya, Robert Fraser Terry, Appiah-Korang Labi, and Anthony D. Harries. "Antimicrobial, Multi-Drug and Colistin Resistance in Enterobacteriaceae in Healthy Pigs in the Greater Accra Region of Ghana, 2022: A Cross-Sectional Study." International Journal of Environmental Research and Public Health 19, no. 16 (August 22, 2022): 10449. http://dx.doi.org/10.3390/ijerph191610449.
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There is little published information on antimicrobial resistance (AMR) in animals in Ghana. We determined the prevalence and factors associated with AMR, multi-drug resistance (MDR-resistance to ≥3 antimicrobial classes) and colistin resistance in Enterobacteriaceae in healthy pigs in Accra, Ghana. Rectal swabs obtained from the pigs on 20 farms from January to March 2022, were examined for Escherichia coli, Enterobacter spp. and Klebsiella pneumoniae. AMR was determined using standard microbiological techniques and the mcr-1 gene detected through molecular analysis. Enterobacteriaceae were isolated from 197 of 200 pigs: these comprised 195 E. coli isolates, 38 Enterobacter spp. and 3 K. pneumoniae, either singly or combined. Over 60% of E. coli were resistant to tetracycline, with 27% and 34% being resistant to amoxicillin/clavulanic acid and ampicillin, respectively; 23% of E. coli and 5% of Enterobacter spp. exhibited MDR phenotypes. Phenotypic colistin resistance was found in 8% of E. coli and Enterobacter spp., with the mcr-1 gene detected in half. Our study findings should be incorporated into on-going AMR, MDR and colistin resistance surveillance programs in Ghana. We further advocate for tailored-specific education for pig farmers on animal antimicrobial use and for strengthened regulatory policy on antimicrobial usage and monitoring in the animal production industry.
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Pajaniradje, Sankar, Kumaravel Mohankumar, Rakesh Radhakrishnan, Shamim Akhtar Sufi, Srividya Subramanian, Parthiban Anaikutti, Surya Prakash Rao Hulluru, and Rukkumani Rajagopalan. "Indole Curcumin Reverses Multidrug Resistance by Reducing the Expression of ABCB1 and COX2 in Induced Multidrug Resistant Human Lung Cancer Cells." Letters in Drug Design & Discovery 17, no. 9 (September 11, 2020): 1146–54. http://dx.doi.org/10.2174/1570180817666200402124503.
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Background: Drug resistance by the cancer cells towards current chemotherapeutic approaches poses a great challenge. In the present study, an indole analogue of a well-known plant derived anticancer molecule, curcumin, was tested for its Multidrug Resistance (MDR) reversing potential in induced multi drug resistant A549 cell line. Materials and Methods: Human lung cancer cell line A549 was made Multidrug Resistant (MDR) by prolonged treatment with low dosage of Docetaxel, an established anticancer drug. The MDR induction was confirmed by morphological evidence, Hoechst 33342 staining, MTT assay, Rhodamine123 staining and RT-PCR of ABCB1 gene. Protein expression studies were carried out using western blotting technique Results and Discussions: The induced MDR A549 cells exhibited significant increase in the gene expression of ABCB1 gene at the transcriptional level. Retention and efflux studies with Pglycoprotein (P-gp) substrate Rh123 indicated that indole curcumin inhibited P-gp mediated efflux of Rhodamine. Furthermore, treatment of MDR A549 cells with indole curcumin showed downregulation of gene expression of ABCB1 and COX 2. This was also confirmed from the decreased protein expression of COX 2. Conclusion: The results of the present study indicate that indole curcumin reverses multi drug resistance by downregulating the expression of ABCB1 and COX 2 genes. Thus, indole curcumin may act as a potent modulator for ABCB1 and COX 2 mediated MDR in lung cancer.
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Thai, Van C., Keith A. Stubbs, Mitali Sarkar-Tyson, and Charlene M. Kahler. "Phosphoethanolamine Transferases as Drug Discovery Targets for Therapeutic Treatment of Multi-Drug Resistant Pathogenic Gram-Negative Bacteria." Antibiotics 12, no. 9 (August 29, 2023): 1382. http://dx.doi.org/10.3390/antibiotics12091382.
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Antibiotic resistance caused by multidrug-resistant (MDR) bacteria is a major challenge to global public health. Polymyxins are increasingly being used as last-in-line antibiotics to treat MDR Gram-negative bacterial infections, but resistance development renders them ineffective for empirical therapy. The main mechanism that bacteria use to defend against polymyxins is to modify the lipid A headgroups of the outer membrane by adding phosphoethanolamine (PEA) moieties. In addition to lipid A modifying PEA transferases, Gram-negative bacteria possess PEA transferases that decorate proteins and glycans. This review provides a comprehensive overview of the function, structure, and mechanism of action of PEA transferases identified in pathogenic Gram-negative bacteria. It also summarizes the current drug development progress targeting this enzyme family, which could reverse antibiotic resistance to polymyxins to restore their utility in empiric therapy.
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Nanovic, Zorica, Biserka Kaeva Jovkovska, Gorica Breskovska, and Milena Petrovska. "Key Issues in the Management of Multi-Drug Resistant Tuberculosis: A Case Report." Open Access Macedonian Journal of Medical Sciences 6, no. 7 (July 14, 2018): 1282–88. http://dx.doi.org/10.3889/oamjms.2018.290.
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BACKGROUND: Global tuberculosis (TB) epidemic is being driven to an increasing extent by the emergence and spread of drug-resistant strains of Mycobacterium tuberculosis complex (MTBC). We present a case of primary multidrug-resistant tuberculosis (MDR-TB), highlighting Macedonian MDR-TB management issues.CASE REPORT: A 39-year old previously healthy Caucasian male, with no previous history of TB or close contact to TB, was admitted in referral TB-hospital due to respiratory bleeding. Chest X-ray revealed opacity with cavernous lesions in the right upper lobe. Sputum samples showed no presence of acid-fast bacilli (AFB) on fluorescence microscopy, but molecular tests (real-time PCR-based assay and multiplex PCR-based reverse hybridisation Line Probe Assay) confirmed the presence of MTBC, also revealing rifampicin and isoniazid resistance and absence of resistance to second-line anti-tubercular drugs. The strain was considered multidrug-resistant, lately confirmed by conventional methods in liquid and solid culture. Following the protocol of the World Health Organization, we started the longer treatment of MDR-TB comprised of at least five effective anti-tubercular drugs. Due to patient’s extreme non-adherence, we had to delay and modify the regimen (i.e. omitting parenteral aminoglycoside) and to discharge him from the hospital a month after directly observed therapy (DOT) in negative pressure room. As there is no legal remedy in our country regarding involuntary isolation, our patient continued the regimen under ambulatory control of referral TB-hospital. Ignoring the risk of additional acquisition of drug resistance and prolonged exposure of the community to MDR-TB strain - for which he was repeatedly advised - he decided to cease the therapy six months after beginning.CONCLUSION: The benefit of molecular tests in the early diagnosis of TB and drug resistance is unequivocal for adequate treatment of resistant forms of TB. Whole genome sequencing ensures additional knowledge of circulating strains and their resistance patterns. These are essentials of effective TB control programs and can provide evidence to medical and legal authorities for more active policies of screening, involuntary confinement and compliance with therapy, and alternative modalities for successful treatment, as a part of infection control.
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Hussain, Mohamed A., Malik Suliman Mohamed, Hisham N. Altayb, Ahmed Osman Mohamed, Ahmed Ashour, Wadah Osman, Asmaa E. Sherif, et al. "Comparative Genomic Analysis of Multi-Drug Resistant Pseudomonas aeruginosa Sequence Type 235 Isolated from Sudan." Microorganisms 11, no. 6 (May 29, 2023): 1432. http://dx.doi.org/10.3390/microorganisms11061432.
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Pseudomonas aeruginosa (P. aeruginosa) is known to be associated with resistance to practically all known antibiotics. This is a cross-sectional, descriptive, laboratory-based analytical study in which 200 P. aeruginosa clinical isolates were involved. The DNA of the most resistant isolate was extracted and its whole genome was sequenced, assembled, annotated, and announced, strain typing was ascribed, and it was subjected to comparative genomic analysis with two susceptible strains. The rate of resistance was 77.89%, 25.13%, 21.61%, 18.09%, 5.53%, and 4.52% for piperacillin, gentamicin, ciprofloxacin, ceftazidime, meropenem, and polymyxin B, respectively. Eighteen percent (36) of the tested isolates exhibited a MDR phenotype. The most MDR strain belonged to epidemic sequence type 235. Comparative genomic analysis of the MDR strain (GenBank: MVDK00000000) with two susceptible strains revealed that the core genes were shared by the three genomes but there were accessory genes that were strain-specific, and this MDR genome had a low CG% (64.6%) content. A prophage sequence and one plasmid were detected in the MDR genome, but amazingly, it contained no resistant genes for drugs with antipseudomonal activity and there was no resistant island. In addition, 67 resistant genes were detected, 19 of them were found only in the MDR genome and 48 genes were efflux pumps, and a novel deleterious point mutation (D87G) was detected in the gyrA gene. The novel deleterious mutation in the gyrA gene (D87G) is a known position behind quinolone resistance. Our findings emphasize the importance of adoption of infection control strategies to prevent dissemination of MDR isolates.
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Seebacher, Nicole A., Maria Krchniakova, Alexandra E. Stacy, Jan Skoda, and Patric J. Jansson. "Tumour Microenvironment Stress Promotes the Development of Drug Resistance." Antioxidants 10, no. 11 (November 11, 2021): 1801. http://dx.doi.org/10.3390/antiox10111801.
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Multi-drug resistance (MDR) is a leading cause of cancer-related death, and it continues to be a major barrier to cancer treatment. The tumour microenvironment (TME) has proven to play an essential role in not only cancer progression and metastasis, but also the development of resistance to chemotherapy. Despite the significant advances in the efficacy of anti-cancer therapies, the development of drug resistance remains a major impediment to therapeutic success. This review highlights the interplay between various factors within the TME that collectively initiate or propagate MDR. The key TME-mediated mechanisms of MDR regulation that will be discussed herein include (1) altered metabolic processing and the reactive oxygen species (ROS)-hypoxia inducible factor (HIF) axis; (2) changes in stromal cells; (3) increased cancer cell survival via autophagy and failure of apoptosis; (4) altered drug delivery, uptake, or efflux and (5) the induction of a cancer stem cell (CSC) phenotype. The review also discusses thought-provoking ideas that may assist in overcoming the TME-induced MDR. We conclude that stressors from the TME and exposure to chemotherapeutic agents are strongly linked to the development of MDR in cancer cells. Therefore, there remains a vast area for potential research to further elicit the interplay between factors existing both within and outside the TME. Elucidating the mechanisms within this network is essential for developing new therapeutic strategies that are less prone to failure due to the development of resistance in cancer cells.