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Polymyxin resistance

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https://www.readbyqxmd.com/read/29203494/polymyxin-b-and-zti-01-fosfomycin-for-injection-against-kpc-producing-klebsiella-pneumoniae-evaluation-of-activity-and-emergence-of-resistance
#1
John K Diep, Rajnikant Sharma, Evelyn J Ellis-Grosse, Cely S Abboud, Gauri G Rao
ZTI-01 (fosfomycin for injection) is a broad spectrum antibiotic with a novel mechanism of action and is currently under development in the USA for treatment of complicated urinary tract infections. Globally, fosfomycin and polymyxin B are increasingly being used to treat multi-drug resistant Gram-negative infections. The objectives were to evaluate the pharmacodynamic activity of polymyxin B and fosfomycin alone and in combination against KPC-producing K. pneumoniae and to assess the rate and extent of emergence of resistance to different antibiotic regimens...
December 4, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29203488/epidemiology-of-carbapenem-resistant-enterobacteriaceae-infections-report-from-china-cre-network
#2
Yawei Zhang, Qi Wang, Yuyao Yin, Hongbin Chen, Longyang Jin, Bing Gu, Liangyi Xie, Chunxia Yang, Xiaobo Ma, Huayin Li, Wei Li, Xiaoqian Zhang, Kang Liao, Sijin Man, Shifu Wang, Hainan Wen, Binbin Li, Zhusheng Guo, Jinjing Tian, Fengyan Pei, Li Liu, Lijun Zhang, Cuimei Zou, Tongping Hu, Jun Cai, Hong Yang, Jiaming Huang, Xianghong Jia, Wenhui Huang, Bin Cao, Hui Wang
Carbapenem-resistant Enterobacteriaceae (CRE) infection is highly endemic in China, but estimates of infection burden are lacking. We established incidence of CRE infection from a multicenter study that covered 25 tertiary hospitals in 14 provinces. CRE cases defined as carbapenem non-susceptible C. freundii, E. coli, E. cloacae, or K. pneumoniae infections during January to December 2015 were collected and reviewed from medical records. Antimicrobial susceptibility testing and carbapenemase genes identification were performed...
December 4, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29189148/identification-of-novel-ligands-for-therapeutic-lipopeptides-daptomycin-surfactin-and-polymyxin
#3
Satya Eswari Jujjavarapu, Swasti Dhagat, Vinay Kurrey
Due to increase in antibiotic-resistance among pathogens, there is a need for potent and safe drugs. An alternative to antibiotics is lipopeptides which are produced as a secondary metabolite by many microorganisms. They exhibit broad-spectrum activities against pathogens along with anti-cancer properties. Among various lipopeptides produced by microorganisms, daptomycin, surfactin, and polymyxin have gained popularity as medicines but their mechanism of action is not described properly. In silico drug design of these lipopeptides becomes a challenge due to their complex structures...
November 29, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/29186402/in-vitro-and-in-vivo-activity-of-single-and-dual-antimicrobial-agents-against-kpc-producing-klebsiella-pneumoniae
#4
Sarath Nath, Farzad Moussavi, Daniel Abraham, David Landman, John Quale
Objectives: Options for treatment of infections due to KPC-producing Klebsiella pneumoniae are limited and combination therapy is often recommended. In this report, the in vitro and in vivo activity of potential therapeutic agents and combinations was assessed against four KPC-producing K. pneumoniae isolates. Methods: Using clinically relevant concentrations, time-kill experiments and the Galleria mellonella model of infection were used to examine the activity of polymyxin B, ceftazidime/avibactam, meropenem, rifampicin and amikacin alone and in combination...
November 23, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29184022/interventions-on-metabolism-making-antibiotic-susceptible-bacteria
#5
Fernando Baquero, José-Luis Martínez
Antibiotics act on bacterial metabolism, and antibiotic resistance involves changes in this metabolism. Interventions on metabolism with drugs might therefore modify drug susceptibility and drug resistance. In their recent article, Martin Vestergaard et al. (mBio 8:e01114-17, 2017, https://doi.org/10.1128/mBio.01114-17) illustrate the possibility of converting intrinsically resistant bacteria into susceptible ones. They reported that inhibition of a central metabolic enzyme, ATP synthase, allows otherwise ineffective polymyxin antibiotics to act on Staphylococcus aureus The study of the intrinsic resistome of bacterial pathogens has shown that several metabolic genes, including multigene transcriptional regulators, contribute to antibiotic resistance...
November 28, 2017: MBio
https://www.readbyqxmd.com/read/29182906/effect-of-polymyxin-b-containing-regimens-on-renal-function-for-the-treatment-of-carbapenem-resistant-enterobacteriacea-mediastinitis
#6
Cely Saad Abboud, Gauri G Rao, Ercilia E Sousa, Alexandre P Zavascki, Carlos Kiffer
A retrospective cohort study, were evaluated: polymyxin B plus aminoglycosides or polymyxin B plus other antibiotics. Any degree of acute kidney injury occurred in 26 (86.6%) patients. The median time to acute kidney injury was 6.0 (95% CI 3-14) days in the polymyxin-aminoglycoside containing regimen group, against 27.0 (95% CI 6-42) days in the polymyxin with other antimicrobial combinations group (p=0.03). Polymyxin B with aminoglycosides group progressed faster to any degree of renal dysfunction.
November 25, 2017: Brazilian Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29182311/polymyxin-induced-lipid-a-deacylation-in-pseudomonas-aeruginosa-perturbs-polymyxin-penetration-and-confers-high-level-resistance
#7
Mei-Ling Han, Tony Velkov, Yan Zhu, Kade D Roberts, Anton P Le Brun, Seong Hoong Chow, Alina D Gutu, Samuel M Moskowitz, Hsin-Hui Shen, Jian Li
Polymyxins are last-line antibiotics against life-threatening multidrug-resistant Gram-negative bacteria. Unfortunately, polymyxin resistance is increasingly reported, leaving a total lack of therapies. Using lipidomics and transcriptomics, we discovered that polymyxin B induced lipid A deacylation via pagL in both polymyxin-resistant and -susceptible P. aeruginosa. Our results demonstrated that the deacylation of lipid A is an 'innate immunity' response to polymyxins and a key compensatory mechanism to the aminoarabinose modification to confer high-level polymyxin resistance in P...
November 28, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/29178957/triple-combination-antibiotic-therapy-for-carbapenemase-producing-klebsiella-pneumoniae-a-systematic-review
#8
REVIEW
David M Jacobs, M Courtney Safir, Dennis Huang, Faisal Minhaj, Adam Parker, Gauri G Rao
BACKGROUND: The spread of carbapenemase-producing K. pneumoniae (CPKP) has become a significant problem worldwide. Combination therapy for CPKP is encouraging, but polymyxin resistance to many antibiotics is hampering effective treatment. Combination therapy with three or more antibiotics is being increasingly reported, therefore we performed a systematic review of triple combination cases in an effort to evaluate their clinical effectiveness for CPKP infections. METHODS: The PubMed database was searched to identify all published clinical outcomes of CPKP infections treated with triple combination therapy...
November 25, 2017: Annals of Clinical Microbiology and Antimicrobials
https://www.readbyqxmd.com/read/29169321/lbjmr-medium-a-new-polyvalent-culture-medium-for-isolating-and-selecting-vancomycin-and-colistin-resistant-bacteria
#9
Lucie Bardet, Stéphanie Le Page, Thongpan Leangapichart, Jean-Marc Rolain
BACKGROUND: Multi-drug resistant bacteria are a phenomenon which is on the increase around the world, particularly with the emergence of colistin-resistant Enterobacteriaceae and vancomycin-resistant enterococci strains. The recent discovery of a plasmid-mediated colistin resistance with the description of the transferable mcr-1 gene raised concerns about the need for an efficient detection method for these pathogens, to isolate infected patients as early as possible. The LBJMR medium was developed to screen for all polymyxin-resistant Gram-negative bacteria, including mcr-1 positive isolates, and vancomycin-resistant Gram-positive bacteria...
November 23, 2017: BMC Microbiology
https://www.readbyqxmd.com/read/29160808/interplay-between-colistin-resistance-virulence-and-fitness-in-acinetobacter-baumannii
#10
REVIEW
Gabriela Jorge Da Silva, Sara Domingues
Acinetobacter baumannii is an important opportunistic nosocomial pathogen often resistant to multiple antibiotics classes. Colistin, an "old" antibiotic, is now considered a last-line treatment option for extremely resistant isolates. In the meantime, resistance to colistin has been reported in clinical A. baumannii strains. Colistin is a cationic peptide that disrupts the outer membrane (OM) of Gram-negative bacteria. Colistin resistance is primarily due to post-translational modification or loss of the lipopolysaccharide (LPS) molecules inserted into the outer leaflet of the OM...
November 21, 2017: Antibiotics
https://www.readbyqxmd.com/read/29158274/dissemination-of-multidrug-resistant-proteus-mirabilis-clones-carrying-a-novel-integron-borne-blaimp-1-in-a-tertiary-hospital
#11
Ana Carolina Ramos, Rodrigo Cayô, Cecilia Godoy Carvalhaes, Thomas Jové, Greice Pereira da Silva, Fernanda Maciel Paschoin Sancho, Thomas Chagas-Neto, Eduardo Alexandrino Servolo Medeiros, Ana Cristina Gales
This study aimed to characterize multi-drug resistant P. mirabilis clones carrying a novel class 1 integron-borne blaIMP-1 In1359 was inserted into a large conjugative plasmid that also carried blaCTX-M-2 The production of carbapenemases in Enterobacteriaceae that are intrinsically resistant to polymyxins and tigecycline is very worrisome, representing a serious challenge to clinicians and infection control teams.
November 20, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29150371/emergence-of-polymyxin-b-resistance-in-a-polymyxin-b-susceptible-kpc-producing-klebsiella-pneumoniae-causing-bloodstream-infection-in-a-neutropenic-patient-during-polymyxin-b-therapy
#12
Alexandre P Zavascki, Raquel Girardello, Cibele M Magagnin, Laura C Antochevis, Rafael A Maciel, Jussara K Palmeiro, Ana C Gales
The emergence of resistance to polymyxins in KPC-producing Klebsiella pneumoniae isolates has been a major clinical problem. This study evaluated the molecular mechanisms associated with polymyxin B (PMB) resistance that emerged in a previously PMB-susceptible KPC-2-producing K. pneumoniae during PMB therapy for a bloodstream infection in a neutropenic patient. The first isolate (PMB-susceptible) was obtained while the patient was receiving meropenem and other isolates were recovered from 2 sets of blood cultures in different dates while the patient was receiving PMB therapy (4 of 6 blood cultures bottles yielded isolates with full PMB resistance)...
October 19, 2017: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/29148380/high-rate-of-mcr-1-producing-escherichia-coli-and-klebsiella-pneumoniae-among-pigs-portugal
#13
Nicolas Kieffer, Marta Aires-de-Sousa, Patrice Nordmann, Laurent Poirel
The mcr-1 (mobile colistin resistance 1) gene, which encodes phosphoethanolamine transferase, has been recently identified as a source of acquired resistance to polymyxins in Escherichia coli. Using the SuperPolymyxin selective medium, we prospectively screened 100 pigs at 2 farms in Portugal for polymyxin-resistant Enterobacteriaceae and recovered 98 plasmid-mediated MCR-1-producing isolates. Most isolates corresponded to nonclonally related E. coli belonging to many sequence types; we also found 2 Klebsiella pneumoniae sequence types...
December 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/29147502/chemical-space-guided-discovery-of-antimicrobial-bridged-bicyclic-peptides-against-pseudomonas-aeruginosa-and-its-biofilms
#14
Ivan Di Bonaventura, Xian Jin, Ricardo Visini, Daniel Probst, Sacha Javor, Bee-Ha Gan, Gaëlle Michaud, Antonino Natalello, Silvia Maria Doglia, Thilo Köhler, Christian van Delden, Achim Stocker, Tamis Darbre, Jean-Louis Reymond
Herein we report the discovery of antimicrobial bridged bicyclic peptides (AMBPs) active against Pseudomonas aeruginosa, a highly problematic Gram negative bacterium in the hospital environment. Two of these AMBPs show strong biofilm inhibition and dispersal activity and enhance the activity of polymyxin, currently a last resort antibiotic against which resistance is emerging. To discover our AMBPs we used the concept of chemical space, which is well known in the area of small molecule drug discovery, to define a small number of test compounds for synthesis and experimental evaluation...
October 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/29146285/rapid-polymyxin-np-test-for-the-detection-of-polymyxin-resistance-mediated-by-the-mcr-1-mcr-2-genes
#15
Laurent Poirel, Yu Larpin, Jan Dobias, Roger Stephan, Jean-Winoc Decousser, Jean-Yves Madec, Patrice Nordmann
The Rapid Polymyxin NP test has been recently developed to rapidly detect polymyxin resistance in Enterobacteriaceae. Here we evaluated this test for detecting MCR-1/MCR-2-producing Enterobacteriaceae using a collection of 70 non-redundant strains either recovered from the environment, animals, or humans. Sensitivity and specificity were found to be 100%.
September 22, 2017: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/29138303/cxc-chemokines-exhibit-bactericidal-activity-against-multidrug-resistant-gram-negative-pathogens
#16
Matthew A Crawford, Debra J Fisher, Lisa M Leung, Sara Lomonaco, Christine Lascols, Antonio Cannatelli, Tommaso Giani, Gian Maria Rossolini, Yohei Doi, David R Goodlett, Marc W Allard, Shashi K Sharma, Erum Khan, Robert K Ernst, Molly A Hughes
The continued rise and spread of antimicrobial resistance among bacterial pathogens pose a serious challenge to global health. Countering antimicrobial-resistant pathogens requires a multifaceted effort that includes the discovery of novel therapeutic approaches. Here, we establish the capacity of the human CXC chemokines CXCL9 and CXCL10 to kill multidrug-resistant Gram-negative bacteria, including New Delhi metallo-beta-lactamase-1-producing Klebsiella pneumoniae and colistin-resistant members of the family Enterobacteriaceae that harbor the mobile colistin resistance protein MCR-1 and thus possess phosphoethanolamine-modified lipid A...
November 14, 2017: MBio
https://www.readbyqxmd.com/read/29136469/novel-linear-lipopeptide-paenipeptins-with-potential-for-eradicating-biofilms-and-sensitizing-gram-negative-bacteria-to-rifampicin-and-clarithromycin
#17
Sun Hee Moon, Xuan Zhang, Guangrong Zheng, Daniel G Meeker, Mark S Smeltzer, En Huang
We report the structure-activity relationship analyses of 17 linear lipopeptide paenipeptin analogues. Analogues 7, 12, and 17 were more potent than the lead compound. Analogue 17 was active against carbapenem-resistant and polymyxin-resistant pathogens. This compound at 40 μg/mL resulted in 3 log and 2.6 log reductions of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, respectively, in catheter-associated biofilms in vitro. Analogue 17 showed little hemolysis at 32 μg/mL and lysed 11% of red blood cells at 64 μg/mL...
November 22, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29117525/membrane-cholesterol-reduces-polymyxin-b-nephrotoxicity-in-renal-membrane-analogs
#18
Adree Khondker, Richard J Alsop, Alexander Dhaliwal, Sokunthearath Saem, Jose M Moran-Mirabal, Maikel C Rheinstädter
Polymyxin B (PmB) is a "last-line" antibiotic scarcely used due to its nephrotoxicity. However, the molecular basis for antibiotic nephrotoxicity is not clearly understood. We prepared kidney membrane analogs of detergent-susceptible membranes, depleted of cholesterol, and cholesterol enriched, resistant membranes. In both analogs, PmB led to membrane damage. By combining x-ray diffraction, molecular dynamics simulations, and electrochemistry, we present evidence for two populations of PmB molecules: peptides that lie flat on the membranes, and an inserted state...
November 7, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/29117270/screening-for-the-presence-of-mcr-1-mcr-2-genes-in-shiga-toxin-producing-escherichia-coli-recovered-from-a-major-produce-production-region-in-california
#19
Daniela Mavrici, Jaszemyn C Yambao, Bertram G Lee, Beatriz Quiñones, Xiaohua He
The rapid spreading of polymyxin E (colistin) resistance among bacterial strains through the horizontally transmissible mcr-1 and mcr-2 plasmids has become a serious concern. The emergence of these genes in Shiga toxin-producing Escherichia coli (STEC), a group of human pathogenic bacteria was even more worrisome, urging us to investigate the prevalence of mcr genes among STEC isolates. A total of 1000 STEC isolates, recovered from livestock, wildlife, produce and other environmental sources in a major production region for leafy vegetables in California during 2006-2014, were screened by PCR for the presence of plasmid-borne mcr-1 and mcr-2...
2017: PloS One
https://www.readbyqxmd.com/read/29114023/mcr-1-inhibition-with-peptide-conjugated-phosphorodiamidate-morpholino-oligomers-restores-sensitivity-to-polymyxin-in-escherichia-coli
#20
Seth M Daly, Carolyn R Sturge, Christina F Felder-Scott, Bruce L Geller, David E Greenberg
In late 2015, the first example of a transferrable polymyxin resistance mechanism in Gram-negative pathogens, MCR-1, was reported. Since that report, MCR-1 has been described to occur in many Gram-negative pathogens, and the mechanism of MCR-1-mediated resistance was rapidly determined: an ethanolamine is attached to lipid A phosphate groups, rendering the membrane more electropositive and repelling positively charged polymyxins. Acquisition of MCR-1 is clinically significant because polymyxins are frequently last-line antibiotics used to treat extensively resistant organisms, so acquisition of this mechanism might lead to pan-resistant strains...
November 7, 2017: MBio
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