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Multidrug resistant

Sandrine Alibert, Joannah N'Gompazza Diarra, Jessica Hernandez, Aurélien Stutzmann, Marwa Fouad, Gérard Boyer, Jean-Marie Pagès
Worrying levels of bacterial resistance have been reported worldwide involving the failure of many available antibiotic treatments. Multidrug resistance (MDR) in Gram-negative bacteria is often ascribed to the presence of multiple and different resistance mechanisms in the same strain. RND efflux pumps play a major role and are an attractive target to discover new antibacterial drugs. Areas covered: This review discusses the prevalence of efflux pumps, their overexpression in clinical scenarios, their polyselectivity, their effect on the intracellular concentrations of various antibiotics associated with the alteration of the membrane permeability and their involvement in pathogenicity are discussed...
October 20, 2016: Expert Opinion on Drug Metabolism & Toxicology
Li Fang, Qiong Chen, Keren Shi, Xi Li, Qiucheng Shi, Fang He, Jiancang Zhou, Yunsong Yu, Xiaoting Hua
Klebsiella pneumoniae is a gram-negative bacterium that causes numerous diseases, including pneumonia and urinary tract infections. An increase in multidrug resistance has complicated the treatment of these bacterial infections, and although tigecycline shows activity against a broad spectrum of bacteria, resistant strains have emerged. In this study, the whole genomes of two clinical and six laboratory-evolved strains were sequenced to identify putative mutations related to tigecycline resistance. Of seven tigecycline-resistant strains, seven (100%) had ramR mutations, five (71...
2016: PloS One
Lauren E Arthur, Russell S Kizor, Adrian G Selim, Mieke L van Driel, Leonardo Seoane
BACKGROUND: Ventilator-associated pneumonia (VAP) is a significant cause of morbidity and mortality, complicating the medical course of approximately 10% of mechanically-ventilated patients, with an estimated attributable mortality of 13%. To treat VAP empirically, the American Thoracic Society currently recommends antibiotic therapy based on the patients' risk of colonisation by an organism with multidrug resistance. The selection of initial antibiotic therapy in VAP is important, as inappropriate initial antimicrobial treatment is associated with higher mortality and longer hospital stay in intensive care unit (ICU) patients...
October 20, 2016: Cochrane Database of Systematic Reviews
Jun Li, Jie Ao, Kai Li, Jie Zhang, Yanyan Li, Le Zhang, Yuyan Wei, Di Gong, Junping Gao, Weiwei Tan, Lugang Huang, Lunxu Liu, Ping Lin, Yuquan Wei
Multidrug resistance (MDR) is one of the most important contributors to the high mortality of cancer and remains a major concern. We previously found that zinc finger protein 32 (ZNF32), an important transcription factor associated with cancer in Homo sapiens, protects tumor cells against cell death induced by oxidative stress and other stimuli. We thus hypothesized that ZNF32 might enable the tolerance of cancer cells to anti-tumor drugs because higher ZNF32 expression has been found in cancer tissues and in drug-resistant lung adenocarcinoma (AC) cells...
October 20, 2016: Cell Death & Disease
Sonia Fieulaine, Rodolphe Alves de Sousa, Laure Maigre, Karim Hamiche, Mickael Alimi, Jean-Michel Bolla, Abbass Taleb, Alexis Denis, Jean-Marie Pagès, Isabelle Artaud, Thierry Meinnel, Carmela Giglione
Peptide deformylase (PDF) is considered an excellent target to develop antibiotics. We have performed an extensive characterization of a new PDF from the pathogen Streptococcus agalactiae, showing properties similar to other known PDFs. S. agalactiae PDF could be used as PDF prototype as it allowed to get complete sets of 3-dimensional, biophysical and kinetic data with virtually any inhibitor compound. Structure-activity relationship analysis with this single reference system allowed us to reveal distinct binding modes for different PDF inhibitors and the key role of a hydrogen bond in potentiating the interaction between ligand and target...
October 20, 2016: Scientific Reports
Julienne K Muenzner, Bernhard Biersack, Alexander Albrecht, Tobias Rehm, Ulrike Lacher, Wolfgang Milius, Angela Casini, Jing-Jing Zhang, Ingo Ott, Viktor Brabec, Olga Stuchlikova, Ion C Andronache, Detlef Schuppan, Leonard Kaps, Rainer Schobert
Four gold(I) carbene complexes featuring 4-ferrocenyl substituted imidazol-2-ylidene ligands were investigated for antiproliferative and antivascular properties. They were active against a panel of seven cancer cell lines, including multidrug-resistant ones, with low micromolar or nanomolar IC50 (72 h) values, according to their lipophilicity and cellular uptake. The delocalised lipophilic cationic complexes 8 and 10 acted by increasing the reactive oxygen species in two ways: via a genuine ferrocene effect and by inhibiting the thioredoxin reductase...
October 20, 2016: Chemistry: a European Journal
Sarah G Whaley, P David Rogers
Candida infections have increased due to the growth and expansion of susceptible patient populations. The azole fluconazole is the most widely prescribed antifungal, but rising rates of clinical resistance among Candida glabrata isolates have greatly limited its utility. A better understanding of the mechanisms of azole antifungal resistance will provide information needed to overcome this clinical problem and reclaim this antifungal class as an option for empiric treatment of Candida infections. By far, the most frequent mechanism of azole resistance in C...
December 2016: Current Infectious Disease Reports
Yushu Yin, Georgia Papavasiliou, Olga Y Zaborina, John C Alverdy, Fouad Teymour
The human gastrointestinal tract is the primary site of colonization of multidrug resistant pathogens and the major source of life-threatening complications in critically ill and immunocompromised patients. Eradication measures using antibiotics carry further risk of antibiotic resistance. Furthermore, antibiotic treatment can adversely shift the intestinal microbiome toward domination by resistant pathogens. Therefore, approaches directed to prevent replacement of health promoting microbiota with resistant pathogens should be developed...
October 19, 2016: Annals of Biomedical Engineering
Yvonne Schaletzki, Marie-Luise Kromrey, Susanne Bröderdorf, Elke Hammer, Markus Grube, Paul Hagen, Sonja Sucic, Michael Freissmuth, Uwe Völker, Andreas Greinacher, Bernhard H Rauch, Heyo K Kroemer, Gabriele Jedlitschky
The multidrug resistance protein 4 (MRP4/ABCC4) has been identified as an important transporter for signalling molecules including cyclic nucleotides and several lipid mediators in platelets and may thus represent a novel target to interfere with platelet function. Besides its localisation in the plasma membrane, MRP4 has been also detected in the membrane of dense granules in resting platelets. In polarised cells it is localised at the basolateral or apical plasma membrane. To date, the mechanism of MRP4 trafficking has not been elucidated; protein interactions may regulate both the localisation and function of this transporter...
October 20, 2016: Thrombosis and Haemostasis
András Füredi, Szilárd Tóth, Kornélia Szebényi, Veronika F S Pape, Dóra Türk, Nóra Kucsma, László Cervenák, József Tóvári, Gergely Szakács
Despite significant progress, resistance to chemotherapy is still the main reason why cancer remains a deadly disease. An attractive strategy is to target the collateral sensitivity of otherwise multidrug resistant (MDR) cancer. In this study our aim was to catalogue various compounds that were reported to elicit increased toxicity in P-glycoprotein (Pgp) overexpressing MDR cells. We show that the activity of most of the serendipitously identified compounds reported to target MDR cells is in fact cell-line specific, and is not influenced significantly by the function of Pgp...
October 19, 2016: Molecular Cancer Therapeutics
Firas El Chaer, Dimpy P Shah, Roy F Chemaly
Cytomegalovirus (CMV) infection is a significant complication in hematopoietic cell transplantation (HCT) recipients. Four antiviral drugs are used for preventing or treating CMV: ganciclovir, valganciclovir, foscarnet, and cidofovir. With prolonged and repeated use of these drugs, CMV can become resistant to standard therapy, resulting in increased morbidity and mortality, especially in HCT recipients. Antiviral drug resistance should be suspected when CMV viremia (DNAemia or antigenemia) fails to improve or continue to increase after 2 weeks of appropriately dosed and delivered antiviral therapy...
October 19, 2016: Blood
Xin-Yu Zhao, Lei Li, Xiao-Bo Wang, Rong-Jie Fu, Ya-Ping Lv, Wei Jin, Chao Meng, Guo-Qiang Chen, Lei Huang, Ke-Wen Zhao
China accounts for almost half of the total number of liver cancer cases and deaths worldwide, and hepatocellular carcinoma (HCC) is the most primary liver cancer. Snail family transcriptional repressor 2 (SNAI2) is known as an epithelial to mesenchymal transition-inducing transcription factor that drives neoplastic epithelial cells into mesenchymal phenotype. However, the roles of endogenous SNAI2 remain controversial in different types of malignant tumors. Herein, we surprisingly identify that anchorage-independent growth, including the formation of tumor sphere and soft agar colony, is significantly increased when SNAI2 expression is inhibited by shRNAs in HCC cells...
2016: PloS One
Wing-Hin Lee, Ching-Yee Loo, Chean-Ring Leong, Paul M Young, Daniela Traini, Ramin Rohanizadeh
The effectiveness of conventional cancer chemotherapy is hampered by the occurrence of multidrug resistance (MDR) in tumor cells. Although many studies have reported the development of novel MDR chemotherapeutic agents, clinical success is lacking owing to the high associated toxicity. Nanoparticle-based delivery of chemotherapeutic drugs has emerged as alternative approach to treat MDR cancers via exploitation of leaky vasculature in the tumor microenvironment. Accordingly, functionalization of nanoparticles with target specific ligands can be employed to achieve significant improvements in the treatment of MDR cancer...
October 19, 2016: Expert Opinion on Drug Delivery
Fernando Sánchez-Vizcaíno, David Singleton, Philip H Jones, Bethaney Heayns, Maya Wardeh, Alan D Radford, Vanessa Schmidt, Susan Dawson, Peter J M Noble, Sally Everitt
Presentation for pruritus comprised 6.5 per cent, 3.6 per cent and 2.0 per cent of canine, feline and rabbit consultations, respectively, between January 2014 and June 2016Topical antimicrobials were the most commonly prescribed pruritus treatments for dogs (33.6 per cent of consultations); for cats, it was systemic glucocorticoids (53.5 per cent)In surveillance of coagulase-positive staphylococci, 16 per cent of 176 coagulase-positive staphylococci isolated from canine diagnostic samples were sensitive to all tested antibacterial classes; multidrug resistance (resistance to three or more antibacterial classes) was found in 6...
October 8, 2016: Veterinary Record
Peng Sang, Yan Shi, Peng Teng, Annie Cao, Hai Xu, Qi Li, Jianfeng Cai
Antibiotic resistance is one of the biggest public concerns in the 21st century. Host-defense peptides (HDPs) can potentially mitigate the problem through the disruption of bacterial membranes; however, they suffer from moderate activity and low stability. We recently developed a new class of peptidomimetics termed "AApeptides". This class of peptidomimetics can mimic the mechanism of action of HDPs, and effectively arrest the growth of multidrug resistant Gram-positive and Gram-negative bacteria. As they are built on unnatural backbone, they are highly resistant to proteolytic degradation...
October 18, 2016: Current Topics in Medicinal Chemistry
Sara A Buckman, Tamara Krekel, Anouk E Muller, John E Mazuski
The treatment of complicated intra-abdominal infections (cIAI) is increasingly challenging due to increased resistance of Gram-negative organisms. These multidrug resistant organisms lead to an increase in morbidity and mortality. This has led to renewed interest in use of older β-lactam antibiotics in combination with newer β-lactamase inhibitors. Ceftazidime-avibactam is one of the newest such combination antibiotics, which has been released for treatment of complicated intra-abdominal infections in combination with metronidazole...
October 19, 2016: Expert Opinion on Pharmacotherapy
Ia Kusradze, Natia Karumidze, Sophio Rigvava, Teona Dvalidze, Malkhaz Katsitadze, Irakli Amiranashvili, Marina Goderdzishvili
Acinetobacter baumannii is a gram-negative, non-motile bacterium that, due to its multidrug resistance, has become a major nosocomial pathogen. The increasing number of multidrug resistant (MDR) strains has renewed interest in phage therapy. The aim of our study was to assess the effectiveness of phage administration in Acinetobacter baumannii wound infections in an animal model to demonstrate phage therapy as non-toxic, safe and alternative antibacterial remedy. Using classical methods for the study of bacteriophage properties, we characterized phage vB-GEC_Ab-M-G7 as a dsDNA myovirus with a 90 kb genome size...
2016: Frontiers in Microbiology
Bushra Jamil, Rashda Abbasi, Shahid Abbasi, Muhammad Imran, Siffat U Khan, Ayesha Ihsan, Sundus Javed, Habib Bokhari, Muhammad Imran
Natural antimicrobial agents, particularly essential oils present an excellent alternative to current antibiotics due to their potent and broad-spectrum antimicrobial potential, unique mechanisms of action and low tendency to induce resistance. However their potential as a viable therapeutic alternative is greatly compromised due to their hydrophobic and volatile nature. The objective of the current research was to explore the anti-pathogenic potential of essential oils in a bio-based nano-carrier system. Six different essential oils were tested on multidrug-resistant bacterial pathogens...
2016: Frontiers in Microbiology
Surjit Singh, Pramod Kumar Sharma, Rimplejeet Kaur
No abstract text is available yet for this article.
July 2016: Indian Journal of Pharmacology
Glennah Kerubo, Evans Amukoye, Stefan Niemann, Samuel Kariuki
BACKGROUND: Anti-tuberculosis drug resistance is an emerging health problem in Kenya and especially in slums. Slum environments create a conducive environment for the spread of tuberculosis (TB) due to high population density and lack of basic amenities such as decent housing, access to clean water, lack of drainage and basic sanitation. Furthermore, ineffective health services in crowded and poorer populations, poor patient compliance, a large pool of untreated cases, delayed diagnosis and inappropriate treatment regimens are likely to favour selection and spread of drug resistant Mycobacterium tuberculosis (Mtb) strains in such settings, however, precise data on this problem are only sparsely available...
October 19, 2016: BMC Infectious Diseases
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