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Multi-Drug resistance

Phei Er Saw, Jinho Park, Sangyong Jon, Omid C Farokhzad
A major problem with cancer chemotherapy begins when cells acquire resistance. Drug-resistant cancer cells typically upregulate multi-drug resistance proteins such as P-glycoprotein (P-gp). However, the lack of overexpressed surface biomarkers has limited the targeted therapy of drug-resistant cancers. Here we report a drug-delivery carrier decorated with a targeting ligand for a surface marker protein Extra-domain B(EDB) specific to drug-resistant breast cancer cells as a new therapeutic option for the aggressive cancers...
October 18, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
Sanjib K Shrestha, Liliia M Kril, Keith D Green, Stefan Kwiatkowski, Vitaliy M Sviripa, Justin R Nickell, Linda P Dwoskin, David S Watt, Sylvie Garneau-Tsodikova
The emergence of multidrug-resistant bacterial and fungal strains poses a threat to human health that requires the design and synthesis of new classes of antimicrobial agents. We evaluated bis(N-amidinohydrazones) and N-(amidino)-N'-aryl-bishydrazones for their antibacterial and antifungal activities against panels of Gram-positive/Gram-negative bacteria as well as fungi. We investigated their potential to develop resistance against both bacteria and fungi by a multi-step resistance-selection method, explored their potential to induce the production of reactive oxygen species, and assessed their toxicity...
October 10, 2016: Bioorganic & Medicinal Chemistry
Shanshan Wang, Yinjuan Guo, Jingnan Lv, Xiuqin Qi, Dan Li, Zengqiang Chen, Xueqing Zhang, Liangxing Wang, Fangyou Yu
BACKGROUND: Quinupristin/dalfopristin (Q/D) is a valuable alternative antibiotic to vancomycin for the treatment of multi-drug resistant Enterococcus faecium infections. However, resistance to Q/D in E. faecium clinical isolates and nosocomial dissemination of Q/D-resistant E. faecium have been reported in several countries and should be of concern. RESULTS: From January 2012 to December 2015, 911 E. faecium clinical isolates were isolated from various specimens of inpatients at the first Affiliated Hospital of Wenzhou Medical University located in Wenzhou, east China...
October 21, 2016: BMC Microbiology
Troy A Skwor, Stephanie Klemm, Hanyu Zhang, Brianna Schardt, Stephanie Blaszczyk, Matthew A Bork
Increasing rates of antibiotic resistance coupled with the lack of novel antibiotics threatens proper clinical treatment and jeopardizes their use in prevention. A photodynamic approach appears to be an innovative treatment option, even for multi-drug resistant strains of bacteria. Three components are utilized in photodynamic inactivation: a photosensitizer, light source, and oxygen. Variations in photosensitizers strongly influence microbial binding and bactericidal activity. In this study, four different cationic metalloporphyrins (Cu(2+), Fe(2+), Pd(2+), Zn(2+)) were compared to the free-base ligand 5,10,15,20-tetrakis(N-methylpyridinium-4-yl)porphyrin regarding their electronic properties and generation of reactive oxygen species upon subsequent 405nm violet-blue irradiation...
October 15, 2016: Journal of Photochemistry and Photobiology. B, Biology
Matteo Bassetti, Alessia Carnelutti, Maddalena Peghin
The isolation of multi-drug-resistant gram-negative (MDRGN) pathogens has progressively increased worldwide and has been associated with important delays in the prescription of an adequate antibiotic treatment, resulting in increased mortality rates. Patient's stratification for MDRGN infections to optimize the prescription of an adequate empiric antimicrobial regimen is crucial. Areas covered: This article covers MDRGN epidemiology, with a specific focus on risk factors for harbouring infections sustained by extended-spectrum-Beta-lactamase (ESBL), carbapenem resistant Enterobacteriacae (CRE), MDR Pseudomonas aeruginosa and MDR Acinetobacter baumanii...
October 21, 2016: Expert Review of Anti-infective Therapy
Gang Li, Mengyu Shen, Shuai Le, Yinling Tan, Ming Li, Xia Zhao, Wei Shen, Yuhui Yang, Jing Wang, Hongbin Zhu, Shu Li, Xiancai Rao, Fuquan Hu, Shuguang Lu
As a third-generation sequencing method, single-molecule real-time (SMRT) technology provides long read length, and it is well suited for re-sequencing projects and de novo assembly. In this study, Pseudomonas aeruginosa PA1 was characterized and re-sequenced using SMRT technology. PA1 was also subjected to genomic, comparative, and pan-genomic analyses. The multi-drug resistant strain PA1 possesses a 6,498,072 bp genome and a sequence type of ST-782. The genome of PA1 was also visualized, and the results revealed the details of general genome annotations, virulence factors, regulatory proteins, secretion system proteins, type II toxin-antitoxin pairs, and genomic islands...
October 20, 2016: Bioscience Reports
Kristen L Lokken, Gregory T Walker, Renée M Tsolis
Non-typhoidal Salmonella enterica serovars (NTS) are generally associated with gastroenteritis; however, the very young and elderly, as well as individuals with compromised immunity, are at risk of developing disseminated infection that can manifest as bacteremia or focal infections at systemic sites. Disseminated NTS infections can be fatal and are responsible for over 600,000 deaths annually. Most of these deaths are in sub-Saharan Africa, where multi-drug resistant NTS clones are currently circulating in a population with a high proportion of individuals that are susceptible to disseminated disease...
October 8, 2016: Pathogens and Disease
Nicolás M Vázquez, Graciela Fiorilli, Paulo A Cáceres Guido, Silvia Moreno
BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is resistant to different commonly used antibiotics, stressing the need for further strategies to treat this human pathogen with worldwide prevalence. The use of phytochemicals within the current pharmacology is a promising approach to enhance the antimicrobial activity of common antibiotics in the battle against these bacteria. PURPOSE: The purpose of this study was to determine the antimicrobial effectiveness of carnosic acid, the major constituent of Rosmarinus officinalis L...
November 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Michael G Ficklin, Michael P Kowaleski, Kevin A R Kunkel, Jonathan T Suber
A two-year-old, 44 kg dog with a right Helica cementless total hip replacement (THR) was radiographically diagnosed with implant loosening eight months after the index total hip replacement procedure. Subsequent synoviocentesis and synovial fluid culture revealed a methicillin-resistant coagulase-negative Staphylococcus spp infection of the right THR. A one-stage revision using a hybrid BFX cementless acetabular cup and CFX cemented femoral stem was performed. Vancomycin and micro-silver antimicrobial powder impregnated cement were used in the revision...
October 20, 2016: Veterinary and Comparative Orthopaedics and Traumatology: V.C.O.T
Athanasios Tselebonis, Evangelia Nena, Christos Nikolaidis, Theocharis Konstantinidis, Christos Kontogiorgis, Maria Panopoulou, Theodore C Constantinidis
OBJECTIVE: To monitor microbes, focusing on drug resistance, on the hands of the personnel of four departments of a tertiary hospital (ICU, neonatal unit, internal medicine ward and surgical ward) and explore differences between departments, professions and genders. MATERIALS AND METHODS: Hand sampling from 125 healthcare employees was conducted followed by isolation, identification and antibiotic resistance profiling of different microbial species. RESULTS: Staphylococcus spp was the most prevalent microbe (76/125, 60...
September 1, 2016: Folia Medica
Sanmuga Priya Ekambaram, Senthamil Selvan Perumal, Ajay Balakrishnan, Nathiya Marappan, Sabari Srinivasan Gajendran, Vinodhini Viswanathan
AIM/BACKGROUND: Medicinal plants have ability to resist microorganisms by synthesizing secondary metabolites such as phenols. Rosmarinic acid (RA) is a phenylpropanoid widely distributed in plants and well known as therapeutic and cosmetic agent. Methicillin-resistant Staphylococcus aureus (MRSA) which is resistant to all kinds of β-lactams, threatens even most potent antibiotics. To improve the efficiency of antibiotics against multi-drug resistant bacteria and to reduce the antibiotic dose, the antibacterial activity and the synergistic effect of RA with standard antibiotics against S...
September 2016: Journal of Intercultural Ethnopharmacology
Keertan Dheda, Kwok Chiu Chang, Lorenzo Guglielmetti, Jennifer Furin, H Simon Schaaf, Dumitru Chesov, Aliasgar Esmail, Christoph Lange
Globally there is a burgeoning epidemic of drug mono-resistant tuberculosis (TB), multi-drug-resistant TB (MDR-TB), and extensively drug-resistant TB (XDR-TB). Almost 20% of all TB strains worldwide are resistant to at least 1 major TB drug including isoniazid. In several parts of the world there is an increasing incidence of MDR-TB, and alarmingly almost a third of MDR-TB cases globally are resistant to either a fluoroquinolone or aminoglycocide. This trend cannot be ignored because DR-TB is associated with greater morbidity compared to drug-sensitive TB, it accounts for almost 25% of global TB mortality, is extremely costly to treat, consuming substantial portions of budgets allocated to national TB programmes in TB endemic countries, and is a major threat to healthcare workers who are already in short supply in resource-poor settings...
October 15, 2016: Clinical Microbiology and Infection
Dar-Chone Chow, Kacie Rice, Wanzhi Huang, Robert L Atmar, Timothy G Palzkill
The β-lactamase inhibitory protein (BLIP) binds and inhibits a wide range of class A β-lactamases including the TEM-1 β-lactamase (Ki= 0.5 nM), which is widely present in Gram-negative bacteria, and the KPC-2 β-lactamase (Ki= 1.2 nM), which hydrolyzes virtually all clinically useful β-lactam antibiotics. The extent to which the specificity of a protein that binds a broad range of targets can be modified to display narrow specificity was explored in this study by engineering BLIP to bind selectively to KPC-2 β-lactamase...
October 18, 2016: ACS Infectious Diseases
Byeong-Keuk Kim
Catheter-based renal sympathetic denervation (RDN) has opened the new world in the treatment of resistant or refractory hypertension. However, SYMPLICITY HTN-3, 2:1 randomization, blinded and sham-controlled study did not show a significant reduction of systolic blood pressure (BP) in patients with resistant hypertension 6 months after RDN as compared with a sham control. After that, substudy investigating the predictors of BP responses in SYMPLICITY HTN-3 trial was reported; racial difference and optimal medical treatment were issued for the optimal denervation therapy...
September 2016: Journal of Hypertension
David John Webb
Treatment-resistant hypertension (TRH) is defined as the failure to achieve an office BP target of <140/90 mmHg (<130/80 mmHg in patients with chronic kidney disease (CKD) or diabetes) in patients with hypertension (HT), despite adherence to at least 3 antihypertensive medications at optimal tolerated doses, ideally including a diuretic (Calhoun et al., Circulation 2008). TRH identifies patients with hard-to-treat HT, who might benefit from specialist investigation and treatment. Although some studies put the prevalence of TRH as >10%, these levels may be inflated by white-coat hypertension and poor adherence...
September 2016: Journal of Hypertension
Gregory D Huhn, Pablo Tebas, Joel Gallant, Timothy Wilkin, Andrew Cheng, Mingjin Yan, Lijie Zhong, Christian Callebaut, Joseph M Custodio, Marshall W Fordyce, Moupali Das, Scott McCallister
BACKGROUND: HIV-infected, treatment-experienced adults with a history of prior resistance and regimen failure can be virologically suppressed but may require multi-tablet regimens associated with lower adherence and potential resistance development. METHODS: We enrolled HIV-infected, virologically suppressed adults with 2- to 3-class drug resistance and at least 2 prior regimen failures into this phase 3, open-label, randomized study. The primary endpoint was the percentage of participants with HIV-1 RNA <50 copies/mL at week 24 (FDA snapshot algorithm)...
October 6, 2016: Journal of Acquired Immune Deficiency Syndromes: JAIDS
E Wardal, A Kuch, I Gawryszewska, D Żabicka, W Hryniewicz, E Sadowy
The objective of this study was to investigate the antimicrobial resistance, Tn1546 transposon variability and plasmid diversity among Polish vancomycin-resistant Enterococcus faecium (VREfm) isolates of VanA phenotype in the context of their clonal structure. Two hundred sixteen clinical VREfm isolates collected between 1997 and 2010 were studied by antimicrobial susceptibility testing, MLST, MLVA and detection of IS16, esp Efm, pilA, intA and plasmid-specific genes by PCR. Tn1546 structure was revealed by overlapping PCR and sequencing...
October 17, 2016: European Journal of Clinical Microbiology & Infectious Diseases
Mélanie V Trudel, Antony T Vincent, Sabrina A Attéré, Myriam Labbé, Nicolas Derome, Alexander I Culley, Steve J Charette
The bacterium Aeromonas salmonicida subsp. salmonicida is a common pathogen in fish farms worldwide. Since the antibiotic resistance of this bacterial species is on the increase, it is important to have a broader view on this issue. In the present study, we tested the presence of known plasmids conferring multi-drug resistance as well as antibiotic resistance genes by a PCR approach in 100 Canadian A. salmonicida subsp. salmonicida isolates. Our study highlighted the dominance of the conjugative pSN254b plasmid, which confers multi-drug resistance...
October 18, 2016: Scientific Reports
Heloise Buys, Rudzani Muloiwa, Colleen Bamford, Brian Eley
BACKGROUND: Klebsiella pneumoniae (KP) is a significant paediatric bloodstream pathogen in children. There is little data from Africa. In this study we describe the epidemiology of multi-drug resistant Klebsiella pneumoniae bloodstream infection (KPBSI) at Red Cross War Memorial Children's Hospital, Cape Town, South Africa. METHODS: We conducted a retrospective cross-sectional study of KPBSI from 1 January 2006 to 31 December 2011 using conventional descriptive and inferential statistical methods...
October 17, 2016: BMC Infectious Diseases
Diego G Ghiano, Agustina de la Iglesia, Nina Liu, Peter J Tonge, Héctor R Morbidoni, Guillermo R Labadie
A collection of 1,2,3-triazoles unsaturated fatty acid mimics were efficiently synthesized by click chemistry. The 1,4-disubstituted analogs prepared covered different alkyl chain lengths and triazole positions. The compounds were subsequently tested against Mycobacterium tuberculosis, being most of them active with some of the analogs displaying activity at micromolar concentration. The most potent member of the series has the triazole moiety on the C-2 position with a carbon chain of eight or ten carbon atoms...
September 28, 2016: European Journal of Medicinal Chemistry
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